Blood Transfusion Guide 19ed 2017

Guide to the
preparation, use and

quality assurance of
BLOOD
COMPONENTS
European Committee EDQM

(Partial Agreement) 19th Edition
on Blood Transfusion 2017
(CD-P-TS )
Guide to the preparation,
use and quality assurance
of blood components
Recommendation No. R (95) 15
19th Edition
European Directorate for the Quality of Medicines & HealthCare

The Guide to the preparation, use and quality assurance of blood
components is published by the European Directorate for the Quality
of Medicines & HealthCare of the Council of Europe (EDQM).
All rights conferred by virtue of the International Copyright
Convention are specifically reserved to the Council of Europe and
any reproduction or translation requires the written consent of the
publisher.
Director of the Publication: Dr S. Keitel
Page layout and cover: EDQM

European Directorate for the Quality
of Medicines & HealthCare (EDQM)
Council of Europe
7, allée Kastner
CS 30026
F-67081 STRASBOURG
FRANCE
Website: www.edqm.eu
To order: www.edqm.eu/store
FAQs & EDQM HelpDesk: www.edqm.eu/hd
ISBN 978-92-871-8415-3
© Council of Europe, 2017
Printed at the Council of Europe
Supported by the European Union.

Contents
FOREWORD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
EUROPEAN COMMITTEE (PARTIAL AGREEMENT)

ON BLOOD TRANSFUSION (CD-P-TS) . . . . . . . . . . . . . . . . . . . . . 29
Chair . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
Members . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
Observers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
MEMBERS OF THE AD HOC GROUP (GTS) . . . . . . . . . . . . . . . . 39

Chair . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
Members . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
Recommendation No. R (95) 15 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
Guide to the preparation, use and quality assurance of blood
components . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
GOOD PRACTICE GUIDELINES . . . . . . . . . . . . . . . . . . . . . . . . . . . 50

Introductory note . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50
Good Practice Guidelines for blood establishments and hospital
blood banks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
1. General principles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
2. Personnel and organisation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
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Guide to the preparation, use and quality assurance of blood components
3. Premises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
4. Equipment and materials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
5. Documentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91
6. Blood collection, testing and processing . . . . . . . . . . . . . . . . . . . 101
7. Storage and distribution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114
8. Outsourced activities management . . . . . . . . . . . . . . . . . . . . . . . . 116
9. Non-conformance and recall . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119
10. Self-inspection, audits and improvements . . . . . . . . . . . . . . . . . 125
11. Quality monitoring and control . . . . . . . . . . . . . . . . . . . . . . . . . 126
PRINCIPLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129
Chapter 1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
Chapter 2 Principles of donor selection . . . . . . . . . . . . . . . . . . . . . 133
1. General remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133
2. Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134
3. Medical assessment of the donor . . . . . . . . . . . . . . . . . . . . . . . . . . 135
Age of the donor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135
Hazardous occupations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135
Donor deferral . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136
Conditions requiring permanent deferral . . . . . . . . . . . . . . . . . . . 136
Conditions requiring temporary deferral (suspension) . . . . . . . . 136
Vaccination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136
Conditions requiring individual assessment . . . . . . . . . . . . . . . . . 136
Post-donation information . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137
Infectious diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138
History of malignancy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140
4. Specific considerations for donors of different components . . 141
Quantity of whole blood donation . . . . . . . . . . . . . . . . . . . . . . . . . . 141
Frequency of whole blood donation . . . . . . . . . . . . . . . . . . . . . . . . . 142
Laboratory examination before donation . . . . . . . . . . . . . . . . . . . . 143
Apheresis donors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144
Designated donations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 148
Directed donations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149
Chapter 3 Principles of blood collection . . . . . . . . . . . . . . . . . . . . 151
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1. Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151
2. Premises for donor sessions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151
3. Equipment used at blood donation sessions . . . . . . . . . . . . . . . . 152
4. Pre-donation checks and labelling . . . . . . . . . . . . . . . . . . . . . . . . 152
5. Venepuncture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 152
Preparation of the venepuncture site . . . . . . . . . . . . . . . . . . . . . . . . 152
Successful venepuncture and proper mixing . . . . . . . . . . . . . . . . . 153
Handling of filled containers and samples . . . . . . . . . . . . . . . . . . . 154
6. Apheresis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155
Pre-medication and apheresis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155
Automated apheresis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155
Manual apheresis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155
7. Repository of archive samples . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155
8. Management of adverse reactions in donors . . . . . . . . . . . . . . . . 155
Prevention of adverse reactions in donors . . . . . . . . . . . . . . . . . . . 157
Treatment of adverse reactions in donors . . . . . . . . . . . . . . . . . . . . 157
Documentation of adverse reactions in donors . . . . . . . . . . . . . . . 158
Information for a donor with adverse reactions . . . . . . . . . . . . . . . 158
9. Donor clinic documentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 158
Chapter 4 Principles of blood component processing . . . . . . . . 161
1. Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161
2. Processing procedures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 162
3. Choice of anticoagulant and bag system . . . . . . . . . . . . . . . . . . . 162
4. Centrifugation of whole blood derived blood components . . . 164
5. Leucocyte depletion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167
6. Freezing and thawing of plasma . . . . . . . . . . . . . . . . . . . . . . . . . . 167
Rationale . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167
Methods of freezing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 168
Methods of thawing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169
Cryoprecipitation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169
7. Open and closed systems and sterile connection devices . . . . 170
8. Irradiation of cellular blood components . . . . . . . . . . . . . . . . . . 170
9. Prevention of CMV transmission . . . . . . . . . . . . . . . . . . . . . . . . . 171
10. Pathogen reduction technologies . . . . . . . . . . . . . . . . . . . . . . . . . 172
11. Purity of components . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173
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12. Bacterial safety of blood components . . . . . . . . . . . . . . . . . . . . . 174

Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 174
Quality control for aseptic collection and processing of blood
components . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175
Release as ‘culture-negative to date’ after bacteriological testing
of all platelets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175
13. Storage of blood components . . . . . . . . . . . . . . . . . . . . . . . . . . . . 176
Equipment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 176
Storage at + 2 to + 6 °C . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 176
Storage of frozen plasma components . . . . . . . . . . . . . . . . . . . . . . . 177
Storage at + 20 to + 24 °C . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 177
Aspects of red cell preservation . . . . . . . . . . . . . . . . . . . . . . . . . . . . 177
Additive solutions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 178
Micro-aggregates in blood components . . . . . . . . . . . . . . . . . . . . . 179
Red cell preparations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179
Platelet preparations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179
Granulocyte preparations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 180
Plasma components could be stored at different temperatures . . 180
14. Transport of blood components . . . . . . . . . . . . . . . . . . . . . . . . . 181
Transport of standard red cell components . . . . . . . . . . . . . . . . . . 181
Transport of platelet components . . . . . . . . . . . . . . . . . . . . . . . . . . . 181
Transport of frozen plasma components . . . . . . . . . . . . . . . . . . . . . 182
15. Component information and principles of labelling . . . . . . . . 182
Chapter 5 Principles of blood component monographs . . . . . . . 183
1. Definition and properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 184
2. Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 184
3. Requirements and quality control . . . . . . . . . . . . . . . . . . . . . . . . . 184
4. Storage and transport . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 185
5. Labelling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 185
6. Warnings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 185
Chapter 6 Principles of blood components for intrauterine,
neonatal and infant use . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 187
1. Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 187
2. Components for intrauterine transfusions . . . . . . . . . . . . . . . . . 188
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3. Components for neonatal exchange transfusion . . . . . . . . . . . . 188

4. Red cells for neonatal and infant small volume transfusion . . 189
5. Fresh frozen plasma for neonatal and infant use . . . . . . . . . . . . 190
6. Platelets for neonatal and infant use . . . . . . . . . . . . . . . . . . . . . . . 190
Chapter 7 Principles of autologous transfusion . . . . . . . . . . . . . . 193
1. Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193
2. Pre-deposit autologous transfusion . . . . . . . . . . . . . . . . . . . . . . . 195
Patient selection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 195
Blood collection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 196
Preparation, storage and distribution of pre-deposit autologous
components . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 197
Labelling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 197
Storage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 197
Records . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 197
Audit . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 198
3. Red cell salvage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 198
Collection system . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 198
Processing system . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 199
Indications for the use of cell salvage . . . . . . . . . . . . . . . . . . . . . . . . 199
Parameters for quality control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 199
Precautions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 200
Chapter 8 Principles of immunohaematology . . . . . . . . . . . . . . . 201
1. Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 201
2. Immunohaematological testing . . . . . . . . . . . . . . . . . . . . . . . . . . . 202
Blood group testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 202
3. Antibody screening and identification . . . . . . . . . . . . . . . . . . . . 203
Pre-transfusion testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 204
Quality control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 206
Internal quality control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 206
Quality control of reagents and techniques . . . . . . . . . . . . . . . . . . 206
Quality control of equipment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 207
External quality assurance (proficiency testing) . . . . . . . . . . . . . . 207
Chapter 9 Principles of screening for markers of infection . . . . 209
1. Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 209
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2. Algorithm for infectious marker screening and

confirmatory testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 210
3. Confirmatory testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 212
Anti-HIV-1/2, anti-HCV and HBsAg . . . . . . . . . . . . . . . . . . . . . . . 212
Anti-HTLV-I-II . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 213
4. Nucleic acid screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 213
5. Additional screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 213
Syphilis screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 213
Anti-HBc screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 214
CMV screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 214
Malaria screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 214
Trypanosoma cruzi screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215
NAT screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215
Chapter 10 Principles of haemovigilance . . . . . . . . . . . . . . . . . . . . 217
1. Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 217
2. Prerequisites for implementation of a haemovigilance
network . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 218
Traceability of blood components . . . . . . . . . . . . . . . . . . . . . . . . . . 218
Co-operation between blood establishments, hospital blood
banks and clinical departments . . . . . . . . . . . . . . . . . . . . . . . . . . . . 220
3. Types of adverse reactions and adverse events collected in a
haemovigilance network . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 221
Adverse reactions in patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 221
Adverse reactions in donors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 222
Adverse events . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223
Device defects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 224
4. Tracing and recall of potentially infectious donations for
HIV, HCV or HBV (look-back) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 225
Post-transfusion infection in a recipient reported to the blood
establishment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 225
Post-donation information . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 226
Recall of blood components . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 226
Tracing of recipients of potentially infectious blood donations
(look-back/review) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 226
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5. Contracts between blood establishments and hospitals for

haemovigilance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 227
Minimum information to be captured in the initial incident
report at hospital level . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 227
6. Reporting haemovigilance data . . . . . . . . . . . . . . . . . . . . . . . . . . . 228
Standardisation of reporting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 228
Data analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 228
Information sent to the haemovigilance database . . . . . . . . . . . . . 228
Component information . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 228
Information about severity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 229
Information about imputability . . . . . . . . . . . . . . . . . . . . . . . . . . . . 229
Information about the type of adverse events and reactions . . . . 230
Chapter 11 Principles of clinical use of blood . . . . . . . . . . . . . . . . 231
1. Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 231
2. Decision to transfuse . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 233
Patient blood management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 234
3. Completion of the transfusion request form, identification
of patient and blood sampling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235
4. Correct identification of the patient and obtaining a pre-
transfusion sample . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235
5. Testing within the laboratory . . . . . . . . . . . . . . . . . . . . . . . . . . . . 236
6. Selection and issue of appropriate blood components . . . . . . . 236
Handling and storage of blood components in hospital clinical
areas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 237
7. Administration of blood components . . . . . . . . . . . . . . . . . . . . . . 237
Special precautions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 238
Transfusion monitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 238
Management and reporting of transfusion reactions . . . . . . . . . . 239
Traceability and haemovigilance . . . . . . . . . . . . . . . . . . . . . . . . . . . 241
8. Hospital transfusion committees . . . . . . . . . . . . . . . . . . . . . . . . . 241
STANDARDS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243
Chapter 1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245
Chapter 2 Standards for selection of donors . . . . . . . . . . . . . . . . . 247
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1. Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 247
2. Information to be provided to the donor . . . . . . . . . . . . . . . . . . . 247
3. Medical assessment of the donor . . . . . . . . . . . . . . . . . . . . . . . . . . 249
Donor eligibility . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 249
Questionnaire and interview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 250
Donor details . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 250
Age of the donor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 250
Donor appearance and inspection . . . . . . . . . . . . . . . . . . . . . . . . . . 251
4. Donor deferral . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 251
Infectious diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 254
5. Specific standards for donors of different types of
components . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 258
Whole blood donors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 258
Quantity of donation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 258
Apheresis donors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 259
6. Post-donation information . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 262
Chapter 3 Standards for collection of blood and blood
components . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 263
1. Premises for donor sessions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 263
2. Procedures and equipment used at blood donation sessions . . 264
3. Pre-donation checks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 264
4. Labelling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 264
5. Venepuncture, bleeding and mixing . . . . . . . . . . . . . . . . . . . . . . . 265
Preparation of the venepuncture site . . . . . . . . . . . . . . . . . . . . . . . . 265
Successful venepuncture and proper mixing . . . . . . . . . . . . . . . . . 266
6. Handling of filled containers and samples . . . . . . . . . . . . . . . . . 267
7. Special requirements for apheresis . . . . . . . . . . . . . . . . . . . . . . . . 267
Return of red blood cells of donors undergoing manual
apheresis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 268
8. Repository of archive samples . . . . . . . . . . . . . . . . . . . . . . . . . . . . 268
Chapter 4 Standards for the processing, storage
and distribution of blood components . . . . . . . . . . . . . . . . . . . . . . . 269
1. Processing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 269
2. Component labelling and information . . . . . . . . . . . . . . . . . . . . 270
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3. Release of blood components . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 271

4. Storage and distribution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 273
5. Irradiation of blood components . . . . . . . . . . . . . . . . . . . . . . . . . . 274
6. Leucocyte depletion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 275
7. Bacterial safety . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 275
Chapter 5 Component monographs . . . . . . . . . . . . . . . . . . . . . . . . 277
Component monographs
Part A. Whole Blood components . . . . . . . . . . . . . . . . . . . . . . . . . . . 279
1. Whole Blood . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 280
Definition and properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 280
Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 280
Requirements and quality control . . . . . . . . . . . . . . . . . . . . . . . . . . 280
Storage and transport . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 281
Labelling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 281
Warnings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 282
2. Whole Blood, Leucocyte-Depleted . . . . . . . . . . . . . . . . . . . . . . . . 283
Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 284
Labelling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 285
Warnings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 286
Part B. Red cell components . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 289
1. Red Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 290
Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 290
Labelling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 291
Warnings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 292
2. Red Cells, Buffy Coat Removed . . . . . . . . . . . . . . . . . . . . . . . . . . . 293
Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 293
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Labelling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 295
Warnings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 295
3. Red Cells, in Additive Solution . . . . . . . . . . . . . . . . . . . . . . . . . . . 297
Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 297
Labelling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 298
Warnings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 299
4. Red Cells, Buffy Coat Removed, in Additive Solution . . . . . . . 300
Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 301
Labelling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 302
Warnings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 303
5. Red Cells, Leucocyte-Depleted . . . . . . . . . . . . . . . . . . . . . . . . . . . .304
Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 304
Labelling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 305
Warnings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 306
6. Red Cells, Leucocyte-Depleted in Additive Solution . . . . . . . . . 307
Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 308
Labelling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 309
Warnings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 310
7. Red Cells, Apheresis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 311
Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 311
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Labelling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 313
Warnings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 314
8. Red Cells, Washed . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 315
Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 315
Labelling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 317
Warnings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 317
9. Red Cells, Cryopreserved . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 318
Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 319
Labelling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 321
Warnings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 322
Part C. Platelet components . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 325
1. Platelets, Recovered, Single Unit . . . . . . . . . . . . . . . . . . . . . . . . . . 326
Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 326
Labelling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 328
Warnings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 329
2. Platelets, Recovered, Pooled . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 330
Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 330
Labelling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 332
Warnings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 333
3. Platelets, Recovered, Pooled, Leucocyte-Depleted . . . . . . . . . . . 334
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Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 334
Labelling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 337
Warnings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 337
4. Platelets, Recovered, Pooled, in Additive Solution . . . . . . . . . . . 339
Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 339
Labelling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 341
Warnings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 342
5. Platelets, Recovered, Pooled, Leucocyte-Depleted, in
Additive Solution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 343
Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 343
Labelling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 345
Warnings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 346
6. Platelets, Pooled, Pathogen-reduced . . . . . . . . . . . . . . . . . . . . . . . 347
Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 348
Labelling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 349
Warnings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 350
7. Platelets, Apheresis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 351
Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 351
Labelling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 353
Warnings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 354
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8. Platelets, Apheresis, Leucocyte-Depleted . . . . . . . . . . . . . . . . . . . 355

Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 355
Labelling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 357
Warnings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 358
9. Platelets, Apheresis, in Additive Solution . . . . . . . . . . . . . . . . . . 359
Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 359
Labelling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 361
Warnings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 362
10. Platelets, Apheresis, Leucocyte-Depleted, in Additive
Solution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 363
Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 363
Labelling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 365
Warnings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 366
11. Platelets, Apheresis, Pathogen-reduced . . . . . . . . . . . . . . . . . . . 367
Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 368
Labelling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 370
Warnings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 370
12. Platelets, Cryopreserved . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 371
Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 372
Labelling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 373
15
Warnings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 374
Part D. Plasma components . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 377
1. Plasma, Fresh Frozen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 378
Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 378
Labelling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 381
Warnings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 381
2. Plasma, Fresh Frozen, Pathogen Reduced . . . . . . . . . . . . . . . . . . 382
Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 383
Labelling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 385
Warnings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 385
3. Cryoprecipitate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 387
Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 387
Labelling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 390
Warnings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 390
4. Cryoprecipitate, Pathogen Reduced . . . . . . . . . . . . . . . . . . . . . . . 391
Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 392
Labelling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 394
Warnings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 395
5. Plasma, Fresh Frozen, Cryoprecipitate-Depleted . . . . . . . . . . . . 396
Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 396
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Labelling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 397
Warnings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 398
Part E. White cell components . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 399
1. Granulocytes, Apheresis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 400
Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 401
Labelling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 402
Warnings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 403
2. Granulocytes, Pooled . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 404
Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 404
Labelling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 406
Warnings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 406
Chapter 6 Standards for blood components for intrauterine,
neonatal and infant use . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 409
Standards for blood components for intrauterine, neonatal
and infant use
Part A. Components for intrauterine transfusions . . . . . . . . . . . . 411
1. Red Cells, Leucocyte-Depleted for Intrauterine Transfusion . 412
Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 412
Labelling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 413
Warnings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 413
2. Platelets, Leucocyte-Depleted for Intrauterine Transfusion . . 414
Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 414
17

Labelling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 415
Warnings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 416
Standards for blood components for intrauterine, neonatal
and infant use
Part B. Components for neonatal exchange transfusion . . . . . . . 417
1. Whole Blood, Leucocyte-Depleted for Exchange Transfusion 418
Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 418
Labelling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 418
Warnings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 419
2. Whole Blood, Leucocyte-Depleted, Plasma Reduced for
Exchange Transfusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 419
Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 420
Labelling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 421
Warnings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 421
3. Red Cells, Leucocyte-Depleted, suspended in Fresh Frozen
Plasma, for Exchange Transfusion . . . . . . . . . . . . . . . . . . . . . . . . . . . 421
Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 422
Labelling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 423
Warnings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 423
Standards of blood components for intrauterine, neonatal
and infant use
Part C. Components (small volume) for neonatal and infant
transfusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 425
18
Contents
1. Red Cells for Neonatal and Infant Small Volume Transfusion 426
Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 426
Quality control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 426
Labelling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 427
Warnings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 427
Chapter 7 Standards for autologous pre-deposit transfusion . . 429
1. Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 429
2. Selection of patients for PAT and blood collection . . . . . . . . . . 430
Role of the physician in charge of collection . . . . . . . . . . . . . . . . . . 430
Information for donors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 430
Contraindications or deferral criteria . . . . . . . . . . . . . . . . . . . . . . . 430
3. Preparation, storage and distribution of pre-deposit
autologous blood components . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 431
Blood typing and microbiological screening . . . . . . . . . . . . . . . . . 431
Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 431
Labelling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 431
Storage and handling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 432
Warnings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 432
Chapter 8 Standards for immunohaematology . . . . . . . . . . . . . . 433
1. Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 433
2. Selection and validation of reagents and methods . . . . . . . . . . . 433
3. Quality control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 434
4. Blood group testing of blood donors and donations . . . . . . . . . 434
ABO and RhD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 434
Additional typing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 435
Irregular antibody testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 435
5. Testing of patient samples . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 435
Blood grouping and antibody detection . . . . . . . . . . . . . . . . . . . . . 436
Compatibility testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 436
Chapter 9 Standards for screening for infectious markers . . . . 439
1. Selection and validation of infectious marker tests . . . . . . . . . . 439
2. Mandatory serological screening tests . . . . . . . . . . . . . . . . . . . . . 440
19
3. Additional serological screening tests . . . . . . . . . . . . . . . . . . . . . 441

4. Management of reactive results in serological screening tests 441
5. Nucleic acid screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 442
6. Selective screening of donations . . . . . . . . . . . . . . . . . . . . . . . . . . 443
Chapter 10 Standards for haemovigilance . . . . . . . . . . . . . . . . . . . 445
1. Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 445
2. Prerequisites for implementation of a haemovigilance
network . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 445
Traceability of blood components . . . . . . . . . . . . . . . . . . . . . . . . . . 445
Confidentiality of haemovigilance data . . . . . . . . . . . . . . . . . . . . . . 446
3. Device defects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 446
4. Post-transfusion infection reported to the blood
establishment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 446
APPENDIX 1.
KEY CRITERIA FOR DONOR ELIGIBILITY . . . . . . . . . . . . . . . 449
APPENDIX 2.
TABLES FOR CALCULATION OF BLOOD VOLUMES . . . . . . 467
APPENDIX 3.
DATA PROCESSING SYSTEMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . 483
1. Planning of a system . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 484
2. Defining the system . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 484
3. Implementation and validation . . . . . . . . . . . . . . . . . . . . . . . . . . . 485
Functional testing of components . . . . . . . . . . . . . . . . . . . . . . . . . . 486
Data migration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 486
Environmental testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 486
Change control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 487
Maintenance of the system . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 487
Quality assurance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 488
4. Electronic signature . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 489
General requirements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 490
Signature manifestations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 490
Signature/record linking . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 490
20
Contents
Controls for identification codes/passwords/biometrics . . . . . . . 490
APPENDIX 4.
STATISTICAL PROCESS CONTROL . . . . . . . . . . . . . . . . . . . . . . . 493
1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 494
2. Implementation of SPC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 494
3. Strategy for statistical sampling . . . . . . . . . . . . . . . . . . . . . . . . . . .494
Tolerance of failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 495
Confidence level . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 495
4. Frequency of control sampling . . . . . . . . . . . . . . . . . . . . . . . . . . . 495
Example 1. Use of control charts . . . . . . . . . . . . . . . . . . . . . . . . . . . 497
Example 2. Method of scan statistics . . . . . . . . . . . . . . . . . . . . . . . . 501
Example 3. Statistical process control for dichotomous
outcomes: an approach based upon hypergeometric/binomial
distributions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 504
APPENDIX 5.
HEALTH ECONOMICS IN BLOOD TRANSFUSION . . . . . . . . 515
1. Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 516
2. Investing in quality . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 516
3. Costing analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 517
4. Modelling cost-effectiveness analysis in transfusion . . . . . . . . . 517
5. Economic aspects of the clinical use of blood . . . . . . . . . . . . . . . 518
DEFINITIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 519
ABBREVIATIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 531
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 535
21
FOREWORD
Founded in 1949, the Council of Europe is the oldest and largest of all
European institutions and currently numbers 47 member states.1 One
of its founding principles is that of increasing co-operation between
member states to improve the quality of life for all Europeans.
Within this context of intergovernmental co-operation in the field
of health, the Council of Europe has consistently selected ethical
problems for study. The most important such ethical issue relates to
the non-commercialisation of human substances, i.e. blood, organs
and tissues.
With regard to blood transfusion, co-operation among member states
started back in the 1950s. From the outset, the activities were inspired
by the following guiding principles: promotion of voluntary, non-
1 Albania, Andorra, Armenia, Austria, Azerbaijan, Belgium, Bosnia and

Herzegovina, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia,
Finland, France, Georgia, Germany, Greece, Hungary, Iceland, Ireland, Italy,
Latvia, Liechtenstein, Lithuania, Luxembourg, Malta, Republic of Moldova,
Monaco, Montenegro, Netherlands, Norway, Poland, Portugal, Romania,
Russian Federation, San Marino, Serbia, Slovak Republic, Slovenia, Spain,
Sweden, Switzerland, ‘the former Yugoslav Republic of Macedonia’, Turkey,
Ukraine, United Kingdom.
23
remunerated blood donation, mutual assistance, optimal use of blood

and blood products and protection of the donor and the recipient.
The first result of this co-operation was the adoption of the European
Agreement on the Exchange of Therapeutic Substances of Human
Origin (European Treaty Series, No. 26) in 1958. It was followed by
the European Agreement on the exchange of blood grouping reagents
(European Treaty Series, No. 39) and of tissue-typing reagents
(European Treaty Series, No. 84) in 1962 and 1976 respectively.
Around these three Agreements, the Council of Europe has
established a blood transfusion programme, the aim of which is to
ensure good quality and safety of blood and blood components.
Since then, the Council of Europe has adopted a number of
recommendations covering ethical, social, scientific and training
aspects of blood transfusion. Whereas Agreements are binding on the
States that ratify them, Recommendations are policy statements to
governments proposing a common course of action to be followed.
Major recommendations include Recommendation No. R (88) 4
on the responsibilities of Health Authorities in the field of blood
transfusion and Recommendation No. R (95) 15, which contains a
technical appendix entitled Guide to the preparation, use and quality
assurance of blood components.
Work on Recommendation No. R (95) 15 started in 1986, when
the Select Committee of Experts on Quality Assurance in Blood
Transfusion Services published proposals on quality assurance in
blood transfusion services.
Based on these proposals, the Select Committee produced a more
comprehensive document entitled Guide to the preparation, use and
quality assurance of blood components referred to hereafter as the
Guide. The immediate success and acceptability of this document
was such that the Committee of Ministers adopted it as a technical
appendix to what then became Recommendation No. R (95) 15.
The purpose of this Recommendation and its technical appendix is to
provide blood transfusion establishments with a set of standards and
24
Foreword
principles relating to the preparation, use and quality assurance of

blood components. The Guide covers all blood components that will
be prepared at a blood transfusion establishment and is intended to
form the basis for standard operating procedures (SOPs).
The Recommendation does not cover plasma products obtained
by fractionation. In respect of plasma-derived products, technical
matters are addressed by the European Pharmacopoeia whilst the
European Union has a substantial body of legislation regarding
pharmaceutical products including plasma-derived medicinal
products.
On 27 January 2003 the European Union adopted Directive 2002/98/
EC on setting standards of quality and safety for the collection,
testing, processing, storage and distribution of human blood and
blood components. As regards technical requirements to be set
under Article 29 of the said Directive, the European Commission
and the Council of Europe work closely together to ensure that these
requirements are compatible with this Guide.
As of the 15th Edition of the Guide, the content has been separated into
two sections. The first, entitled Principles, encompasses background
information that has to be considered in forming policy decisions as
well as educational aspects thus providing the ‘why and how’. It also
refers to developments that are not yet incorporated into standards,
thus providing advance information about technical changes in
the field. It was anticipated that in the subsequent editions of the
Guide, apart from changes to its technical content, the Principles
Section would be further expanded. The second section, entitled
Standards, contains the matters that are considered to be ‘minimum
standards’ aligning closely to the European Pharmacopoeia and
European Commission Directives. It is intended to assist other
jurisdictions to transpose these into legislation. The Standards section
states ‘what must be done’. Whereas blood establishments in EEA
member states are required to comply with legislation derived from
the European Commission Directives, this Guide is intended to
facilitate ongoing improvements on the preparation, use and quality
25
assurance of blood components through education and the provision

of non-binding recommendations. The Guide therefore provides
additional information and guidance on best practices consistent
with current scientific knowledge and expert opinion. At any given
time, implementation of these recommendations may vary among
member states and individual blood transfusion establishments, and
alternative procedures, practices and standards may be in place.
Recommendation No. R (95) 15 also states that its technical appendix,
the Guide, will be regularly updated to keep it in line with scientific
progress. This task was assigned to the European Committee (Partial
Agreement) on Blood Transfusion (CD-P-TS), a Steering Committee
of the Council of Europe pursuing activities in the field of blood
transfusion. The European Directorate for the Quality of Medicines &
HealthCare (EDQM)2 is in charge of the scientific secretariat for these
activities.
This is the 19th Edition of the Guide. This publication was elaborated
by a dedicated ad hoc working group of experts nominated by the
CD-P-TS and entrusted with the responsibility of updating its text
as instructed by the Committee of Ministers in Recommendation
No. R (95) 15.
2 EDQM is a Directorate of the Council of Europe, created in 1964 on the legal

basis of the Convention on the Elaboration of a European Pharmacopoeia, to
which 37 member states and the European Union are signatory.
Members: Austria, Belgium, Bosnia and Herzegovina, Bulgaria, Croatia,
Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany,
Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg,
Malta, Montenegro, Netherlands, Norway, Poland, Portugal, Romania, Serbia,
Slovak Republic, Slovenia, Spain, Sweden, Switzerland, ‘the former Yugoslav
Republic of Macedonia’, Turkey, Ukraine, United Kingdom, and the European
Union.
Observers: Albania, Algeria, Argentina, Armenia, Australia, Azerbaijan,
Belarus, Brazil, Canada, China, Georgia, Guinea, India, Israel, Japan,
Kazakhstan, Republic of Korea, Madagascar, Malaysia, Republic of Moldova,
Morocco, Russian Federation, Senegal, Singapore, South Africa, Syria, Tunisia,
the United States of America, the Taiwan Food and Drug Administration and
the World Health Organization.
26
Foreword
The elaboration of the 19th Edition of the Guide included a large

public consultation of the draft version by stakeholders. All comments
received were considered by the ad hoc expert working group in order
to produce a final version by amending the text where necessary.
The CD-P-TS approved the text of the Guide in November 2016 and
released it for publication as the 19th Edition.
The 19th Edition of the Guide contains an updated version of the
Good Practice Guidelines to fully reflect the most recent changes
in good manufacturing practices relevant for blood establishments.
The Good Practice Guidelines have been jointly developed by the
European Directorate for the Quality of Medicines & HealthCare
and the Commission of the European Union. This section of the
Guide describes standards and specifications for the quality system
to be implemented by blood establishments. In the European Union,
Directive (EU) 2016/1214, published in July 2016, requests member
states to ensure that blood establishments comply with the Good
Practice Guidelines for their quality system by 15 February 2018.
The elaboration of the text of the 19th Edition of the Guide would
not have been possible without the outstanding contributions of the
ad hoc working group. Special thanks should be made to all those
experts for their enlightening contributions and to the Chairperson
for her dedication. A detailed list showing the composition of this
working group is included. Furthermore, all participants in the public
consultation and members of the CD-P-TS who have submitted many
constructive comments are also warmly acknowledged.
The drafting and the publication of the 19th Edition of the Guide
was co-ordinated within the EDQM by Dr Guy Rautmann with the
assistance of Ms Ines Khraief-Zouari, Ms Nevena Kojic, Ms Mary
Quinn and Mr David Crowe.
27
EUROPEAN COMMITTEE
(PARTIAL AGREEMENT)
ON BLOOD TRANSFUSION
(CD-P-TS)
Composition of the Committee as of 31 October 2016
Chair
FLESLAND Oystein
The Norwegian Knowledge
Centre for the Health Services
PO Box 7004 St Olavs plass
NO – 0130 OSLO
oystein.flesland@helsedir.no
Members
Austria Belgium
SCHENNACH Harald Nomination pending
Central Institute for Blood
Transfusion and Immunology Bosnia and Herzegovina
(ZIB) Nomination pending
TILAK – University Clinics –
Regional Hospital
Anichstrasse 35
AT – 6020 INNSBRUCK
harald.schennach@tirol-kliniken.at
29
Bulgaria Denmark
MASHAROVA Natalia BAGGE HANSEN Morten
National Centre of Transfusion Blood Transfusion Centre
Haematology Righospitalet
112 Bratia Miladinovi St. Blegdamsvej, 9
BG – 1202 SOFIA DK – 2100 COPENHAGEN
nathalie_54@abv.bg morten.bagge.hansen@regionh.dk
Croatia Estonia
VUK Tomislav KULLASTE Riin
Croatian Institute of Transfusion North Estonia Medical Centre’s
Medicine Blood Centre
Petrova 3 2 Adala Street
CRO – 10 000 ZAGREB ZES – 10614 TALLINN
tomislav.vuk@hztm.hr riin.kullaste@regionaalhaigla.ee
Cyprus Finland
KIOUPI Stala CASTRÉN Johanna
Cyprus Ministry of Health Finnish Red Cross Blood Service
Medical and Public Health Kivihaantie, 7
Services FI – 00310 HELSINKI
Giorgio Prodromou 1 and johanna.castren@bloodservice.fi
Hilonos 17
CY – 1449 NICOSIA France
s.kioupi@cytanet.com.cy DELBOSC Arlette
Direction Générale de la Santé,
Czech Republic Ministère de la Santé
TUREK Petr 14 Avenue Duquesne, Bureau PP4
Thomayer Hospital FR – 75007 PARIS
Videnskà, 800 arlette.delbosc@sante.gouv.fr
RTC – 140 59 PRAHA 4
petr.turek@ftn.cz
30
European Committee (Partial Agreement) on Blood Transfusion (CD-P-TS)
Germany Hungary
STAHL Dorothea BAROTI TOTH Klara
Paul Ehrlich Institute Hungarian National Blood
Paul Ehrlich Strasse, 51-59 Transfusion Service
DE – 63207 LANGEN 19-21 Karolina St.
dorothea.stahl@pei.de H – 1113 BUDAPEST
barotine.toth.klara@ovsz.hu
STROBEL Johanna (substitute)
Federal Ministry of Health Ireland
DE – 53107 BONN
Nomination pending
johanna.strobel@bmg.bund.de
Italy
Greece LIUMBRUNO Giancarlo
POLITIS Constantina Italian National Blood Centre
Ministry of Health, National Istituto Superiore di Sanità
Blood Centre Via Giano della Bella No 27
Coordinating Haemovigilance IT – 00162 ROME
Centre, Hellenic CDC giancarlo.liumbruno@iss.it
10 Averof Str,
GR – 10433 ATHENS DE ANGELIS Vincenzo
(substitute)
cpolitis@keelpno.gr
Udine University Hospital
DADIOTIS Loukas (substitute) P. le S. Maria della
General Hospital of Piraeus Misericordia, 15
Tzaneio IT – 33100 UDINE
GR – 18536 PIRAEUS deangelis.vincenzo@aoud.sanita.
aimodosia@tzaneio.gr fvg.it
Latvia
DAUGAVVANAGA Anita
State Blood Donor Center, Riga
Selpils Street 9
LV – 1007 RIGA
anita.daugavvanaga@vadc.gov.lv
31
Lithuania Montenegro
NAUJOKAITE Alvyda RASOVIC Gordana
Ministry of Health of the Institute for Blood Transfusion
Republic of Lithuania of Montenegro
Vilniaus St., 33 Dzona Dzeksona BB
LT – 01506 VILNIUS ME – 81000 PODGORICA
alvyda.naujokaite@sam.lt gordana.rasovic@ztkcg.me
OGINSKIENE Rasa (substitute) Netherlands

Ministry of Health
Nomination pending
28 Naikupės str.
LT - 93194 KLAIPĖDA Poland
r.oginskiene@kraujodonoryste.lt RADZIWON Piotr Marek
Regional Centre for Transfusion
Luxembourg Medicine
COURRIER Paul Ul.M.Sklodowskiej Curie 23
Centre de Transfusion PL – 15-950 BIALYSTOK
sanguine de la Croix Rouge pradziwon@rckik.bialystok.pl
luxembourgeoise
42 boulevard Joseph II Portugal
L – 1840 LUXEMBOURG
SOUSA Ana Paula
paul.courrier@croix-rouge.lu Centro de Sangue e da
Transplantação de Lisboa
Malta Parque de Saúde de Lisboa, Av.
LASPINA Stefan do Brasil
Mater Dei Hospital Blood Bank PT – 1749-005 LISBOA
Pathology Department, Block C, ana.paula@ipst.min-saude.pt
Level -1
MT – MSD 2090 TAL-QROQQ CHIN TAD MUON Mário
Centro de Sangue e da
stefan.laspina@gov.mt
Transplantação de Coimbra
Rua Escola Inês Castro Póvoa
PT – 3040-226 COIMBRA
mario.chin@ipst.min-saude.pt
32
Romania Irena RAZBORSEK (substitute)

DOBROTA Alina Mirella Blood Transfusion centre of
Regional Blood Transfusion Slovenia
Centre Slajmerjeva ulica 6
St. Nicolas lorga, n 85 SI – 1000 LJUBLJANA
Constanta County irena.razborsek@ztm.si
RO – 900587 CONSTANTA
alina_mirella@yahoo.com Spain
FERNANDEZ ALVAREZ
Serbia Carmen
VASILJEVIC Nada Ministry of Health, Social
Ministry of Health Services and Equality
Direction of Biomedicine Servicio de Hematologia Hospital
Pasterova 1 de Cabuenes
SRB – 11000 BELGRADE Calle Los Prados nº 395
ES – 33394 GIJON
vnada12345@gmail.com
carmen.fernandez@sespa.princast.
Slovak Republic es
contactsetscfa@gmail.com
ROSOCHOVA Jana
Ministerstvo zdravotníctva SR
Sweden
Limbova 2
SK – 837 52 Bratislava NORDA Rut
Klinisk immunologi och
rosochova@ntssr.sk transfusionsmedicin
Uppsala University Hospital
Slovenia Akademiska Sjukhuset, ing 61
ROZMAN Primoz SE – 751 85 UPPSALA
Blood Transfusion Centre of
rut.norda@akademiska.se
Slovenia
Slajmerjeva ulica 6
SI – 1000 LJUBLJANA
primoz.rozman@ztm.si
33
STROM Helena (substitute) Turkey

Socialstyrelsen ERTUGRUL ORUC Nigar
The National Board of Health Blood Transfusion Centre
and Welfare Diskapi Yildirim Beyazit
SE – 106 30 STOCKHOLM Training and Research Hospital
helena.strom@socialstyrelsen.se Ministry of Health
TR – 06110 ANKARA
Switzerland nigarertugrul@gmail.com
AMSLER Lorenz
Swissmedic United Kingdom
Hallerstrasse 7 MACLENNAN Sheila (Vice
CH – 3000 BERN 9 Chair)
lorenz.amsler@swissmedic.ch NHS Blood and Transplant
Leeds Centre
AMAR EL-DUSOUQUI Soraya Bridle Path
(substitute) UK – LEEDS LS15 7TW
Croix Rouge Suisse
Service de la Transfusion sheila.maclennan@nhsbt.nhs.uk
Sanguine
Laupenstrasse, 37
CP 5510
CH – 3001 BERN
soraya.amar@blutspende.ch
‘The former Yugoslav

Republic of Macedonia’
VELKOVA Emilija
Institute of Transfusion
Medicine
Mother Theresa 17
MAC – 1000 SKOPJE
emavelkova@yahoo.com
34
Observers
Albania Canada
DURO Vjollca AGBANYO Francisca
Boulevard Bajram Curri Centre for Biologics Evaluation
AL – 1001 TIRANA 3rd floor, Room 3379 AL 0603C3
1000 Eglantine Driveway
Armenia K1A 0KP
DAGHBASHYAN Smbat CA – OTTAWA, ONTARIO
Center of Haematology
francisca_agbanyo@hc-sc.gc.ca
Ministry of Health
7 H. Nersisyan Str.
Georgia
AM – 0017 YEREVAN
AVALISHVILI Levan
armhaem@gmail.com The Jo Ann Medical Centre
21 Lubliana St.
Australia GE – 0159 TBILISI
SMITH Glenn
levanavali@gmail.com
Therapeutic Goods
Administration Laboratories
Moldova
Office of Scientific Evaluation
136, Narrabundah Lane CEBOTARI Svetlana
Symonston National Blood Transfusion
PO Box 100 Centre
AU – ACT 2609 WODEN Str. Academi 11
MD – 2028 CHIȘINĂU
glenn.smith@tga.gov.au
cebotaris@mail.ru
PROSSER Ian
Therapeutic Goods
Administration Laboratories
136 Narrabundah Lane
AUS –2606 SYMONSTON ACT
ian.prosser@tga.gov.au
35
Republic of Belarus USA

POTAPNEV Michael EPSTEIN Jay
Belarusian Research and U.S. Food and Drug
Production Centre for Administration
Haematology – Tranfusiology Office of Blood Research and
Dolginovski tract, 160 Review
BY – 220053 MINSK 10903 New Hampshire Avenue
rspk@anitex.by USA – SILVER SPRING, MD
20993
Republic of Singapore jay.epstein@fda.hhs.gov
TEO Diana
WILLIAMS Alan (substitute)
Health Sciences Authority
U.S. Food and Drug
11 Outram Road
Administration
SGP – 169078 SINGAPORE
Division of Blood Applications
diana_teo@hsa.gov.sg 10903 New Hampshire Avenue
USA – SILVER SPRING, MD
Russian Federation 20993
EIKHLER Olga alan.williams@fda.hhs.gov
Federal Medico-Biological
Agency of Russia DH-BIO (Bioethics Committee,
Volokalamskoye shosse, 30 Council of Europe)
RU – 123182 MOSCOW
LWOFF Laurence
blood@fmbamail.ru Head of Bioethics Unit
Human Rights Directorate
Council of Europe
FR – 67075 STRASBOURG
laurence.lwoff@coe.int
36
European Commission
VAN DER SPIEGEL Stefaan
DG Health & Food Safety (Santé)
Froissart Straat 101, 08/66
BE – 1040 BRUXELLES
stefaan.van-der-spiegel@ec.europa.
eu
World Health Organization

Nomination pending
37
MEMBERS OF THE AD HOC
GROUP (GTS)
Composition of the ad hoc group as of 31 October 2016
Chair
NORDA Rut
Klinisk immunologi och
transfusionsmedicin
Uppsala University Hospital
Akademiska Sjukhuset, ing 61
S – 751 85 UPPSALA
rut.norda@akademiska.se
Members
BAROTI TOTH Klara BOGDANOVA Vera
Hungarian National Blood Federal medico-biological
Transfusion Service Agency, ‘ROSPLASMA’
19-21 Karolina St. Volokalamskoye shosse, 30
H – 1113 BUDAPEST RU – 123182 MOSCOW
barotine.toth.klara@ovsz.hu bodgdanova@nic-itep.ru
39
CASTREN Johanna ERTUGRUL ORUC Nigar

Finnish Red Cross Blood Service Blood Transfusion Centre
Kivihaantie 7 Diskapi Yildirim Beyazit
FI – 003010 HELSINKI Training and Research Hospital
johanna.castren@bloodservice.fi Ministry of Health
TR – 06110 ANKARA
CHIN TAD MUON Mário nigarertugrul@gmail.com
Centro de Sangue e da
Transplantação de Coimbra FERNANDEZ ALVAREZ
Rua Escola Inês Castro Póvoa Carmen
PT – 3040-226 COIMBRA Ministry of Health, Social
mario.chin@ipst.min-saude.pt Services and Equality
Servicio de Hematologia Hospital
DE ANGELIS Vincenzo de Cabuenes
Udine University Hospital Calle Los Prados nº 395
P. le S. Maria della Misericordia, ES – 33394 GIJÓN
15 carmen.fernandez@sespa.princast.
IT – 33100 UDINE es
deangelis.vincenzo@aoud.sanita. contactsetscfa@gmail.com
fvg.it
FLANAGAN Peter
DE KORTE Dirk New Zealand Blood Service
Sanquin Private Bag 92071, Victoria Street
PO Box 9190 West
NL – 1066 AD AMSTERDAM NZ – 1142 AUCKLAND
d.dekorte@sanquin.nl peter.flanagan@nzblood.co.nz
DOBROTA Alina Mirella FLESLAND Oystein

Regional Blood Transfusion The Norwegian Knowledge
Centre Centre for the Health Services
St. Nicolas lorga, n 85 PO Box 7000 St Olavs plass
Constanta County NO – 0130 OSLO
RO – 900587 CONSTANTA oystein.flesland@helsedir.no
alina_mirella@yahoo.com
40
Members of the ad hoc group (GTS)
FONTANA Stefano KAMMER Winfried

Blutspendedienst SRK Bern AG Paul Ehrlich Institute
Murtenstrasse 133 Paul Ehrlich Strasse 51-59
CH – 3001 BERN DE – 63225 LANGEN
stefano.fontana@itransfusion.ch winfried.kammer@pei.de
GARRAUD Olivier KLUTER Harald

Institut National de la Institut für Transfusionsmedizin
Transfusion Sanguine und Immunologie
6 rue Alexandre-Cabanel Friedrich-Ebert-Strasse 107
FR – 75739 PARIS DE – 68167 MANNHEIM
ogarraud@ints.fr harald.klueter@medma.uni-
heidelberg.de
GUDMUNDSSON Sveinn
Blood Bank LASPINA Stefan
Snorrabraut 60 Mater Dei Hospital Blood Bank
IS – 101 REYKJAVIK Pathology Department, Block C,
sveinn@landspitali.is Level -1
MT – MSD 2090 TAL-QROQQ
HOPKINS Andrew stefan.laspina@gov.mt
MHRA
151 Buckingham Palace Road MACLENNAN Sheila
Victoria NHSBT
UK – SW1W 9SZ LONDON Leeds Blood Centre
andrew.hopkins@mhra.gsi.gov.uk Bridle Path
UK – LEEDS LS15 7TW
ILLOH Orieji sheila.maclennan@nhsbt.nhs.uk
Food and Drug Administration
10903 New Hampshire Avenue
USA – SILVER SPRING, MD
20993-0002
orieji.illoh@fda.hhs.gov
41
MEGESSIER Pascal POLITIS Constantina

French National Agency for Ministry of Health, National
Medicines and Health Products Blood Centre
Safety Coordinating Haemovigilance
143/147, boulevard Anatole Centre, Hellenic CDC
France 10 Averof Str.
FR – 93285 SAINT-DENIS GR – 10433 ATHENS
CEDEX cpolitis@keelpno.gr
pascal.megessier@ansm.sante.fr
RADZIWON Piotr Marek
NAUJOKAITE Alvyda Regional Centre for Transfusion
Ministry of Health of the Medicine
Republic of Lithuania Ul.M. Sklodowskiej Currie 23
Vilniaus St. 33 PL – 15-950 BIALYSTOK
LT – 01506 VILNIUS pradziwon@rckik.bialystok.pl
alvyda.naujokaite@sam.lt
RAPAILLE André
O DONGHAILE Diarmaid Croix-Rouge de Belgique
Irish Blood Transfusion Service 18 rue Bidaut
National Blood Centre BE – 4000 LIÈGE
James’s Street andre.rapaille@croix-rouge.BE
IRL – DUBLIN 8
Diarmaid.ODonghaile@ibts.ie REHACEK Vit
University Hospital Hradec
PINK Joanne Kralove
Australian Red Cross Blood Transfusion Department
Service Sokolksa str. 581
44 Musk Avenue CZ – 500 05 HRADEC
AU – KELVIN GROVE QLD, KRALOVE
4059 rehacekv@lfhk.cuni.cz
jpink@redcrossblood.org.au
42
Members of the ad hoc group (GTS)
ROSOCHOVA Jana SORENSEN Betina

National Transfusion Service Aarhus University Hospital
Ďumbierska 3L Brendstrupgaardsvej 100, Skejby
SK - 831 01 BRATISLAVA DK – 8200 AARHUS N
rosochova@ntssr.sk betina.sorensen@skejby.rm.dk
SÄFWENBERG Jan VASILJEVIC Nada

Uppsala University Hospital Ministry of Health
Blood Centre Direction of Biomedicine
SE – SE751 85 UPPSALA Pasterova 1
jan.safwenberg@akademiska.se SRB – 11000 BELGRADE
vnada12345@gmail.com
SCHÄRER Christian
Swissmedic VUK Tomislav
Hallerstrasse 7 Croatian Institute for Blood
CH – 3000 BERN 9 Transfusion
christian.schaerer@swissmedic.ch Petrova 3
HR – 10000 ZAGREB
SCHENNACH Harald tomislav.vuk@hztm.hr
Central Institute for Blood
Transfusion and Immunology
(ZIB)
TILAK – University Clinics –
Regional Hospital
Anichstrasse 35
AT – 6020 INNSBRUCK
harald.schennach@tirol-kliniken.at
43
of the Committee of Ministers to member states
on the preparation, use and quality

assurance of blood components
(Adopted by the Committee of Ministers

on 12 October 1995 at the 545th meeting of the Ministers’ Deputies)
The Committee of Ministers, under the terms of Article 15.b of the
Statute of the Council of Europe;
Considering that the aim of the Council of Europe is to achieve
greater unity between its members and that this aim may be pursued,
inter alia, by the adoption of common action in the health field;
Recalling its Resolution (78) 29 on harmonisation of legislations of
member states relating to removal, grafting and transplantation of
human substances;
Recalling also its Recommendations No. R (80) 5 concerning blood
products for the treatment of haemophiliacs, No. R (81) 14 on
preventing the transmission of infectious diseases in the international
transfer of blood, its components and derivatives, No. R (84) 6 on
the prevention of the transmission of malaria by blood transfusion,
45
No. R (85) 12 on the screening of blood donors for the presence

of Aids markers, No. (86) 6 on guidelines for the preparation,
quality control and use of fresh frozen plasma, No. R (88) 4 on the
responsibilities of health authorities in the field of blood transfusion
and No. R (93) 4 concerning clinical trials involving the use of
components and fractionated products derived from human blood or
plasma;
Taking into account the Council Directive 89/381/EEC extending the
scope of Directives 65/65/EEC and 75/319/EEC on the approximation
of provisions laid down by law, regulation or administrative action
relating to proprietary medical products and laying down special
provisions for medicinal products derived from human blood or
human plasma;
Taking into account Agreement No. 26 on the exchange of therapeutic
substances of human origin;
Considering the importance of blood components in modern
haemotherapy and the necessity to ensure their safety, efficacy and
quality;
Considering that such components are of human origin and that
hence specific ethical and technical principles have to be taken into
account;
Considering the need for harmonisation of such principles in member
states;
Considering that biotechnology does not provide substitutes for most
blood products;
Convinced, therefore, of the need to provide health authorities,
transfusion services as well as hospital blood banks and clinical
users with a set of guidelines for the preparation, use and the quality
assurance of blood components;
Aware that the Guide to the preparation, use and quality assurance
of blood components published by the Council of Europe has already
become the generally accepted European standard and that it is
therefore appropriate to give a legal basis to this guide;
46
Considering that this guide will be regularly updated by the

committee of experts of the Council of Europe;
Recommends that the governments of member states take all
necessary measures and steps to ensure that the preparation, use and
quality control of blood components are carried out in accordance
with the guidelines set out in the appendix to this recommendation.
47
Guide to the preparation,
use and quality assurance
of blood components
Appendix to Recommendation No. R (95) 15
GOOD PRACTICE GUIDELINES
for standards and specifications

for implementing the quality
system in blood establishments
Introductory note
Good Practice Guidelines have been prepared through an ad hoc
co-operation between the European Directorate for the Quality of
Medicines & HealthCare of the Council of Europe (EDQM/CoE) and
the Commission of the European Union (EU).
These Good Practice Guidelines are included in this 19th Edition
of the Guide to the preparation, use and quality assurance of
blood components, Appendix to Recommendation No. R (95) 15
of the Committee of Ministers on the preparation, use and quality
assurance of blood components.
EU Member States shall ensure, according to Directive 2005/62/EC,
that the quality system in place in all blood establishments complies
with the standards and specifications set out in the Annex to that
Directive.
In order to implement the standards and specifications set out in the
Annex to Directive 2005/62/EC, its Article 2, as amended by Directive
(EU) 2016/1214, is replaced by the following:
50
Good Practice Guidelines
Member States shall ensure that, in order to implement the

standards and specifications set out in the Annex to this Directive,
there are good practice guidelines available to and used by all
blood establishments, in their quality system, good practice
guidelines which take fully into account, where relevant for blood
establishments, the detailed principles and guidelines of good
manufacturing practice, as referred to in the first subparagraph of
Article 47 of Directive 2001/83/EC. In doing so, Member States shall
take into account the Good Practice Guidelines jointly developed
by the Commission and the European Directorate for the Quality
of Medicines & HealthCare of the Council of Europe and published
by the Council of Europe.
Council of Europe Member States should take the necessary
measures and steps to implement the Good Practice Guidelines
published in this 19th Edition of the Guide to the preparation, use
and quality assurance of blood components. These Good Practice
Guidelines provide guidance on how to implement the standards
and specifications of quality systems that Member States shall
ensure are in place in blood establishments and hospital blood
banks.
51

for blood establishments
and hospital blood banks
1. General principles

1.1. General requirements
1.1.1. Each blood establishment must develop and maintain
a Quality System that is based on EU Good Manu-
facturing Practices (GMP) Directive 2003/94/EC and
meets the requirements identified in the Directive
2005/62/EC.
1.1.2. For blood and blood components imported from third
countries and intended for use or distribution in the
EU, there must be a Quality System for blood estab-
lishments in the stages preceding importation equiva-
lent to the Quality System provided for in Article 2 of
Directive 2005/62/EC.
1.1.3. Quality must be recognised as being the responsibility
of all persons involved in the processes of the blood
establishment, with management ensuring a system-
atic approach towards quality and the implementa-
tion and maintenance of a Quality System (Directive
2005/62/EC/Annex 1.1.1).
1.1.4. Attainment of this quality objective is the responsibil-
ity of executive management. It requires the participa-
tion and commitment both of staff in many different
departments and at all levels within the organisation
and of the organisation’s suppliers and distributors. To
achieve this quality objective reliably there must be a
comprehensively designed and correctly implemented
52
Quality System incorporating Good Practice and

Quality Risk Management.
1.1.5. Each actor in the supply chain should establish,
document, and fully implement a comprehensively
designed Quality System to deliver Quality Assurance
based on the principles of Quality Risk management
by incorporating Good Practice and Quality Control.
1.1.6. The basic concepts of Quality Management, Good
Practice and Quality Risk Management are interre-
lated. They are described here in order to emphasise
their relationships and fundamental importance to
the preparation of blood and blood components.
1.2. Quality system

1.2.1. Quality Management is a wide-ranging concept cover-
ing all matters, which individually or collectively in-
fluence the quality of blood and blood components. It
is the sum total of the organised arrangements made
with the objective of ensuring that blood components
are of the quality required for their intended use.
Quality Management therefore incorporates Good
Practice.
1.2.2. The Quality System encompasses quality manage-
ment, quality assurance, continuous quality im-
provement, personnel, premises and equipment,
documentation, collection, testing and processing,
storage, distribution, quality control, blood com-
ponent recall, and external and internal auditing,
contract management, non-conformance and self-in-
spection (Directive 2005/62/EC/Annex 1.1.2).
1.2.3. The Quality System must ensure that all critical
processes are specified in appropriate instructions
and are carried out in accordance with the standards
and specifications of Good Practice and comply with
53
appropriate regulations as set out in the chapters on

Standards in this Guide (which includes the Annex to
Directive 2005/62/EC).
1.2.4. The Quality System must be designed to assure the
quality and safety of prepared blood and blood com-
ponents, as well as ensure donor and staff safety and
customer service. This strategy requires the develop-
ment of clear policies, objectives and responsibilities.
It also requires implementation by means of quality
planning, quality control, quality assurance and
quality improvement to ensure the quality and safety
of blood and blood components, and to provide cus-
tomer satisfaction.
1.2.5. Executive management has the ultimate responsibility
to ensure that an effective Quality System is in place
and resourced adequately, and that roles and responsi-
bilities, are defined, communicated and implemented
throughout the organisation. Executive management’s
leadership and active participation in the Quality
System is essential. This leadership should ensure the
support and commitment of staff at all levels and sites
within the organisation to the Quality System.
1.2.6. Executive management should establish a quality
policy that describes the overall intentions and direc-
tion of the blood establishment and/or hospital blood
bank (hereinafter referred to as ‘organisation’) related
to quality. They should also ensure Quality System
management and Good Practice governance through
management review to ensure its continuing suitabil-
ity and effectiveness.
1.2.7. The Quality System should be defined and docu-
mented. A Quality Manual or equivalent document
should be established and contain a description
54
of the Quality System (including management

responsibilities).
1.2.8. All blood establishments and hospital blood banks
must be supported by a quality assurance function
(whether internal or related) for fulfilling quality
assurance. That function must be involved in all
quality-related matters, and must review and approve
all appropriate quality-related documents (Directive
2005/62/EC/Annex 1.2.1).
1.2.9. An independent function with responsibility for
quality assurance must be established. This quality
assurance function will be responsible for the over-
sight of all quality processes but need not necessarily
be responsible for carrying out the activities.
1.2.10. All procedures, premises and equipment that have
an influence on the quality and safety of blood and
blood components must be validated before introduc-
tion and must be re-validated at regular intervals, as
determined as a result of these activities (Directive
2005/62/EC/Annex 1.2.2).
1.2.11. A general policy regarding qualification of facilities
and equipment as well as validation of processes,
automated systems and laboratory tests must be in
place. The formal objective of validation is to ensure
compliance with the intended use and regulatory
requirements.
1.2.12. A formal change control system must be in place to
plan, evaluate and document all changes that may
affect the quality, traceability, availability or effect of
components, or the safety of components, donors or
patients. The potential impact of the proposed change
must be evaluated, and the degree of revalidation or
additional testing, qualification and validation needed
must be determined.
55
1.2.13. A formal system for the handling of deviations and

non-conformances must be in place. An appropriate
level of root-cause analysis should be applied during
the investigation of deviations, suspected product
defects, and other problems. This strategy can be de-
termined using Quality Risk Management principles.
If the true root cause(s) of the issue cannot be deter-
mined, consideration should be given to identifying
the most likely root cause(s) and to addressing them.
Where human error is suspected or identified as the
cause, this should be justified having taken care to
ensure that process, procedural or system-based errors
or problems have not been overlooked, if present. Ap-
propriate corrective actions and/or preventive actions
(CAPAs) should be identified and taken in response to
investigations. The effectiveness of such actions should
be monitored and assessed in accordance with Quality
Risk Management principles.
1.2.14. Management must review the system at regular inter-
vals to verify its effectiveness and introduce corrective
measures if deemed necessary (Directive 2005/62/EC/
Annex 1.1.3).
1.2.15. There should be periodic management review and
monitoring both of its effectiveness, with the involve-
ment of executive management and of the operation of
the Quality System to identify opportunities for con-
tinual improvement of blood and blood components
processes and the system itself.
1.2.16. Product quality reviews should be conducted with the
objective of verifying the consistency of the existing
process and the appropriateness of current specifica-
tions in order to highlight trends and to identify im-
provements in both component and process.
56
1.2.17. A product quality review may also be considered as

an instrument for surveying the overall quality status
of a blood component and its manufacturing pro-
cesses, including the collection. Such a review should
normally be conducted annually and should be docu-
mented. It may include:
1.2.17.1. review of starting materials;
1.2.17.2. review of critical in-process controls;
1.2.17.3. review of results of quality control and quality
monitoring;
1.2.17.4. review of all changes;
1.2.17.5. review of the qualification status of equipment;
1.2.17.6. review of technical agreements and contracts;
1.2.17.7. review of all significant deviations, non-
conformances, and the corrective actions
implemented;
1.2.17.8. review of the findings of internal and external
audits and inspections, and the corrective actions
implemented;
1.2.17.9. review of complaints and recalls;
1.2.17.10. review of donor acceptance criteria;
1.2.17.11. review of donor deferrals;
1.2.17.12. review of look-back cases.
1.3. Good practice

1.3.1. Good Practice is the part of Quality Management
that ensures that blood and blood components are
produced and controlled consistently to the quality
standards appropriate to their intended use. Good
Practice is concerned with collection, processing,
testing release and storage (hereinafter included in the
57
generic term ‘preparation’) and quality control. The

basic requirements are:
1.3.1.1. All processes are defined clearly and reviewed sys-
tematically in the light of experience and shown to
be capable of consistently delivering blood and blood
components of the required quality and complying
with their specifications. This strategy includes ensur-
ing that:
1.3.1.1.1. critical steps and significant changes to the process are
validated;
1.3.1.1.2. all requirements are provided including:
1.3.1.1.2.1. appropriately qualified and trained personnel;
1.3.1.1.2.2. adequate premises and space;
1.3.1.1.2.3. suitable equipment and services;
1.3.1.1.2.4. correct materials, containers and labels;
1.3.1.1.2.5. approved procedures and instructions;
1.3.1.1.2.6. suitable storage and transport;
1.3.1.1.3. instructions and procedures are written in an instruc-
tional form in clear and unambiguous language, and
are applicable specifically to the facilities provided;
1.3.1.1.4. operators are trained to carry out procedures
correctly;
1.3.1.1.5. records are made, manually and/or by recording in-
struments, during preparation which demonstrate
that all the steps required by the defined procedures
and instructions were in fact taken and that the quan-
tity and quality of the blood or blood component was
as expected;
1.3.1.1.6. any significant deviations are fully recorded and
investigated;
58
1.3.1.1.7. records of preparation (including distribution) that

enable the complete history of the blood or blood
component to be traced are retained in a comprehen-
sible and accessible form;
1.3.1.1.8. the distribution of the blood and blood components
minimises any risk to their quality;
1.3.1.1.9. a system is available to recall any blood or blood
component (including those prepared using a batch of
critical materials that have been distributed or issued);
1.3.1.1.10. complaints about blood and blood components are ex-
amined, the causes of quality defects investigated, and
appropriate measures taken in respect of the defective
blood components to prevent reoccurrence.
1.3.1.2. Quality Control is the part of Good Practice that is
concerned with sampling, specifications and testing,
as well as with the organisation, documentation and
release procedures which ensure that materials are not
released for use in preparation, and blood and blood
components are not released for distribution, until
their quality has been judged to be satisfactory and
that the necessary and relevant tests have been carried
out. The basic requirements are:
1.3.1.2.1. adequate facilities, trained personnel and approved
procedures are available for sampling, inspecting/
testing starting materials, packaging materials, inter-
mediate components, and finished blood and blood
components and, if appropriate, for monitoring envi-
ronmental conditions;
1.3.1.2.2. samples of starting materials, packaging materials, in-
termediate, and finished blood components are taken
by approved personnel and methods;
1.3.1.2.3. test methods are validated;
59
1.3.1.2.4. records are made, manually and/or by recording in-

struments, which demonstrate that all the required
sampling, inspecting and testing procedures were
actually carried out. Any deviations are recorded and
investigated fully;
1.3.1.2.5. the finished blood and blood components comply
with the specifications and are correctly labelled;
1.3.1.2.6. records are made of the results of inspection, and that
testing of materials, intermediate and finished blood
and blood components are formally assessed against
specifications;
1.3.1.2.7. no blood or blood components are released for distri-
bution that do not comply with the requirements of
the relevant authorisations.
1.3.1.3. Rolling quality reviews of all blood and blood com-
ponents (including export-only blood components)
should be conducted with the objective of contin-
uously verifying the: consistency of the existing
process; appropriateness of current specifications for
both starting materials and finished blood compo-
nents to highlight any trends and to identify product
and process improvements.
1.4. Quality risk management

1.4.1. Quality Risk Management is the part of the Quality
System that ensures that the process performance
and quality monitoring and review systems are based
on risk. Appropriate statistical tools should be used
(where appropriate) in the assessment of ongoing
process capability.
1.4.2. The Quality System should ensure that processes are
in place to ensure the control of outsourced activities
and quality of purchased materials. These processes
60
should incorporate the principles of Quality Risk

Management and systematically ensure that:
1.4.2.1. the evaluation of the risk to quality is based on sci-
entific knowledge, experience with the process and,
ultimately, is connected to protection of the donor and
patient;
1.4.2.2. the level of effort, formality and documentation of the
quality risk management process is commensurate
with the level of risk.
2. Personnel and organisation

2.1. Personnel must be available in sufficient numbers
to carry out the activities related to the collection,
testing, processing, storage and distribution of blood
and blood components and be trained and assessed
to be competent to perform their tasks (Directive
2005/62/EC/Annex 2.1).
2.2. The organisation should have an adequate number of
personnel with the necessary qualifications and ex-
perience. Management has the ultimate responsibility
to determine and provide adequate and appropriate
resources (human, financial, materials, facilities and
equipment) to implement and maintain the Quality
Management System and continually improve its
suitability and effectiveness through participation in
management review. The responsibilities placed on
any one individual should not be so extensive as to
present any risk to quality.
2.3. There should be an organisation chart in which the
relationships between key personnel are clearly shown
in the managerial hierarchy. Key personnel include
the following functions and their substitutes:
61
2.3.1. a ‘Responsible Person’ following Article 9 of Directive

2002/98/EC;
2.3.2. a processing manager, responsible for all processing
activities;
2.3.3. a quality control manager, responsible for all quality
control activities;
2.3.4. a quality assurance manager, responsible for ensuring
that there are appropriate quality systems and pro-
tocols in place for the safe and secure release of all
materials, equipment, reagents and blood and blood
components;
2.3.5. a physician with the responsibility for ensuring the
safety of donors and a physician or pharmacist with
responsibility for the safety of the distributed blood
components.
2.4. All personnel must have up-to-date job descriptions,
which clearly set out their tasks and responsibilities.
Responsibility for processing management and quality
assurance must be assigned to different individuals,
and who function independently (Directive 2005/62/
EC/Annex 2.2).
2.5. Personnel in responsible positions should have ad-
equate authority to carry out their responsibilities.
Their duties may be delegated to designated deputies
of a satisfactory qualification level. There should be no
gaps or unexplained overlaps in the responsibilities
of those personnel concerned with the application of
Good Practice.
2.6. Individual responsibilities should be clearly defined
and their correct understanding by individuals should
be assessed and recorded. Personnel signature lists
should be available.
62
2.7 All personnel must receive initial and continued

training appropriate to their specific tasks. Training
records must be maintained. Training programmes
must be in place and must include Good Practice (Di-
rective/2005/62/EC/Annex 2.3).
2.8. Training should be provided for all personnel whose
duties take them into preparation areas or into lab-
oratories (including the technical, maintenance and
cleaning personnel).
2.9. There should be written policies and procedures to
describe the approach to training, including a record
of training that has taken place, its contents, and its
effectiveness.
2.10. The contents of training programmes must be peri-
odically assessed and the competence of personnel
evaluated regularly (Directive/2005/62/EC/Annex 2.4).
2.11. Only persons who are authorised by defined proce-
dures and documented as such may be involved in
the collection, processing, testing and distribution
processes, including quality control and quality
assurance.
2.12. There must be written safety and hygiene instructions
in place, adapted to the activities to be carried out,
and in compliance with Council Directive 89/391/EEC
and Directive 2000/54/EC of the European Parliament
and of the Council (Directive/2005/62/EC/Annex 2.5).
2.13. Visitors or untrained personnel should, preferably, not
be taken into the processing and laboratory areas. If
this is unavoidable, they should be given information
in advance, particularly about personal hygiene and
the prescribed protective clothing. They should be
closely supervised.
63
2.14. It is the organisation’s responsibility to provide in-

structions on hygiene and health conditions that can
be of relevance to the quality of blood components
(e.g. during collection) and to ensure that staff report
relevant health problems. These procedures should
be understood and followed in a strict way by all staff
members whose duties take them into the processing
and laboratory areas. Personnel should be instructed
to use the hand-washing facilities.
2.15. Steps should be taken to ensure as far as is practica-
ble that no person affected by an infectious disease
or having open lesions on the exposed surface of the
body is engaged in the preparation of blood compo-
nents. Medical examinations should be carried out
when necessary to assure fitness for work and per-
sonal health. There should be instructions ensuring
that health conditions that can be of relevance to the
quality of blood and blood components are reported
by the personnel.
2.16. There should be a written policy outlining the require-
ments for wearing of protective garments in the differ-
ent areas. The requirements should be appropriate to
the activities to be carried out.
2.17. Eating, drinking, chewing or smoking, or the storage
of food, drink, smoking materials or personal med-
ication in the processing, testing and storage areas
should be prohibited. In general, any unhygienic
practice within the preparation areas or in any other
area where the blood or blood components might be
adversely affected should be forbidden.
64
3. Premises
3.1. General
3.1.1. Premises including mobile sites must be located, con-
structed, adapted and maintained to suit the activities
to be carried out. They must enable work to proceed in
a logical sequence so as to minimise the risk of errors,
and must allow for effective cleaning and mainte-
nance in order to minimise the risk of contamination
(Directive/2005/62/EC/Annex 3.3.1).
3.1.2. Lighting, temperature, humidity and ventilation
should be appropriate and such that they do not
adversely affect (directly or indirectly) blood com-
ponents during their processing and storage, or the
accurate functioning of equipment.
3.1.3. Premises should be designed and equipped so as to
afford protection against the entry of insects or other
animals.
3.1.4. Steps should be taken to prevent the entry of un
authorised people. Areas for processing, laboratory,
storage, and quality control should not be used as a
right of way by personnel who do not work in them.
3.1.5. Facilities should permit ease of maintenance and
cleaning. Open drains should be avoided.
3.1.6. Preparation areas should be ventilated effectively, with
air-control facilities (including temperature and, if
necessary, humidity and filtration) appropriate to the
operations undertaken within them and to the exter-
nal environment.
3.1.7. Preparation areas should be suitably lit, particularly
where visual checks are carried out.
65
3.1.6. Component sampling may be carried out within the

processing area provided it does not carry any risk for
other components.
3.2. Blood donor area

3.2.1. There must be an area for confidential personal inter-
views with, and assessment of, individuals to assess
their eligibility to donate. This area must be separated
from all processing areas (Directive/2005/62/EC/
Annex 3.3.2).
3.2.2. Premises must satisfy common-sense requirements
for the health and safety of both the staff (including
those of mobile teams) and the donors concerned with
due regard to relevant legislation or regulations.
3.3. Blood collection area

3.3.1. Blood collection must be carried out in an area in-
tended for the safe withdrawal of blood from donors
that is appropriately equipped for the initial treatment
of donors experiencing adverse reactions or injuries
from events associated with blood donation. This
area must be organised in such a way as to ensure the
safety of both donors and personnel as well as to avoid
errors in the collection procedure (Directive/2005/62/
EC/Annex 3.3.3).
3.3.2. Before premises are accepted for mobile donor ses-
sions, their suitability must be assessed against the
following criteria:
3.3.2.1. sufficient size to allow proper operation and ensure
donor privacy;
3.3.2.2. safety for staff and donors;
3.3.2.3. the presence of ventilation, electrical supply, lighting,
toilet and hand-washing facilities;
66
3.3.2.4. reliable communication, blood storage and transport;

3.3.2.5. guarantee of adequate interim storage.
3.3.3. The arrangement of the collection room and proce-
dures should ensure that blood is collected in a safe
and clean environment to minimise the risk of errors
and microbial contamination.
3.3.4. Consideration should be given to the arrangement
of donor beds and the handling of bags, samples and
labels.
3.4. Blood testing and processing areas

3.4.1. There must be a dedicated laboratory area for testing
that is separate from the blood-donor and blood-com-
ponent processing area, with access restricted to
authorised personnel, and must be used only for the
intended purpose (Directive/2005/62/EC/Annex
3.3.4).
3.4.2. Laboratories should be designed to suit the operations
to be carried out in them. Sufficient space should be
given to avoid mix-ups and cross-contamination.
There should be adequate suitable storage space for
samples and records.
3.4.3. Special provisions may be necessary to protect sen-
sitive instruments from vibration, electrical interfer-
ence, humidity, and extremes of temperature.
3.5. Storage area

3.5.1. Storage areas must provide for appropriately secure
and segregated storage of different categories of blood
and blood components and materials, including quar-
antine and released materials as well as units of blood
or blood components collected under special criteria
(e.g. autologous donation). Access must be restricted
67
to authorised persons (Directive/2005/62/EC/Annex

3.3.5.1).
3.5.2. Provisions must be in place in the event of equipment
failure or power failure in the main storage facility
(Directive/2005/62/EC/Annex 3.3.5.2).
3.5.3. Storage facilities should be clean and free from litter,
dust and pests (e.g. insects, rodents).
3.5.4. Storage areas should be of sufficient capacity to allow
orderly storage of the various categories of materials
and blood components including packaging materials,
intermediate and finished components, and materials
in quarantine, released, rejected, returned or recalled.
3.5.5. Storage areas should be designed or adapted to ensure
good storage conditions. In particular, they should be
clean and dry and maintained within predefined tem-
perature limits. Where special storage conditions are
required (e.g. temperature, humidity) these should be
provided, checked and monitored. An alarm system
should alert users in a timely manner to any excursion
outside predefined limits.
3.5.6. Receiving and dispatch bays should protect materi-
als and products from the weather. Reception areas
should be designed and equipped to allow containers
of incoming materials to be cleaned where necessary
before storage. The reception area should be separate
from the storage area.
3.5.7. If quarantine status is ensured by storage in separate
areas, these areas must be marked clearly and their
access restricted to authorised personnel. Any system
replacing the physical quarantine (e.g. computerised
system) should provide equivalent security.
3.5.8. Segregated areas should be allocated and identi-
fied appropriately for storage of rejected, discarded,
68
recalled or returned materials, or blood and blood

components.
3.5.9. Special attention should be paid to the safe and secure
storage of printed packaging materials (including sets
of donation identifier labels).
3.6. Ancillary areas

3.6.1. Staff rest and refreshment areas should be separate
from other rooms.
3.6.2. Facilities for changing clothes and for washing and
toilet purposes should be readily accessible and
appropriate for the number of users. Toilets should
not directly open to processing, laboratory or storage
areas.
3.6.3. Maintenance workshops should, as far as possible, be
separated from preparation areas. If parts and tools
are stored in processing and laboratory areas, they
should be kept in a location reserved for that use.
3.7. Waste disposal area

3.7.1. An area must be designated for the safe disposal of
waste, disposable items used during collection, testing
and processing and for rejected blood or blood com-
ponents (Directive/2005/62/EC/Annex 3.6).
4. Equipment and materials

4.1. General requirements
4.1.1. All equipment must be qualified, calibrated and main-
tained to suit its intended purpose. Operating instruc-
tions must be available and appropriate records kept
(Directive/2005/62/EC/Annex 4.1).
69
4.1.2. Equipment must be selected to minimise any hazard

to donors, personnel or blood components (Direc-
tive/2005/62/EC/Annex 4.2).
4.1.3. All validated processes must use qualified equipment.
Qualification results must be documented. Regular
maintenance and calibration must be carried out and
documented according to established procedures. The
maintenance status of each item of equipment must be
available.
4.1.4. All critical equipment must have regular, planned
maintenance to detect or prevent avoidable errors and
keep the equipment in its optimum functional state.
The maintenance intervals and actions must be deter-
mined for each item of equipment.
4.1.5. New and repaired equipment must meet qualification
requirements when installed and must be authorised
before use.
4.1.6. All modifications, enhancements or additions to
validated systems and equipment must be managed
through the change control procedure of the blood es-
tablishment. The effect of each change to the system or
equipment, as well as its impact on quality and safety,
must be determined to identify the extent of revalida-
tion required.
4.1.7. Instructions for use, maintenance, servicing, cleaning
and sanitation must be available.
4.1.8. Procedures must be available for each type of equip-
ment that detail the action to be taken if malfunctions
or failures occur.
4.1.9. Only reagents and materials from approved suppliers
that meet the documented requirements and specifica-
tions must be used. Critical materials must be released
by a person qualified to perform this task. If relevant,
70
materials, reagents and equipment must meet the

requirements of Council Directive 93/42/EEC for
medical devices and Directive 98/79/EC of the Eu-
ropean Parliament and of the Council for in vitro
diagnostic medical devices, or comply with equivalent
standards in the case of collection in third countries
4.1.10. Manufacturers of sterile materials (e.g. blood bag
systems, anticoagulant solutions) should provide a
certificate of release for each batch. The blood estab-
lishment should define acceptance criteria for such
certificates in writing, and should include at least the
name of the material, manufacturer, compliance with
relevant requirements (e.g. pharmacopoeias or regu-
lations for medical devices) and confirmation that the
materials are sterile and pyrogen-free.
4.1.11. Status of materials (quarantined, released, rejected)
should be indicated clearly.
4.1.12. Materials and reagents should be stored under the
conditions established by the manufacturer and in an
orderly manner that permits segregation by batch and
lot as well as stock rotation.
4.1.13. Storage and use of materials should follow the ‘first-in
first-out’ principle (i.e. the material that entered
storage first should be used first) taking into account
the expiry date of materials.
4.1.14. Inventory records must be retained for a period ac-
ceptable to and agreed with the competent authority
4.1.15. Equipment and material inventory records must be
kept as a means to build up a history for a processed
component to facilitate recalls.
71
4.1.16. Repair and maintenance operations should not

present any hazard to the donor, staff or quality of the
blood and blood components.
4.1.17. Equipment should be designed or selected so that
it can be thoroughly cleaned (and where necessary
decontaminated). This should be performed according
to detailed and written procedures. It should be stored
only in a clean and dry condition.
4.1.18. Washing/cleaning solutions and equipment should
be chosen and used so that they are not sources of
contamination.
4.1.19. Equipment should be installed in such a way as to
prevent any risk of error or of contamination.
4.1.20. Parts of equipment and materials that come into
contact with blood and blood components must not
be reactive, additive or absorptive to such an extent
that they affect the quality of the component and thus
present any hazard.
4.1.21. Balances and measuring equipment of an appropriate
range and precision should be available. Equipment
for measuring, weighing, recording and control
should be calibrated and checked at defined inter-
vals using appropriate methods. Adequate records of
such tests should be maintained, including the values
obtained prior to any adjustment. Calibration reports
should include the accuracy of any testing equipment
and traceability to a national standard. The report
and/or calibration certificate must be reviewed and
signed to show acceptance of the document. Any
failed calibrations will require mention of non-con-
formance to allow investigation of the potential
impact.
72
4.1.22. Defective equipment should be labelled clearly as such

and, if possible, removed from preparation areas.
4.2. Data processing systems

4.2.1. If computerised systems are used, software, hardware
and back-up procedures must be checked regularly
to ensure reliability, be validated before use, and be
maintained in a validated state. Hardware and soft-
ware must be protected against unauthorised use or
unauthorised changes. The back-up procedure must
prevent loss of or damage to data at expected and
unexpected down-times or function failures (Direc-
4.2.2. Systems must be properly maintained at all times.
Documented maintenance plans must be developed
and implemented. This strategy must include audits of
quality assurance systems.
4.2.3. Changes in computerised systems must be validated;
applicable documentation must be revised and rel-
evant personnel trained appropriately before any
change is introduced into routine use. Computerised
systems must be maintained in a validated state. This
must include user-testing to demonstrate that the
system is correctly performing all specified func-
tions both at initial installation and after any system
modifications.
4.2.4. There must be a hierarchy of permitted user access
to enter, amend, read or print data. Methods of pre-
venting unauthorised entry must be in place, such as
personal identity codes or passwords that are changed
regularly.
4.2.5. All necessary measures must be taken to ensure pro-
tection of data. These measures must ensure that safe-
guards against unauthorised additions, deletions or
73
modifications of data and transfer of information are

in place to resolve data discrepancies, and to prevent
unauthorised disclosure of such information.
4.2.6. Computer systems designed to control decisions
related to inventories and release of blood compo-
nents should prevent the release of all blood or blood
components considered not acceptable for release.
Preventing release of any components from a future
donation from a deferred donor should be possible.
4.3. Qualification and validation

4.3.1. General principles
4.3.1.1. Facilities and equipment need to be qualified prior to
implementation. Systems, processes and tests should
be validated, which involves wider consideration
beyond the facilities and equipment used. In this
document, however, the term validation is used in a
generic sense, encompassing both qualification and
validation activities.
4.3.1.2 The principles of qualification and validation are
applicable to the collection, preparation, testing,
distribution and issuance of blood components. It is
a requirement of Good Practice that blood establish-
ments and hospital blood banks control the critical
aspects of their operations through the life cycle of the
blood components and the associated processes. Any
planned changes to the facilities, equipment, utilities
and processes should be formally documented and the
impact on the quality of blood components should be
validated.
4.3.1.3 A quality risk management approach, consisting of a
systematic process for the assessment, control, com-
munication and review of risks to quality across the li-
fecycle of the blood component, should be applied. As
74
part of a quality risk management system, decisions

on the scope and extent of qualification and validation
should be based on a justified and documented risk
assessment of the facilities, equipment, utilities and
processes.
4.3.1.4 Data supporting qualification and/or validation
studies which were obtained from sources outside of
the blood establishment/hospital blood banks own
quality system may be used provided that this ap-
proach has been justified and that there is adequate
assurance that controls were in place throughout the
acquisition of such data.
4.3.2. Organising and planning for validation
4.3.2.1. All qualification and validation activities should be
planned and take the life cycle of facilities, equipment,
utilities, process and product into consideration.
4.3.2.2. Qualification and validation activities should only be
performed by suitably trained personnel who follow
approved procedures and report as defined in the
blood establishment quality system. There should be
appropriate quality oversight over the whole valida-
tion life cycle.
4.3.2.3. The key elements of the site qualification and val-
idation programme should be clearly defined and
documented in a validation master plan (VMP) or
equivalent document.
4.3.2.4. The VMP or equivalent document should define the
qualification/validation system and include or refer-
ence information on at least the following:
4.3.2.4.1. qualification and validation policy;
4.3.2.4.2. the organisational structure including roles and
responsibilities for qualification and validation
activities;
75
4.3.2.4.3. summary of the facilities, equipment, systems, pro-

cesses on site and their qualification and validation
status;
4.3.2.4.4. change control and deviation management for qualifi-
cation and validation;
4.3.2.4.5. guidance on developing acceptance criteria;
4.3.2.4.6. references to existing documents;
4.3.2.4.7. the qualification and validation strategy, including
requalification, where applicable.
4.3.2.5. For large and complex projects, planning takes on
added importance and separate validation plans may
enhance clarity. These should be linked and traceable.
4.3.2.6. A quality risk management approach should be used
for qualification and validation activities. In light of
increased knowledge and understanding from any
changes during the qualification and validation phase,
the risk assessments should be repeated, as required.
The way in which risk assessments are used to support
qualification and validation activities should be clearly
documented.
4.3.2.7 Appropriate checks should be incorporated into qual-
ification and validation work to ensure the integrity of
all data obtained.
4.3.3. Documentation including VMP
4.3.3.1 Good documentation practices are important to
support knowledge management throughout the
product lifecycle. Validation protocols should be pre-
pared which specify how qualification and validation
should be performed and which define the critical
systems, attributes and parameters and the associated
acceptance criteria.
76
4.3.3.2. All documents generated during qualification and

validation should be approved and authorised by ap-
propriate personnel as defined in the quality system.
4.3.3.3. Qualification documents may be combined together,
where appropriate, e.g. installation qualification (IQ)
and operational qualification (OQ).
4.3.3.4. Any significant changes to the approved protocol
during execution, e.g. acceptance criteria, operating
parameters etc., should be documented as a deviation
and be scientifically justified.
4.3.3.5. The interrelationship between documents in complex
validation projects should be clearly defined.
4.3.3.6. Where validation protocols and other documentation
are supplied by a third party providing validation
services, appropriate personnel at the blood establish-
ment should confirm suitability and compliance with
internal procedures before approval. Vendor protocols
may be supplemented by additional documentation/
test protocols before use.
4.3.3.7. Results which fail to meet the pre-defined acceptance
criteria should be recorded as a deviation and be fully
investigated according to local procedures. Any impli-
cations for the validation should be discussed in the
report.
4.3.3.8. The review and conclusions of the validation should
be reported and the results obtained summarised
against the acceptance criteria. Any subsequent
changes to acceptance criteria should be scientifically
justified and a final recommendation made as to the
outcome of the validation.
4.3.3.9. A formal release for the next stage in the qualification
and validation process should be authorised by the
relevant responsible personnel either as part of the
77
validation report approval or as a separate summary

document. Conditional approval to proceed to the
next qualification stage can be given where certain
acceptance criteria or deviations have not been fully
addressed and there is a documented assessment that
there is no significant impact on the next activity.
4.3.4. Qualification stages for equipment, facilities, and
systems
4.3.4.1. Qualification activities should consider all stages from
initial development of the user requirements specifi-
cation through to the end of use of the equipment, fa-
cility or system. The main stages and some suggested
criteria (although these depend on individual project
circumstances and may be different) which could be
included in each stage are indicated below.
4.3.4.2. User requirements specification (URS): the specifi-
cation for equipment, facilities, utilities or systems
should be defined in a URS and/or a functional
specification. The essential elements of quality need
to be built in at this stage and any Good Practice risks
mitigated to an acceptable level. The URS should be a
point of reference throughout the validation life cycle.
4.3.4.3. Design Qualification (DQ). The next element of the
validation of new facilities, systems or equipment is
DQ. This involves demonstration and documentation
of the compliance of the design with Good Practice
(i.e. the design is suitable for the intended purpose).
The requirements of the user requirements specifica-
tion should be verified during the design qualification.
4.3.4.4. Factory Acceptance Testing (FAT) / Site Acceptance
Testing (SAT): equipment, especially if incorporating
novel or complex technology, may be evaluated, if ap-
plicable, at the vendor prior to delivery. Prior to instal-
lation, equipment should be confirmed to comply with
78
the URS / functional specification at the vendor site,

if applicable. Where appropriate and justified, docu-
mentation review and some tests could be performed
at the FAT or other stages without the need to repeat
on site at IQ/OQ if it can be shown that the function-
ality is not affected by the transport and installation.
FAT may be supplemented by the execution of a SAT
following the receipt of equipment at the manufactur-
ing site.
4.3.4.5. Installation Qualification (IQ). It should be performed
on new or modified facilities, systems and equipment.
IQ should include, but is not limited to, the following:
4.3.4.5.1. installations of components, equipment, piping, ser-
vices and instrumentation, which are checked against
up-to-date engineering drawings and specifications;
4.3.4.5.2. verification of the correct installation against pre-de-
fined criteria;
4.3.4.5.3. collection and collation of supplier operating and
working instructions and maintenance requirements;
4.3.4.5.4. calibration requirements;
4.3.4.5.5. verification of construction materials.
4.3.4.6. Operational Qualification (OQ). The completion of a
successful OQ should allow finalisation of calibration,
operating and cleaning procedures, operator training
and preventive maintenance requirements. OQ nor-
mally follows IQ but depending on the complexity of
the equipment, it may be performed as a combined In-
stallation/Operation Qualification (IOQ). OQ should
include, but is not limited to, the following:
4.3.4.6.1. tests that have been developed from knowledge of pro-
cesses, systems and equipment to ensure the system is
operating as designed;
79
4.3.4.6.2. tests to confirm upper and lower operating limits,

and/or ‘worst case’ conditions.
4.3.4.7. Performance Qualification (PQ). Although PQ is
described as a separate activity, in some cases it may
be appropriate to perform it in conjunction with OQ
or Process Validation. PQ should follow successful
completion of IQ and OQ. PQ should include, but is
not limited to, the following:
4.3.4.7.1. tests, using production materials, qualified substi-
tutes or simulated blood components proven to have
equivalent behaviour, under normal and worst case
operating conditions. The frequency of sampling used
to confirm process control should be justified;
4.3.4.7.2. tests should cover the operating range of the intended
process, unless documented evidence from the devel-
opment phases confirming the operational ranges is
available.
4.3.5. Re-qualification
4.3.5.1 Equipment, facilities and systems should be evalu-
ated at an appropriate frequency to confirm that they
remain in a state of control.
4.3.5.2 Where requalification is necessary and performed
over a specific time period, the period should be
justified and the criteria for evaluation defined. Fur-
thermore, the possibility of small changes over time
should be assessed.
4.4. Process validation

4.4.1. General
4.4.1.1. The requirements and principles outlined in this
section are applicable to the preparation, distribu-
tion and issuance of blood components. They cover
the initial validation of new processes, subsequent
80
validation of modified processes or site transfers for

maintaining of the validated state (ongoing process
verification). It is implicit in this section that a robust
product development process is in place to enable
successful process validation.
4.4.1.2. Processes should be shown to be robust and ensure
consistent blood component quality prior to their
distribution and routine clinical use. Processes should
undergo a prospective validation programme, wher-
ever possible. Retrospective validation is no longer an
acceptable approach.
4.4.1.3. Process validation of new blood components should
cover all intended processes and sites of manufacture.
A scientific and risk-based validation approach could
be justified for new blood components based on exten-
sive process knowledge from the development stage
in conjunction with an appropriate ongoing statistical
process control. The design assumes that the vali-
dation performed is representative for all process or
product settings.
4.4.1.4. For validation of processes for preparation of blood
components that are transferred from one site to
another or within the same site, the number of blood
components used for process validation could be
reduced based on existing process knowledge, includ-
ing the content of the previous validation that should
be available. The same approach may be used for
different blood bag sizes or volumes, if justified.
4.4.1.5. Process validation should establish whether all
quality attributes and process parameters, which
are considered important for ensuring the validated
state and acceptable blood component quality, can
be consistently met by the process. A critical quality
attributes (CQA) is a physical, chemical, biological or
81
microbiological property or characteristic that should

be within an approved limit, range or distribution
to ensure the desired component quality. A criti-
cal process parameter (CPP) is a process parameter
whose variability has an impact on a critical quality
attribute and which therefore should be monitored or
controlled to ensure the process produces the desired
quality. The basis by which process parameters and
quality attributes were identified as being critical or
non-critical should be clearly documented, taking into
account the results of any risk assessment activities.
4.4.1.6. The facilities, systems and equipment to be used
should be qualified before use and analytical testing
methods should be validated. Facilities, systems,
equipment, utilities and processes should be periodi-
cally evaluated to ensure that they are still operating
appropriately.
4.4.1.7. For all blood components, process knowledge from
development studies or other sources should be ac-
cessible to the blood establishment, unless otherwise
justified, and be the basis for validation activities.
4.4.1.8. During process validation a variety of personnel may
be involved in the preparation of blood components.
Blood components should only be prepared by trained
personnel in accordance with good practice using
approved documentation. It is expected that process-
ing personnel are involved in the preparation of blood
components during validation to facilitate under-
standing of the process.
4.4.1.9. The suppliers of critical materials should be qualified
prior to the preparation of blood components during
process validation; otherwise a justification based on
the application of quality risk management principles
should be documented.
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4.4.1.10. Where blood components prepared during process

validation are released for clinical use, this should be
pre-defined. The conditions under which they are pro-
duced should fully comply with the requirements of
Good Practice, with the validation acceptance criteria
and with any continuous process verification criteria
(if used).
4.4.2. Concurrent validation
4.4.2.1. In exceptional circumstances and justified on the
basis of significant patient benefit, where there is
a strong benefit-risk ratio for the patient and with
systematic control of each blood component unit
for their conformity to regulatory requirements, it
may be acceptable to execute the validation protocol
concurrently with distribution of the units produced
during validations and not to complete a validation
programme before routine production. However, the
decision to carry out concurrent validation should be
documented in the VMP for visibility and approved
by authorised personnel.
4.4.2.2. Where a concurrent validation approach has been
adopted, there should be sufficient data to support a
conclusion that any given blood component meets the
defined acceptance criteria. The results and conclusion
should be formally documented and available to the
Responsible Person prior to release for clinical use.
4.4.3. Prospective validation
4.4.3.1. Using this approach, a number of blood components
may be prepared under the proposed new conditions.
The number of process runs carried out, the number
of samples taken and the number of observations
made should be based on quality risk management
principles and be sufficient to allow the normal
range of variation and trends to be established and to
83
provide sufficient data for evaluation. Each blood es-

tablishment should determine and justify the number
of blood component units necessary to demonstrate
assurance that the process is capable of consistently
delivering quality blood components.
4.4.3.2 Preparation of blood components during the valida-
tion phase should reflect the numbers intended to be
produced under normal production circumstances.
4.4.3.3 A process validation protocol should be prepared
which defines the critical process parameters (CPP),
critical quality attributes (CQA) and the associated
acceptance criteria which should be based on develop-
ment data or documented process knowledge.
4.4.3.4 Process validation protocols should include, but are
not limited to the following:
4.4.3.4.1. short description of the process;
4.4.3.4.2. functions and responsibilities;
4.4.3.4.3. summary of the CQAs to be investigated;
4.4.3.4.4. summary of CPPs and their associated limits;
4.4.3.4.5. summary of other (non-critical) attributes and
parameters which will be investigated or monitored
during the validation activity, and the reasons for
their inclusion;
4.4.3.4.6. list of the equipment/facilities/personnel to be used
(including measuring/monitoring/recording equip-
ment) together with the calibration status;
4.4.3.4.7. list of analytical methods and method validation, as
appropriate.
4.4.3.4.8. proposed in-process controls with acceptance crite-
ria and the reason(s) why each in-process control is
selected;
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4.4.3.4.9. additional testing to be carried out with acceptance

criteria;
4.4.3.4.10. sampling plan and the rationale behind it;
4.4.3.4.11. methods for recording and evaluating results;
4.4.3.4.12. process for release and certification of units (if
applicable);
4.4.3.4.13. conclusion.
4.4.4. Ongoing process, verification and maintenance of the
validated state
4.4.4.1. Ongoing process verification should provide docu-
mented evidence, using statistical process control,
that the process remains in a state of control during
routine manufacture.
4.4.4.2. All critical processes should be constantly moni-
tored and periodically evaluated to confirm that they
remain valid. Where no significant changes have
been made to the validated status, a review with evi-
dence that the process meets the prescribed require-
ments may be deemed acceptable in place of a full
revalidation.
4.4.4.3. Blood establishments should monitor blood compo-
nent quality using statistical process control to ensure
that a state of control is maintained throughout the
blood component lifecycle with the relevant process
trends evaluated.
4.4.4.4. The extent and frequency of ongoing process verifi-
cation should be reviewed periodically. At any point
throughout the product life-cycle, it may be appropri-
ate to modify the requirements taking into account
the current level of process understanding and process
performance.
85
4.4.4.5. Ongoing process verification should be conducted

under an approved protocol or equivalent documents
and a corresponding report should be prepared to
document the results obtained. Statistical tools should
be used, where appropriate, to support any conclu-
sions with regard to the variability and capability of a
given process and to ensure a state of control.
4.4.4.6. The following items are essential to maintain a vali-
dated state:
4.4.4.6.1. calibration and monitoring;
4.4.4.6.2. preventive maintenance;
4.4.4.6.3. training and competency;
4.4.4.6.4. supplier requalification;
4.4.4.6.5. periodic review;
4.4.4.6.6. performance monitoring;
4.4.4.6.7. system retirement.
4.4.4.7. Maintenance of the validated status of the blood com-
ponents should be documented in the Product Quality
Review. Incremental changes over time should also be
considered and the need for any additional actions,
e.g. enhanced sampling, should be assessed.
4.4.4.8. Operational change control, document control and
quality control procedures support the maintenance
of the validated state.
4.5. Validation of test methods

4.5.1. All analytical test methods used in qualification
or validation exercises should be validated with an
appropriate detection and quantification limit, where
necessary, as defined in 11.2.
4.5.2. Where microbial testing of blood components is
carried out, the method should be validated to
86
confirm that the product or residues, e.g. antibiotics,

do not interfere with the analysis and influence the
recovery of microorganisms.
4.5.3. Where microbial testing of surfaces is carried out,
validation should be performed on the test method
to confirm that sanitising agents do not influence the
recovery of microorganisms.
4.6. Change control

4.6.1. Change control procedures should ensure that suffi-
cient supporting data are generated to demonstrate
that the revised process results in a blood component
of the desired quality, consistent with the approved
specifications. Supporting data, e.g. copies of docu-
ments, should be reviewed to confirm that the impact
of the change has been demonstrated prior to final
approval.
4.6.2. Written procedures should be in place to describe the
actions to be taken if a planned change is proposed for
a starting material, blood component specification,
process, equipment, environment (or site), product
range, method of production or testing or any other
change that may affect donor safety , blood compo-
nent quality or reproducibility of the process.
4.6.3. Changes should be authorised and approved by the
responsible persons or relevant functional personnel
in accordance with the blood establishment’s quality
system.
4.6.4. Quality risk management should be used to evaluate
planned changes to determine the potential impact on
blood component quality, the blood establishment’s
quality systems, documentation, validation, regula-
tory status, calibration, maintenance and on any other
system to avoid unintended consequences and to plan
87
for any necessary process validation, verification or

requalification efforts.
4.6.5. Following implementation, where appropriate, an
evaluation of the effectiveness of change should be
carried out to confirm that the change has been
successful.
4.6.6. Some changes may require notification to, or licence
amendment, from a national regulatory authority.
4.7. Control of equipment and materials

4.7.1. General principles
4.7.1.1. Documented systems for purchasing equipment and
materials should be available. These should identify
the specific requirements for establishing and review-
ing contracts for the supply of both equipment and
materials.
4.7.1.2. The contracting process should include:
4.7.1.2.1. checks prior to awarding the contract to help ensure
suppliers meet the organisation’s needs;
4.7.1.2.2. appropriate checks on received goods to confirm they
meet specifications;
4.7.1.2.3. the requirement for manufacturers to provide a certif-
icate of analysis for critical material;
4.7.1.2.4. checks to ensure that goods in use continue to meet
specifications;
4.7.1.2.5. regular contact with suppliers to help understand and
resolve problems;
4.7.1.2.6. performance of regular audits.
4.7.1.3. Assessment of the performance of equipment should
occur in the following situations:
88
4.7.1.3.1. upon commissioning of new equipment, which must

include design, installation, operational and perfor-
mance qualifications, and full validation data from
the manufacturer;
4.7.1.3.2. after any relocation, repairs or adjustments that might
potentially alter equipment functioning;
4.7.1.3.3. if ever a doubt arises that the equipment is not func-
tioning appropriately.
4.7.1.4. Consideration should be given to the quality, safety
and efficacy of any blood components prepared before
discovery of the fault adjustment.
4.7.2. Calibration and monitoring of equipment
4.7.2.1. It is necessary to establish a mechanism to ensure the
adequacy of the calibration and monitoring pro-
grammes, and that qualified personnel are available
for their implementation. A calibration and monitor-
ing plan should be used to define the requirements for
establishing and implementing a calibration pro-
gramme that includes the frequency of monitoring.
4.7.2.2. Trending and analyses of calibration and monitoring
results should be a continuous process. Intervals of
calibration and monitoring should be determined
for each item of equipment to achieve and maintain
a desired level of accuracy and quality. The calibra-
tion and monitoring procedure should be based on
a recognised international standard. The calibration
status of all equipment that requires calibration
should be readily available.
4.7.2.3. To ensure appropriate performance of a system or
equipment, a monitoring plan should be developed
and implemented. The plan should take into account
the criticality of the system or equipment, and
should outline monitoring, user-notification and
89
problem-resolution mechanisms. If an unusual event

is observed, personnel should follow the standard
response described in the monitoring plan. The stand-
ard response should involve notifying affected person-
nel and, possibly, initiation of a resolution response
to the problem and risk assessment of the affected
blood components. Depending on the severity of the
problem and the criticality of the system or equip-
ment, a back-up plan may need to be implemented to
keep the process or system operating.
4.7.2.4. In addition to testing that evaluates the suitability of
the implemented changes, sufficient validation should
be conducted on the entire system to demonstrate that
portions of the system not involved in the change are
not adversely impacted.
4.7.2.5. The training programme should be reassessed for
any critical change in environment, equipment or
processes. Training records (including plans and
protocols of training status) must ensure that training
needs are identified, planned, delivered and docu-
mented appropriately for maintenance of validated
systems and equipment.
4.7.2.6. The ability of a supplier to maintain its activities
relating to a system or equipment must be re-qualified
on a regular basis; notably to anticipate weaknesses in
services or to manage changes in the system, equip-
ment or supplier. The periodicity and detail of the
re-qualification process depends on the level of risk of
using the system or equipment, and should be planned
for each supplier.
4.7.2.7. A periodic review process should be established to
ensure that documentation for the system or equip-
ment is complete, current and accurate. A report
of the review process should be produced. When
90
deviations or problems are found, actions should be

identified, prioritised, planned and implemented.
5. Documentation
5.1. General principles
5.1.1. Good documentation constitutes an essential part of
the Quality System and is key to operating in com-
pliance with Good Practice requirements. Various
types of documents and media used should be defined
fully in the Quality Management System of the
organisation.
5.1.2. Documentation may exist in various forms:
paper-based, electronic or photographic. The main
objective of the system of documentation used must
be to establish, control, monitor and record all activi-
ties that directly or indirectly impact on all aspects of
the quality and safety of blood and blood components
as well as any derived medicinal products. The Quality
Management System should include sufficient instruc-
tional detail to facilitate common understanding of
the requirements, in addition to providing for ade-
quate recording of the various processes and evalua-
tion of any observations, so that ongoing application
of the requirements may be demonstrated.
5.1.3. There are two primary types of documentation used
to manage and record Good Practice compliance:
instructions (directions, requirements) and records/
reports. Appropriate practices should be applied
with respect to the type of document. Suitable con-
trols should be implemented to ensure the accuracy,
integrity, availability and legibility of documents.
Instruction documents should be free from errors
and available in writing. The term ‘written’ means
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recorded or documented on media from which data

may be rendered in a readable form for humans.
5.2. Required good practice documentation (by type)

5.2.1. Documents setting out specifications, procedures and
records covering each activity undertaken by a blood
establishment must be in place and kept up-to-date
5.2.2. Instructions (directions or requirements)
5.2.2.1. Specifications describe in detail the requirements to
which the blood and blood components or materials
used or obtained during preparation and distribution
must conform. They serve as a basis for quality evalu-
ation (specifications set out in the Standards section of
Chapter 5 – Component monographs contained in the
Guide to the preparation, use and quality assurance of
blood components published by the Council of Europe
may be used).
5.2.2.2. Testing instructions detail all the starting materials,
equipment and computerised systems (if any) to be
used and specify all sampling and testing instructions.
If applied, in-process controls should be specified,
together with their acceptance criteria.
5.2.2.3. Procedures (otherwise known as Standard Operating
Procedures or SOPs) give directions for performing
certain operations.
5.2.2.4. Protocols give instructions for performing certain
discreet operations, and may record the outcome (e.g.
qualification and validation protocols).
5.2.2.5. Technical agreements are agreed between contract
givers and acceptors for outsourced activities.
5.2.3. Records/reports
92
5.2.3.1. Records provide evidence of various actions taken

to demonstrate compliance with instructions, e.g.
activities, events, investigations and, in the case of
processed blood and blood components, a history of
each unit (including its distribution). Records include
the raw data that is used to generate other records.
For electronic records, regulated users should define
which data are to be used as raw data. All data on
which quality decisions are based should be defined as
‘raw data’.
5.2.3.2. Certificates of analysis provide a summary of testing
results on samples of reagents, products or materials,
together with the evaluation for compliance with a
stated specification.
5.2.3.3. Reports document the carrying out of particular exer-
cises, projects or investigations, together with results,
conclusions and recommendations.
5.3. Generation and control of documentation

5.3.1. All types of documents should be defined and adhered
to. Requirements apply equally to all forms of docu
ment media types. Complex systems need to be
understood, well documented and validated, and ad-
equate controls should be in place. Many documents
(instructions and/or records) may exist in hybrid
forms (i.e. some elements are electronic and others are
paper-based). Relationships and control measures for
master documents, official copies, data handling and
records need to be stated for both hybrid and homo
geneous systems.
5.3.2. A document control system, defined in a written
procedure, must be established for the review, revision
history and archiving of documents, including SOPs.
Appropriate controls for electronic documents, such
93
as templates, forms and master documents, should be

implemented. Appropriate controls should be in place
to ensure the integrity of the record throughout the
retention period.
5.3.3. Documents should be designed, prepared, reviewed,
and distributed with care. Reproduction of working
documents from master documents should not allow
errors to be introduced through the reproduction
process.
5.3.4. Documents containing instructions should be ap-
proved, signed and dated by appropriate and au-
thorised persons. This may also be undertaken
electronically. Documents should have unambiguous
content and be uniquely identifiable. The effective date
should be defined.
5.3.5. Documents containing instructions should be laid
out in an orderly fashion and be easy to check. The
style and language of documents should fit with their
intended use. Standard Operating Procedures, Work
Instructions and Methods should be written in an
imperative mandatory style.
5.3.6. Documents within the Quality Management System
should be regularly reviewed and kept up-to-date.
5.3.7. All significant changes to documents must be acted
upon promptly, and must be reviewed, dated and
signed by a person authorised to undertake this task
5.3.8. Instructional documents should not be hand-written;
although, where documents require the entry of data,
sufficient space should be provided for such entries.
94
5.4. Good documentation practices

5.4.1. Records must be legible and may be handwritten,
transferred to another medium such as microfilm,
or documented in a computerised system (Direc-
5.4.2. Records should be made or completed at the time each
action is taken and in such a way that all significant
activities concerning the donation, collection, pro-
cessing, testing and distribution of blood and blood
components are traceable.
5.4.3. The record system must ensure continuous documen-
tation of the procedures performed from the blood
donor to the recipient. That is, each significant step
must be recorded in a manner that permits a com-
ponent or procedure to be traced, in either direction,
from the first step to final use/disposal.
5.4.4. Any alteration made to the entry on a document
should be signed and dated; the alteration should
permit reading of the original information. Where
appropriate, the reason for the alteration should be
recorded.
5.5. Retention of documents

5.5.1. It should be clearly defined which record is related to
each activity and where this record is located. Secure
controls must be in place to ensure the integrity of the
record throughout the retention period. These con-
trols must be validated if appropriate.
5.5.2. Specific retention requirements for certain documen-
tation apply.
5.5.2.1. Records must be retained for a period according to
local, national or EU requirements, as appropriate.
95
5.5.2.2. Traceability data (that allow tracing from donor to

recipient and vice versa) should be retained for a
minimum of 30 years (Directive 2002/98 Article 14.3).
5.5.2.3. Documentation regarding investigations into Serious
Adverse Events and Serious Adverse Reactions should
be retained for a minimum of 15 years.
5.5.2.4. Quality System documentation and associated records
should be retained for a minimum of 10 years.
5.5.2.5. For other types of documentation, the retention
period must be defined on the basis of the business
activity that the documentation supports. These reten-
tion periods should be specified.
5.6. Specifications
5.6.1. There should be appropriately authorised and dated
specifications for starting and packaging materials, as
well as finished blood and blood components.
5.6.2. Specifications for starting and primary or printed
packaging materials should include or provide refer-
ence to, if applicable:
5.6.2.1. a description of the materials, including:
5.6.2.1.1. the designated name and the internal code reference;
5.6.2.1.2. the approved suppliers and, if reasonable, the original
producer of the material;
5.6.2.1.3 a sample of printed materials;
5.6.2.2. directions for sampling and testing;
5.6.2.3. qualitative and quantitative requirements with accept-
ance limits;
5.6.2.4 storage conditions and precautions;
5.6.2.5. the maximum period of storage before
re-examination.
96
5.6.3. Specifications for in-process and finished compo-

nents should be available (specifications set out in the
Standards section of Chapter 5 - Component mono-
graphs contained in the Guide to the preparation, use
and quality assurance of blood components published
by the Council of Europe may be used). Compo-
nents must be labelled in accordance with Directive
2002/98/EC.
5.7. Preparation instructions

5.7.1. Approved, written instructions for preparation should
exist for each type of component that is produced.
These should include:
5.7.1.1. a process flow for each stage in the preparation of the
component, including where it is undertaken and any
critical equipment used;
5.7.1.2. methods (or reference to the methods) to be used for
starting up and maintaining critical equipment (e.g.
cleaning, assembly, calibration);
5.7.1.3. the requirement to check that the equipment and
work station are clear of previous blood components,
documents or materials not required for the planned
process, and that equipment is clean and suitable for
use;
5.7.1.4. detailed stepwise processing instructions (e.g. checks
on materials, pre-treatments, sequence for adding
materials, and critical process parameters such as time
and temperature);
5.7.1.5. the instructions for any in-process controls with their
limits;
5.7.1.6. requirements for storage of the components and any
critical materials and consumables;
5.7.1.7. any special precautions to be observed.
97
5.8. Labelling
At all stages of the preparation, labelling should
identify the individual components and their nature
clearly.
5.8.1. Requirements for in-process labelling. The label on an
intermediate component should always allow the stage
of processing to be determined and should always
include:
5.8.1.1. the name of the component;
5.8.1.2. the unique numeric or alpha-numeric donation
identification;
5.8.1.3. the name of the producing blood establishment.
5.8.2 Preparation record: each unit is considered to be a
unique batch, but preparation records should provide
sufficient information to build the history and trace-
ability of a prepared component. Usually this infor-
mation is captured in the computerised systems of the
blood establishment. In general, the blood establish-
ment should have access to the following processing
records for each unit:
5.8.2.1. the name and unique identifier of the component;
5.8.2.2. the dates and times of commencement of significant
intermediate stages and of completion of processing:
5.8.2.3. the identification (initials) of the operator(s) who per-
formed each critical step of the process (including the
process controls) and, where appropriate, the name of
any person who verified such steps;
5.8.2.4. the batch number of any relevant consumables and/or
analytical control number of each consumable;
5.8.2.5. a record of the in-process controls and identity of the
person(s) carrying them out, as well as the results
obtained;
98
5.8.2.6. the results of testing undertaken on the donation and/

or the component (excluding quality monitoring);
5.8.2.7. notes on any deviation, including details of the proce-
dures with signed authorisation;
5.8.2.8. information on the processing of non-standard com-
ponents with signed authorisation.
5.9. Procedures and records

5.9.1. Receipt
5.9.1.1. There should be written procedures and records for
the receipt of each delivery of materials and reagents
that can impact on the quality and safety of blood
and blood components. Records of the receipts should
include:
5.9.1.1.1. the name of the material on the delivery note and the
containers;
5.9.1.1.2. the ‘in-house’ code (if any) of the material;
5.9.1.1.3. date of receipt;
5.9.1.1.4 the names of the supplier and manufacturer;
5.9.1.1.5. the batch or reference number of the manufacturer;
5.9.1.1.6 the total quantity and number of items received;
5.9.1.1.7. the batch number assigned after receipt (as applicable);
5.9.1.1.8. the name/ID of the person who received the shipment;
5.9.1.1.9. any relevant comments.
5.9.1.2. There should be written procedures for the internal
labelling, quarantine and storage of starting mate-
rials, packaging materials and other materials, as
appropriate.
99
5.10. Sampling
5.10.1. There should be written procedures for sampling,
which include the methods and equipment to be used,
the amounts to be taken, and any precautions to be
observed to avoid contamination of the material or
any deterioration in its quality.
5.10.2. Quality monitoring of blood components should be
consistent with the current specifications for in-
process and finished components.
5.10.3. There should be written procedures for testing
materials and blood components at different stages of
processing, describing the methods and equipment to
be used. The tests performed should be recorded.
5.11. Other
5.11.1. Written release and rejection procedures should be
available.
5.11.2. Records should be maintained of the distribution of
blood components to facilitate recall of any unit, if
necessary.
5.11.3. There should be written policies, procedures, pro-
tocols, reports and the associated records of actions
taken or conclusions reached (if appropriate) for the
following issues:
5.11.3.1. validation and qualification of processes, equipment
and systems;
5.11.3.2. equipment assembly and calibration;
5.11.3.3. maintenance, cleaning and sanitation;
5.11.3.4. personnel matters, including signature lists, train-
ing in Good Practice and technical matters, clothing
and hygiene, and verification of the effectiveness of
training;
100
5.11.3.5. environmental monitoring;

5.11.3.6. pest control;
5.11.3.7. complaints;
5.11.3.8. recalls;
5.11.3.9. returns;
5.11.3.10. change control;
5.11.3.11. investigations of deviations and non-conformances;
5.11.3.12. audits of compliance with internal quality/Good
Practice;
5.11.3.13. summaries of records, where appropriate (e.g. review
of the quality of blood components);
5.11.3.14. supplier audits.
5.11.4. Records should be kept for major or critical analytical
testing, processing equipment, and areas where blood
components have been processed. They should be
used to record in chronological order (as appropriate)
any use of the area, equipment/method, calibrations,
maintenance, cleaning or repair operations (including
the dates and identity of people who carried out these
operations).
6. Blood collection, testing and processing

6.1. Donor eligibility
6.1.1. Procedures for safe identification of donors, suitability
interview, and eligibility assessment must be imple-
mented and maintained. They must take place before
each donation and comply with the requirements set
out in Annex II and Annex III to Directive 2004/33/
EC (Directive/2005/62/EC/Annex 6.1.1).
6.1.2. There must be secure and unique identification, as
well as recording of the contact details, of donors.
101
Robust mechanisms must link donors to each of their

donations.
6.1.3. Upon arrival at the blood establishment, donors must
provide evidence of their identity. All donors must
undergo a systematic screening process to assess their
suitability.
6.1.4. Only healthy persons with a good medical history can
be accepted as donors of blood or blood components.
6.1.5. The selection process must include assessment of each
donor carried out by a suitably qualified individual
who has been trained to use accepted guidelines and
who works under the direction of a physician. This
assessment involves an interview, a questionnaire and
further direct questions, if necessary.
6.1.6. The questionnaire must be designed to elicit informa-
tion relevant to the health and lifestyle of the donor. It
must be designed to be understandable by the donor
and given to all donors each time they attend. On
completion, it must be signed by the donor.
6.1.7. Relevant acceptance/deferral criteria must be in place
at the blood establishment to control acceptance and
deferral of donors.
6.1.8. The donor interview must be conducted in such a way
as to ensure confidentiality (Directive/2005/62/EC/
Annex 6.1.2).
6.1.9. The confidential interview must be conducted by spe-
cifically trained staff to ask further direct questions to
supplement the information in the questionnaire. The
person who carries out the assessment must certify
that the relevant questions have been asked.
6.1.10. Records of suitability and final assessment of donors
must be signed by a qualified healthcare professional
102
6.1.11. Records should be kept for each activity associated

with the selection of the donor. The record should
reflect the decision to accept the donor by taking
into consideration the medical history, history of
deferral, donor interview, and results of the physical
examination. Rejection of a donor and the reason for
deferral should be recorded. A system must be in place
to ensure that the donor is prevented from making
future donations during a permanent or temporary
deferral period (including for the duration of a tempo-
rary deferral).
6.1.12. Donors must be instructed to inform the blood estab-
lishment if signs or symptoms occur after a donation.
This scenario indicates that the donation may have
been infectious or that any other information not dis-
closed during the health screening may render prior
donation unsuitable for transfusion.
6.1.13. Procedures must be in place to ensure that any abnor-
mal findings arising from the donor selection process
are properly reviewed by a qualified health profes-
sional and that appropriate action is taken.
6.2. Collection of blood and blood components

6.2.1. The procedure for blood collection must be designed
to ensure that the identity of the donor is verified and
recorded securely, and that the link between the donor
and blood, blood components and blood samples is es-
tablished clearly (Directive/2005/62/EC/Annex 6.2.1).
6.2.2. Donor identity must be confirmed before each critical
step in the process but, at the very least, before donor
selection and venepuncture.
6.2.3. A system of unique donation numbers should be used
to identify each donor and the related donation and
103
all of its associated components, samples and records,

as well as to link each one to each of the others.
6.2.4. During or following the donation, all records, blood
bags and laboratory samples should be checked for
the issued donation number. Donation number labels
that have not been used should be discarded using a
controlled procedure.
6.2.5. Systems of sterile blood bags used for the collection
of blood and blood components and their processing
must be CE-marked or comply with equivalent stand-
ards if the blood and blood components are collected
in third countries. The batch number of the bag
must be traceable for each blood component (Direc-
tive/2005/62/EC/Annex 6.2.2).
6.2.6. All handling of materials and reagents, such as receipt
and quarantine, sampling, storage, labelling, process-
ing, packaging and distribution, should be done in
accordance with written procedures or instructions
and, if necessary, recorded.
6.2.7. Only reagents and materials from approved suppliers
that meet documented requirements and specifica-
tions should be used.
6.2.8. Blood collection procedures must minimise the risk
of microbial contamination (Directive/2005/62/EC/
Annex 6.2.3).
6.2.8.1. Sterile collection and processing systems for blood
should be used for blood and blood components.
Collection systems should be used in accordance with
manufacturer instructions.
6.2.8.2. Before venepuncture, a check should be made to
ensure that the collection system to be used is not
damaged or contaminated, and that it is appropriate
104
for the intended collection. Abnormal moisture or

discolouration could suggest a defect.
6.2.8.3. Appropriate procedures for hand disinfection and
personal hygiene should be in place, and should be
performed by personnel before each donation.
6.2.8.4. The skin at the venepuncture site must be free from
lesions, including eczema.
6.2.8.5. The venepuncture site must be prepared using a
defined and validated disinfection procedure. The
antiseptic solution must be allowed to dry completely
before venepuncture. The prepared area must not be
touched with fingers before needle insertion.
6.2.8.6. The effectiveness of the disinfection procedure must
be monitored and corrective action taken where it is
indicated to be defective.
6.2.8.7. The expiry date of the disinfectant should be checked.
The date of manufacture and the date of opening of
in-house disinfectants should be stated on their labels.
6.2.8.8. The blood container must be checked after dona-
tion for any defect. The integral blood bag collection
tubing should be sealed off at the end as close as possi-
ble to the blood bag.
6.2.8.9. Standard Operating Procedures should be in place
describing the actions to be taken following an unsuc-
cessful donation. These should specify how to handle
already-labelled material and the circumstances under
which a repeat venepuncture might be possible.
6.2.9. Laboratory samples must be taken at the time of
donation and be appropriately stored prior to testing
6.2.10. The procedure used for the labelling of records, blood
bags, and laboratory samples with donation numbers
105
must be designed to avoid any risk of identification

error and mix-up (Directive/2005/62/EC/Annex 6.2.5).
6.2.11. After blood collection, blood bags must be handled
in a way that maintains the quality of the blood and
at a storage temperature and transport temperature
appropriate to the requirements for further processing
6.2.12. Blood and blood components should be placed in con-
trolled and validated conditions as soon as possible
after venepuncture. Donations and samples should be
transported to the processing site in accordance with
procedures that ensure a constant approved tempera-
ture and secure confinement. There should be valida-
tion data to demonstrate that the method of transport
maintains the blood within the specified temperature
range throughout the period of transportation. Alter-
natively, portable temperature loggers may be used to
record the temperature during transportation of blood
to the processing site.
6.2.13. If a deviation occurs, it should be approved in writing
by a competent person.
6.2.14. Where the blood is not transported by the processing
establishment itself, the responsibilities of the trans-
port company should be clearly defined and periodic
audits should be conducted to ensure compliance.
6.2.15. There must be a system in place to ensure that each
donation can be linked to the collection and process-
ing system into which it was collected and/or pro-
cessed (Directive 2005/62/EC/Annex 6.2.7).
6.3. Laboratory testing

6.3.1. All blood donations should be tested to ensure that
they meet specifications and to ensure a high level of
safety to the recipient.
106
6.3.2. All laboratory testing procedures must be validated

before use (Directive 2005/62/EC/Annex 6.3.1).
6.3.3. In addition to the validation of the test system by the
manufacturer, an on-site validation of the test system
in the laboratory is required prior to its use in routine
testing. This validation should demonstrate that:
6.3.3.1. the performance specifications of the system es-
tablished by the kit manufacturer are met by the
laboratory;
6.3.3.2. laboratory personnel are thoroughly instructed,
trained and competent to operate the test system.
6.3.4. All donation testing activities, handling of donor
specimens, sampling, analysis and data processing
should be undertaken independently of diagnostic
testing of patients.
6.3.5. Each step of the handling and processing of samples
should be described, as should the conditions of
pre-analytical treatment of specimens (e.g. centrifuga-
tion), storage and transportation (duration, tempera-
ture, type of container, storage after testing).
6.3.6. Upon receipt of samples at the laboratory, positive
identification of the samples received against those
expected should be carried out.
6.3.7. There must be data confirming the suitability of any
laboratory reagents used in testing of donor samples
and blood-component samples (Directive 2005/62/EC/
Annex 6.3.4).
6.3.8. Testing of blood components should be carried out in
accordance with the recommendations of the manu-
facturer of reagents and test kits (unless an alternative
method has been validated before their use) before
release of the blood component.
107
6.3.9. Pre-acceptance testing must be performed on samples

before purchasing batches of commercial reagents.
Prospective purchasers must require potential sup-
pliers to provide them with full validation data for all
lots of reagents. Each lot of reagent must be qualified
by the purchaser to demonstrate suitability for its
intended purpose within the system used for testing.
6.3.10. There must be a reliable process in place for transcrib-
ing, collating and interpreting results.
6.3.11. The quality of the laboratory testing must be assessed
regularly by participation in a formal system of profi-
ciency testing, such as an external quality-assurance
programme (Directive/2005/62/EC/Annex 6.3.5).
6.4. Testing for infectious markers

6.4.1. Testing of donations for infectious agents is a key
factor in ensuring that the risk of disease transmission
is minimised and that blood components are suitable
for their intended purpose.
6.4.2. Each donation must be tested in conformity with the
requirements laid down in Annex IV to Directive
2002/98/EC (Directive 2005/62/EC/Annex 6.3.2).
6.4.3. Additional testing for other agents or markers may
be required, taking into account the epidemiological
situation in any given region or country.
6.4.4. Serological testing should be performed on samples
transferred directly into the analyser from the original
sample tube. Secondary aliquot samples may be used
for NAT testing of mini-pools of individual samples.
6.4.5. If NAT testing is performed by assembling various
samples in mini-pools, a thoroughly validated system
of labelling/identification of samples, a validated strat-
egy and pooling process, and a validated algorithm to
108
reassign pool results to individual donations should be

in place.
6.4.6. There must be clearly defined procedures to resolve
discrepant results. Blood and blood components
that have a repeatedly reactive result in a serological
screening test for infection with the viruses men-
tioned in Annex IV to Directive 2002/98/EC must
be excluded from therapeutic use and must be stored
separately in a dedicated environment. Appropriate
confirmatory testing must take place. In the case of
confirmed positive results, appropriate donor man-
agement must take place, including the provision of
information to the donor and follow-up procedures
(Directive 2005/62/EC/Annex 6.3.3).
6.4.7. Screening algorithms should be defined precisely in
writing (i.e. Standard Operating Procedures) to deal
with initially reactive specimens, and to resolve dis-
crepancies in results after retesting.
6.5. Blood group serological testing of donors and donations

6.5.1. Blood group serology testing must include procedures
for testing specific groups of donors (e.g. first-time
donors, donors with a history of transfusion) (Direc-
tive/2005/62/EC/Annex 6.3.6).
6.5.2. Each donation should be tested for ABO and RhD
blood groups and at least all first-time donors should
be tested for clinically significant irregular red-cell
antibodies.
6.5.3. ABO and RhD blood groups should be verified on
each subsequent donation.
6.5.4. Comparison should be made with the historically
determined blood group. If a discrepancy is found,
the applicable blood components should not be
109
released until the discrepancy has unequivocally been

resolved.
6.5.5. Donors with a history of transfusions or pregnancy
since their last donation should be tested for clinically
significant irregular red-cell antibodies. If clinically
significant red-cell antibodies are detected and, if
applicable, the blood or blood component should be
labelled accordingly.
6.5.6. Only test reagents that have been licensed or evalu-
ated and considered to be suitable by a responsible
National Health Authority/Competent Authority must
be used. In the EU, these reagents are considered as in
vitro diagnostic devices and must be CE-marked.
6.5.7. EU Directive 98/79/EC classifies ABO, Rh (C, c, D, E,
e) anti-Kell reagents in list A of Annex II. The manu
facturer of such reagents must have a full Quality
System certified by an authorised body, and must
submit an application containing all the control
results for each lot.
6.5.8. Quality-control procedures must be implemented for
the equipment, reagents and techniques used for ABO
and RhD blood grouping and phenotyping as well as
detection and identification of allo-antibodies. The
frequency of the control is dependent on the method
used.
6.6. Processing and validation

6.6.1. All equipment and technical devices must be used
in accordance with validated procedures (Direc-
tive/2005/62/EC/Annex 6.4.1).
6.6.2. The processing of blood components must be carried
out using appropriate and validated procedures,
including measures to avoid the risk of contamination
110
and microbial growth in the prepared blood compo-

nents (Directive/2005/62/EC/Annex 6.4.2).
6.6.3. The use of closed systems is strongly recommended
for all steps in component processing. Open systems
may exceptionally be necessary due to local con-
straints and should be undertaken in an environment
specifically designed to minimise the risk of bacte-
rial contamination. When open systems are used,
careful attention should be given to the use of aseptic
procedures.
6.6.4. Validation of freezing processes should consider
worst-case scenarios that take into account minimum
and maximum loads and positions in the freezer.
6.6.5. Sterile connecting devices must be used in accordance
with a validated procedure. When validated, con-
nections made using sterile connecting devices are
regarded as closed system processing. The resulting
weld must be checked for satisfactory alignment and
its integrity must be confirmed.
6.7. Labelling
6.7.1. At all stages, all containers must be labelled with
relevant information on their identity. In the absence
of a validated computerised system for status control,
the labelling must clearly distinguish released from
non-released units of blood and blood components
6.7.2 Type of label to be used, as well as the labelling meth-
odology, should be defined and established in written
Standard Operating Procedures.
6.7.3. Labels applied to containers, equipment or premises
should be clear, unambiguous and in the agreed
format of the blood establishment.
111
6.7.4. Labelling system for collected blood, intermediate and

finished blood components, and samples must unmis-
takably identify the type of content, and comply with
the labelling and traceability requirements referred to
in Article 14 of Directive 2002/98/EC and Directive
2005/61/EC. The label for a final blood component
must comply with the requirements of Annex III to
Directive 2002/98/EC (Directive 2005/62/EC/Annex
6.5.2).
6.7.5. Blood establishments responsible for the preparation
of blood components must provide clinical users of
blood components with information on their use,
composition, and any special conditions that do not
appear on the component label.
6.7.6. For autologous blood and blood components, the label
must also comply with Article 7 of Directive 2004/33/
EC and the additional requirements for autologous
donations specified in Annex IV to that Directive
6.8. Release of blood and blood components

6.8.1. There must be a safe and secure system to prevent any
single blood sample and blood component from being
released before all mandatory requirements set out in
Directive 2005/62/EC have been fulfilled. Each blood
establishment must be able to demonstrate that each
blood or blood component has been formally released
by an authorised person. Records must demonstrate
that before a blood component has been released, all
current declaration forms, relevant medical records,
and test results have met all acceptance criteria
6.8.2. There should be Standard Operating Procedures that
detail the actions and criteria that determine whether
112
the blood or blood component can be released. The

release criteria and specifications of blood compo-
nents should be defined, validated, documented and
approved.
6.8.3. There should be a defined procedure for exceptional
release of non-standard blood and blood compo-
nents under a planned non-conformance system. The
decision to allow such release should be documented
clearly and traceability should be ensured.
6.8.4. Before release, blood and blood components must be
kept administratively and physically segregated from
released blood and blood components. In the absence
of a validated computerised system for status control,
the label of a unit of blood or blood component must
identify the release status in accordance with point
6.5.1 stated above (Directive 2005/62/EC/Annex 6.5.1
and 6.6.2).
6.8.5. There should be a system of administrative and phys-
ical quarantine for blood and blood components to
ensure that components cannot be released until all
mandatory requirements have been met.
6.8.6. In the event that the final component fails to be re-
leased due to a confirmed positive test result for infec-
tion for an agent mentioned in Annex IV of Directive
2002/98/EC, a check must be made to ensure that
other components from the same donation and com-
ponents prepared from previous donations given by
the donor have been identified. An immediate update
must be made to the donor record (Directive 2005/62/
EC Annex 6.3.2, 6.3.3 and 6.6.3).
6.8.7. In the event that a final component fails release due
to a potential impact on patient safety, the donor
record must be immediately updated to ensure, where
113
appropriate, that the donor(s) cannot make a further

donation.
7. Storage and distribution

7.1. The Quality System of the blood establishment must
ensure that, for blood and blood components intended
for the manufacture of medicinal products, the re-
quirements for storage and distribution must comply
with Directive 2003/94/EC (Directive 2005/62/EC/
Annex 7.1).
7.2. Procedures for storage and distribution must be vali-
dated to ensure the quality of blood and blood compo-
nents during the entire storage period, and to exclude
mix-ups of blood components. All transportation and
storage actions, including receipt and distribution,
must be defined by written procedures and specifica-
tions (Directive 2005/62/EC/Annex 7.2).
7.3. Storage conditions must be controlled, monitored
and checked. Appropriate alarms must be present
and checked regularly; all checks must be recorded.
Appropriate actions on alarms must be defined.
7.4. There should be a system to ensure stock rotation
involving regular and frequent checks that the system
is operating correctly. Blood and blood components
beyond their expiry date or shelf-life should be sepa-
rated from usable stock.
7.5. Before distribution, blood components must be visu
ally inspected.
7.6. Autologous blood and blood components, as well as
blood components collected and prepared for spe-
cific purposes, must be stored separately (Directive
2005/62/EC/Annex 7.3).
114
7.7. Appropriate records of inventory and distribution

must be kept (Directive 2005/62/EC/Annex 7.4).
7.8. Records should be kept of the distribution of blood
components between blood establishments, blood
establishments and hospital blood banks and between
hospital blood banks. These records should show the
date of supply, unique component identifier and name
of the blood component, the quantity received or sup-
plied, name and address of the supplier or consignee.
7.9. Packaging must maintain the integrity and storage
temperature of blood and blood components during
distribution and transportation (Directive 2005/62/
EC/Annex 7.5).
7.10 Verification of transportation
7.10.1 Blood components should be transported in accord-
ance with the defined conditions.
7.10.2 It is recognised that verification of transportation may
be challenging due to the variable factors involved;
however, transportation routes should be clearly
defined. Seasonal and other variations should also be
considered during verification of transport.
7.10.3 A risk assessment should be performed to consider
the impact of variables in the transportation process
other than those conditions which are continuously
controlled or monitored, e.g. delays during transpor-
tation, failure of cooling and/or monitoring devices,
blood component susceptibility and any other relevant
factors.
7.10.4 Due to the variable conditions expected during trans-
portation, continuous monitoring and recording of
any critical environmental conditions to which the
blood component may be subjected should be per-
formed, unless otherwise justified.
115
7.11. Return of blood and blood components into inven-

tories for subsequent re-issue must be allowed only if
all requirements and procedures relating to quality as
laid down by the blood establishment to ensure the
integrity of blood components are fulfilled (Directive
2005/62/EC/Annex 7.6).
7.12. Blood components must not be returned to the blood
establishment for subsequent distribution unless there
is a procedure for the return of blood components that
is regulated by a contract, and if there is, documented
evidence for each returned blood component that
the agreed storage conditions have been met. Before
subsequent distribution, records must identify that the
blood component has been inspected before reissue.
8. Outsourced activities management

8.1. General principles
8.1.1. Tasks that are performed externally must be defined
in a specific written contract (Directive 2005/62/EC/
Annex 8).
8.1.2. Outsourced activities that may impact on the quality,
safety or efficacy of the blood components should
be correctly defined, agreed and controlled in order
to avoid misunderstandings which could result in a
blood component or work of unsatisfactory quality.
There should be a written contract covering these
activities, the products or operations to which they
are related, and any technical arrangements made in
connection with it.
8.1.3. All outsourced arrangements for blood collection,
processing and testing, including any proposed
changes, should be made in accordance with a written
contract, with reference to the specification for the
blood or blood component(s) concerned.
116
8.1.4. The responsibilities of each party should be docu-

mented to ensure that Good Practice principles are
maintained.
8.1.5. The contract giver is the establishment or institution
that subcontracts particular work or services to a
different institution and is responsible for setting up
a contract defining the duties and responsibilities of
each side.
8.1.6. The contract acceptor is the establishment or institu-
tion that performs particular work or services under a
contract for a different institution.
8.2. The contract giver

8.2.1. The contract giver is responsible for assessing the
competence of the contract acceptor to successfully
carry out the work being outsourced and for ensur-
ing, by means of the contract, that the principles and
guidelines of Good Practice are followed.
8.2.2. The contract giver should provide the contract accep-
tor with all the information necessary to carry out
the contracted operations correctly and in accordance
with the specification and any other legal require-
ments. The contract giver should ensure that the
contract acceptor is fully aware of any problems asso-
ciated with the materials, samples or the contracted
operations that might pose a hazard to the premises,
equipment, personnel, other materials or other blood
components of the contract acceptor.
8.2.3. The contract giver should ensure that all blood and
blood components, analytical results and materials
delivered by the contract acceptor comply with their
specifications and that they have been released under
a Quality System approved by the Responsible Person
or other authorised person.
117
8.3. The contract acceptor

8.3.1. The contract acceptor should have adequate premises,
equipment, knowledge, experience and competent
personnel to satisfactorily carry out the work re-
quested by the contract giver.
8.3.2. The contract acceptor should ensure that all products,
materials or test results delivered by the contract giver
are suitable for their intended purpose.
8.3.3. The contract acceptor should not pass to a third party
any of the work entrusted under the contract without
the contract giver’s prior evaluation and approval of
the arrangements. Arrangements made between the
contract acceptor and any third party should ensure
that the relevant blood collection, processing and
testing information is made available in the same way
as between the original contract giver and contract
acceptor.
8.3.4. The contract acceptor should refrain from any activity
that may adversely affect the quality of the blood and
blood components prepared and/or analysed for the
contract giver.
8.4. The contract

8.4.1. A contract should be drawn up between the contract
giver and the contract acceptor that specifies their
respective responsibilities relating to the contracted
operations. All arrangements for blood collection,
processing and testing should be in compliance with
the requirements of Good Practice and regulatory
requirements and agreed by both parties.
8.4.2. The contract should specify the procedure, including
the necessary requirements to be provided by the
contract acceptor, by which the Responsible Person or
other authorised person releasing the blood and blood
118
components for sale or supply can ensure that each

component has been prepared and/or distributed in
compliance with the requirements of Good Practice
and regulatory requirements.
8.4.3. The contract should clearly describe who is respon-
sible for purchasing materials, testing and releasing
materials, undertaking blood collection, and for
processing and testing (including in-process controls).
In the case of subcontracted analyses, the contract
should state the arrangements for the collection of
samples and the contract acceptor should understand
that they may be subject to inspections by the Compe-
tent Authorities.
8.4.4. Preparation and distribution records, including
reference samples if relevant, should be kept by, or be
available to, the contract giver. Any records relevant
to assessment of the quality of the blood or a blood
component in the event of complaints or a suspected
defect should be accessible and specified in the defect/
recall procedures of the contract giver.
8.4.5. The contract should permit the contract giver to audit
the facilities of the contract acceptor.
9. Non-conformance and recall

9.1. Deviations
9.1.1. Blood components deviating from required standards
set out in Annex V to Directive 2004/33/EC shall
be released for transfusion only in exceptional cir-
cumstances and with the recorded agreement of the
prescribing physician and the blood establishment
physician (Directive 2005/62/EC/Annex 9.1).
9.1.2. For components not listed in Annex V to Directive
2004/33/EC, quality and safety standards set out
119
in the Standards section of Chapter 5 – Component

monographs contained in the Guide to the preparation,
use and quality assurance of blood components pub-
lished by the Council of Europe may be used to meet
the intent of 9.1.1 above.
9.1.3. There should be a defined procedure for the release
of non-standard blood and blood components under
a planned non-conformance system. The decision
for such release should be clearly documented and
authorised by a designated person and traceability
should be ensured.
9.1.4. There should be systems in place to ensure that devia-
tions, adverse events, adverse reactions and non-con-
formances are documented, carefully investigated for
causative factors of any defect and, where necessary,
followed up by the implementation of corrective
actions to prevent recurrence.
9.1.5. The corrective and preventive actions (CAPAs) system
should ensure that existing component nonconform-
ity or quality problems are corrected and that recur-
rence of the problem is prevented.
9.1.6. Deviations from established procedures should be
avoided as much as possible and should be doc-
umented and explained. Any errors, accidents or
significant deviations that may affect the quality or
safety of blood and blood components should be fully
recorded and investigated in order to identify system-
atic problems that require corrective action. Appro-
priate corrective and preventive actions should be
defined and implemented.
9.1.7. Investigations relating to serious deficiencies, signifi-
cant deviations and serious component defects should
include an assessment of component impact, includ-
ing a review and evaluation of relevant operational
120
documentation and an assessment of deviations from

specified procedures.
9.1.8. There should be procedures for notifying responsible
management in a timely manner of deficiencies, de-
viations or non-compliance with regulatory commit-
ments (e.g. in submissions and responses to regulatory
inspections), component or product defects, or testing
errors and related actions (e.g. quality-related com-
plaints, recalls, regulatory actions, etc.).
9.1.9. Executive management and the Responsible Person
should be notified in a timely manner of serious defi-
ciencies, significant deviations and serious component
or product defects and adequate resource should be
made available for their timely resolution.
9.1.10. A regular review of all significant deviations or
non-conformances should be conducted, including
their related investigations, to verify the effectiveness
of the corrective and preventive actions taken.
9.2. Complaints
9.2.1. All complaints and other information, including
serious adverse reactions and serious adverse events
that may suggest that defective blood components
have been issued, must be documented, carefully
investigated for causative factors of the defect and,
where necessary, followed up by recall and the im-
plementation of corrective actions to prevent recur-
rence. Procedures must be in place to ensure that the
Competent Authorities are notified, as appropriate, of
serious adverse reactions or serious adverse events in
accordance with regulatory requirements (Directive
2005/62/EC/Annex 9.2).
9.2.2. A person should be designated as responsible for
handling complaints and deciding the measures to be
121
taken. This person should have sufficient support staff.

If this person is not the Responsible Person, the latter
should be made aware of any complaint, investigation
or recall.
9.2.3. If a blood or blood component defect or testing error
is discovered or suspected, consideration should be
given to checking related blood and blood compo-
nents in order to determine whether they are also
affected.
9.2.4. All the decisions and measures taken as a result of
a complaint should be recorded. Complaint records
should be reviewed regularly for any indication of
specific or recurring problems requiring attention
and the possible recall of distributed blood and blood
components.
9.2.5. The Competent Authorities should be informed in
cases of complaints resulting from possible faulty
processing, component deterioration or any other
serious quality problems, including the detection of
counterfeiting.
9.3. Recall
9.3.1. There must be personnel authorised within the blood
establishment to assess the need for blood and blood
component recalls and to initiate and co-ordinate the
necessary actions (Directive 2005/62/EC/Annex 9.3.1).
9.3.2. An effective recall procedure must be in place, includ-
ing a description of the responsibilities and actions to
be taken. This must include notification of the Com-
petent Authority (Directive 2005/62/EC/Annex 9.3.2).
9.3.3. Actions must be taken within pre-defined periods of
time and must include tracing all relevant blood com-
ponents and, where applicable, must include trace-
back. The purpose of the investigation is to identify
122
any donor who might have contributed to causing the

transfusion reaction and to retrieve available blood
components from that donor, as well as to notify con-
signees and recipients of components collected from
the same donor in the event that they might have been
put at risk (Directive 2005/62/EC/Annex 9.3.3).
9.3.4. Recall operations should be capable of being initiated
promptly and at any time. In certain cases recall oper-
ations may need to be initiated to protect public health
prior to establishing the root cause(s) and full extent
of the quality defect.
9.3.5. The persons authorised to initiate and co-ordinate the
recall actions should normally be independent of the
commercial management within the organisation. If
they do not include the executive management and
the Responsible Person (blood establishment), the
latter should be made aware of any recall operation.
9.3.6 Recalled blood components or products should be
identified and stored separately in a secure area while
awaiting a decision on their fate.
9.3.7. The progress of the recall process should be recorded
and a final report issued, including reconciliation of
the delivered and recovered quantities of the blood
and blood components or products.
9.3.8. The effectiveness of the arrangements for recalls
should be regularly evaluated.
9.4. Deviation management and corrective

and preventive actions
9.4.1. A system to ensure corrective and preventive actions
for blood component nonconformity and quality
problems must be in place (Directive 2005/62/EC/
Annex 9.4.1).
123
9.4.2. Data must be routinely analysed to identify quality

problems that may require corrective action or to
identify unfavourable trends that may require preven-
tive action (Directive 2005/62/EC/Annex 9.4.2).
9.4.3. All errors and accidents must be documented and in-
vestigated in order to identify problems for correction
9.4.4. Deviations with the potential to affect quality should
be investigated, and the investigation and its conclu-
sions should be documented including all the original
details. The validity and extent of all reported quality
defects should be assessed in accordance with Quality
Risk Management principles in order to support deci-
sions regarding the degree of investigation and action
taken. Where appropriate, corrective actions should
be taken prior to distribution of blood and blood
components or reporting of a test result. The potential
impact of the source of the deviation on other compo-
nents or results should also be considered and preven-
tive action should be taken to eliminate the root cause
of the deviation and thereby avoid recurrences.
9.4.5. Investigations should include a review of previous
reports or any other relevant information for any
indication of specific or recurring problems requir-
ing attention and possibly further regulatory action.
Processes and relevant data should be monitored with
a view to taking preventive action to avoid potential
deviations occurring in the future. Where appropri-
ate, statistical or other tools should be used to assess
and monitor process capabilities. As comprehensive
information on the nature and extent of the quality
defect may not always be available at the early stages
of an investigation, the decision-making processes
should still ensure that appropriate risk-reducing
124
actions are taken at an appropriate time-point during

such investigations.
9.4.6. An appropriate level of root cause analysis work
should be applied during the investigation of devia-
tions. In cases where the true root cause(s) cannot be
determined, consideration should be given to identi-
fying the most likely root cause(s) and to addressing
those. Where human error is suspected or identified
as the cause of the deviation, this should be formally
justified and care should be exercised so as to ensure
that process, procedural or system-based errors or
problems are not overlooked, if present.
9.4.7. The decisions that are made during and following
investigations should reflect the level of risk that is
presented by the deviation as well as the seriousness of
any non-compliance with respect to the requirements
of the blood component specifications or GP. Such
decisions should be timely to ensure that patient safety
is maintained, in a way that is commensurate with the
level of risk that is presented by those issues.
9.4.8. As part of periodic Quality System reviews, an
assessment should be made of whether corrective
and preventive actions or any revalidation should be
undertaken. The reasons for such corrective actions
should be documented. Agreed CAPAs should be
completed in a timely and effective manner. There
should be procedures for the ongoing manage-
ment and review of these actions and the effective-
ness of these procedures should be verified during
self-inspection.
10. Self-inspection, audits and improvements

10.1. Self-inspection or audit systems must be in place
for all elements of operations to verify compliance
125
with the standards set out in the Annex to Directive

2005/62/EC. They must be carried out regularly by
trained and competent persons, in an independent
way, and according to approved procedures (Directive
2005/62/EC/Annex 10.1).
10.2. All results must be documented and appropriate
corrective and preventive actions must be taken in a
timely and effective manner (Directive 2005/62/EC/
Annex 10.2).
11. Quality monitoring and control

11.1. Quality monitoring
11.1.1. Acceptance criteria must be based on a defined spec-
ification for each blood donation and blood compo-
nent (specifications set out in the Standards section of
Chapter 5 – Component monographs contained in the
Guide to the preparation, use and quality assurance of
blood components published by the Council of Europe
may be used).
11.2. Quality control

11.2.1. All quality control procedures must be validated
before use.
11.2.2. Results of quality-control testing must be evaluated
continuously and steps taken to correct defective pro-
cedures or equipment.
11.2.3. Standard procedures for the quality control of blood
components must be in place. The suitability of each
analytical method to provide the intended informa-
tion must be validated.
11.2.4. Quality control of blood and blood components must
be carried out according to a sampling plan designed
to provide the intended information.
126
11.2.5. Testing must be done in accordance with the in-

structions recommended by the manufacturer of the
reagents and/or test kits.
11.2.6. The performance of the testing procedures must be
regularly assessed by participation in a formal system
of proficiency testing.
11.2.7. Records of quality-control procedures must include
identification of the person(s) undertaking the tests or
procedures. Any corrective action taken must also be
recorded. If corrections in records are necessary, the
original recording must not be obliterated, but must
remain legible.
127
PRINCIPLES
Chapter 1
Introduction
The Principles section of this Guide contains background information
to support the Standards. It also provides information on develop-
ments that have yet to be incorporated into Standards and on tech-
nical changes in the field. This includes information on the ‘why and
how’ for work in blood establishments and hospital blood banks.
In addition, several appendices are provided at the end of this Guide.
These appendices provide detailed information on specific areas of
relevance to blood establishments and hospital blood banks which are
not addressed in detail elsewhere in the Guide.
131
Chapter 2
Principles of donor selection
1. General remarks

Principles of self-sufficiency from voluntary and non-remunerated
donations have been recommended and promoted by the Council
of Europe and have been defined in Article 2 of Council of Europe
Recommendation No. R (95) 14 as follows:
The definition of voluntary and non-remunerated donation is:
Donation is considered voluntary and non-remunerated if the
person gives blood, plasma or cellular components of his/her own
free will and receives no payment for it, either in the form of cash,
or in kind which could be considered a substitute for money. This
would include time off work other than that reasonably needed for
the donation and travel. Small tokens, refreshments and reimburse-
ments of direct travel costs are compatible with voluntary, non-re-
munerated donation.
They have also been adopted by the EU in Directive 2002/98 EC,
which states in the preamble (23): ‘The definition of voluntary and
unpaid donation of the Council of Europe should be taken into
account’, and, in Article 20 paragraph 1: ‘Member states shall take
the necessary measures to encourage voluntary and unpaid blood
133
donations with a view to ensuring that blood and blood components

are in so far as possible provided from such donations.’
Specific immunisation programmes are not considered in this doc-
ument, but donors enrolled for this purpose should at least fulfil the
minimum criteria outlined above (see also Annex 2, Requirements for
the collection, processing and quality control of blood, blood compo-
nents and plasma derivatives, WHO Technical Report Series, No. 840,
1994).
2. Overview
This chapter considers the principles for the selection of donors of
whole blood and also donors of components obtained by different
apheresis procedures. There are general principles which apply to all
donors. Some criteria for the selection of donors vary according to the
type of donation involved. There are also further requirements specific
to donors of different components collected by different methods.
Selection of donors of haematopoietic progenitor cells is discussed in
the Guide to the quality and safety of tissues and cells for human appli-
cation (EDQM/Council of Europe).
The main purpose of selecting individuals for blood and blood com-
ponent donation is to determine whether the person is in good health
so as to safeguard the health of both donor and recipient. All donors
undergo a screening process to assess their eligibility (see Standards).
The screening process involves:
• provision of pre-donation educational material to all donors of
blood or blood components;
• medical assessment of each donor.
Since blood establishments are ultimately responsible for the quality
and safety of the blood and blood components collected, they are
entitled to decide on the final acceptance or deferral of a donor or a
prospective donor (Resolution CM/Res (2008) 5 on donor responsi-
bility and on limitation to donation of blood and blood components,
134
Chapter 2 Principles of donor selection
adopted by the Committee of Ministers on 12 March 2008 at the 1021st

meeting of the Ministers’ Deputies).
3. Medical assessment of the donor

In practice, a complete medical and physical examination of donors
is generally not possible. It is necessary to rely on the donors’ appear-
ance, their answers to questions concerning their medical history,
general health, and relevant risk factors (e.g. lifestyle, travel history)
and on laboratory tests.
Based on this information, a decision on the eligibility of the donor
will be made using accepted guidelines. Conditions that are not
covered by guidelines should be referred to the physician in charge
with responsibility for making the final decision.
To obtain relevant and consistent information about the donor’s
medical history and general health, a standard questionnaire is to
be completed at each donation. Adaptation of the questionnaire
to the type of donor (first time, regular, apheresis donor, etc.) is
recommended.
The key topics for donor eligibility to be covered by the questionnaire
or by direct questions, the intentions of the interview questions, and
examples of sample questions are included in Appendix 1.
Age of the donor

The standards set out in this Guide define age-limits for donation
and provide discretion for the responsible physician to accept donors
outside of these limits. This medical discretion can be applied either
on an individual basis for a given donor or else through a systematic
approach based on an appropriate risk assessment.
Hazardous occupations
Hazardous occupations or hobbies should normally require that
there is an interval of not less than 12 hours between donation and
returning to the occupation or hobby. Examples of such hazardous
occupations or hobbies include piloting, bus or train driving, crane
135
operation, climbing of ladders or scaffolding, gliding, climbing and

diving.
Donor deferral
Considering the requirement that only healthy people are acceptable
as blood donors, deferral criteria can be grouped into:
• conditions requiring permanent deferral;
• conditions requiring temporary deferral for a defined duration;
• vaccination;
• conditions requiring individual assessment;
• infectious diseases.
Conditions requiring permanent deferral

See Standards.
Conditions requiring temporary deferral (suspension)

See Standards.
Vaccination
See Standards.
Conditions requiring individual assessment

As donors may present with a variety of prior or current medical
problems, only some of the more common examples are considered in
Table 2.1 below.
136
Table 2.1. Conditions requiring individual

assessment of the donor
Condition requiring Criteria for deferral

individual
assessment
Allergy Individuals with a documented history of anaphylaxis

should not be accepted as donors.
Auto-immune diseases If more than one organ is affected this leads to permanent deferral.
Beta-thalassaemia trait Heterozygote carriers of beta-thalassaemia trait may
give blood provided they are in good health and have a
haemoglobin level within acceptable values.
Bronchitis Persons with symptoms of severe chronic bronchitis
should not be accepted as donors.
Common cold Accept, if asymptomatic and feels well on the day of donation.
Hypertension A person who presents with a systolic blood pressure of more than 180
mm Hg or a diastolic blood pressure of more than 100 mm Hg should
not be accepted as a blood donor. A mild hypertensive, whose diastolic
blood pressure is maintained at less than 100 mm Hg, may be accepted.
Pulse a The pulse should be regular and between 50 beats per minute (bpm)
and 100 bpm. Exceptions may be made to accept donors with a lower
pulse rate following individual medical review, e.g. athletes.
Jaundice and hepatitis Hospital staff coming into direct contact with patients with hepatitis
(see Standards) are accepted at the discretion of the physician in charge of the blood-
collecting unit providing they have not suffered an inoculation injury or
mucous membrane exposure, in which case they must be deferred.
Chagas disease In some countries, donors who were born or have been transfused in
(see Standards) areas where the disease is endemic are deferred or tested. The blood
of persons who were born or have been transfused in areas where
the disease is endemic should be used only for plasma fractionation
products unless a validated test for infection with T. cruzi is negative.
a Where measured.
Post-donation information
See Standards.
137
Systems should be in place to define the actions to be taken if a donor

informs the blood establishment that he/she previously donated
blood but should not have done so in the light of donor selection
criteria aimed at protection of the health of recipients (e.g. in retro-
spect, the donor did not fulfil the criteria mentioned in the donor
questionnaire).
Infectious diseases
Transmission of infectious agents by transfusion can be minimised
by careful and appropriate use of donor questionnaires and/or labora-
tory testing. Donors should be questioned on their risk of exposure to
infectious agents, which includes taking a travel history.
For infections in which the agent has been fully cleared from the
donor’s blood on recovery, the donor should be deferred from dona-
tion until they are no longer infectious (usually 2 weeks from cessation
of symptoms).
In cases of known contact with an infectious agent, the donor should
be deferred for approximately twice the length of the incubation
period. In case of a geographical risk of exposure to multiple infec-
tious agents, the longest deferral period applies.
Other measures are needed for infections where there is a possibility
of asymptomatic infection or existence of a carrier state. Question-
ing donors about symptoms in these circumstances does not always
prevent transmission.
Many infections that can be transmitted by transfusion have defined
geographical limits, and the risk of transfusion transmission can be
minimised by temporary deferral or testing donors travelling from af-
fected areas (see Table 2.2). Testing becomes especially relevant when
deferral policies may potentially affect supply.
138
Table 2.2. Recommended donor deferral after exposure

to infectious agents if testing is not in place
Infectious agents Incubation Strategies to Strategies to

period (days) prevent TTI from prevent TTI after
healthy donors clinical disease
West Nile virus 2-14

Chikungunya virus 1-12 28-day deferral 120-day deferral
after leaving after resolution
Dengue virus 5-6 the risk area of symptoms
Zika virus 3-12
Blood services should maintain a watching brief on changes to risks

of infectious diseases worldwide. Risk-benefit analyses should be
carried out to determine appropriate measures to decrease the risks
of infectious diseases in their own country. The risk of importation
of an infectious agent through donors visiting an affected area should
be balanced by considering the likelihood of this occurring, and the
impact of introducing a new donor deferral ruling on blood collection.
This risk will vary between countries.
New and emerging infectious agents or those that have moved to
infect a new geographical area can also pose a significant challenge.
The West Nile virus, dengue virus, Babesiosis, Q fever and the Chi-
kungunya virus are examples of such viruses/diseases. In this situa-
tion, donor deferral may not be an option in the newly affected area.
Donation testing is then the main tool to reduce the risk of transmis-
sion. For plasma and platelets, pathogen-reduction technology may
also be considered.
Information about new and emerging infections should be communi-
cated between countries without delay to allow blood establishments
to consider their own risks and appropriate actions.
Variant Creutzfeldt-Jakob disease (vCJD) was first described in the
UK in 1996. Clinical presentation differs from classical CJD in that it
139
tends to affect a younger age group, and there is greater involvement of

lymphoid tissue.
Estimating the potential size of the vCJD epidemic has been very
difficult. Transfusion transmission of vCJD has been documented in
animal studies and in humans.
Several measures have been taken in the UK to reduce the risk of
further transmission by blood transfusion. Measures include: uni-
versal depletion of leucocytes; importation of plasma for fractiona-
tion and clinical use in children who have not been exposed to BSE
through their diet; lifetime deferral of donors who have been trans-
fused; reducing inappropriate transfusions (particularly for surgical
indications). In addition, patients deemed to be ‘at risk’ because of
receiving blood from an implicated donor or receiving a large amount
of blood, including fractionated products, are advised not to donate
blood, tissues or organs, and have special measures taken during
surgery such as use of disposable or dedicated instruments.
Many countries outside the UK defer donors who have lived in the UK
for a minimum defined period between 1980 and 1996; the European
Medicines Agency (EMA) mandates 1 year of UK residence for donors
of plasma for fractionation. In some instances the deferrals have been
extended to include donors from other countries with a significant
number of cases.
Endogenous risk of vCJD differs between countries. Therefore, dif-
ferent measures to reduce risk will be appropriate depending on each
country’s own risk assessment: balancing risk with sufficiency of
supply.
History of malignancy
Individuals with a malignant disease or a history of malignancy are
usually permanently deferred (see Standards). However, there is a lack
of evidence to support the theoretical concerns that cancer is trans-
mitted via blood.
140
Large observational studies have provided convincing evidence that

the risk of transmitting cancer via blood transfusions is undetectable
or not significant.
Based on this, donors with a history of malignancy may be considered
using the following criteria:
• permanent deferral for any history of haematological malignan-
cies (e.g. leukaemia, lymphoma, myeloma);
• permanent deferral for any history of malignancies known to be
associated with viraemic conditions (except for carcinoma in situ
of the cervix, see below);
• for other cancers, the donor should have fully recovered with no
expectation of recurrence (i.e. cured) and the following condi-
tions apply:
–– for cancers with negligible metastatic potential (e.g. basal cell
carcinoma and carcinoma in situ of the cervix), the donor
may be accepted immediately following successful removal
and cure;
–– for all other cancers, at least 5 years should have elapsed since
completion of active treatment;
• no deferral is required for pre-malignant conditions.
4. Specific considerations for donors of different

components
Quantity of whole blood donation
In addition to the standard volume of a whole-blood donation (see
Standards), up to 35 mL of blood is collected for laboratory tests and
for retention of a donation sample.
Because of the risk of adverse reactions, no more than 15 % of the es-
timated blood volume should be collected as whole blood during one
blood donation. The blood volume of the donor can be calculated from
their weight, height and gender using a validated formula (it is recom-
mended to calculate the blood volume using the formula developed by
141
the International Council for Standardisation in Haematology, ICSH).

The ICSH formula is derived from a large European study population
in which measurements of red cell mass and plasma volume were
carried out.1
It is generally accepted that all men weighing ≥ 50 kg have a suffi-
ciently large blood volume to donate a total 535 mL of blood (500 mL
plus 35 mL for testing and retention of a donation sample), whilst all
women weighing ≥ 50 kg have a sufficiently large blood volume to
donate a total 485 mL of blood (450 mL plus 35 mL for testing and
retention of a donation sample).
In the case of women weighing < 65 kg and donating a total > 485 mL,
the estimated blood volume should be calculated. The calculated blood
volume should exceed the minimum acceptable blood volume for the
volume of blood to be collected (see Table 2.3). If the calculated blood
volume is less than acceptable, a smaller volume should be collected or
the donor should be deferred.
If the donation volume may exceed 15 % of the blood volume of the
donor, blood establishments should use a blood-volume table prepared
according to the ICSH formula for checking the blood volume of the
donor (see examples in Appendix 2).
Frequency of whole blood donation

It is recommended that an active donor panel of sufficient size be
maintained to allow donors to be bled less often than the maximum
annual rates stated in Standards. Four whole blood donations for
males and three donations for females should ordinarily not be
exceeded per year, thereby affording the donors extra protection
and giving the system flexibility to deal with large-scale emergency
situations.
1 Pearson TC, Guthrie DL, Simpson J, Chinn C, Barosi G, Ferrant A, Lewis SM,

Najean Y. Interpretation of measured red cell mass and plasma volume in
adults: Expert Panel on Radionuclides of the International Council for Stand-
ardisation in Haematology. Br J Haem 1995, 89: 748-56.
142
Table 2.3. Calculated minimum blood volume of a female

donor donating 485 mL, 510 mL or 535 mL
Volume of blood Maximum percentage of Minimum acceptable

to be collected blood volume collected blood volume
450 mL + 35 mL 15 % 3 233 mL

475 mL + 35 mL 15 % 3 400 mL
500 mL + 35 mL 15 % 3 567 mL
Laboratory examination before donation

Hb level
Haemoglobin should be measured at each donation, preferably before
collection. Abnormally high and abnormally low haemoglobin values
should be confirmed by a full blood count on a venous sample and,
if appropriate, subsequently investigated (as should a fall in haemo-
globin concentration of more than 20 g/L between two successive
donations).
Iron stores
It is recognised that blood donation may result in iron deficiency in
repeat blood donors. This problem may arise without it being evident
through pre-donation haemoglobin measurements. This may be es-
pecially important in women of child-bearing age and in donors with
inadequate dietary iron intake. Blood establishments should include
appropriate measures to minimise this problem, and to protect donor
health. Such measures may include:
• the provision of materials for donor education, particularly in
regard to dietary counselling to increase iron intake and the
impact of blood donation on iron stores;
• the individual tailoring of donation frequency and/or type of
blood component donation based on iron status;
143
• the use of tests to assess iron status, such as ferritin, soluble

transferrin receptor, zinc protoporphyrin and/or RBC indices;
• iron supplementation may be considered, taking into account the
risk of delaying the diagnosis of unapparent underlying diseases,
such as gastric/intestinal cancer. The donor needs to be informed
of the side-effects of the iron preparation.
At the same time, blood establishments should recognise that many
donors currently deferred because of low haemoglobin levels are in a
satisfactory state of health. Iron stores recover following an appropri-
ate temporary deferral period. Therefore, use of appropriate measures
for the prevention and management of iron deficiency in blood donors
not only improves their wellbeing, but may also contribute signifi-
cantly to achieving sufficiency of blood supply.
Apheresis donors
General remarks
Written informed consent should be obtained before the first apheresis
procedure.
The standards require that the maximum extracorporeal volume
(ECV) of 20 % not be exceeded. For donors weighing 50-65 kg, the
total blood volume should be estimated using the approach described
in Appendix 2.
The standards identify the maximum annual donation frequency,
the minimum inter-donation intervals and the maximum volumes of
components to be collected by apheresis.
The impact of incomplete apheresis procedures, including consid-
eration of non-reinfusion of red cells and the amount of primary
component already collected, needs to be taken into account when
determining compliance with these requirements.
For apheresis procedures where cells are harvested, the haemoglobin
levels defined in the standards apply.
144
There is increasing concern about long-term effects in donors in inten-

sive apheresis programmes. This includes risks associated with citrate
exposure in regular platelet apheresis donors, leading to problems
with bone mineral density and diminished IgG levels after long-term
intensive plasmapheresis.
Special attention should be given to the following conditions:
• abnormal bleeding episodes;
• a history suggestive of fluid retention (of special interest if ster-
oids and/or plasma expanders are to be used);
• intake of drugs containing acetylsalicylic acid or other
platelet-inhibiting components. Platelet apheresis should not be
undertaken within 48 h after the last intake of acetylsalicylic
acid or piroxicam;
• a history of gastric symptoms (if steroids are to be used);
• adverse reactions to previous donations.
Frequency of apheresis donation and maximal

amount of collected plasma
Current recommendations are made in the absence of conclusive
studies of outcomes from different regimes of volumes and frequen-
cies of plasmapheresis. Despite some data being available from studies
with several years of follow-up, further short- and long-term prospec-
tive studies are needed and should be undertaken.
The collection volume (excluding anti-coagulant) for each plas-
mapheresis procedure must not exceed 16 % of the estimated total
blood volume (see Standards). The total blood volume should be
calculated on the basis of gender, height and weight. Alternatively, a
collection volume based on 10.5 mL per kg of body weight broadly
equates to 16 % of estimated total blood volume. Short-term effects
can be reduced by observing the maximum extracorporeal volume
(ECVmax), which must never exceed 20 % (see Standards), with a
recommended guidance value of 16 %.
145
Sampling and residual blood remaining in the plasmapheresis devices

can result in a non-negligible loss of red cells, with a consequent
reduction in serum iron and ferritin. This is especially important
for female donors. Haemoglobin levels should be determined at each
donation. The minimum value for plasmapheresis should be 120 g/L
and 130 g/L for female and male donors, respectively.
Additional recommendations for platelet apheresis

If undertaking high-dose platelet collection (> 5 × 1011 platelets/unit),
care should be taken to ensure that the post-donation count does not
fall below 100 × 109/L.
Additional recommendations for granulocytapheresis

Clinical efficacy, indications and dosage of granulocyte transfusion
have not been established. Prior to collection, the potential donor of
granulocytes needs to receive medication, and sedimenting agents
may be needed during the apheresis procedure. Both of these have po-
tentially severe side-effects that need to be communicated to the donor
as part of the informed consent process.
In addition to the recognised complications of routine donor aphere-
sis, the following side-effects may occur.
• Hydroxyethyl starch (HES): acts as a plasma volume expand-
er. Potential donors should be questioned and/or screened for
evidence of renal disease as HES may exacerbate pre-existing
disease. Donors who have received HES may experience head-
aches or peripheral oedema because of expanded circulatory
volume. HES may accumulate, which can result in pruritus, and
allergic reactions.
• Corticosteroids: may cause, for example, hypertension, diabetes
mellitus, cataracts, peptic ulcer, and psychiatric problems.
• Granulocyte-colony stimulating factor (G-CSF): the most
common short-term complication following G-CSF admin-
istration in peripheral blood stem cell (PBSC) donors is bone
pain; although, on very rare occasions, splenic rupture or lung
146
injury may occur. Concerns relating to the development of acute

myeloid leukaemia (AML)/myelodysplasia (MDS) after G-CSF
administration are based primarily on reports of increased
rates of these disorders among women with breast cancer who
received chemotherapy or patients with severe chronic neutro-
penia (SCN) who received G-CSF support. To date, however,
registry data from Europe and the United States have not iden-
tified any increased risk of AML/ MDS in over 100 000 healthy
individuals who donated PBSCs and received G-CSF as pre-
treatment. The median follow-up of these studies is, however, less
than 5 years. Therefore, if G-CSF is given to a donor, a protocol
for long-term follow-up should be in place (as advised by JACIE/
FACT).1
Additional recommendations for donors of

red cells for anti-RhD immunisation
Specific protocols for donors of red cells for anti RhD immunisation
should be in place and should at least include the following:
• additional testing of markers of infectious disease, such as anti-
HTLV-I/II, anti-HBc and NAT tests for pro-viral HIV-DNA and
HIV-RNA, HCV-RNA, HBV-DNA, HAV RNA and parvovirus
B19DNA or parvovirus B19- antibodies;
• extensive red cell phenotyping should be performed at least
twice, and may be supplemented by genotyping;
• the red cells for immunisation should be stored for at least
6 months. After 6 months, all the infectious markers stated
above should have been found to be negative (or indicate absence
of infection) on a new donor sample before release of the stored
red cells for immunisation.
1 JACIE/FACT. International Standards for Cellular Therapy Product Collec-

tion, Processing and Administration [available from: www.jacie.org, accessed
4 December 2014].
147
In order to manage the impact of changes in donor selection criteria

and infectious marker testing that may occur over time, protocols
should require:
• maintenance of retention samples from each donation suitable
for future testing;
• re-qualification of past donations by assessing conformance
with additional donor acceptance requirements including, where
appropriate, testing of the donor and/or the retention sample.
Exemption of past donations from current standards is not recom-
mended and should only be considered in exceptional circumstances
after careful considerations of the risks to the immunised donors and
ultimate plasma product recipients.
Designated donations
Although blood donation is voluntary, non-remunerated and anony-
mous, in some special circumstances it may be necessary to make use
of designated donations. This should happen only for clear medical
indications. Designated donors should be screened and tested like
volunteer allogeneic donors.
Designated donations are those intended for named patients based on
medical indications. These donations may involve family members,
in which case the physician responsible should weigh up the risks
and benefits for the patient. The practice of transfusing parental
blood to infants is not without risk. Mothers may have antibodies to
antigens that are present on the infant’s red blood cells, platelets or
white blood cells. Therefore, maternal plasma should not be trans-
fused. Fathers should not serve as cell donors to neonates because
maternal antibodies to antigens inherited from the father may have
been transmitted through the placenta to the foetus. In addition,
due to partial histocompatibility, transfusions of cells from parental
or family donors carry an increased risk of transfusion-associated
graft versus host disease, even in the immunocompetent recipient,
and so such components should be irradiated. In the case of platelets,
148
pathogen-reduction technologies for components may be used as an

alternative to irradiation.
Circumstances where designated donations may be indicated include:
• for patients with rare blood types, where no compatible anony-
mous donations are available;
• where donor-specific transfusions are indicated for immune
modulation or immunotherapy; for instance, in the preparation
procedure for kidney transplants or for lymphocyte transfusions
aimed at a graft-versus-leukaemia effect;
• in certain cases of allo-immune neonatal thrombocytopaenia;
for instance, if HPA-typed platelets are not available and intrave-
nous immunoglobulin therapy is not sufficient.
Directed donations
Directed donations are those intended for named patients, where
the request for the donation has been made by patients, relatives or
friends. The public often believes that directed donations are safer
than anonymous, voluntary, non-remunerated donations. However,
this is not the case: even if directed donations are screened and tested
in the same manner as voluntary non-remunerated donations, in-
fectious disease marker rates are generally higher among directed
donors.
Directed donations are not considered good practice and should be
discouraged.
149
Chapter 3
Principles of blood collection
1. Overview
Records should be kept for each activity associated with the donation.
The record should also reflect any unsuccessful donation, the rejection
of a donor, adverse reactions or unexpected events. A qualified health
professional should sign the donor selection records and the final
assessment.
Sterile collection systems should be used in accordance with the
instructions of the manufacturer. A check should be made before use
to ensure that the collection system used is not damaged or contami-
nated and that it is appropriate for the intended collection. Defects in
blood bags should be reported to the supplier and subjected to trend
analysis.
The donor identification, donor selection interview and donor assess-
ment should take place before each donation. The donor should be
re-identified immediately prior to venepuncture.
2. Premises for donor sessions

When the venue of the donor session is permanent and under the
control of the transfusion establishment, provision should be made
for proper cleaning by, for example, the use of a non-slip, washable
151
floor material that is installed so as not to have inaccessible corners

and by avoiding having internal window ledges, etc. If possible, air-
conditioning units should be used to provide ventilation to avoid the
need for open windows. Air changes, together with temperature and
humidity control, should be adequate to cope with the maximum
number of people likely to be in the room and with the heat output
from any equipment used.
When sessions are performed by mobile teams, a realistic attitude
towards environmental standards may be taken. Factors to consider
should include adequate heating, lighting and ventilation, general
cleanliness, provision of a secure supply of water and electricity, ade-
quate sanitation, compliance with fire regulations, satisfactory access
for unloading and loading of equipment by the mobile team, adequate
space to allow free access to the bleed and rest beds.
3. Equipment used at blood donation sessions

It is recommended that the manufacturer’s identity and container
information (catalogue number and the container number of the set),
as well as the manufacturer’s lot number, should be given in eye- and
machine-readable codes.
4. Pre-donation checks and labelling

Defects may be hidden behind the label pasted on the container. Ab-
normal moisture or discolouration on the surface of the bag or label
after unpacking suggests leakage through a defect.
The unique identity number usually consists of a code for the respon-
sible blood collection organisation, the year of donation and a serial
number.
5. Venepuncture
Preparation of the venepuncture site
The venepuncture site should be prepared using a defined and val-
idated disinfection procedure. Compliance with the disinfection
152
Chapter 3 Principles of blood collection
procedure should be monitored and corrective action taken where

indicated.
Although it is impossible to guarantee sterility of the skin surface for
phlebotomy, a strict, standardised procedure for the preparation of the
phlebotomy area must exist (see Standards). Of particular importance
is that the antiseptic solution used be allowed to dry completely before
venepuncture. The time taken for this to happen will vary with the
product used, Manufacturer’s instructions should be followed.
The prepared area must not be touched before the needle has been
inserted (see Standards).
Successful venepuncture and proper mixing

If an anticoagulant solution is used, the collection bag should be
mixed gently immediately after collection has begun and at regular
intervals thereafter during the entire collection period. The maximum
collection time for acceptance of the donation for component pro-
cessing should be specified and controlled. Donations that exceed the
maximum time period should be recorded and discarded.
Proper mixing of the blood with the anticoagulant is essential at all
phases of the collection.
Attention should be paid to the following:
• as the blood begins to flow into the collection bag, it must imme-
diately come into contact with the anticoagulant and be properly
mixed;
• the flow of the blood must be sufficient and uninterrupted;
• donation of a whole blood unit should ideally not last more
than 10 minutes. If the duration of the collection is longer than
12 minutes, the blood should not be used for the preparation
of platelets. If the duration of the collection is longer than
15 minutes, the plasma should not be used for direct transfusion
or for the preparation of coagulation factors;
153
• in apheresis, any unexpected interruption of the flow occurring

during the procedure should be assessed to determine if the
component is acceptable for use.
Handling of filled containers and samples

At completion of the donation, the donation number issued should
be checked on all records, blood bags and laboratory samples. Dona-
tion number labels that have not been used should be destroyed via a
controlled procedure. Routine procedures to prevent misidentification
should be in place.
If integral blood bag collection tubing is to be used to prepare seg-
ments for testing, it should be sealed off at the end and then filled with
anti-coagulated blood as soon as possible after blood collection.
After blood collection, the blood bags should be handled, transported
and placed into storage according to defined procedures.
Immediately after sealing the distal end of the collection bag, the con-
tents of the bag line should be completely discharged into the bag.
Procedures should be designed to avoid the possibility of errors in
labelling of blood containers and blood samples. It is recommended
that each donor bed should have individual facilities for the handling
of samples during donation and labelling.
Donor screening samples should be taken at the time of donation.
Procedures should be designed to minimise the risk of bacterial con-
tamination of the collected blood or deterioration of the sample, and
to prevent potential misidentification.
The test samples should be taken directly from the bleed line or from a
sample pouch (deviation bag) of the collection system.
If samples are taken at the end of donation, this must be done
immediately.
The blood bag and corresponding samples must not be removed
from the donor’s bedside until correct labelling has been checked and
verified.
154
After collection, blood bags should be placed promptly into

controlled-temperature storage and transported to the processing site
under temperature conditions appropriate for the component that is to
be prepared. There should be validation data to demonstrate that the
storage and transport conditions used after collection ensure mainte-
nance of the blood within the specified temperature range.
6. Apheresis
Pre-medication and apheresis
With the exception of granulocyte donors, pre-medication of donors
for the purpose of increasing component yield is not recommended.
Caution is recommended regarding pre-treatment of donors with
corticosteroids and G-CSF.
Automated apheresis
It is recommended to exercise caution to prevent any misconnection
of the different components of the apheresis set; in particular, confu-
sion between anticoagulant and saline, which could result in serious
adverse reaction in donors.
Manual apheresis
Manual apheresis is no longer recommended.
7. Repository of archive samples

Retention of donor samples for a period of time may provide useful
information. Provision of such systems is contingent on the availabil-
ity of adequate resources.
If archive samples from the donations are kept, then procedures must
be in place prescribing their use and final disposal (see Standards).
8. Management of adverse reactions in donors

Special attention should be given to all donors in whom an adverse
reaction in relation to blood donation has been identified.
155
In the case of an adverse reaction, the donor should be referred as

soon as possible to a designated healthcare worker/physician of the
session.
The source of the adverse reaction should be identified and corrective
and preventive measures considered.
All adverse reactions, including the treatment and preventive actions
taken, should be documented in the donor’s records and those of the
quality system.
Severe adverse reactions in donors should be reported to the nation-
ally established haemovigilance system (see Chapter 10, Principles of
haemovigilance; and Chapter 10, Standards of haemovigilance).
Table 3.1. Examples of adverse reactions

related to blood collection
Local reactions related to needle insertion
Vessel injuries Haematomas

Arterial puncture
Thrombophlebitis
Nerve injuries Injury of nerve
Injury of nerve by haematoma
Other complications Tendon injury
Allergic reaction (local)
Infection (local)
General reactions
Vasovagal reaction Immediate type

Delayed type
156
Rare, significant complications
Related to vessel injury Pseudoaneurysm in the brachial artery

Arteriovenous fistulae
Compartment syndrome
Accidents Accidents or injuries related to vasovagal syncope
Other kinds of accidents
Cardiovascular reactions Angina pectoris
Myocardial infarction
Cerebral ischaemia
Related to apheresis procedures Citrate toxicity
Systemic allergic reaction
Anaphylaxis
Haemolysis
Air embolism
Prevention of adverse reactions in donors

Prospective donors must be informed of the possible adverse reactions
of blood donation and how they can be prevented.
Training of the personnel collecting blood should include preventing
and recognising the (early) signs of adverse reactions and their rapid
treatment.
The physician in charge is responsible for the medical supervision of
blood collection, and each session must be staffed with a qualified
healthcare professional.
Treatment of adverse reactions in donors

The treatment of adverse reactions related to blood donation must be
described in standard operating procedures.
Staff must be properly and regularly trained to be attentive for the
early signs of an adverse reaction and be able to respond immediately
with the appropriate action.
In each collection facility, a specific space should be reserved for
dealing with donors who have an adverse reaction.
157
The donor should be observed until fully recovered and, in the event
of a serious adverse reaction, the blood establishment must remain in
contact with the donor until the complication has disappeared or the
donor is in a stable condition.
Documentation of adverse reactions in donors

The treatment and outcome of all adverse reactions related to blood
donation, at any stage of the procedure, must be fully documented.
The physician in charge must be immediately informed about all
serious adverse reactions.
Data should be collected and analysed in order to initiate corrective
actions that could prevent or reduce the frequency or minimise the
severity of adverse reactions in the future.
Serious adverse reactions must also be reported to the appropriate
national authority.
Information for a donor with adverse reactions

When an adverse reaction occurs, the donor must be informed about
the reaction, its treatment and the expected outcome. The donor
should be given the opportunity to contact the on-call healthcare pro-
fessional of the blood establishment at any time.
The collection staff should instruct the donor in post-collection care
and they should keep the donor under observation until he/she is
released.
In particular, a donor who has experienced vasovagal reactions should
be informed about the risk of delayed fainting. The donor should not
drive a vehicle or resume work or any hazardous occupation or hobby
in the ensuing 12 hours if delayed fainting could put the donor or
other persons at risk.
9. Donor clinic documentation

Full records should be maintained at blood donation sessions to cover
the following parameters:
158
• the blood component (s) collected, the date, donation number,

identity and medical history of the donor;
• the date, donation number, identity and medical history of the
donor for each unsuccessful donation, together with reasons for
the failure of the donation;
• recording of rejected donors following assessment, together with
the reasons for their rejection;
• full details of any adverse reactions in a donor at any stage of the
procedure;
• in the case of apheresis, the volumes of blood collected, blood
processed, and replacement solution and anticoagulant used.
As far as possible, the records of blood donation sessions should allow
blood transfusion staff to identify each important phase associated
with the donation. These records should be used for the regular com-
pilation of statistics, which should be studied by the individual with
ultimate responsibility for the blood donation session, who can take
appropriate actions as deemed necessary.
159
Chapter 4
Principles of blood component processing
1. Overview
In the past, transfusion therapy was largely dependent on the use of
whole blood. While whole blood may still be used in certain limited
circumstances, the main thrust of modern transfusion therapy is to
use the specific component that is clinically indicated. Components
are those therapeutic constituents of blood that can be prepared by
centrifugation, filtration and freezing using conventional blood bank
methodologies.
Transfusions are used mainly for the following purposes:
• to maintain oxygen/carbon dioxide transport;
• to correct or avoid bleeding and coagulation disorders.
Clearly, whole blood is not necessarily suitable for all these purposes,
unless the patient requiring treatment has multiple deficiencies. Even
then, frequent storage defects in whole blood make it unsuitable.
Patients should only be given the component needed to correct their
specific deficiency. This avoids unnecessary and possibly harmful
infusions of surplus constituents. The change from collecting blood in
glass bottles to multiple plastic bag systems has greatly facilitated the
161
preparation of high-quality components. Storage considerations are a

major reason for promoting the use of individual blood components.
Optimal conditions and, consequently, shelf-lives vary for different
components. Red cells maintain optimal functional capability when
they are refrigerated. The quality of plasma constituents is best main-
tained in the frozen state while platelet storage is optimal at room
temperature (20-24 °C) with continuous agitation. Thus, only the
storage requirements of red cells are fulfilled if whole blood is refriger-
ated, with a consequent loss of therapeutic effectiveness of most of the
other constituents.
Component therapy also offers logistic, ethical and economic advan-
tages. The majority of patients requiring transfusions do not need the
plasma in a whole blood unit. Production of plasma-derived prod-
ucts can thus be facilitated by the use of red cells rather than whole
blood. Leucocyte depletion may further improve the quality of blood
components.
2. Processing procedures

Blood components may be prepared during collection using apheresis
technology. Plasma, leucocytes, platelets and red cell concentrates may
be obtained in this way. Alternatively, whole blood may be collected in
the traditional manner, with individual components extracted using
post-donation processing of whole blood.
Time and temperature limits should be defined for the processing of
blood components including filtration. Due to the potential deteriora-
tion of activity and functionality of labile blood components, the con-
ditions of storage and time before processing are vital to preparation
of high-quality blood components. Delays in preparation or unsuita-
ble storage conditions may affect the quality of the final components
adversely.
3. Choice of anticoagulant and bag system

Whole blood is collected into a bag containing an anticoagulant
solution. The solution contains citrate and cell nutrients such as
162
Chapter 4 Principles of blood component processing
glucose and adenine. The first centrifugation steps remove more

than half of these nutrients from the residual red cells. Thus, it may
be more logical to provide the proper nutrients for the cells using a
re-suspension medium instead of incorporating them in the initial
anticoagulant solution.
Plasticware used for blood collection, apheresis and component
preparation should comply with the requirements of the relevant
monographs of the European Pharmacopoeia with regard to haemo-
compatibility, in addition to its suitability for achieving the respec-
tive technological goal. Polyvinylchloride (PVC) has been found to
be satisfactory for red blood cell storage. Biocompatibility of any
plasticisers used must be ensured. Storage of platelets at + 20-24 °C
necessitates use of a plastic with increased oxygen permeability. This
feature has been achieved by plastic materials of alternative physical
and/or chemical characteristics. Leaching of plasticisers into blood/
blood component should not pose undue risk to the recipient. Any
possible leaching of adhesives from labels or other device components
should be kept within acceptable safety limits. Care should be taken to
minimise the levels of residual toxic substances after sterilisation (e.g.
ethylene oxide).
Whenever use of new plastics is being considered, an adequate study
of component preparation and/or storage should be conducted. The
following parameters could be useful:
• red blood cells: glucose, pH, haematocrit, haemolysis, ATP,
lactate, extracellular potassium and 2,3-bisphosphoglycerate;
• platelets: pH, pO2, pCO2, bicarbonate ion, glucose, lactate accu-
mulation, ATP, P-selectin, LDH release, beta thromboglobulin
release, response from hypotonic shock and swirling phenome-
non, morphology score and extent of shape change;
• plasma: Factor VIII and signs of coagulation activation (e.g.
thrombin–anti-thrombin complexes).
163
These studies are normally carried out by the manufacturer before

introduction of the new plastics and the results should be made availa-
ble to the transfusion services.
The suitability of new plastics can be determined by the evaluation of
post-transfusion in vivo recovery and survival of autologous red cells
after 24 hours and by the assessment of platelet recovery, survival and
corrected count increments (CCI).
In order to maintain a closed system throughout the separation
procedure, a multiple bag configuration (either ready-made or
sterile-docked) should be used. The design and arrangement of the
packaging system should permit sterile preparation of the desired
component.
Although use of closed systems is recommended for all steps in
component processing, open systems may sometimes be necessary
due to local constraints. If open systems are employed, they should
be carried out in an environment designed specifically to minimise
the risk of bacterial contamination, and careful attention should be
given to use of aseptic procedures. Red cells prepared in open systems
should be transfused within 24 hours of processing. Platelets prepared
in open systems should be transfused within 6 hours of processing.
4. Centrifugation of whole blood derived blood

components
The sedimentation behaviour of blood cells is determined primarily
by their size as well as the difference of their density from that of the
surrounding fluid (see Table 4.1 below). Other factors are the viscos-
ity of the medium and flexibility of the cells (which is temperature-
dependent). The optimal temperature for centrifugation with respect
to these factors is + 20 °C or higher.
164
Table 4.1. Volume and density of principal blood constituents
Mean density (g/mL) Mean corpuscle volume (fL)
Plasma 1.026
Platelets 1.058 9
Monocytes 1.062 470
Lymphocytes 1.070 230
Neutrophils 1.082 450
Red cells 1.100 87
Saline / SAGM 1.003 N/A
In the first phase of centrifugation, the surrounding fluid is a mixture

of plasma and anticoagulant solution. Leucocytes and red cells centri-
fuge out more rapidly than platelets as they both have a bigger volume
than platelets. Depending on the time and speed of centrifugation,
most of the leucocytes and red cells settle in the lower half of the bag
and the upper half contains platelet-rich plasma. More prolonged
centrifugation results also in platelet sedimentation, driven by a force
proportional to the square of the number of rotations per minute and
the distance of each cell to the centre of the rotor, whereas the leu-
cocytes (now surrounded by a fluid of higher density, i.e. the red cell
mass) move upwards. At the end of centrifugation, cell-free plasma
occupies the upper part of the bag and red cells are at the bottom.
Platelets accumulate on top of the red cell layer, while the majority
of leucocytes are to be found immediately below the platelets in the
top 10 mL of the red cell mass. Haematopoietic progenitor cells have
similar characteristics to normal mononuclear blood cells. However,
this component may be contaminated with immature or malignant
cells from different haematopoietic lineages, which commonly have
larger sizes and lower densities than their mature counterparts.
165
The conditions of centrifugation, such as g-force, acceleration, time,

deceleration, etc., determine the composition of the desired compo-
nent. For example, if platelet-rich plasma is desired, centrifugation
should stop prior to the phase where platelet sedimentation com-
mences. A low centrifugation speed allows for some variation in cen-
trifugation time. If cell-free plasma is required, fast centrifugation for
an adequate time allows separation into cell-poor plasma and densely
packed cells. It is important that the optimal conditions for good
separation be carefully standardised for each centrifuge. A number of
options exist for the selection of a procedure for centrifugation for the
preparation of components from whole blood.
Classical component preparation is performed by centrifuging the
bags in a centrifuge with a capacity of 4 or 12 bags, followed by trans-
fer of the bags to a manual or semi-automated expresser. Recently,
technologies have become available integrating the expresser function
into the centrifuge. These technologies can perform the classical com-
ponent preparation methods, but also allow a novel method whereby
an interim platelet unit is made after a hard spin. This interim platelet
unit contains the major part of the platelets and some leucocytes, but
no red cells that would need to be removed in a second separation step.
The choice to be made is whether or not the buffy coat is to be sepa-
rated from the sedimented cells. The advantage of separation of the
buffy coat is that red cells are relatively leucocyte-poor, which pre-
vents formation of aggregates during storage. The red cells can be
resuspended into a solution designed to offer optimal conditions for
red cell storage, e.g. saline-adenine-glucose-mannitol (SAGM). The
resuspension can still be done within the closed system. Plasma, after
separation, can be frozen and stored as fresh frozen plasma to be used
as such or as a starting material for other products, such as medicinal
products derived from human plasma.
Filtration
At present, two major types of filtration are available for blood compo-
nent preparation:
166
• the separation of plasma from blood by tangential filtration;

• the removal of leucocytes from cell suspensions by depth-filtra-
tion or surface filtration.
Washing of cellular components

This technique is occasionally used when there is a requirement for
cellular blood components with a very low level of plasma protein.
5. Leucocyte depletion

To enable a comparison of the filters that can be used for leucocyte de-
pletion and to facilitate selection between them, manufacturers should
report data on their system performances under defined conditions.
Manufacturers should also provide performance data to the blood
establishment on variations between different filter types or modifica-
tions and between batches.
Mathematical models have been developed to calculate the sample size
necessary to validate and control the leucocyte depletion process.
After full validation of the process, tools such as statistical process
controls could be used to detect any on-going changes in the process
and/or the procedures.
Particular problems may arise with donations from donors with red
cell abnormalities (e.g. sickle-cell traits) where adequate leucocyte
depletion may not be achieved and more detailed quality control pro-
cedures are necessary (e.g. leucocyte counting of every donation). The
quality of the red cells collected after slow filtration processes needs
further investigation.
6. Freezing and thawing of plasma

Rationale
Freezing is a critical step in the preservation of some plasma proteins,
including coagulation factors (in particular Factor VIII). During
freezing, pure ice is formed and the plasma solutes are concentrated
in the remaining water. Each solute forms crystals when the solubility
167
of the solutes is exceeded, but this may be influenced by the anti-

coagulants used.
Ice formation depends on the rate of heat extraction, whereas the
diffusion rates of the solutes determine their displacement. At slow
freezing rates, the diffusion of solutes is better adapted to the rate
of ice formation and so solutes are increasingly concentrated in the
middle of a plasma unit.
Since all solutes are displaced simultaneously, the Factor VIII mol-
ecules are exposed to a high concentration of salts for a prolonged
period of time and are thus inactivated. At a high freezing rate, ice
formation overtakes solute displacement. Hence, small clusters of
solidified solute are trapped homogeneously in the ice without pro-
longed contact between the highly concentrated salts and Factor VIII.
To achieve the highest yield of Factor VIII, plasma should be frozen to
− 25 °C or lower.
A reduction in Factor VIII content occurs during freezing when the
solidification of plasma takes more than one hour. This can be mon-
itored by measuring the total protein content of a core sample of the
frozen plasma; the protein concentration should be identical to the
total protein content of plasma before freezing. Heat extraction of
38 kcal per hour per unit of plasma is an optimal freezing rate, and
can be monitored by use of thermocouples.
To incorporate these methods effectively into a coherent daily routine,
the staff of the blood establishment must be familiar with the ration-
ale behind the method, as well as its potential limitations and pitfalls.
Methods of freezing
If freezing plasma, the rate of cooling should be as rapid as possible
and, optimally, should bring the core temperature down to − 25 °C or
below within 60 minutes.
Experience has shown that without the use of a snap-freezer, it takes
several hours to reach this temperature. This time can be reduced,
for example, by placing plasma batches in a regular configuration to
168
maximise exposure to the freezing process (e.g. bags laid flat or, if
vertical, in formers) and immersed in an environment at a very low
temperature. If a liquid environment is used, it should have been
demonstrated that the container cannot be penetrated by the solvent
(see Standards, Chapter 5, Component monographs, and the rele-
vant European Pharmacopoeia monographs for the required storage
conditions of individual blood components for further fractionation
and manufacturing of medicinal products derived from human
plasma).
Methods of thawing
Frozen units should be handled with care since the bags may be brittle.
The integrity of the pack should be verified before and after thawing to
exclude any defects and leakages. Leaky containers must be discarded.
The product should be thawed immediately after removal from storage
in an appropriately controlled environment at + 37 °C and according
to a validated procedure. After thawing of frozen plasma, the content
should be inspected to ensure that no insoluble cryoprecipitate is
visible.
The product should not be used if insoluble material is present. To
preserve labile factors, plasma should be used as soon as possible after
thawing. Post-thaw shelf life may be extended for a validated period
to facilitate urgent transfusion for some indications. It should not be
refrozen.
Thawing of the plasma is an inevitable part of some current viral in-
activation processes, after which the products may be refrozen within
the production process. In order to preserve component quality, the
final component should be used as soon as possible following thawing
for clinical use and not further refrozen.
Cryoprecipitation
The isolation of some plasma proteins, most importantly Factor VIII,
vWF, fibronectin and fibrinogen, can be achieved by making use of
their reduced solubility at low temperatures. In practice, this is done
169
by freezing units of plasma, thawing and then centrifuging them at

low temperature.
Details regarding the freezing, thawing, and centrifugation condi-
tions required for cryoprecipitate production are given in Standards,
Chapter 5, Component monographs.
7. Open and closed systems and sterile connection

devices
It is recommended that any new developments in component prepara-
tion involving an open system should be subjected to intensive testing
during the developmental phase to ensure maintenance of sterility.
Blood components prepared by an open system should be used as
quickly as possible.
Components prepared in systems using fully validated sterile connect-
ing devices may be stored as if prepared in a closed system. Monitor-
ing should be carried out by pressure testing of all connections and
regular traction tests.
8. Irradiation of cellular blood components

Viable lymphocytes in blood components can cause fatal transfu-
sion-associated graft versus host disease, particularly in severely
immune-compromised patients, e.g. patients undergoing haemato-
poietic transplantation, children with inherited cellular immunodefi-
ciency syndromes and some low birth weight neonates. Other clinical
settings with an increased risk of this rare complication include
intrauterine transfusion, transfusion between family members and
transfusion of HLA-matched components.
Lymphocytes can be rendered non-viable by exposure to irradiation.
Irradiation at doses specified in the Standards does not cause signif-
icant harm to other blood cells. Therefore, an irradiated component
can be given safely to all patients. However, the in vitro quality of
irradiated red cells deteriorates faster during storage than the quality
of non-irradiated red cell components. Therefore, irradiation leads to
a reduced shelf-life of red cell components (see Standards).
170
9. Prevention of CMV transmission

Cytomegalovirus (CMV) is a common infectious agent that can be
transmitted via the transfusion of blood components. The risk of
disease transmission is highest with fresh components containing
mono- and poly-morphonuclear leucocytes. CMV infection is often
asymptomatic in healthy persons. Antibodies usually appear 4 to
8 weeks after infection and can be demonstrated in standard screen-
ing tests. Since the infection is common, the test has to be repeated on
each donation from a previously seronegative donor.
Infection caused by this virus is usually not clinically significant in
immunocompetent recipients, but can cause severe, even fatal, disease
in certain patients not previously exposed to the virus such as:
• transplant recipients;
• patients with severe immunodeficiency;
• foetuses (intrauterine transfusion);
• anti-CMV-negative pregnant women;
• low-weight premature infants and neonates.
These patients should receive components selected or processed to
minimise the risk of CMV infectivity. The use of components from
anti-CMV-negative donors or leucocyte-depleted components sig-
nificantly reduces the risk of CMV transmission and CMV disease
in immunocompromised patients. However, neither method nor a
combination of them can completely prevent transmission due to oc-
casional cases of CMV viraemia in the early stage of acute infection.
There is no consensus on the requirement for CMV screening in blood
services that undertake universal leucocyte depletion of blood com-
ponents. Some services (especially in areas that have a high seropreva-
lence of CMV) have ceased antibody screening, but others believe that
the combination of antibody screening and leucocyte depletion may
confer additional safety.
171
10. Pathogen reduction technologies

The aim of pathogen reduction technologies (PRT) is to remove or
inactivate bacteria and/or other pathogens (viruses, parasites) using
physical and/or chemical methods. So far, it has not been possible to
treat whole blood donations, so blood must be separated into its com-
ponent parts before use of PRT.
Systems for PRT of plasma components have been available and used
routinely in Europe for many years. There are currently no licensed
systems for PRT of red cells, but such systems are currently under
development.
Several devices are CE-marked for PRT of platelets. These involve the
addition of a photo-sensitising chemical to platelets in combination
with exposure to UV light. An alternative system is being developed,
which is based on exposure of platelets to UV light alone and does not
require the addition of any chemicals.
Currently available systems have been demonstrated to inactivate a
wide range of viruses, bacteria, parasites and leucocytes. They do not
reduce infectivity associated with prion proteins and, hence, vCJD
risk.
With regard to the efficacy of PRT of platelets, there is some loss of
platelets in the process. However, this can be compensated for by an
increase in collection volume for apheresis platelets or an increase
in the number of buffy coats used in pooled platelets. Most clinical
studies have demonstrated a reduced corrected count increment com-
pared to untreated control platelets, and one study found an increase
in bleeding risk associated with this phenomenon. Other studies have
not shown a significant effect on clinical bleeding parameters. Other
potential risks include toxicity and neo-antigen formation; neither has
been observed in haemovigilance studies of short duration, but longer-
term surveillance studies will be required to confirm the absence of
long-term toxicity. One study has shown that PRT of platelets can be
implemented in routine practice without impacting on utilisation of
platelets or red blood cells or with a reduction of acute transfusion
172
reactions. PRT of platelets potentially allows the extension of the

shelf-life of platelets to 7 days, with the consequent benefit in reducing
platelet wastage. A further advantage of some PRT is inactivation of
lymphocytes, which obviates the need for irradiation of platelets.
A symposium was held under the aegis of the EDQM/Council of
Europe on implementation of PRT for blood components on 2 and
3 September 2010. A consensus on implementation did not emerge. It
was noted that countries have adopted different positions with regard
to the implementation of PRT depending on differences in the risk of
pathogens. An executive summary including recommendations has
been published online.1 Several blood establishments in Europe have
now implemented PRT of platelets, and others are actively considering
it. The value and cost-effectiveness of implementation of these tech-
nologies should be assessed in conjunction with current and alter-
native methods for risk reduction (see section 12, Bacterial safety of
blood components).
When using PRT, blood establishments should introduce quality-
control measures to monitor the effectiveness of the process and, if
applicable, removal of active substances and/or their metabolites.
11. Purity of components

Since blood components are used to correct a known deficit, each
preparation process must be subjected to strict quality control. The
aim is to produce ‘pure’ components, but a very high degree of purity
can be difficult and expensive to obtain and might not even be neces-
sary in all instances. However, it is absolutely necessary to declare the
quality and to be able to make different types of preparations in order
to give the clinicians a reasonable choice for patients with different
transfusion demands.
For example, a red cell concentrate can be produced with varying
concentrations of contaminating leucocytes and platelets. A buffy
1 www.edqm.eu/medias/fichiers/Executive_Summary_Pathogen_Reduction.
pdf.
173
coat-depleted preparation (in which most of the leucocytes and

platelets have been removed) is useful for most recipients because
formation of micro-aggregates during storage is inhibited. If the pro-
spective patient has antibodies against leucocyte antigens or if it can
be foreseen that he/she will need a very large number of transfusions,
leucocyte depletion will be more effective.
12. Bacterial safety of blood components

Overview
Although blood collection and processing procedures are intended to
produce non-infectious blood components, bacterial contamination
may still occur. Bacterial cultures of platelet components provide the
best indication of the overall rate of contamination of whole blood
donation provided that the sample for culture is obtained in a suitable
volume and at a suitable time after collection. Surveillance studies
have found rates of contamination as high as 0.4 % in single donor
platelets, although rates at or below 0.2 % are more often reported. The
causes of bacterial contamination include occult bacteraemia in the
donor, inadequate or contaminated skin preparation at the phlebot-
omy site, coring of a skin plug by the phlebotomy needle and breaches
of the closed system from equipment defects or mishandling. Plate-
let components are more likely than other blood components to be
associated with sepsis due to their storage at room temperature, which
facilitates bacterial growth.
A variety of procedures may be used to obtain a valid platelet sample
for bacterial culture. Aseptic techniques are required in order to
minimise the risk of false positive cultures due to contamination at
the time of sampling or upon inoculation in culture. Additionally, it is
prudent to retain a sample that can be used for repeat culture to vali-
date a positive result. Large volume samples (8-16 mL) removed from
a multiple-unit pooled platelet component or single donor apheresis
platelets can be cultured any time post-collection. However, small
volume samples (e.g. 2-5 mL removed from a single whole blood unit)
should be taken for culture after a 24 to 48 hour delay post-collection.
174
Delayed sampling of a small volume permits bacterial growth to a

level that subsequent assays can detect reliably, thereby overcoming
sampling errors at low contamination levels.
PRT may offer an alternative approach to assuring the bacterial safety
of blood components. Currently, systems are available for platelets, but
not for red cells.
Quality control for aseptic collection

and processing of blood components
• Data on routine bacterial monitoring should be analysed using
statistical process control techniques to ensure that the process
remains in control.
• Whenever the analysis indicates data that is outside of speci-
fied control limits then an investigation into potential causes of
contamination should be undertaken and, where appropriate,
collection and processing procedures should be revalidated.
• If routine bacterial monitoring of platelet components is not
performed, e.g. when pathogen reduction of platelet components
is in place, other methods for monitoring aseptic collection and
processing should be considered.
Release as ‘culture-negative to date’

after bacteriological testing of all platelets
Sampling of platelets for the purpose of establishing a release crite-
rion based on a negative result of bacterial cultures requires that the
integrity of the closed system should be maintained. This is because
platelets may continue to be stored for variable periods after sampling
and before use. Suitable methods of sampling in this case include the
use of integral satellite containers or the stripping, refilling and then
pinching off of duplicate pigtails. Sampling may also be done into
collection containers via the use of sterile connecting devices.
175
13. Storage of blood components

Storage conditions for blood components are designed to preserve
optimal viability and functionality during the entire storage period.
The risk of bacterial contamination decreases substantially if only
closed separation and storage systems are used.
Equipment
• Blood components are stored at different temperatures (for
example at + 20-24 °C, at + 2-6 °C or at different temperatures
below 0 °C).
Whatever type of storage device is chosen, the following points should
be considered before purchase:
• identification of user requirements, specifications and quality
criteria;
• refrigerators and freezers must have surplus capacity;
• the space should be easy to inspect;
• the operation must be reliable and temperature distribution
must be uniform within the unit;
• the equipment must have temperature recording and alarm
devices;
• the equipment should be easy to clean and should withstand
strong detergents;
• the equipment should also conform to local safety requirements.
Storage at + 2 to + 6 °C
The space for each of the component types should be clearly indicated.
The temperature within the storage device should be continuously
recorded. In large refrigerated rooms, two or more sensors should
be used. These should be placed in the part of the refrigerator space
which has been identified to represent the worst conditions.
The alarm system should preferably have both acoustic and optical
signals and should be regularly tested.
176
Refrigerators for blood components should ideally be connected to a

reserve power unit, as well as to the main supply.
There should be a system in place to maintain and control the storage
of blood components throughout their shelf-life, including any
transportation that may be required. Autologous blood and blood
components should be stored separately. Temperature and hygienic
conditions should be continuously monitored. Warning systems
should be used where applicable.
Storage of frozen plasma components

Freezers with automatic defrosting should be avoided, unless it can be
guaranteed that the low temperature is maintained during defrosting.
Freezers should ideally be connected to a reserve power source, as well
as to the main supply.
Storage at + 20 to + 24 °C
Platelets are stored at + 20-24 °C. A closed device that permits tem-
perature control is recommended. If such a device is unavailable, the
storage location chosen should be capable of maintaining the required
constant temperature.
Platelets should be stored in agitators that:
• enable satisfactory mixing in the bag, as well as gas exchange
through the wall of the bag;
• avoid folding of the bags;
• have a set speed to avoid foaming.
Aspects of red cell preservation

The anticoagulant solutions used in blood collection have been
developed to prevent coagulation and to permit storage of red cells
for a certain period of time. Designed originally for storage of whole
blood, they have also been used in blood from which components are
prepared. All of the solutions contain sodium citrate, citric acid and
177
glucose, and some of them may also contain adenine, guanosine and
phosphate.
Citrate binds calcium and prevents clotting of the blood. Glucose is
used by red cells during storage. Each glucose molecule gives two
molecules of adenosine triphosphate (ATP), which is formed by phos-
phorylation of adenosine diphosphate (ADP). ATP is an energy-rich
molecule used to support the energy-demanding functions of red
cells, such as membrane flexibility and certain transport functions
in the cell membrane. During energy-consuming operations, ATP
reverts back to ADP. Citric acid is added to anticoagulants to obtain a
concentration of hydrogen ions that is suitably high at the beginning
of storage at + 4 °C. Without the addition of citric acid, blood is too
alkaline at storage temperature.
Acidity increases during storage, which reduces glycolysis. Conversely,
the content of adenosine nucleotides (ATP, ADP, AMP) decreases
during storage. By adding adenine, which is the main component of
adenosine nucleotides, red cells can synthesise new AMP, ADP and
ATP and compensate for (or reduce) this decrease. When red cell con-
centrates are prepared, a considerable part of the glucose and adenine
is removed with the plasma. If not compensated for in other ways (e.g.
by adding a larger amount than normal of adenine and glucose in the
anticoagulant or by separate addition of a suspension/preservative
medium), sufficient viability of the red cells can only be maintained if
the cells are not over-concentrated. Therefore, normal CPD adenine
red cell concentrate should not have an average haematocrit above
0.70. This also keeps the viscosity sufficiently low to permit transfu-
sion of the concentrate without pre-administrative dilution.
Additive solutions
An additive solution should allow maintenance of red cell viability
even if more than 90 % of the plasma is removed. The use of glucose
and adenine is necessary for the maintenance of red blood cell
post-transfusion viability. Phosphate may be used to enhance glycoly-
sis and other substances (e.g. mannitol, citrate) may be used to prevent
178
in vitro haemolysis. Sodium chloride or disodium phosphate may be

used to give the additive solution a suitable osmotic strength.
Micro-aggregates in blood components

Platelets and leucocytes rapidly lose their viability at + 4 °C. They
form micro-aggregates that are present in considerable amounts even
after 3-4 days of storage of whole blood and, even more so, in concen-
trates of red cells. Micro-aggregates can pass through the filters of or-
dinary blood transfusion sets. Micro-aggregates can cause decreased
lung function by blocking lung capillaries and this may be of clinical
importance in massive transfusions. Removal of platelets during
component preparation reduces micro-aggregate formation. Likewise,
leucocyte depletion by buffy coat removal also reduces the frequency
of febrile transfusion reactions, and helps to achieve high-grade deple-
tion of leucocytes if leucocyte-removal filters are used for this purpose.
Red cell preparations

The maximum duration of storage (expiry date) should be noted on
each container. This duration may vary with the type of preparation
(concentration of cells, formula of anticoagulant, use of additive solu-
tion) and should ensure a mean 24-hour post-transfusion survival of
no less than 75 % of transfused red cells.
Red cells may be stored in a fluid state at a controlled temperature of
+ 2-6 °C. The performance of the storage refrigerator must be con-
trolled very carefully.
Frozen red cells should be prepared and reconstituted according to
an approved protocol, be stored at < – 60 °C, and produce satisfactory
post-transfusion survival figures.
Platelet preparations
Platelets must be stored under conditions that guarantee that their
viability and haemostatic activities are optimally preserved (see
Standards).
179
Plastic bags intended for platelet storage should be sufficiently per

meable to gases to guarantee oxygen availability to platelets and diffu-
sion of carbon dioxide. The amount of oxygen required is dependent
on the number of platelets and their concentration in the component.
Lack of oxygen increases anaerobic glycolysis and lactic acid produc-
tion. The quality of platelets is preserved if the pH remains consist-
ently above 6.4 throughout the storage period.
Agitation of platelets during storage should be sufficient to guarantee
oxygen availability but as gentle as possible to prevent induction of
activation and storage lesions. The storage temperature should be
+ 20-24 °C. Platelets undergo membrane phase transition, and cold ac-
tivation (below + 20 °C) means that the discoid structure of platelets
gradually converts to a sphere.
Granulocyte preparations
Typically, granulocyte suspensions are prepared for a specific patient
and administered immediately.
Plasma components could be stored

at different temperatures
Recommended storage conditions for fresh frozen plasma and cryo
precipitate and for cryoprecipitate-depleted plasma are given in
Table 4.2 below.
Table 4.2. Recommended storage conditions for fresh frozen

plasma, cryoprecipitate and cryoprecipitate-depleted plasma
Blood componenta Length of storage and temperatureb
Fresh frozen plasma, cryoprecipitate 36 months at or below – 25 °C

Cryoprecipitate-depleted plasma 3 months at – 18 °C to – 25 °C
a For plasma intended for fractionation, refer to the European Pharmacopoeia monograph Human plasma for
fractionation (0853).
b The recommended temperature ranges are based upon practical refrigeration conditions.
180
14. Transport of blood components

Blood components should be transported by a system that has been
validated to maintain the integrity of the component over the pro-
posed maximum time and extremes of ambient temperature of trans-
port. It is recommended that some form of temperature indicator be
used to monitor the temperature in transit. Also, the temperature on
receipt can be monitored as follows:
• take two bags from the container;
• place a thermometer between the bags and fix them together
with rubber bands;
• quickly place them back into the container and close the lid;
• read the temperature after 5 minutes.
Alternatively an electronic sensing device may be used to take imme-
diate measurements from the surface of a pack.
On receipt, if not intended for immediate transfusion, the product
should be transferred to storage under the recommended conditions.
Transport of standard red cell components

Red cell components should be kept between + 2 and + 6 °C. The
temperature of red-cell bags should not go below + 1 °C nor exceed
+ 10 °C. A maximum transit time of 24 hours at temperatures not
above 10 °C is recommended. Otherwise, transport conditions must
be validated to ensure maintenance of the quality of red blood cells.
Transport of platelet components

Platelet components are usually not agitated during transport and,
therefore, oxygen delivery to platelets is reduced. Agitation of platelets
can be interrupted (simulated shipping conditions) for up to 30 hours
for one to three periods without a major impact on the in vitro quality
of the platelets at the end of a storage time of 5-7 days. The pH of the
platelet components is better preserved when agitation is interrupted
for several short periods compared to one long period.
181
Platelet components should be transported in an insulated container

with temperature-stabilising elements that ensure transport temper-
ature is maintained as close as possible to the recommended storage
temperature. Transport conditions should be chosen to maintain
component quality and must be validated for this purpose. It is
recommended not to exceed 24 hours if transported without agitation.
On receipt, unless intended for immediate therapeutic use, platelet
components should be transferred to storage under the recommended
conditions (including further agitation).
The impact of transport conditions on the quality of platelet compo-
nents should be validated by quality control tests, e.g. swirling tests
and pH measurements of components at the end of the storage period.
Transport of frozen plasma components

Frozen plasma components should be transported in the frozen state
as close as possible to the recommended storage temperature.
15. Component information and principles of labelling

Brief information about the various blood components should be
made available to clinicians with regard to composition, indications,
and storage and transfusion practices. This includes the proviso
that the blood must not be used for transfusion if there is abnormal
haemolysis or any other deterioration, and that all blood components
must be administered through a 150–230-µm filter (if not stated
otherwise). This information should be presented to clinicians in a
booklet and/or in an information leaflet on blood components.
The label on the component that is ready for distribution should
contain the information (in eye-readable format) necessary for safe
transfusion. That is: unique identity number (preferably consisting
of a code for the blood-collection organisation, the year of donation,
and a serial number); ABO and RhD blood group; name of the blood
component; essential information about the properties and handling
of the blood component; expiry date (see also labelling requirements
in Chapter 5, Component monographs).
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Chapter 5
Principles of blood component

monographs
Monographs with detailed information on the different categories of
blood components are given in the Standards section, Chapter 5,
Component monographs.
• Part A – Whole blood components, page 279
• Part B – Red cell components, page 289
• Part C – Platelet components, page 325
• Part D – Plasma components, page 377
• Part E – White cell components, page 399
The blood components described in these monographs are to be
regarded as standard blood components across Europe. However,
some components are in use only in a few countries. Based on future
consensus, the number of variant components may be reduced.
The component monographs have a standardised structure, which
encompasses the headings as listed hereafter.
183
1. Definition and properties

Here, information is given about the component, including its origin,
the active constituents and contaminating cells (if appropriate).
2. Preparation
Here, a short description is given about the method(s) of preparation.
It differentiates between primary and secondary processing. Primary
processing results in different blood components, each of which
is described in Chapter 5 of the Standards section. Secondary
processing leads to variant preparations, which are very similar to
the primary component and do not differ in handling, release and
application aspects. More detailed information about preparation
processes is described in Chapter 4 of the Principles section.
3. Requirements and quality control

Typical component-specific handling and testing parameters for
quality control are given in tables, which are formatted as follows:
Parameter to be checked Requirements Frequency of control
If appropriate, the requirements may be met by performing the test

on the donation sample that was taken as part of the donor screening
process in place of individual component testing.
The monographs provide advice on frequency of control. An
alternative approach to identify the number of units to be tested is
Statistical Process Control (SPC) (see Appendix 4).
Quality control may be carried out either as a separate quality control
procedure for the given component or as a routine part of the issuance
and transfusion of these components. Detailed information on the
preparation processes are given in Chapter 4, Principles of blood
component processing.
184
Chapter 5 Principles of blood component monographs
4. Storage and transport

Typical mandatory storage and transport conditions for the respective
blood components are given. Detailed and descriptive information
about the processes of storage and transport are given in Chapter 4,
Principles of blood component processing.
5. Labelling
The labelling should comply with the relevant national legislation and
international agreements. The given information should be shown on
the label or contained in the component information leaflet.
6. Warnings
Typical warnings and side-effects are described that should be
communicated to the physician (in written form, such as in a
component information leaflet).
185
Chapter 6
Principles of blood components

for intrauterine, neonatal and infant use
1. Overview
Specially designed blood components are required for intrauterine and
infant transfusions. The following factors must be considered when
transfusing neonates: (1) smaller blood volume, (2) reduced metabolic
capacity, (3) higher haematocrit and (4) an immature immunological
system. All these aspects are particularly important in foetal
transfusions and for small premature infants.
There is a significant risk of transfusion-associated graft versus host
disease (TA-GvHD) and Cytomegalovirus (CMV) transmission when
a foetus or small infant is transfused. These patients should receive
cellular components selected or processed to minimise the risk of
CMV transmission.
The rate of transfusion should be controlled to avoid excessive
fluctuations in blood volume.
Consideration should be given to producing red cell components
for these patients from donors who have screened negative for
haemoglobin S.
187
There are specific national regulations or guidelines for pre-

transfusion blood grouping and compatibility testing of neonates.
2. Components for intrauterine transfusions

All components for intrauterine transfusion (IUT) must be irradiated.
To minimise the effect of potassium load, red cells for IUT must be
used within five days of donation and within 24 hours of irradiation.
Indications for use:
• intrauterine red cell transfusions are performed to treat severe
foetal anaemia;
• intrauterine platelets are administered for the correction of
severe thrombocytopenia, which may be due to antenatal HPA
allo-immunisation.
3. Components for neonatal exchange transfusion

Exchange transfusion is a special type of massive transfusion. The
components used must be fresh enough so that metabolic and
haemostatic disturbances can be minimised.
A number of components can be utilised for exchange transfusion,
including:
• whole blood (LD);
• whole blood (LD and plasma-reduced);
• red cells (LD and resuspended in fresh frozen plasma).
ABO and Rh groups, as well as other red cell antigens to which the
mother has become sensitised, have to be taken into account when
selecting blood for exchange transfusion.
Whole blood and red cell components for exchange transfusion should
be irradiated, unless compelling clinical circumstances indicate that a
delay would compromise the clinical outcome. Irradiation is essential
if the infant has had a previous IUT.
To minimise the effect of potassium load, components of whole blood
and red cells must be used within five days of donation and within 24
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Chapter 6 Principles of blood components for intrauterine, neonatal and infant use
hours of irradiation. For reconstituted components, the shelf-life is

24 hours.
• exchange transfusions of neonates;
• these components are also suitable for large volume (massive)
transfusion of neonates and small infants;
• if the platelet count of the infant undergoing/following exchange
or other massive transfusion is very low, specific platelet
transfusion should be given.
4. Red cells for neonatal and infant small volume

transfusion
Preterm infants are amongst the most intensively transfused of
all hospital patients and have the greatest potential for long-term
survival. Therefore, minimising the number of donor exposures
is a central aim in designating proper components and guiding
transfusion practice.
It is good practice to divide a component unit into several sub-batches
and to dedicate all the satellite units from a donation to a single
patient. Fresh blood and red cells are used in IUT and exchange
transfusions. Hence, it is often thought that fresh blood is necessary
for all neonatal transfusions. There is no scientific or clinical
evidence to support this concept in the case of small volume, top-up
transfusions, provided that transfusion rates are carefully controlled.
The component may be irradiated where clinically indicated.
• anaemia of premature infants;
• to replace the blood loss due to investigative sampling;
• suitable for surgical replacement in infants and children.
189
5. Fresh frozen plasma for neonatal and infant use

In order to reduce donor exposure, a fresh frozen plasma (FFP) unit
can be divided into approximately equal volumes in satellite packs,
prior to freezing, by using a closed or functionally closed system.
Three to four such bags can be dedicated to one patient.
ABO blood group-compatible plasma should be used. National
requirements may require the use of plasma only from AB RhD-
negative and -positive donors.
• FFP may be used in coagulation defects, particularly in those
clinical situations in which a multiple coagulation deficit exists
and only where no suitable viral-inactivated alternative is
available;
• congenital deficiency of single clotting factors where no virally-
inactivated concentrate exists.
Contraindications:
• FFP should not be used simply to correct a volume deficit in
babies in the absence of a coagulation defect nor as a source of
immunoglobulins;
• FFP should not be used where a suitable virally-inactivated
clotting factor concentrate is available;
• FFP should not be used in a patient with intolerance to plasma
proteins.
6. Platelets for neonatal and infant use

When preparing platelets for infants, every effort should be made to
minimise donor exposure.
Apheresis-derived platelets offer the greatest potential to reduce donor
exposure and can be divided into satellite packs by using a closed
system as for FFP.
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Chapter 6 Principles of blood components for intrauterine, neonatal and infant use
The clinical situation of a small child may necessitate the use of

volume-reduced platelets; volume reduction to around 25 mL causes
about a 10 % loss of platelets.
The platelet component must be used within 24 hours of any washing
procedure and within 6 hours of any concentration process. The
platelet component should be irradiated where clinically indicated.
• severe neonatal thrombocytopenia (of any cause).
191
Chapter 7
Principles of autologous transfusion
1. Overview
Several techniques of autologous transfusion, including pre-deposit
autologous collection and intraoperative or postoperative red cell
salvage, may be useful in surgery. These techniques have been
designed to avoid the risks of the allo-immune complications of
blood transfusion, and to reduce the risk of transfusion-associated
infections. Each technique has its own separate risks that are also
presented and discussed. The choice of different techniques (including
allogeneic transfusion) should be balanced for the patient’s benefit.
Pre-deposit autologous transfusion (PAT) comprises the collection,
processing and storage of autologous blood components in the weeks
preceding surgery for reinfusion in the perioperative period. In
selected conditions, red cell or platelet components can be collected
using a cell separator. The equivalent of 2 units of red cells or up
to 3 standard adult doses of platelets can be collected in a single
procedure. The incidence of severe adverse reactions and severe
adverse events associated with the collection of whole blood has
been shown to be significantly increased in autologous blood donors
compared with allogeneic blood donors.
193
The principle of pre-deposit autologous collection and transfusion was

popular in the 1990s among surgeons and patients because it was seen
primarily as a means to reduce the risk of transfusion-transmitted
infections. Since then, however, questions have been raised as to its
benefits and its use remains controversial.
The frequency of some adverse effects of transfusion, such as bacterial
contamination or administrative errors, is not reduced by PAT, and
the latter may be increased. However, PAT may be the only option for
a patient with an antibody for which compatible blood is difficult to
find.
Some other disadvantages are that patients may be rendered anaemic
prior to surgery, thus leading to increased transfusion requirements,
blood wastage is increased (it is estimated that only 50 % of autologous
blood is used) and cost effectiveness is low. In some circumstances,
autologous blood may be inappropriately transfused, even if
transfusion is not indicated. In addition, where efforts have been
made to reduce the use of blood in surgery by improved pre-operative
assessment and intraoperative management, the benefit of PAT has
been reduced further.
Pre-deposit autologous blood components obtained from PAT must be
collected, prepared and stored in the same conditions as for allogeneic
donations. For these reasons, PAT must be collected by or under the
control of blood establishments or in authorised clinical departments
that are subject to the same rules and controls as blood establishments
(see Standards).
Acute normovolemic haemodilution is the collection of blood
immediately before surgery, with blood volume compensation
(leading to a haematocrit below 0.32), with subsequent re-infusion
during or after surgery.
Red cell salvage during surgery is another means of autologous
transfusion. Blood collected from the operation site may be given back
to the patient either after a simple filtration or a washing procedure.
These techniques do not allow storage of the collected blood. They are
194
Chapter 7 Principles of autologous transfusion
usually performed under the responsibility of anaesthesiologists and/

or surgeons.
2. Pre-deposit autologous transfusion

Patient selection
Role of the physician in charge of the patient
In elective surgery, in which blood transfusion is expected, the
physician in charge of the patient (usually the anaesthesiologist or
surgeon) may prescribe preoperative collections.
The prescription should indicate:
• the diagnosis;
• the type and number of components required;
• the date and location of scheduled surgery.
The patient should be informed of the respective risks and constraints
of autologous and allogeneic transfusion, and that allogeneic
transfusion may also have to be used if necessary.
Indications
Autologous transfusion should only be considered if there is a clear
reason for preferring PAT to allogeneic blood, and there is a strong
likelihood that blood will be used.
Special consideration should be given to the use of PAT in exceptional
circumstances, such as patients with rare blood groups where
allogeneic blood is likely to be difficult to obtain.
Contraindications
Appropriate autologous pre-deposit collection may be carried out
safely in elderly patients. However, more careful consideration may
need to be given in the case of a patient aged more than 70 years.
Haemoglobin levels should be measured before each collection.
Autologous pre-deposit collection should not be done in patients with
a haemoglobin concentration below 100 g/L.
195
In patients with a haemoglobin concentration between 100 and

110 g/L, autologous pre-deposit collection may be discussed according
to the number of scheduled collections and aetiology of anaemia.
The presence of cardiac disease is a relative contraindication, and the
assessment of a cardiologist may be required. Patients with unstable
angina, severe aortic stenosis or uncontrolled hypertension should not
be considered.
Pre-deposit autologous transfusion in children

Pre-deposit autologous collection may be considered in children
undergoing harvesting of bone marrow and in exceptional cases
whereby suitable allogeneic blood is not available for elective surgery.
The child should understand the nature of the procedure and be
willing to co-operate.
Children under 10 kg should not be included in an autologous pre-
deposit collection programme and PAT programme. For children
between 10 and 20 kg, the use of volume compensation solutions is
usually needed.
The maximum volume that can be drawn at each collection is
10 mL/kg or 12 % of the estimated blood volume.
The volume of anticoagulant in the pack should be adjusted as
required to maintain an appropriate ratio of blood to anticoagulant.
Paediatric packs of 200 mL or 250 mL (available with small gauge
needles) should be used wherever possible.
Adverse reactions related to blood collection, such as haemodynamic
disturbances, occur significantly more often in children. Volume
replacement with crystalloid solutions reduces the rate of these
adverse reactions.
Blood collection
Surgical admission and the day of the surgical procedure should be
guaranteed. Sufficient time to enable optimal collection of blood
should be allowed before surgery, but should not exceed the storage
time of the collected blood component.
196
Sufficient time should be given from the date and time of the final
blood collection prior to surgery for the patient to make a full
circulatory and volaemic recovery. This should be at least 72 hours
(preferably 7 days).
Iron and/or erythropoietin should be considered to supplement the
patient’s haemoglobin in conjunction with PAT.
For patients undergoing double-unit red cell apheresis, shorter
collection intervals can be accepted at the discretion of the physician
responsible for blood collection.
Preparation, storage and distribution of pre-deposit

autologous components
See Standards.
Labelling
See Standards.
Storage
See Standards.
Records
Blood establishments and hospitals should both maintain the
following records for every patient included in a pre-deposit
autologous transfusion programme:
• the date and type of surgery;
• the name of the anaesthesiologist or the surgeon;
• the time of transfusion, specifying whether blood was used
during surgery or postoperatively;
• the actual use of the prepared pre-operative autologous blood
components;
• the concurrent use of perioperative autologous transfusion
techniques;
197
• the technique used and volume of autologous blood re-infused;

• the use of allogeneic blood components;
• the occurrence of any adverse reactions.
Audit
Blood establishments should audit the use of PAT, where it is provided
on a regular basis.
3. Red cell salvage

Cell salvage (CS) is the process of collecting a patient’s blood during
surgery for transfusion back into the patient. It is also known as
‘autotransfusion’ and covers a range of techniques that scavenge blood
from operative fields or wound sites and re-infuse the blood back
into the patient. CS can be performed during intraoperative and/
or postoperative periods. The aim of CS is to reduce or eliminate the
need for allogeneic blood transfusion. At least one allogeneic packed
red cell should be saved. The blood salvage system can, in general, be
broken down into a collection and a processing system.
Collection system
The collection system consists of:
• the suction line and suction tip used in the surgical field;
• suction;
• an anticoagulant;
• collection reservoir.
During collection of red blood cells, an appropriate anticoagulant is
added to salvaged blood. Then, anticoagulated blood is filtered and
collected in a reservoir. When a sufficient amount of blood has been
collected (approximately the equivalent of one packed red blood cell
should be the result at the end of the entire process), separation of
blood by centrifugation and washing of red blood cells follows.
198
Processing system
Various separation devices use centrifuge bowls for stepwise
processing or a disc-shaped separation chamber enabling continuous
processing of salvaged red cells. The washing procedure removes (to
a large extent) free haemoglobin, plasma, platelets, white blood cells,
and anticoagulant. Remaining red blood cells are then resuspended
in normal (0.9 %) saline. The resulting haematocrit should be 0.60
and 0.80. Small washing volumes, fast washing rates, and half-full
bowls should be avoided. Salvaged red cells should be transfused
immediately or at least within 6 hours. Blood filters and standard
blood-administration filters are required. Some manufacturers
recommend micro-aggregate or leucodepletion filters to remove
bacteria, cancer cells or amniotic-fluid contaminants depending on
the different clinical settings.
Indications for the use of cell salvage

• patients undergoing cardiothoracic, vascular, transplant and
major orthopaedic surgery;
• anticipated blood loss of 1000 mL or of 20 % estimated blood
volume;
• patients with low haemoglobin levels or at an increased risk of
bleeding;
• patients with multiple antibodies or rare blood types;
• patients with objections to receiving allogeneic blood.
Parameters for quality control

Parameters for quality control of the component should be:
• volume;
• haematocrit;
• haemolysis at the end of the process;
• protein content of the supernatant.
199
Precautions
Some substances should not be aspirated with blood: antibiotics not
licensed for intravenous use; iodine; hydrogen peroxide; alcohol;
topical clotting factors; orthopaedic cement; sterile water.
Careful use of a large-bore suction tip under low vacuum pressure can
reduce the risk of shear-induced haemolysis.
Colorectal surgery: Salvaged blood can (under special preventive
measures) be gained during colorectal surgery or other types of
surgery if the blood has come into contact with bacteria. Use of
leucodepletion filters and washing of salvaged blood reduces the
risk of microbial contamination because these methods also help to
minimise the risk of activation of coagulation factors or influx of
cytokines and other biologically active substances. As an additional
precaution, broad-spectrum antibiotics should be administered to the
patient.
Haemorrhage in cancer patients: although the passing of blood
through a leucodepletion filter significantly reduces the number of
retransfused tumour cells, the salvaged cells should be irradiated.
Obstetric haemorrhage: use of leucodepletion filters in obstetric
haemorrhage provides a significant reduction in contamination of
cells from amniotic fluid. This is also true for caesarean section.
There is also concern regarding reinfusion of foetal red cells
from the operative field. If the mother is RhD-negative and the
foetus RhD-positive, the extent of maternal exposure should be
determined as soon as possible, and a suitable dose of human anti-D
immunoglobulin should be administered.
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Chapter 8
Principles of immunohaematology
1. Overview
The main purpose of immunohaematology testing is to ensure that
a compatible blood component is issued to the right patient. It is
therefore essential to obtain accurate results when undertaking
blood grouping, and antibody screening on donors and patients and
compatibility testing.
Errors at any stage of the performance of such tests can lead to
incompatible or incorrect blood components being transfused, with
significant adverse health effects in patients. These can be due to
inadequate training or procedures and/or human error resulting in
misidentification of samples from donors or patients, technical failures
in testing or misinterpretation of results, and transcription errors.
Haemovigilance data indicate that, in many cases, a combination of
errors lead to patient harm with the original error being perpetuated
or compounded by the lack of adequate procedural controls within the
laboratory or at the bedside.
The implementation of a quality system helps to reduce the number
of errors made in laboratories. Elements of the quality system include
the use of standard operating procedures, staff training, periodic
assessment of the technical competence of staff, documentation and
201
validation of techniques, reagents and equipment, procedures that

monitor day-to-day reproducibility of test results and methods to
detect errors in analytical procedures.
2. Immunohaematological testing

Immunohaematological testing includes blood group determination,
antibody screening, antibody identification as applicable and
compatibility testing. All tests could be manual or automated and
performed by serologic or molecular methods as appropriate.
Blood group testing

Serological testing
Serological blood group testing includes ABO/RhD typing and
additional phenotyping. This is currently the standard technique used
in most transfusion laboratories.
Molecular testing
Molecular testing is becoming increasingly available and used as a
supplemental technique to serological testing. In time, molecular
testing may replace the need for routine serological testing. Current
indications for molecular typing include situations: in which
serological testing of blood donors and patients renders unclear
results; if there is a suspicion of weak antigens or variants (within
ABO, RHD, RHCE, JK, FY); if serological reagents directed to specific
antigens do not exist or are not readily available.
Increased utilisation and access to this technology will support
further indications:
• multi-transfused patients that cannot be typed with serological
techniques who may benefit from matched erythrocyte
transfusions, for example, patients with sickle cell anaemia,
thalassaemia and others who depend on treatment by chronic
transfusion;
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Chapter 8 Principles of immunohaematology
• patients that cannot be typed with indirect agglutination

techniques because of positive direct agglutination tests (DAT
pos);
• patients that may be expected to present with unusual and
unexpected phenotypes/genotypes;
• blood donors with unusual phenotypes in serological typing;
• donors of panel cells if extended typing is needed or if
heterozygosity or homozygosity needs to be established;
• foetal RHD, RHCE, KEL, FY, JK or other clinically significant
genotypes (in samples of maternal blood, amniocentesis or
chorionic villi) in cases of maternal immunisation against the
corresponding antigens.
Testing can be undertaken on samples from blood, amniocentesis,
biopsy of chorionic villi, and plasma.
Available test methods include, for example: polymerase chain
reaction-restriction fragment length polymorphism (PCR-RFLP),
sequence-specific priming (PCR-SSP), allele-specific PCR (AS-
PCR), allelic discrimination (AD), real-time PCR and sequence-
based typing. Commercial reagents and kits are available for these
techniques. Micro-array and mass spectrometry-based techniques are
also available.
Molecular investigations may be carried out at regional, national or
international laboratories. Before ordering such typing, information
on how to handle and ship samples, material or prepared DNA should
be requested.
3. Antibody screening and identification

Antibody screening is performed to detect clinically significant non-
ABO red cell antibodies. Testing is usually performed using an anti-
human globulin technique.
203
In addition donors may be investigated for high titres of anti-A and/

or anti-B to avoid transfusing plasma-containing blood components
(FFP, platelets in plasma) with a high titre of these antibodies.
Antibody screening, identification and quantitation may also be
performed in pregnant women to evaluate the risk of haemolytic
disease of the foetus and newborn.
Most often, red cell antibody quantitation is confined to the
quantitation of anti-RhD. It is recommended that quantitation of anti-
RhD be carried out by automated techniques rather than by manual
titration. If an automated technique is not available, manual titration
by the anti-globulin test is recommended.
Pre-transfusion testing
The purpose of pre-transfusion testing is to select compatible blood
components that will survive normally in the circulation, and to avoid
clinically significant haemolysis of red blood cells during or after
transfusion.
ABO/RhD typing of donor and recipient is the most important test.
Antibody screening is performed to detect clinically significant non-
ABO red cell antibodies. Positive results of screening tests should be
investigated fully to identify antibody specificity. If appropriate, red
cell components lacking antigens should be selected for transfusion.
A compatibility test should be undertaken before issuing red cell
components for transfusion. This process may involve serological
testing or may be achieved with electronic release of the component
using a type and screen procedure. The appropriate method for
compatibility testing will be determined by the results of screening of
blood groups and antibodies on the current sample as well as results of
previous testing and clinical urgency of the transfusion.
Serological compatibility testing

The principle of serological compatibility testing is to test donor
red cells with the recipient’s plasma/serum. In patients with
clinically significant red cell antibodies, serologic crossmatch must
204
be performed using an indirect anti-globulin test. When clinically

significant antibodies are absent, an immediate spin crossmatch may
be performed immediately before issue of the red cell component.
However, immediate spin crossmatch is effective only for excluding
ABO incompatibility.
Electronic issue following a type and screen procedure

Electronic issue (EI) should be employed only when a test for clinically
significant antibodies is negative and there is no history of clinically
significant antibodies in the patient.
The overall process for determining eligibility for EI must be
controlled. Supplementary checks (e.g. review of the clinical details
on the request form) should be performed. It should not be possible to
issue ABO-incompatible red cells. The computer system should have
a record of the history of transfusion and antibodies of the patient as
well as serological status of the current sample.
The following process criteria should be met:
• samples and reagents are registered and identified within the
analyser via barcodes;
• entry of the testing and results of the blood group and antibody
screening are fully automated;
• results are transmitted electronically from the analyser to the
computer;
• the computer controls the suitability of patients and their
samples for EI;
• the computer enables permanent exclusions of patients from EI
in the presence of antibodies of likely clinical significance;
• the computer enables temporary exclusions of patients from EI
(e.g. limited period of exclusion after transplantation of solid
organs);
205
• stock entry of unique donation number, component code, blood

group and expiry date from the unit’s label is by barcode reader
or other electronic means.
The following criteria for patient and sample should be met:
• interpretation of blood group in the current sample is identical
to the historical record;
• no manual amendments have been made to automated results;
• the current antibody screening is negative;
• results of the patient’s group and antibody screening are
complete and fully authorised in the computer;
• the patient does not have a previously known antibody of likely
clinical significance;
• the current sample meets the requirements for timing and
storage.
Quality control
The quality control procedures for immunohaematology can be
divided into internal and external control programmes. They must be
implemented for reagents, techniques, methods and equipment used.
Internal quality control

Quality control of reagents and techniques
Quality control procedures recommended are applied to the reagents
used for manual and automated techniques. However, reagents for
automated instruments are generally specific for that instrument.
Each new lot must be tested for control against specifications.
For antigen testing, quality controls should include positive, preferably
heterozygous, and negative controls. For antibody testing a positive,
preferably weak, control is included.
The controls should be carried out with each test series or at least once
a day provided the same reagents are used throughout.
206
Quality control of equipment

Equipment used (in particular centrifuges, automatic cell washers,
incubators, refrigerators and freezers) should undergo regular
quality controls. Equipment for automated blood grouping should
also be systematically controlled according to the manufacturer’s
instructions.
External quality assurance (proficiency testing)

In external quality assurance, blood samples for proficiency tests
coded as ‘normal’ and ‘problem’ are distributed from a national or
regional laboratory to the participants, at least twice a year. The
exercise can be limited to compatibility testing, since ABO-typing,
RhD-typing and additional phenotyping, as well as alloantibody
detection, are automatically included. The proficiency test panel may
consist of multiple blood samples and the participants are asked to test
each red cell sample against each plasma/serum for compatibility. The
test panel should be composed in such a way that compatible as well
as incompatible combinations occur. A titration of one or two of the
detected antibodies may also be requested as part of the proficiency test.
The results are collated and accuracy scores are determined. These
should be communicated to all participating laboratories (in coded or
uncoded form, according to local agreements) in order to enable each
laboratory to compare its own quality standards with those of a large
number of other laboratories.
If no proficiency programme is available in a particular geographical
area, the laboratory should arrange mutual proficiency testing with
another laboratory. Although such external quality control is not as
informative as participation in a comprehensive proficiency-testing
programme, it is a valuable addition to the internal quality control
procedure.
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Chapter 9
Principles of screening for markers

of infection
1. Overview
Quality assurance for screening tests for infectious markers is particu-
larly important and implies both general and specific approaches.
Only tests that have been licensed or evaluated and considered suita-
ble by the relevant regulatory authorities can be used. In the EU, these
tests are considered as in vitro diagnostic devices and must be CE
marked. EU Directive 98/79/EC classifies the HIV, HTLV, hepatitis B
and C screening tests in list A, Appendix II. The manufacturer must
have a full quality system, certified by an authorised body, and must
submit batch release certificates containing all the control results for
each lot.
In addition, proper validation demonstrates control, generates useful
knowledge of the test and establishes future requirements for internal
quality control, external quality assurance, calibration and mainte-
nance of equipment and training of personnel, etc.
There must be special emphasis on training of staff, assessment of staff
competency, maintenance and calibration of equipment, as well as the
209
monitoring of the storage conditions of test materials and reagents,

together with documentation of all of these actions.
Current tests for the screening of donations are based on the detection
of relevant antigens and/or antibodies and viral genomes.
It is further recommended that the tests include an external weak pos-
itive control in order to allow for statistical process monitoring.
Ideally, confirmatory tests should be as sensitive as, and more spe-
cific than, those used for screening. However, some screening tests
are more sensitive than the available confirmatory tests. It is recom-
mended that confirmatory algorithms be developed nationally to
enable the appropriate and consistent investigation and resolution of
screen reactivity.
2. Algorithm for infectious marker screening and

confirmatory testing
Figure 9.1 shows a widely used algorithm for infectious marker screen-
ing and confirmatory testing.
Figure 9.1. Algorithm for infectious marker

screening and confirmatory testing
Discard donation sam- Check record if previously re-
Repeatedly reactive
ple(s) of donation peatedly reactive c
screening test a
to confirmatory lab Block in-house products of donor
Counsel and defer donor e

Confirmatory test
Positive b Confirm results and donor iden-
results d
tity on a new sample
Donor notification optional
b
Reinstate to donor base
Negative Label donor record as repeat
reactive
Notify and defer donor
Indeterminate Arrange retesting after max
window-period c
210
Chapter 9 Principles of screening for markers of infection
Repeatedly reactive
Discard donation
screening test of a donor
Sample(s) of donation Block in-house products of donor
previously screening test
to confirmatory lab
repeatedly reactive c
Notify, advise and defer donore

Confirmatory test
Positive b Confirm results and donor iden-
results d
tity on a new sample
Negative b Notify and defer donor

Notify and defer donor
Indeterminateb Arrange retesting after max
window-period if indicated by
confirmatory lab b, d
a For example, a repeatedly reactive serological screening test or a positive NAT on a single donation. Confirmatory
testing is performed by a certified or accredited medical microbiology reference laboratory, which is responsible
for results and may use tests at its discretion. The confirmatory laboratory should be kept informed about the
type of screening test used by the blood establishment, and is contracted to use tests at least as sensitive as the
screening test and, if feasible, based on other principles.
b The confirmatory laboratory is contracted to provide overall confirmatory test results or interpretations as
follows: ‘positive’, which means infected; ‘negative’, which means not infected; or ‘indeterminate’, which means
a diagnosis cannot be established (may include a demand for follow-up testing). If a confirmatory test(s) is less
sensitive than the screening assay, the conclusion of confirmatory testing should read ‘uncertain’ (unless positive).
c The blood establishment keeps a donor record allowing longitudinal recording of confirmatory laboratory test
results as: screening test positive; confirmatory lab positive; negative; or indeterminate.
d The confirmatory laboratory is contracted to keep longitudinal records of the unique donor ID, linked to laboratory
test results.
e Refer donor to a medical doctor (general practitioner or specialist). Inform plasma fractionation centre(s) if
plasma from earlier donation(s) has been issued. Inform hospital(s) to allow look back if component(s) from
earlier donation(s) have been issued.
The specific approach to the quality of the screening process must rely
on the following categories of measures:
• internal day-to-day quality control covering both reagents
and techniques. Batch pre-acceptance testing (BPAT) of new
manufacturer’s lots of kits should be performed as an additional
measure of quality assurance;
• external quality checks. In particular, confirmation of screen
reactivity should be carried out by an appropriate and certified
reference laboratory;
• occasional internal exercises as part of process qualification at
implementation and/or after a significant process change using
211
a panel of sera that have been established by comparison with

available standards;
• external proficiency exercises involving the testing of a panel
of sera circulated to laboratories by an approved or otherwise
competent expert institution;
• collection of representative data may be useful to monitor test
performance.
It is recommended that repeatedly reactive rates and confirmed pos-
itive results of screening for infectious markers and epidemiological
data be collected and monitored at least on a national level. This will
allow international comparisons to be made.
It should be noted that following hepatitis B immunisation, a transient
positive HBsAg result may be obtained and this can be identified by
follow-up HBsAg testing of the donor.
3. Confirmatory testing

Anti-HIV-1/2, anti-HCV and HBsAg
The approaches currently used to confirm HIV or HCV infection
consist of the use of a nationally established algorithm, which may
include alternative immunoassay (IA), western blot or recombinant
immuno-blots. Tests for antigens and the use of nucleic acid ampli-
fication techniques (NAT) may be of value in the interpretation of
uncertain antibody test results. The positive confirmatory test should
be repeated on an additional sample taken as soon as possible and not
later than 4 weeks after the first sample. External referral of the donor
could be used for this repeat sample.
Confirmation of HBsAg reactivity should include specific neutral-
isation. The stage of infection of the donor may be determined by
anti-HBc (total and IgM-specific) and HBe antigen/antibody (HBeAg/
anti-HBe).
212
Anti-HTLV-I-II
The approach to anti-HTLV-I-II confirmation testing is similar to
that of HIV and involves nationally established algorithms as well as
specific assays including immuno-blotting and NAT. Sensitive tests for
genome detection (including typing) may be helpful in defining the
infection status of the donor. NAT detection of chromosomal inte-
grated proviral HTLV (e.g. in whole blood or PBMCs) may be more
sensitive compared with plasma test material.
4. Nucleic acid screening

The Committee for Medicinal Products for Human Use (CHMP)
has recommended a strategy of pre-testing by manufacturers of
mini-pools (of donations or of samples representative of donations)
for HCV in order to avoid the loss of a complete manufacturing pool
and to facilitate trace-back to the donor in the event of a positive test
result.
In order to achieve a sensitivity that detects 5 000 IU/mL of HCV
RNA for donations tested in mini-pools of, for example 100 donations,
50 IU/mL should be detected with 95 per cent confidence by the NAT
assay. Validated enrichment steps like centrifugation may counteract
the dilution effect of mini-pools. Each assay run should include an ex-
ternal run control (usually at 3 times the 95 per cent detection limit).
This reagent must be reactive in every run. The external run control
may be omitted if the test is licensed (CE marked) and there are other
procedures that ensure robustness.
5. Additional screening

Syphilis screening
There is ongoing discussion over the need to test blood donors for
syphilis, but the test may be used as an indicator of risk behaviours for
sexually transmitted diseases and is still required by most European
countries. Most blood establishments use a Treponemal antibody test
employing a variant of the Treponema pallidum particle agglutination
assay (TPPA) or another IA. Reactive syphilis screening results should
213
ideally be confirmed by an appropriate Treponemal antibody test

including; TPPA, fluorescent treponemal antibody test (FTA) or an
immunoblot test. This test is not required for plasma for fractionation.
Anti-HBc screening
Donors or donations may be tested by an approved test that will detect
antibodies to hepatitis B core antigen (anti-HBc). The approach to de-
ferral or re-entry of an anti-HBc positive donor should be established
in an algorithm.
Re-entry into the donor base of an anti-HBc positive donor and the
subsequent release of his/her donations should only be considered
when the donor has been shown to have anti-HBs with a titre of at
least 100 IU/L and each subsequent donation should test negative for
both HBsAg and HBV DNA using approved assays.
CMV screening
Testing for CMV antibodies is most commonly performed using an
IA or the latex particle agglutination test. The screening of donations
for anti-CMV enables the establishment of a panel of anti-CMV nega-
tive components for dedicated use in highly susceptible patients. This
test is not required for plasma for fractionation.
Malaria screening
At present, only a few reliable and robust malaria antibody tests
are commercially available. Any malarial antibody-testing require-
ment necessitates integration within local approaches to the taking
of donor histories. If malaria antibody testing is used to determine
donor acceptance or rejection, the test employed should be shown
to detect antibodies to the malaria types that are likely to pose a risk
of transfusion transmission. Currently, NAT for malaria cannot be
recommended for use in screening of blood donors because it may fail
to detect the small number of parasites in a blood donation that can
infect a transfusion recipient. Confirmation of reactivity in malaria
antibody tests should be performed by a competent and certified refer-
ence laboratory that can define the malaria status of the donor. Users
214
need to be aware that assays may depend on the detection of hetero-

typic antibodies. Users must ensure that the assay detects antibodies
to the Plasmodium species prevalent in their donor panel. This test is
not required for plasma for fractionation.
Trypanosoma cruzi screening

Donors who were born or have been transfused in areas where
trypanosomiasis is endemic can be selected to be tested for antibodies
against T. cruzi. This test is not required for plasma for fractionation.
NAT screening
Selective testing of donations might also be used to protect specific
vulnerable recipient populations at increased risk of a particular infec-
tion e.g. hepatitis E virus or parvovirus B19.
215
Chapter 10
Principles of haemovigilance
1. Overview
Haemovigilance is defined as the use of organised surveillance proce-
dures related to adverse events or adverse reactions either in donors
or in recipients as well as the epidemiological follow-up of infectious
disease markers in donors.
The ultimate goal of haemovigilance is to prevent the occurrence and
recurrence of adverse events and reactions. For that purpose, results
of data analyses should be fed back to their providers periodically and
communicated to the Competent Authority (or Regulatory Author-
ity) indicating (if possible) preventive or corrective measures to be
adopted.
Haemovigilance should also incorporate an early alert/warning
system. Haemovigilance provides useful information on morbidity
arising from donations and transfusions of blood, and gives guidance
on corrective measures to prevent recurrence of certain incidents.
Moreover, haemovigilance is considered to be a part of total health-
care vigilance (along with e.g. pharmacovigilance and vigilance on
medical devices).
217
The information provided by haemovigilance contributes to improv-

ing the safety of blood collection and transfusion by:
• providing the medical community with a reliable source of
information about adverse events and reactions associated with
blood collection and transfusion;
• indicating corrective measures required to prevent the
recurrence of some incidents or mistakes in the transfusion
process;
• warning hospitals and blood establishments about adverse events
and reactions that could involve more individuals than a single
recipient, including:
–– those related to the transmission of infectious diseases;
–– those related to blood bags, solutions or blood processing.
2. Prerequisites for implementation

of a haemovigilance network
Haemovigilance should be a responsibility of the national Competent
Authority (or Regulatory Authority) for blood safety. Haemovigi-
lance networks should embody operational linkages between clinical
departments, hospital blood banks, blood establishments and national
authorities.
Traceability of blood components

Traceability, which is a prerequisite for haemovigilance, may be
defined as the ability to trace in all directions each individual unit of
blood or the blood components derived from it from the donor to its
final destination, whether this is a patient, a manufacturer of medici-
nal products or its disposal.
The essential element for traceability is a unique identification
numeric or alphanumeric code for each donation, with a subsidiary
code for each component prepared from that donation (Recommen-
dation No. R (96) 11 of the Council of Europe on documentation
and record-keeping to guarantee the traceability of blood and blood
218
Chapter 10 Principles of haemovigilance
components especially in hospital). This unique identifier must be

linked to data that identifies both the donor and the recipient. In this
way, all patients transfused with a particular donor’s blood (or all
donors who donated the blood components that a patient received)
may be traced.
Traceability is essential for:
• tracing, retrospectively, a possibly infectious donor in case of
transmission of an infectious agent to a recipient;
• tracing, retrospectively, a possibly infected recipient in case of
infectivity of a donor;
• tracing recipients in case of systemic problems that put recipients
at risk of serious adverse reactions or events.
Traceability can provide information on the total number of:
• patients that have been transfused;
• blood units or components that have been issued or used;
• blood donors that have provided the transfused blood units or
components.
Without this information, it is difficult to calculate the incidence of
adverse events and reactions and, thus, to estimate risk. The number
of adverse events and adverse reactions over a given time period may
help to identify critical issues within the various processes of collec-
tion, preparation and/or transfusion.
Information systems should be available to facilitate rapid traceabil-
ity by using patients, blood components and donors as data-access
keys. To ensure the reliability of the database, confirmation is needed
that the blood component was transfused to the designated patient
for whom it was issued. Without this, proving the link between donor
and patient requires verification in the patient’s notes that the blood
component was appropriately transfused. The document confirming
the transfusion should also include information on the existence or
non-existence of immediate adverse events or reactions.
The following accurate data should be made available:
219
• personal data uniquely identifying the donor and providing a

means to contact him/her;
• the blood establishment in which the blood or blood component
collection has been carried out;
• the date of donation;
• the blood components produced and additional component
information, if appropriate;
• the blood establishment or hospital blood bank to which the
blood component has been distributed, if different from the
production facility;
• the hospital and the ward to which the blood component has
been issued for transfusion;
• the date and time of issue;
• the final fate of the unit; either the identity of the patient who
received it or other use (e.g. quality assurance, reagents, discards,
etc.);
• the date and starting time of transfusion.
When blood components have not been issued for transfusion, data
should be available to identify the facility where the units have been
used or disposed of.
Co-operation between blood establishments, hospital

blood banks and clinical departments
The responsibility of reporting adverse events and reactions does not
imply a responsibility for individual patient care.
Reporting and analysis of adverse events and reactions associated
with transfusion requires close co-operation between the clinical de-
partment where transfusion took place, the hospital blood bank that
issued the transfused blood component and the blood establishment
that collected and distributed the blood unit (if different from the
hospital blood bank).
220
This co-operation is essential to ensure a complete investigation of any

adverse event or reaction, including uneventful transfusion errors. In
the blood establishment and/or the hospital blood bank, the physician
involved may be the person responsible for blood component deliv-
ery, or a physician may be specifically in charge of haemovigilance.
Similarly, in clinical departments, the responsible person can be the
physician in charge of the patient or another physician specifically in
charge of haemovigilance.
In case of serious adverse reactions in blood recipients, which may be
related to the transfused blood components, notification should be
sent as soon as possible to the blood establishment where the compo-
nents were collected.
Prompt reporting enables the blood establishment to take action to
block blood components from related donors, donations or produc-
tion methods.
Serious adverse reactions include: acute haemolytic transfusion
reactions, sepsis due to bacterial contamination, delayed haemolysis,
transfusion-related acute lung injury (TRALI), transfusion-associated
graft versus host disease (TA-GvHD), transfusion-transmitted infec-
tious diseases, anaphylaxis, transfusion-associated circulatory over-
load (TACO), hypocalcaemia, hypothermia, post-transfusion purpura
(PTP).
3. Types of adverse reactions and adverse events

collected in a haemovigilance network
Adverse reactions in patients
Adverse reactions associated with transfusion of blood components
are the primary scope of a haemovigilance system, which should
collect reports concerning patients of events such as:
• immediate adverse reactions during transfusion, such as:
haemolysis; non-haemolytic febrile transfusion reaction;
rash; erythema; urticarial; anaphylactic shock; bacterial
contamination;
221
• TRALI, TACO and TA-GvHD;

• delayed adverse reactions after transfusion, such as haemolysis,
PTP, iron overload, etc.;
• bacterial, viral, parasitical or TSE transmission;
• occurrence of allo-immunisation against red cell, HLA or
platelet antigens.
The rules for reporting may differ according to the type and severity of
adverse reaction. In case of minor reactions (such as non-haemolytic
febrile transfusion reaction, rash, erythema and urticaria), individual
reports should only be sent by the clinical departments to the blood
bank. Then, depending on the organisation of the haemovigilance
network, the blood bank may send periodic reports to its associated
blood establishment or to the Competent Authority (Regulatory Au-
thority) describing the incidence of such events.
This applies to any event that may involve several individuals and to
serious hazards. Moreover, in case of viral transmission, the extent of
required investigations should be clearly defined.
Adverse reactions in donors

See also Chapter 3, Principles of blood collection.
Adverse reactions in donors are defined as an unintended response
associated with the collection of blood or blood components.
Adverse reactions in a donor should be fully documented in donor
records and serious adverse reactions should also be documented in
the records of the quality system.
Haemovigilance for donors may:
• facilitate the creation of a list of adverse events and reactions in
relation to blood collection;
• allow analysis of data and enhance safety of blood collection
by implementing corrective actions to prevent recurrences of
incidents;
222
• allow analysis of data and improve transfusion safety depending

on donor selection (frequency and causes of blood donation
exclusion) and epidemiological follow-up of the donor
population (confirmed positive donors in infectious marker
screening);
• allow tracing of donors in case of an emerging threat to the
safety of blood components (such as a new disease endemic
situation).
Adverse events related to blood donation can occur in several fields:
• donor selection: the donor does not fulfil the local medical
selection criteria, but has been given clearance for donating
blood (with a possible consequence for his/her health or quality
of blood components), e.g. insufficient haemoglobin level before
donation, insufficient weight, etc.;
• blood collection: inappropriate procedure, e.g. excessive blood
loss during blood or blood component donation, inadequate
volume of anti-coagulant used for apheresis procedures;
• donor suitability: post-donation information may have
consequences for the safety of donated blood components.
Both adverse events and reactions in donors may also have conse-
quences for the quality of the donated blood components.
Data concerning adverse reactions and adverse events in donors
should be collected and evaluated within blood establishments and,
if appropriate, should be reported at least annually to the national
haemovigilance system. Information on adverse events and adverse
reactions in donors should be considered to be part of the haemovigi-
lance system.
Adverse events
An adverse event is defined as any untoward occurrence associated
with the collecting, testing, processing, storage and distribution of
blood and blood components that might lead to an adverse reaction in
blood recipients or blood donors.
223
Serious adverse events are those that might have led to death or
life-threatening, disabling or incapacitating conditions for patients
or donors (but did not), or which might have resulted in prolonged
hospitalisation or morbidity (but did not). Examples of such serious
adverse events are: failures to detect an infectious agent; errors in
ABO typing; incorrect labelling of blood samples or blood compo-
nents from donors. For instance, if components were not transfused
or an incorrect or inappropriate component was administered due to
incorrect identification of the recipient, Directive EC 2002/98 requires
that these events must be notified to the Competent Authority.
‘Near-miss’ events are a subgroup of adverse events. A near-miss event
is defined as any error which, if undetected, could result in determi-
nation of a wrong blood group or failure to detect a red cell antibody
or the issuance, collection or administration of an incorrect, inappro-
priate or unsuitable component, but where the mistake was recognised
before transfusion took place.
Adverse events include incorrect, inappropriate or unsuitable blood
component transfusions that did not lead to harm to the recipient
(but could have). For example, administration of a mismatched ABO-
compatible component or failure to give irradiated components when
prescribed.
Notification of adverse events which are transfusion errors that do not
cause an adverse reaction may help to identify weaknesses in the clin-
ical transfusion process and thereby reduce risk. The haemovigilance
system should inform relevant staff of the importance of reporting of
adverse events. The haemovigilance system should provide a system
for reporting near misses with anonymisation to protect individuals
from blame and to stimulate voluntary reporting.
Information technology systems may facilitate reporting and analysis
of haemovigilance data.
Device defects
Reporting of device defects can be viewed as part of haemovigilance
(see Standards).
224
4. Tracing and recall of potentially infectious donations

for HIV, HCV or HBV (look-back)
Post-transfusion infection in a recipient reported to the
blood establishment
Hospitals must inform the blood establishment whenever a recipient
of blood components develops laboratory test results and/or disease
symptoms indicating that a blood component may have transmitted
an infectious agent (see Standards).
It is important that the blood establishment be informed without delay
by the hospital so as to allow further action on implicated donations
and donors and in order to prevent harm to other recipients.
Test results from donations of implicated donors may be re-analysed,
or additional or confirmatory tests on archived or freshly obtained
samples from the implicated donors may be performed with the aim
of excluding infection by HIV, HCV or HBV in the donor(s). If such
analyses reasonably exclude infection, such donor(s) may be re-
released for future donations and (temporarily) blocked components
derived from their donations may be re-released.
Where feasible and appropriate, the blood establishment should
(temporarily) defer all implicated donors from further donations and
retrieve (temporarily) or quarantine all in-date components for trans-
fusion collected from the implicated donors.
If an implicated donor is found with a confirmed positive test for in-
fection by HIV, HCV or HBV, the blood establishment should act ac-
cordingly with regard to deferral of the donor and initiate a look-back
procedure on previous potentially infectious donations and inform
the hospital(s) concerned.
The incident should be reported to the national haemovigilance
system and/or Competent Authorities (or Regulatory Authorities).
225
Post-donation information
The blood establishment should (temporarily) block all in-house
components from the donor and retrieve all in-date components. The
relevant plasma fractionation institute must be notified.
The blood establishment should perform a risk analysis to assess
whether the incident indicates a potentially infectious blood com-
ponent destined for recipient(s). Test results from donations of the
implicated donors may be re-analysed, or additional or confirmatory
tests on archived or freshly obtained samples from the donor may be
performed.
If a confirmed HBV, HCV or HIV infection is shown in the donor, the
blood establishment should defer the donor and undertake a look-
back procedure on previous potentially infectious donations.
Recall of blood components

In the case of a quality deviation (e.g. for HBV, HCV or HIV), the
blood establishment must retrieve all in-date blood components dis-
tributed to the hospital(s) as a precautionary measure. This procedure
may be a temporary measure and implies that certain retrieved blood
components may be re-released after appropriate risk analyses and/or
additional testing. The measure is taken in order to prevent harm to
potential recipients. The relevant plasma fractionation institute must
also be notified.
Tracing of recipients of potentially infectious blood

donations (look-back/review)
Blood establishments should initiate a look-back procedure that is
aimed at tracing recipients of blood components from a potentially
infectious blood donation and notifying these recipient(s), via their
treating physicians, whenever a blood donation may have taken place
within the window period of a (repeat) donor with a confirmed HIV,
HBV or HCV infection.
226
Implicated donations include those within a timeframe equal to the

maximum test-specific window period of the infection preceding the
last negative screening test result in the donor.
The blood establishment should inform the hospital in writing about
the incident and advise the hospital to trace the recipient(s) of the im-
plicated blood component(s) and inform the treating physician about
the potentially infectious transfusion. The relevant plasma fractiona-
tion institute must also be notified.
It is the responsibility of the treating physician to inform the recipient
about a potentially infectious transfusion, unless there are medical
arguments not to do so. If the recipient is tested in order to establish
or to exclude infection, the blood establishment should be informed
by the hospital about such test results. If testing of the recipient is not
performed, the blood establishment should also be informed of this by
the hospital.
If the recipient is confirmed to be positive for the infection, the inci-
dent must be reported to a national haemovigilance system and/or to
the Competent Authorities.
Consistent with the recommendations of the national health author-
ity, blood establishments should consider the need to trace and notify
blood component recipients and/or their physicians in cases where a
blood donor is subsequently diagnosed with vCJD infection.
5. Contracts between blood establishments and

hospitals for haemovigilance
In those situations in which blood collection and processing is carried
out in facilities located outside of hospitals, the look-back, trace-back
and recall procedures may be described in the contract(s) between the
blood establishment and the hospital(s).
Minimum information to be captured in the initial incident

report at hospital level
Information about transfused patients must be managed according to
the confidentiality requirements/legislation of individual countries.
227
Reported patient identifiers should include at least date of birth,

gender and a unique case number. Any clinical signs observed should
be documented in a standardised fashion, either specific for a given
adverse event or reaction or the same format for every untoward effect.
The clinical outcome of all adverse reactions should be stated.
6. Reporting haemovigilance data

Standardisation of reporting
Reports of adverse events and reactions should be made in the same
way in all the institutions that participate in the haemovigilance
network. This strategy implies not only use of common report forms,
but also a common training programme that ensures a similar
method of interpretation for a given incident as well as a common and
agreed definition of the different types of adverse events and adverse
reactions among all participants. In this respect, the persons specifi-
cally in charge of haemovigilance may contribute to the standardisa-
tion of both reports and definitions.
In practice, standardisation of reporting requires an active training
policy initiated inside the network.
Data analysis
All the reports should be carefully analysed before inclusion in the
haemovigilance database, which can be exploited at different levels:
institutional, regional, national or international. Whatever the magni-
tude of the network, an individual institution should have permanent
and full access to its own data.
Information sent to the haemovigilance database

Information about transfused patients must be managed according to
the confidentiality requirements/legislation of individual countries.
Component information
This information should include a detailed description of the compo-
nent involved:
228
• unit number and appropriate codes for components;

• description of the component, including:
–– the type of component, i.e. red cell, platelet or plasma;
–– the type of preparation, i.e. from whole blood or from apheresis;
–– other characteristics, i.e. leucocyte-depleted, irradiated, plasma-
reduced, etc.;
–– conditions and duration of storage prior to transfusion.
Information about severity

Severity should be graded. A suggested scale is as follows:
Severity scale
0 No clinical signs
1 Immediate signs without vital risk and full resolution
2 Immediate signs with vital risk
3 Long-term morbidity
4 Death
Information about imputability

The possible relationship between the observed adverse reaction and
the transfusion of blood components given (imputability) should be
identified. A scale, required in the EU, is as follows (Directive 2005/61/
EC):
Imputability scale Explanation
0 Excluded When there is conclusive evidence beyond reasonable doubt

for attributing the adverse reaction to alternative causes.
0 Unlikely When the evidence is clearly in favour of attributing the adverse
reaction to causes other than the blood or blood components.
229
Imputability scale Explanation
N/A Not assessable When there is insufficient data for causality assessment.
1 Possible When the evidence is indeterminate for attributing
the adverse reaction either to the blood or blood
component or to alternative causes.
2 Likely, probable When the evidence is clearly in favour of attributing the
adverse reaction to the blood or blood component.
3 Certain When there is conclusive evidence beyond reasonable doubt for
attributing the adverse reaction to the blood or blood component.
Information about the type of adverse events and reactions

Report forms should enable differentiation between adverse reactions
in patients and donors, as well as from adverse events.
Report forms should include a brief summary that describes the event,
as well as the corrective actions taken.
In order to provide an evaluation of the incidence of untoward effects,
each participating institution should provide the number of blood
components used per year and the number of patients transfused,
together with details of all reported events.
Additional information about the current guidelines and procedures
in regard to the use of blood components is useful in comparing the
results from different institutions or even different countries.
230
Chapter 11
Principles of clinical use of blood
1. Overview
The clinical transfusion process encompasses the ‘transfusion of the
right blood component to the right patient at the right time, in the
right condition and according to appropriate guidelines’. It is a chain
of inter-related events beginning with the appropriate decision that
the patient needs transfusion of one or more blood components and
ending with the assessment of the clinical outcome of the transfusion.
The safety of transfusion of blood components is underpinned by
several key measures:
• the decision to transfuse;
• the completion of the transfusion request form;
• the correct identification of the patient and obtaining a
pre-transfusion sample;
• the pre-transfusion testing within the laboratory;
• the selection and issue of appropriate blood components;
• the administration of the component to the patient with appro-
priate monitoring.
231
For a safe and appropriate use of blood in therapy, it is necessary to

have in place a ‘Quality System for Clinical Transfusion’ involving
different health professionals. Structures and individuals that contrib-
ute to the governance of the process include the hospital management,
the Hospital Transfusion Committee (HTC), the hospital blood bank
and/or the blood establishment providing blood components to the
hospital or to the patient, and all hospital staff involved in the transfu-
sion chain and in the haemovigilance system.
Elements of the quality system include:
• adoption and regular updating of clear guidelines for appropri-
ate use of blood and blood components;
• adoption of SOPs for the implementation and surveillance of
appropriate blood utilisation;
• thorough dissemination of guidelines and SOPs;
• appropriate selection of suitable blood components for each
clinical condition;
• safe storage, issue and handling of blood components;
• ensuring correct patient identification throughout the transfu-
sion process;
• safe administration of the component and monitoring of the
patient;
• recognition, management and prevention of adverse effects of
transfusion;
• constant monitoring of quality and revision of the processes,
results, and blood components of transfusion medicine activities;
• definition of staff responsibilities and needs for training and
education.
232
Chapter 11 Principles of clinical use of blood
2. Decision to transfuse

Transfusion of blood components must follow appropriate evi-
dence-based guidelines that are updated regularly. The indication for
transfusion should be documented in the patient clinical record.
Where possible, informed consent should be obtained from the patient
prior to transfusion. This is mandatory in some countries. It is the
responsibility of the prescribing physician and the consent should be
documented in the clinical record of the patient. Information could be
delivered orally but is preferable in written form and should include
appropriate information on the risks and benefits of transfusion
therapy and its alternatives. The written information provided should
be approved by the Hospital Transfusion Committee.
Before ordering the transfusion, the treating doctor should be aware
of the patient’s transfusion history including any adverse reactions.
The decision to transfuse should be evidence-based. Therefore, profes-
sionals should be familiar with the recommendations of good quality
and regularly updated transfusion guidelines that take into account
the best available current evidence.
These guidelines should contain detailed instructions on appropriate
use of blood components for each clinical condition, guidance on the
dosage and need for special requirements (e.g. irradiated, washed).
It is strongly recommended that specific guidelines or recommenda-
tions are available, at least for transfusion management in:
• critical/massive haemorrhage;
• obstetric haemorrhage;
• paediatrics;
• intensive care patients;
• cardiovascular surgery;
• patients with haemoglobinopathies and other
haematological-transfusion dependent chronic disorders;
• haematopoietic stem cell transplant;
233
• patients with immune cytopenias, thrombotic thrombocyto-

penic purpura, coagulation factor deficiencies and disseminated
intra-vascular coagulation.
The HTC should plan and review the results of regular transfusion
audits and make the audit reports available to prescribing clinicians
so that when significant deviations from the guidelines are observed,
corrective actions can be put in place.
It is recommended that clinical services include blood components’
quality indicators as part of their quality programme management.
The medical staff of the blood establishment and hospital blood bank
should provide transfusion medicine clinical support and advice on
all aspects of the process.
Patient blood management

Blood transfusion medicine/therapy is a key part of patient blood
management (PBM) programmes. These aim to provide the best clin-
ical care, optimising the patient blood counts, reducing unnecessary
blood losses and procuring a judicious use of blood components. PBM
is based on an interdisciplinary overview of patient´s necessities.
Blood transfusion services and all blood establishments’ stakeholders
should be directly involved in PBM programmes.
Medical schools, hospitals and blood establishments must support
education in transfusion medicine including a specific educational
programme in PBM for clinicians in training.
Transfusion of blood components should be ordered when there are
no better alternatives. When available, possible alternatives should
be discussed with the patient and his/her opinion must be taken
into account. Physicians should be aware of alternative treatments
which can be less harmful or more specific, and could substitute or
avoid blood-component transfusion: coagulation factor concentrates;
erythropoietin; agonists of thrombopoietin receptor; antifibrinolytic
agents, blood recovering devices and other autotransfusion modalities.
234
Considering that blood components are a scarce, high-cost resource,

they should only be prescribed when some clinical benefit is expected.
A transfusion should not be ordered when it could be considered a
futile treatment or when potential side effects outweigh their benefit.
3. Completion of the transfusion request form,

identification of patient and blood sampling
The transfusion request should be made by a medical doctor or, if
permitted, by specially trained nurses.
Detailed instructions for the completion of the request form and the
taking of pre-transfusion samples should be available and all staff
permitted to make these requests should be trained and competent to
undertake this role.
The number of units, type(s) of blood component(s) and associated
special requirements (e.g. irradiation or washing), date and location of
the transfusion, clinical indication and the urgency of the transfusion
should be indicated on the request form. Information on transfu-
sion history and recent pregnancy is also necessary to determine the
period of validity of the pre-transfusion sample.
A procedure for auditing transfusion requests should be in place in
order to identify compliance with local clinical guidelines and to facil-
itate interventions to improve this and, where appropriate, to update
the guidelines. Validated information technology tools which provide
alerts or support physicians in transfusion decision-making are useful.
4. Correct identification of the patient and obtaining a

pre-transfusion sample
Collection of blood samples from the intended recipient for pre-trans-
fusion testing is a crucial point in the safety of the transfusion chain.
Where appropriate, the request form must be accompanied by the
appropriate blood samples for pre-transfusion testing.
Procedures should be in place to ensure that samples have been
drawn from the correct patient. Minimum requirements for patient
235
identification are family name, given name(s) and date of birth.

Where applicable, these data should be supplemented by a unique
patient identity number.
Whenever possible, at the time of sampling positive patient identifica-
tion must be performed. The patient should be asked to state his/her
name and date of birth if conscious and/or these or other identifiers
should be checked on a wrist band securely attached to the patient.
The information, on the tube label must be crosschecked and be iden-
tical with that on the request form.
In newborn infants, the gender and the number on the identification
wristband should also be recorded on the request form and the sample
tube.
If it is not possible to establish a patient’s identity, a procedure must be
in place to otherwise uniquely identify the intended recipient.
Any patient identification discrepancy at any step of the process must
be investigated and corrected.
5. Testing within the laboratory

Information on this is provided in Chapter 8, Principles of
immunohaematology.
6. Selection and issue of appropriate blood

components
Before issuing a blood component, the hospital blood bank will check
that the correct component has been selected, special requirements
have been fulfilled and the component(s) remains in-date. A check of
the integrity of the unit will also be made.
A compatibility label will then be attached to the component contain-
ing the patient identifiers obtained from the sample and/or request
form.
236
Handling and storage of blood components in hospital

clinical areas
Transport should be undertaken using systems that maintain the
integrity of blood components. Procedures should be in place to docu-
ment receipt of the issued blood components in the clinical area.
To avoid compromising clinical effectiveness and safety, blood com-
ponents should be transfused within the time limits required by the
current rules or local procedures. It is recommended that the blood
component should not remain out of controlled storage for more than
30 minutes if it is not transfused and it is to be returned to storage.
Relevant staff should be properly trained in the principles and practice
of handling different types of blood components and written proce-
dures should be available.
7. Administration of blood components

Procedures must be in place to verify the identity of the recipient
at the bedside in order to ensure that the blood component is to be
transfused to the intended recipient. This involves asking the patient
to state his/her name and date of birth and/or by checking the iden-
tification details on the patient’s wrist-band against the information
provided on the compatibility label.
In addition, confirmation of compatibility between patient and blood
component should be carried out by:
• checking the written – or electronic – prescription (including
special requirements);
• checking the record of the patient’s blood group against the
blood group on the blood component label;
• checking that the unique identification number on the blood
component label matches that on the compatibility label and/or
on the hospital blood bank report, where available. Prior to com-
mencing the transfusion a check should be made to verify that
the expiry date of the blood component has not been passed and
that there is no visible deterioration of the blood components
237
(with particular emphasis on discolouration or detectable

micro-perforations of the bag).
Where undertaken, the bedside confirmation of ABO group should
then be performed.
Blood components must be administered using an approved blood
administration set that incorporates an integral mesh filter (usually
150–230 microns) to filter out large clots and aggregates and ensure an
effective flow rate. This set and any other infusion equipment should
be used in accordance with manufacturer recommendations. It is
recommended that no transfusion sets be used for more than 6 hours.
Transfusion should be completed within 4 hours of removal from
controlled storage.
To ensure traceability, all blood components administered should be
recorded in the clinical patient record, including the component iden-
tification number and the start and end times of the transfusion.
Special precautions
Warming of blood
Hypothermia induced by rapid/massive transfusion (more than
50 mL/kg/hour in adults and 15 mL/kg/hour in children) increases
the risks of organ failure and coagulopathy. If warming of blood is
indicated, only validated and regularly controlled warming devices
should be used in accordance with manufacturer instructions.
Addition of medicinal products or infusion

Because of the risk of damage to the blood components, addition of
medicinal products or infusion solutions to blood units should be
avoided unless their safety has been demonstrated.
Transfusion monitoring
Observation of the patient during and after transfusion is essential.
Observation during the first 15 minutes of the transfusion is especially
important to allow early detection of signs of serious acute reactions.
238
Requirements should be documented in procedures and personnel

should be trained.
Vital signs such as blood pressure, pulse, respiratory rate and tempera-
ture should be measured before starting the transfusion, at 15 minutes
after the start of the transfusion and at the end of the transfusion of
every blood component transfused.
The time when transfusion is started, interrupted and stopped should
be clearly reported in patient records, as well as vital signs or any
other symptoms that could indicate a transfusion reaction.
Confirmation of transfusion of the blood component should be sent
back to the hospital blood bank.
An assessment of the effectiveness of the transfusion should be
performed (by post-transfusion increment rates or improvements in
patient symptoms and clinical signs) and documented in a clinical
record, identifying whether the desired effect was obtained and the
likely need for further transfusion.
Management and reporting of transfusion reactions

Complications may occur during or immediately after the transfusion,
or after a delay of hours, days or months. Therefore, careful documen-
tation of the transfusion as well as recording and reporting of transfu-
sion complications is essential.
Transfusion complications include both adverse events and adverse
reactions associated with transfusions and even failure of expected
therapeutic response. Careful recording and reporting of any ob-
served reaction is the responsibility of the attending physician.
In the event of a suspected transfusion reaction, the transfusion
should be stopped and the line should be maintained with normal
saline. The patient should be assessed for severity of the reaction and
treated accordingly. Where the reaction is a mild allergic or febrile
reaction and settles with treatment, the transfusion may be restarted
at a slower rate with more frequent observations. For severe reactions
the key priority is resuscitating the patient and treating any specific
239
symptoms or suspected causes of the reaction. As ABO-incompatible

red cells can cause such a reaction, a clerical check of the documenta-
tion associated with the transfusion should be undertaken, including
an identification check of the recipient and blood component and
a check that the ABO and RhD blood group of the component is
compatible with the patient’s blood group. New samples should be
taken from the patient and the transfusion packs and, together with a
transfusion reaction report, these should be sent to the hospital blood
bank for further investigation if clinically indicated. In order to assist
laboratory investigations of suspected reactions, transfusion packs
should not be discarded for at least 24 hours after commencement of
the transfusion.
Respiratory complications of blood transfusion are increasingly
recognised and have been shown by haemovigilance schemes to be
associated with a high mortality in vulnerable patient groups. Any
patient experiencing new or worsening breathlessness during or after
a transfusion should be fully assessed by a medical doctor to deter-
mine if there is an allergic reaction, TACO or TRALI which should
then be investigated and managed accordingly. Air embolism is now a
rare complication of blood transfusion.
When clinical symptoms and signs suggest the possibility of bacterial
infection, blood cultures should be obtained from the patient as well
as bacterial culture from the blood component bag. Care should be
taken not to contaminate the content of the bag after disconnecting
from the patient.
In countries where universal pre-storage leucocyte depletion has not
been implemented, the use of leucocyte-depleted blood components
for subsequent transfusions is recommended for patients with re-
peated, febrile non-haemolytic transfusion reactions.
Long-term complications may also occur. These mainly comprise im-
munological complications e.g. allo-immunisation and transmission
of infectious pathogens.
Haemosiderosis is a serious complication of chronic red cell trans-
fusion affecting patients suffering from transfusion-dependent
240
conditions. Unless patients undergo iron-chelation therapy to control

iron overload in the liver and heart, this complication may lead to
severe organ impairment and death before the third decade of life.
There should be co-operation between the clinician responsible for the
patient and the hospital blood banks/blood establishment to facilitate
investigation of possible transfusion-transmitted infections (TTI).
Suspected TTI may require investigation when the recipient develops
a viral or bacterial infection after transfusion or a donor is found to
have developed an infectious disease marker. Medical follow-up of
recipients and donors will be required to determine causality.
Follow-up and patient counselling, where appropriate, is also neces-
sary when significant allo-immunisation against transfused cells may
have taken place.
Traceability and haemovigilance

Facilities where transfusion occurs should have procedures in place to
ensure retention of at least the following data: identification of blood
component supplier, the identity and type of blood component trans-
fused, the name of the recipient and the date of transfusion. For any
issued blood component that is not transfused, confirmation and date
of subsequent disposal should be included.
Each adverse reaction or event related to the transfusion should be
investigated, recorded and notified to the haemovigilance system,
including errors with no consequence for the patient. Procedures must
be in place to notify blood establishments without delay of any serious
adverse reactions which may be attributable to the quality or safety of
blood and blood components.
These issues are considered in further details in Chapter 10, Principles
of haemovigilance.
8. Hospital transfusion committees

Establishment of hospital transfusion committees (HTCs) is to be
encouraged. The hospital chief executive and senior hospital manage-
ment have the responsibility to support and resource the HTC.
241
A hospital blood transfusion committee should include representa-

tives of the hospital blood bank, the blood establishment and the main
clinical units with significant transfusion activity. It is recommended
that physicians, nurses and administrative personnel be represented
on these committees.
The main goals of HTCs are:
• to define blood transfusion policies adapted to local clinical
activities;
• to perform regular evaluation of blood transfusion practices;
• to analyse adverse events and adverse reactions related to blood
transfusion;
• to take any corrective and preventive measures if necessary;
• to ensure that all staff involved in transfusion practice receive
adequate training.
Audit systems for the clinical use of components further enhance the
efficacy and safety of transfusion practices.
242
STANDARDS
Chapter 1
Introduction
The Standards section of this Guide contains minimum standards for
blood establishments and hospital blood banks that are required to
comply with European Union (EU) Directive 2005/62/EC. The Stand-
ards are aligned closely with European Commission Directives, and
include blood component monographs that mirror the structure used
in the European Pharmacopoeia. This section states what must be
done.
Elements of the Standards that are transcribed from EU Directives are
legally binding on blood establishments and hospital blood banks within
the EU. These are highlighted within this section of this Guide. The
specific numbering used in Directive 2005/62/EC is to assist in cross-
referencing of EU requirements. The Standards may also be of benefit to
Council of Europe member states outside the EU and to other organisa-
tions involved in transfusion activities outside Europe.
245
Chapter 2
Standards for selection of donors
1. Overview
Measures must be taken to promote the collection of blood and blood
components from voluntary non-remunerated donations accord-
ing to the principles set out in the Convention for the Protection of
Human Rights and Dignity of the Human Being with Regard to the
Application of Biology and Medicine (Convention on Human Rights
and Biomedicine, ETS No. 164) and its Additional Protocol concern-
ing Transplantation of Organs and Tissues of Human Origin (ETS
No. 186).
Blood establishments are ultimately responsible for the quality and
safety of the blood and blood components collected, and must be
entitled to decide on the final acceptance or deferral of a donor or a
prospective donor, taking into account Resolution CM/Res (2008) 5
on donor responsibility and on the limitations to donation of blood
and blood components.
2. Information to be provided to the donor

The following information must be provided to prospective donors of
blood or blood components:
247
• accurate educational materials that are understandable for

members of the general public about the: essential nature of
blood; blood-donation procedure; components derived from
whole blood and apheresis donations; important benefits to
patients;
• for both allogeneic and autologous donations, the reasons for
requiring a medical assessment, health and medical history, the
testing of donations and the significance of ‘informed consent’:
–– for allogeneic donations, self-deferral, and temporary and
permanent deferral, and the reasons why individuals must not
donate blood or blood components if there could be a risk for the
recipient or the donor;
–– for autologous donations, the possibility of deferral and the
reasons why the donation procedure cannot take place in the
presence of a health risk to the individual, whether as a donor or
recipient of the autologous blood or blood components;
• information on the protection of personal data: no unauthorised
disclosure of the identity of the donor, of information concern-
ing the donor’s health or of the results of the tests performed;
• the reasons why individuals must not make donations that may
be detrimental to their health;
• specific information on the nature of the procedures involved in
the allogeneic or autologous donation process and their respec-
tive associated risks. For autologous donations, the possibility
that the autologous blood and blood components may not suffice
for the intended transfusion requirements;
• all blood donors must be provided with accurate and updated in-
formation on HIV/AIDS and hepatitis transmission and be given
the opportunity for self-exclusion so that those persons who
have unsafe sex practices or other risk behaviours exposing them
to potential infectious sources refrain from donating;
• information on the option for donors to change their mind about
donating before proceeding further, or the option to withdraw
248
Chapter 2 Standards for selection of donors
or self-defer at any time during the donation process without

undue embarrassment or discomfort;
• the reasons why it is important that donors inform the blood
establishment of any subsequent event that may render any prior
donation unsuitable for transfusion;
• information on the responsibility of the blood establishment
to inform the donor, through an appropriate mechanism, if
test results show any abnormality of significance to the donor’s
health;
• information why unused autologous blood and blood compo-
nents are discarded and not transfused to other patients;
• information that test results detecting markers for viruses, such
as HIV, HBV, HCV or other relevant blood-transmissible micro-
biologic agents, will result in donor deferral and destruction of
the collected unit and, when required by law, that the results will
be reported to health authorities;
• information on the opportunity for donors to ask questions at
any time.
This information provides the basis for informed consent from the
donor that must be obtained before proceeding to donation.
3. Medical assessment of the donor

Donor eligibility
Procedures for safe donor identification, the suitability interview and eligibility assessment must
be implemented and maintained. They must take place before each donation and comply with
the requirements set out in Annex II and Annex III to Directive 2004/33/ EC (Directive 2005/62/EC
Annex 6.1.1).
All donors must undergo a screening process to assess their suitability.

Only healthy individuals with an appropriate medical history can be
accepted as donors of blood or blood components.
The donor must be properly identified.
249
The selection process must include assessment of each donor carried

out by a suitably qualified individual who has been trained to use
accepted guidelines and who works under the direction of a physician.
This assessment involves an interview, a questionnaire and further
direct questions, if necessary.
Questionnaire and interview

The questionnaire must be designed to elicit information relevant to
the health and lifestyle of the donor. It must be designed to be under-
standable by the donor and given to all donors each time they attend.
On completion, it must be signed by the donor.
A confidential interview must be conducted by specifically trained
staff to ask further direct questions to supplement the information in
the questionnaire. The person who carries out the assessment must
certify that the relevant questions have been asked.
The donor interview must be conducted in such a way as to ensure confidentiality (Directive
2005/62/EC Annex 6.1.2).
The donor suitability records and final assessment must be signed by a qualified health professional
(Directive 2005/62/EC Annex 6.1.3).
Donor details
There must be secure, unique donor identification, contact details and
robust mechanisms linking the donors to each of their donations.
Age of the donor

The age limits for donation are a minimum of 18 years and maximum
of 65 years.
Where allowed by national legislation, blood donation may be consid-
ered from donors aged 17.
Donation by first-time donors above the age of 60 years is at the dis-
cretion of the responsible physician.
Donation by regular donors over 65 years is at the discretion of the
responsible physician. Permission to continue donating after the age
250
of 65 years can be given annually by the responsible physician either

individually to each donor or based on a medical risk assessment for a
given donor population.
Donor appearance and inspection

Special note must be taken in case of plethora, poor physique, debili-
tation, undernutrition, anaemia, jaundice, cyanosis, dyspnoea, mental
instability and intoxication from alcohol or drugs.
4. Donor deferral

Deferred donors must be given a clear explanation of the reasons for
deferral.
Tables 2.1, 2.2 and 2.3 list conditions for deferral. Specific conditions
for infectious diseases are listed.
Table 2.1. Conditions leading to permanent deferral
Cancer/ malignant Individuals with a malignant disease, or a history of such, are usually
diseases permanently deferred. The physician in charge may make exceptions to
this rule in selected cases (see Principles).
Creutzfeldt-Jakob disease All individuals who have in the past been treated with extracts derived
from human pituitary glands, have been recipients of dura mater or
corneal grafts or who have been told of a family risk of Creutzfeldt-
Jakob disease or any other transmissible spongiform encephalopathy. a
Diabetes If insulin therapy is required, rDNA insulin is used.
Drugs Any history of injectable drug abuse.
Cardiovascular disease Persons with a history of serious heart disease, especially coronary
disease, angina pectoris, severe cardiac arrhythmia, a history of
cerebrovascular diseases, arterial thrombosis or recurrent venous
thrombosis (see also Principles, Chapter 2).
a A family history of CJD carries a presumption of family risk unless it is determined that: (a) the affected family
member had vCJD, not CJD; or (b) the affected family member did not have a genetic relationship to the donor;
or (c) the cause of CJD in the affected family member was iatrogenic; or (d) the donor was tested and is known to
have a normal genetic polymorphism for PrPc.
b Deferral requirements may be waived by the blood establishment if the donation is used exclusively for plasma
for fractionation.
251
Infectious conditions Certain infectious states and diseases necessitate permanent deferral:
a) Carriers of HIV 1/2, HTLV I/II, HBV and HCV
b) Babesiosis b
c) Leishmaniasis; (Kala-Azar) visceral leishmaniasisb
d) Chronic Q fever b
e) Trypanosomiasis cruzi (Chagas disease) b
(see also Chapters 2 and 9 Infectious diseases)
f ) Persons whose sexual behaviour puts them at high risk of acquiring
severe infectious diseases that can be transmitted by blood.
Xenotransplantation All recipients.
a A family history of CJD carries a presumption of family risk unless it is determined that: (a) the affected family
member had vCJD, not CJD; or (b) the affected family member did not have a genetic relationship to the donor;
or (c) the cause of CJD in the affected family member was iatrogenic; or (d) the donor was tested and is known to
have a normal genetic polymorphism for PrPc.
b Deferral requirements may be waived by the blood establishment if the donation is used exclusively for plasma
for fractionation.
Table 2.2. Conditions leading to temporary

deferral (suspension)
Condition Deferral period
Endoscopy with biopsy using flexible 6 months (or 4 months, provided a NAT test for hepatitis C
instruments, inoculation injury, is negative).
acupuncture, a tattooing a or body-
piercing, mucosal splashes with blood,
tissue or cell transplant of human
origin
Transfusion of blood components 6 months or for 4 months provided a NAT test for hepatitis C
is negative. Injection of red cells as part of an approved
immunisation programme will need clinical assessment.
Epilepsy 3 years off treatment and without an attack.
Fever above 38 °C, flu-like illness 2 weeks following cessation of symptoms.
a Exceptions can be made according to national risk assessments.
252
Condition Deferral period
Kidney disease Acute glomerulonephritis: 12 months deferral period

following full recovery (well, on no treatment and
discharged from specialist care).
Medication The taking of a medication may indicate an underlying
disease which may disqualify the donor. It is recommended
that a list of commonly used drugs, with rules for
acceptability of donors, approved by the medical staff
of the transfusion centre, be made available. Donors
treated with prescribed drugs, particularly those with
proven teratogenic effect, should be deferred for a period
consistent with the pharmacokinetic properties of the drug.
Osteomyelitis 2 years after having been declared cured.
Pregnancy 6 months after delivery or termination, except in
exceptional circumstances and at the discretion of a
physician.
Rheumatic fever 2 years following attack with no evidence of chronic heart
disease. The latter complication is a cause for permanent
deferral.
Surgery After surgery, persons should not donate until they have
recovered fully and are fit to be donors (typically about
6 months for major surgery).
Tooth extraction If no complications, 1 week (because of possible risk of
transient bacteraemia).
Tropical infections 6 months following return from tropical areas and then
only if they have not suffered an unexplained fever or
illness (see Chapters 2 and 9, Infectious diseases).
a Exceptions can be made according to national risk assessments.
253
Table 2.3. Vaccinations
Inoculations, vaccinations Deferral period
Vaccines with attenuated bacteria and viruses: BCG, yellow 4 weeks

fever, rubella, measles, poliomyelitis (oral), mumps, live Vaccinia for smallpox at 8 weeks
attenuated typhoid fever, vaccinia, live attenuated cholera
vaccine
Vaccines with killed bacteria: Accept, if well
cholera, typhoid, capsular polysaccharide typhoid fever
vaccine
Vaccines with inactivated viruses: Accept, if well
poliomyelitis (injection), influenza
Toxoids: diphtheria, tetanus Accept, if well
Other vaccines: Accept, if well and no exposure is
hepatitis A and B vaccine, hepatitis B vaccine, rabies, tick- reported
borne encephalitis 1 week in order to prevent vaccine-
related positivity in HBs-antigen result
Accept, if well
One year if post-exposure
Infectious diseases
HIV/AIDS
Persons whose sexual behaviour puts them at a high risk of acquiring
severe infectious diseases that can be transmitted by blood must be
deferred permanently.
Current sexual partners of people with HIV must be deferred. Previ-
ous sexual partners of people with HIV are acceptable 12 months after
the last sexual contact.
Brucellosis (confirmed)
Deferral for at least two years following full recovery.
254
The deferral period does not apply when the donation is used exclu-
sively for plasma fractionation.
Chagas disease
Individuals with Chagas disease or who have had Chagas disease must
be permanently deferred.
The blood of persons who were born or have been transfused in areas
where the disease is endemic should be used only for the production
of plasma that is used exclusively for fractionation into plasma deriva-
tives, unless a validated test for infection with T. cruzi is negative.
Jaundice and hepatitis

Individuals with a history of jaundice or hepatitis may, at the discre-
tion of the appropriate Competent Authority, be accepted as blood
donors provided a CE-marked test for HBsAg and anti-HCV is
negative.
Persons who have been in close household contact with an individual
infected by the hepatitis-B virus (acute or chronic) must be deferred
for 6 months (4 months if appropriate testing has been performed)
from the time of contact unless demonstrated to be immune.
Current sexual partners of people with HBV must be deferred, unless
demonstrated to be immune.
Previous sexual partners of people with HBV are acceptable after
6 months since the last sexual contact. This can be reduced to
4 months if HBV NAT and anti-HBc are performed and both test
results are negative.
Malaria1
Since questioning a donor as to the country(s) in which he/she was
born, brought up or has visited is essential for effective detection,
every blood establishment must have a current map or list of the
endemic zones and time frames in the countries concerned.
1 Tests and deferral periods may be waived by the blood establishment if the
donation is used exclusively for plasma fractionation.
255
Persons who have lived in a malaria-endemic area for a continuous

period of 6 months or more at any time in their life
These persons may become asymptomatic carriers of the malaria
parasite. Therefore, the following rules must apply to these individuals
after each return from a malaria area:
• may be accepted as blood donors if the result of a validated
immunological test for antibodies to the malaria parasite, per-
formed at least 4 months after the last visit to a malaria area, is
negative;
• if the test is repeatedly reactive, the donor must be deferred and
may be re-evaluated after a suitable period when the antibody
test may have reverted to negative (a period of 3 years is sug-
gested);
• if the test is not performed, the donor must be deferred until the
test is performed and negative.
Persons who give a history of malaria
• Must be deferred until asymptomatic and off treatment.
• May be accepted as blood donors if the result of a validated
immunological test for antibodies to the malaria parasite
performed at least 4 months since cessation of treatment/last
symptoms is negative.
• If the test is repeatedly reactive, the donor must be deferred and
gested).
• If the test is not performed, the donor should be deferred until
the test is performed and negative.
Persons who report an undiagnosed febrile illness consistent with
malaria during or within 6 months of the end of a visit to a malaria area
immunological test for antibodies to the malaria parasite,
256
performed at least 4 months since cessation of treatment/last

symptoms, is negative.
• If the test is repeatedly reactive, the donor should be deferred
and may be re-evaluated after a suitable period when the anti-
body test may have reverted to negative (a period of 3 years is
suggested).
• If the test is not performed, the donor should be deferred until
the test is performed and negative.
All other persons who have visited a malaria-endemic area without
reporting any clinical symptoms consistent with malaria
immunological test for antibodies to the malaria parasite per-
formed at least 4 months after the last visit to a malaria-endemic
area is negative.
• If the test is repeatedly reactive, the donor must be deferred and
gested).
• If the test is not performed, the donor may be re-accepted once
a period of 12 months has elapsed after the most recent return
from a malaria area.
Q Fever1
Deferral until two years following the date confirmed as cured.
Syphilis1
Deferral until one year following the date confirmed as cured.
Toxoplasmosis
Deferral until 6 months following clinical recovery.
257
Tuberculosis
Deferral until two years after having been declared as cured.
Variant Creutzfeldt-Jakob disease

Deferral of donors as a preventative measure for vCJD must be based
on appropriate risk assessment.
West Nile virus1 (WNV)

Deferral until 28 days after leaving an area with ongoing transmis-
sion of the disease to humans unless a validated NAT is performed.
Persons with a diagnosis of WNV must be deferred until 120 days
after recovery.
Zika virus
Deferral until 28 days after leaving an area with ongoing transmis-
sion of the disease to humans unless a validated NAT is performed.
Persons with a diagnosis of Zika virus infection must be deferred until
120 days after recovery.
5. Specific standards for donors of different types of

components
Whole blood donors
A standard donation must not be collected from persons weighing less
than 50 kg.
Quantity of donation
Volume of donation
A standard donation of whole blood (excluding anticoagulants) must
not exceed 500 mL and usually consists of a donation of 450 mL
± 10 %. This does not include any allowance for samples taken for
laboratory tests and for retention of a donor sample. The volume of
258
a standard donation of whole blood (including samples) must not

exceed 15 % of the calculated blood volume of the donor.
Frequency of whole blood donations

A maximum of 6 standard donations per year can be taken from men
and up to 4 per year from women, with a minimum interval between
standard donations of 2 months.
These maximum donation rates must never be exceeded under any
circumstances, and should only be adopted after careful consider-
ation of the dietary habits of the populations concerned and in the
knowledge that extra care may be necessary, beyond routine haemo-
globin or haematocrit estimation, in the monitoring of donors for iron
deficiency.
Laboratory examination
• Haemoglobin concentration must be determined each time the
donor attends to donate blood or blood components.
• Minimum values before donation:
–– female donors: 125 g/L or 7. 8 mmol/L (minimum haematocrit =
0.38)
–– male donors: 135 g/L or 8. 4 mmol/L (minimum haematocrit =
0.4)
• Individual donations may be accepted below these levels after
consultation with the responsible physicians or as established
by a Competent Authority, based on norms for their specific
populations.
Apheresis donors
The supervision and medical care of apheresis donors must be under
the responsibility of a physician specially trained in these techniques.
Other than in exceptional circumstances (to be decided by the re-
sponsible physician), donors for apheresis procedures must meet the
criteria for whole blood donations.
259
People with sickle cell trait must not donate red cell components by
apheresis.
Donors taking medicinal drugs that inhibit platelet functions must be
temporarily deferred from donation by platelet apheresis.
Frequency of donation and maximal amounts

of plasma and red cells to be collected
The total blood volume of each donor must be estimated.
The maximal extra-corporeal volume during apheresis must never be
higher than 20 %.
The collection volume (excluding anticoagulant) for each plasma-
pheresis procedure must not exceed 16 % of the estimated total blood
volume, and should never exceed 750 mL unless fluid replacement is
undertaken.
Not more than 1.5 L of plasma may be collected from any one donor
per week.
A maximum of 33 plasmapheresis procedures may be performed per
donor per year. This equates to a maximum annual collection volume
of 25 L, based on the maximum volume of 750 mL plasma (excluding
anticoagulant) per procedure.
In any apheresis procedure involving collection of plasma, platelets
and/or red cells in one apheresis procedure, the total volume of all
components collected (plasma, platelets and red cells) must not exceed
16 % of total blood volume, with a maximum of 750 mL (exclusive of
anticoagulant), unless fluid replacement is undertaken.
The total amount of red cells collected must not exceed the theoret-
ical amount of red cells that would bring the donor haemoglobin in
isovolemic situation below 110 g/L.
The interval between one plasmapheresis or plateletpheresis procedure
and a donation of whole blood or apheresis procedure incorporating
collection of a single or double unit of red cells (whereby one unit is
equivalent to a red cell component obtained from one whole blood
donation) must be at least 48 hours. The interval between a whole
260
blood donation, an apheresis red cell collection or a failed return of

red cells during apheresis, and the next apheresis procedure without
red cell collection, must be at least one month. The interval between
two single-unit red cell collections must be the same as for collections
of whole blood.
Additional requirements for donors undergoing plasmapheresis

Protein analysis, such as determination of total serum or plasma
protein and/or electrophoresis and/or quantitation of single proteins
(especially albumin and IgG) must be performed. Analysis must be
carried out at the first donation and at least every year thereafter.
Total proteins must not be less than 60 g/L. IgG levels must be within
reference values of the normal population and should not fall below
6.0 g/L. Donors with results below these limits must be deferred until
IgG and total protein levels are back to normal.
Additional requirements for donors undergoing plateletpheresis

Platelet apheresis must not be carried out on individuals whose plate-
let count is less than 150 × 109/L. Donors must not be subjected to a
platelet apheresis procedure more often than once every 2 weeks. An
exception to the donation interval and platelet count may be made
in the case of HLA-/HPA-matched donations and for IgA-negative
donors at the discretion of the physician responsible for the procedure.
Additional requirements for donors undergoing

double unit red cell apheresis
The donor must have an estimated blood volume of > 4 500 mL. The
total blood volume must be calculated on the basis of gender, height
and weight (see Appendix 2, Tables 1 and 2).
Haemoglobin levels must be determined before each donation and
the minimum value must be > 140 g/L. The haemoglobin level of the
donor must not fall below 110 g/L after donation.
The interval between a whole blood donation and the donation of
a double unit of red cells must be at least 3 months. The interval
between a double-unit red cell apheresis and a donation of whole
261
blood or another double-unit red cell apheresis must be at least

6 months for women and 4 months for men.
The maximum volume of red cells collected must not exceed 400 mL
(without re-suspension solution) per collection procedure.
Total red cell volume collected per year must not exceed that accept-
able for whole blood donors.
6. Post-donation information

Blood donors must be instructed to inform the blood establishment
when signs or symptoms occur after a donation that might indicate
that the donation may have been infectious.
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Chapter 3
Standards for collection of blood

and blood components
1. Premises for donor sessions

Premises (including those of mobile teams) must satisfy general re-
quirements for the health and safety of the staff and donors concerned
with due regard to relevant legislation or regulations.
Suitable facilities must be provided to allow a private interview with
each donor, assuring privacy and confidentiality.
Before premises are accepted for mobile donor sessions, their suitabil-
ity must be assessed against the following criteria:
• sufficient size to allow proper operation and ensure donor
privacy;
• safety for staff and donors;
• the presence of ventilation, electrical supply, lighting,
hand-washing facilities, reliable communication, blood storage
and transport.
263
2. Procedures and equipment used at blood donation

sessions
The blood collection procedure must be designed to ensure that the identity of the donor is verified
and securely recorded and that the link between the donor and the blood, blood components and
blood samples is clearly established (Directive 2005/62/EC Annex 6.2.1).
The sterile blood bag systems used for the collection of blood and blood components and their
processing must be CE marked or comply with equivalent standards if the blood and blood
components are collected in third countries. The batch number of the blood bag must be traceable
for each blood component (Directive 2005/62/EC Annex 6.2.2).
Blood collection procedures must minimise the risk of microbial contamination (Directive 2005/62/
EC Annex 6.2.3).
Sterile collection systems must be used for the collection of blood

and blood components. These must be used in accordance with the
instructions of the manufacturer. A check must be made before use
to ensure that the collection system employed has not been damaged
or contaminated, and that it is appropriate for the intended collection
procedure. Defects in blood bags must be reported to the supplier and
be subjected to trend analysis.
3. Pre-donation checks

The blood container must be inspected before use for defects and must
be inspected for the prescribed content and appearance of the anti-
coagulant solution. If one or more bags in any package is found to be
abnormally damp, all the bags in the package must be rejected.
The donor must be re-identified immediately prior to venepuncture.
4. Labelling
Laboratory samples must be taken at the time of donation and be appropriately stored prior to
testing (Directive 2005/62/EC Annex 6.2.4).
The procedure used for the labelling of records, blood bags and laboratory samples with donation
numbers must be designed to avoid any risk of identification error and mix-up (Directive 2005/62/
EC Annex 6.2.5).
Laboratory samples (blood or plasma) must be taken at the time of

each donation. Procedures must be designed to minimise the risk of
264
Chapter 3 Standards for collection of blood and blood components
microbial contamination of the collected blood or deterioration of the

sample, and to prevent potential misidentification of donations and
samples.
At the time of blood donation, the blood container and those of the
samples collected for testing must be labelled to uniquely identify
the blood donation. The labelling system must comply with relevant
national legislation and international agreements.
The blood donation must be identified by a unique identity number
which is both eye- and machine-readable. The labelling system must
allow full traceability to all relevant data registered by the blood estab-
lishment about the donor and the blood donation.
A careful check must be made of the identity indicator of the donor
against the labels issued for that donation.
The manufacturer’s label on the collection containers must contain the
following eye-readable information:
• the manufacturer’s name and address;
• the name of the collection container and/or the name of the
plastic material;
• the name, composition and volume of anti-coagulant or additive
solution (if any);
• the product catalogue number and the lot number.
5. Venepuncture, bleeding and mixing

Preparation of the venepuncture site
The skin at the venepuncture site must be free from lesions, including
eczema.
The venepuncture site must be prepared using a defined and validated
disinfection procedure. The antiseptic solution must be allowed to
dry completely before venepuncture. The prepared area must not be
touched with fingers before the needle has been inserted.
265
The effectiveness of the disinfection procedure must be monitored and

corrective action taken where it is indicated to be defective.
Successful venepuncture and proper mixing

The needle must be inserted into the vein at the first attempt. A second
venepuncture with a new needle in the other arm is acceptable with
the consent of the donor, provided that bacterial sterility of the system
is not compromised.
Where an anticoagulant solution is used in the collection, the collec-
tion bag must be mixed gently immediately after starting collection
and at regular intervals during the entire collection period. The flow
of blood must be sufficient and uninterrupted.
The maximum collection time for acceptance of the donation for com-
ponent processing must be specified and controlled. Donations that
exceed the maximum time period must be recorded and discarded.
If the duration of the bleeding is longer than 12 minutes, the blood
must not be used for the preparation of platelets.
If the duration of the bleeding is longer than 15 minutes, the plasma
must not be used for direct transfusion or the preparation of coagula-
tion factors.
If manual mixing is used, the blood bag must be inverted every 30-45
seconds. When an automated mixing system is used, an appropriately
validated system is required.
At completion of the donation, the donation number must be checked
on all records, blood bags and laboratory samples. Donation number
labels of a given donation that have not been used must be destroyed
via a controlled procedure. Procedures to prevent mislabelling must
be in place.
Each activity associated with the donation must be recorded. This
also applies to any unsuccessful donations, the rejection of a donor,
adverse reactions and adverse events. An authorised interviewer must
sign the donor selection records and the final assessment.
266
Chapter 3 Standards for collection of blood and blood components
6. Handling of filled containers and samples

After blood collection, the blood bags must be handled in a way that maintains the quality of the
blood and at a storage and transport temperature appropriate to further processing requirements
There must be a system in place to ensure that each donation can be linked to the collection and
processing system into which it was collected and/or processed (Directive 2005/62/EC Annex 6.2.7).
The blood container must be checked after donation for any defect.
During separation from the donor, a completely efficient method of
sealing the tube is obligatory.
The blood bag and corresponding samples must not be removed from
the donor’s bedside until labelling has been checked and is verified as
correct.
After collection, blood bags must be placed promptly into controlled
temperature storage and transported to the processing site under
temperature conditions appropriate for the component that is to be
prepared. Validation data must be available to demonstrate that the
storage parameters after collection and the method of transport used
maintains the blood within the specified temperature range through-
out the period of transportation.
7. Special requirements for apheresis

Separation and collection of blood components by cell separators
requires premises of suitable size, regular servicing and maintenance
of machines (and adequately trained personnel for operating such
machines).
The donor must be observed closely during the procedure. A qualified
healthcare professional familiar with all aspects of apheresis must be
available to provide assistance and emergency medical-care proce-
dures in case of an adverse reaction.
Collection of adequate granulocyte yields by apheresis requires
pre-medication of the donor. The potential risk to the donor must be
evaluated against the anticipated benefit to the intended recipient.
267
Return of red blood cells of donors undergoing manual

apheresis
Since the biggest inherent danger in manual apheresis is an accidental
interchange between two bags of concentrated red blood cells during
their centrifugation and return to individual donors, a robust identifi-
cation system must be in place.
8. Repository of archive samples

If archive samples from donations are kept, then procedures must be
in place prescribing their use and final disposal.
268
Chapter 4
Standards for the processing, storage

and distribution of blood components
1. Processing
All equipment and technical devices must be used in accordance with validated procedures
The processing of blood components must be carried out using appropriate and validated
procedures, including measures to avoid the risk of contamination and microbial growth in the
prepared blood components (Directive 2005/62/EC Annex 6.4.2).
The premises used for the processing of blood components must be

kept in a clean and hygienic condition and the microbial contamina-
tion load on critical equipment, surfaces and in the environment of
the processing areas must be monitored.
Procedures must detail the specifications for any materials that will
influence the quality of the final blood component. In particular,
specifications must be in place for blood and blood components (inter-
mediate and final components), starting materials, additive solutions,
primary packaging material (bags) and equipment.
Procedures must be developed and validated for all processing activi-
ties. These must include time and temperature limits for the process-
ing of blood components.
269
Sterile connecting devices must be used in accordance with a vali-

dated procedure. The resulting weld must be checked for satisfactory
alignment and its integrity must be validated. When validated, con-
nections made using sterile connecting devices are regarded as closed
system processing.
2. Component labelling and information

At all stages, all containers must be labelled with relevant information of their identity. In
the absence of a validated computerised system for status control, the labelling must clearly
distinguish released from non-released units of blood and blood components (Directive 2005/62/
EC Annex 6.5.1).
The labelling system for the collected blood, intermediate and finished blood components and
samples must unmistakably identify the type of content and comply with the labelling and
traceability requirements referred to in Article 14 of Directive 2002/98/EC and Directive 2005/61/EC.
The label for a final blood component must comply with the requirements of Annex III to Directive
2002/98/EC (Directive 2005/62/EC Annex 6.5.2).
For autologous blood and blood components, the label also must comply with Article 7 of Directive
2004/33/EC and the additional requirements for autologous donations specified in Annex IV to that
Directive (Directive 2005/62/EC Annex 6.5.3).
Before use, all blood components must be labelled with relevant iden-
tity information. The type of label to be used, as well as the labelling
methodology, must be established in written procedures. Critical in-
formation must be provided in machine-readable format to eliminate
transcription errors.
The blood establishment responsible for the preparation of blood
components must provide clinical users of blood components with
information on their use, composition and any special conditions that
do not appear on the component label.
270
Chapter 4 Standards for the processing, storage and distribution of blood components
3. Release of blood components

There must be a safe and secure system to prevent each single blood and blood component from
being released until all mandatory requirements set out in Directive 2005/62/EC have been fulfilled.
Each blood establishment must be able to demonstrate that each blood or blood component has
been formally released by an authorised person. Records must demonstrate that before a blood
component is released, all current declaration forms, relevant medical records and test results meet
all acceptance criteria (Directive 2005/62/EC Annex 6.6.1).
Before release, blood and blood components must be kept administratively and physically
segregated from released blood and blood components. In the absence of a validated computerised
system for status control, the label of a unit of blood or blood component must clearly distinguish
released from non-released units of blood and blood components (Directive 2005/62/EC Annex
6.5.1 and 6.6.2).
Each blood establishment must be able to demonstrate that a blood

or blood component has been approved for release by an author-
ised person, preferably assisted by validated information technology
systems. The specifications for release of blood components must be
defined, validated and documented.
Where release is subject to computer-derived information, the follow-
ing requirements must be met:
• the computer system must be validated to be fully secure against
the possibility of blood and blood components being released
that do not fulfil all test or donor selection criteria;
• the manual entry of critical data, such as laboratory test results,
must require independent verification by a second authorised
person;
• the computer system must block the release of all blood or blood
components considered not acceptable for release. There must
also be a means to block the release of any future donations from
the donor.
In the absence of a computerised system for component status control,
or in the event of computer system failure, the following requirements
must be met:
271
• the label of a blood component must identify the component

status and must clearly distinguish a released from a non-re-
leased (quarantined) component;
• records must demonstrate that before a component is released,
all current donor declaration forms, relevant medical records
and test results have been verified by an authorised person;
• before final component release, if blood or blood component(s)
have been prepared from a donor who has donated on previous
occasions, a comparison with previous records must be made to
ensure that current records accurately reflect the donor history;
• there must be a system of administrative and physical quaran-
tine for blood and blood components to ensure that they cannot
be released until all mandatory requirements have been satisfied.
In the event that the final component fails release due to a confirmed positive infection test result
for Hepatitis B virus, Hepatitis C virus or HIV 1/2 (Annex IV of Directive 2002/98/EC), a check must
be made to ensure that other components from the same donation and components prepared from
previous donations given by the donor are identified. There must be an immediate update of the
donor record (Directive 2005/62/EC Annex 6.6.3, 6.3.2 and 6.3.3)
In the event that a final component fails release due to a potential

impact on patient safety, then all other implicated components must
be identified and appropriate action must be taken. A check must be
made to ensure that (if relevant) other components from the same
donation(s) and components prepared from previous donations given
by the donor(s) are identified. The donor record must be updated
immediately to ensure (if appropriate) that the donor(s) cannot make
a further donation.
272
4. Storage and distribution

The quality system of the blood establishment must ensure that, for blood and blood components
intended for the manufacture of medicinal products, the storage and distribution requirements
comply with Directive 2003/94/EC (Directive 2005/62/EC Annex 7.1).
Procedures for storage and distribution must be validated to ensure blood and blood component
quality during the entire storage period and to exclude mix-ups of blood components. All
transportation and storage actions, including receipt and distribution, must be defined by written
procedures and specifications (Directive 2005/62/EC Annex 7.2).
Storage and distribution routines must take place in a safe and con-
trolled way in order to ensure component quality during the entire
storage period and to avoid any risk of identification error and mix-up
of blood components.
All transportation and storage actions, including receipt and distribu-
tion, must be defined by written procedures and specifications.
Storage conditions must be controlled, monitored and checked. Ap-
propriate alarms must be present and regularly checked, and these
checks must be recorded. Appropriate actions on alarms must be
defined.
Intermediate storage and transport must be carried out under defined
conditions to ensure that the specified requirements are met.
Prior to distribution, blood components must be visually inspected.
There must be a record identifying the person distributing the compo-
nents and the institution receiving them.
Autologous blood and blood components, as well as blood components collected and prepared for
specific purposes, must be stored separately (Directive 2005/62/EC Annex 7.3).
Storage areas must provide effective segregation of quarantined and

released materials or components. There must be a separate area for
storage of rejected components and materials.
273
Appropriate records of inventory and distribution must be kept (Directive 2005/62/EC Annex 7.4).
Packaging must maintain the integrity and storage temperature of blood or blood components
during distribution and transportation (Directive 2005/62/EC Annex 7.5).
Return of blood and blood components into inventory for subsequent re-issue can only be accepted
when all quality requirements and procedures laid down by the blood establishment to ensure
blood component integrity are fulfilled (Directive 2005/62/ EC Annex 7.6).
Blood components must not be returned to the blood establishment

for subsequent distribution, unless there is a procedure for return of
blood components that is regulated by a contract and that there is
documented evidence for each returned blood component that the
agreed storage conditions have been met. Before subsequent distri-
bution the records must identify that the blood component has been
inspected before reissue.
5. Irradiation of blood components

The irradiation process must ensure that no part of the component
receives a dose less than 25 Gray or more than 50 Gray. The expo-
sure time must be set to ensure that all blood and blood components
receive the specified recommended minimum dose, with no part
receiving more than the maximum recommended dose. Regular
dose-mapping of equipment must be undertaken. Exposure time must
be standardised for each irradiation source and revalidated at suitable
intervals.
Radiation indicators must be used as an aid to differentiating irra-
diated from non-irradiated blood and blood components. A defined
procedure must ensure the segregation of components that have not
been irradiated from those that have been irradiated.
Red cell components may be irradiated up to 28 days after collection.
Irradiated cells must be transfused as soon as possible, but no later
than 14 days after irradiation and, in any case, no later than 28 days
after collection. More stringent requirements are included in specific
component monographs (see Chapter 5).
274
6. Leucocyte depletion

Processes used for leucocyte depletion must be validated. The valida-
tion must be carried out by the blood establishment using the manu
facturer’s instructions and against the requirements for leucocyte
depletion and other quality aspects of the components (including
those for plasma for fractionation).
For quality control, an appropriate validated method must be used for
counting leucocytes.
7. Bacterial safety

A systematic programme to assure the bacterial safety of blood collec-
tion and processing procedures must be in place.
275
Chapter 5
Part A. Whole Blood components

1. Whole Blood, 280
2. Whole Blood, Leucocyte-Depleted, 283
Part B. Red cell components
1. Red Cells, 290
2. Red Cells, Buffy Coat Removed, 293
3. Red Cells, in Additive Solution, 297
4. Red Cells, Buffy Coat Removed, in Additive Solution, 300
5. Red Cells, Leucocyte-Depleted, 304
6. Red Cells, Leucocyte-Depleted in Additive Solution, 307
7. Red Cells, Apheresis, 311
8. Red Cells, Washed, 315
9. Red Cells, Cryopreserved, 318
Part C. Platelet components
1. Platelets, Recovered, Single Unit, 326
2. Platelets, Recovered, Pooled, 330
277
3. Platelets, Recovered, Pooled, Leucocyte-Depleted, 334

4. Platelets, Recovered, Pooled, in Additive Solution, 339
5. Platelets, Recovered, Pooled, Leucocyte-Depleted, in Additive
Solution, 343
6. Platelets, Pooled, Pathogen-reduced, 347
7. Platelets, Apheresis, 351
8. Platelets, Apheresis, Leucocyte-Depleted, 355
9. Platelets, Apheresis, in Additive Solution, 359
10. Platelets, Apheresis, Leucocyte-Depleted, in Additive
Solution, 363
11. Platelets, Apheresis, Pathogen-reduced, 367
12. Platelets, Cryopreserved, 371
Part D. Plasma components
1. Plasma, Fresh Frozen, 378
2. Plasma, Fresh Frozen, Pathogen Reduced, 382
3. Cryoprecipitate, 387
4. Cryoprecipitate, Pathogen Reduced, 391
5. Plasma, Fresh Frozen, Cryoprecipitate-Depleted, 396
Part E. White cell components
1. Granulocytes, Apheresis, 400
2. Granulocytes, Pooled, 404
278
Part A. Whole Blood components
279
1. Whole Blood

Definition and properties
Whole Blood is blood taken from a suitable donor using a sterile and
pyrogen-free anticoagulant and container. Whole Blood is a source
material for component preparation, which is its major use. Whole
Blood for transfusion is used without further processing.
Whole Blood for transfusion should not contain irregular antibodies of
clinical significance.
Preparation
By definition, no (post-donation) preparation is required to produce a
unit of Whole Blood.
Requirements and quality control

Table 5A-1 lists the requirements for whole blood for direct transfu-
sion. Additional testing might be required to comply with national
requirements (see also Chapter 9, Standards for screening for infec-
tious markers).
Table 5A-1
ABO, RhD Grouping All units

Anti-HIV 1 & 2 Negative by approved All units
screening test
HBsAg Negative by approved All units
screening test
Anti-HCV Negative by approved All units
screening test
280
Chapter 5 Component monographs
Volume a 450 mL ± 50 mL volume as determined by SPC

(excluding anticoagulant)
A non-standard donation should
be labelled accordingly
Haemoglobin a Minimum 45 g per unit as determined by SPC
Haemolysis at the end of storage a < 0.8 % of red cell mass as determined by SPC
a A minimum of 90 % of units tested should meet the required value.
Storage and transport

Whole Blood for transfusion must be kept at a controlled temperature,
i.e. between + 2 and + 6 °C. The storage time depends on the anti
coagulant/preservative solution used. For example, the storage time is
35 days if stored in CPDA-1. Validated transport systems must ensure
that at no time during a maximum transit time of 24 hours does the
temperature exceed + 10 °C.
Whole Blood for preparation of blood components may be kept up to
24 hours in conditions validated to maintain a temperature between
+ 20 °C and + 24 °C, which is a prerequisite for the production of
platelet preparations from Whole Blood.
Labelling
The labelling must comply with the relevant national legislation and
international agreements. The following information must be shown
on the label or contained in the component information leaflet, as
appropriate:
• the producer’s identification;
• the unique identity number;
• the name of the blood component;
• the ABO and RhD groups;
• blood group phenotypes other than ABO and RhD (optional);
281

• the date of expiry;
• the name of the anticoagulant solution;
• additional component information: irradiated, etc. (if appropri-
ate);
• the volume or weight of the blood component;
• the storage temperature;
• that the component must not be used for transfusion if there is
abnormal haemolysis or other deterioration;
• that the component must be administered through an approved
blood administration set.
Warnings
Compatibility of Whole Blood for transfusion with the intended recip-
ient must be verified by suitable pre-transfusion testing.
RhD-negative female recipients of child-bearing age or younger
should not be transfused with Whole Blood from RhD-positive
donors.
Micro-aggregates are formed on storage.
Whole Blood for transfusion is not recommended in cases of:
• anaemia without blood volume loss;
• plasma intolerance;
• intolerance due to allo-immunisation against leucocyte antigens.
Adverse reactions include:
• haemolytic transfusion reaction;
• non-haemolytic transfusion reaction (mainly chills, fever and
urticaria);
• anaphylaxis;
• allo-immunisation against red cell and HLA antigens;
282
• transfusion-related acute lung injury (TRALI);

• post-transfusion purpura;
• graft versus host disease (TA-GvHD);
• sepsis due to inadvertent bacterial contamination;
• viral transmission (hepatitis, HIV, etc.) is possible, despite
careful donor selection and screening procedures;
• syphilis can be transmitted if components are stored for less
than 96 hours at + 4 °C;
• protozoal transmission (e.g. malaria) may occur in rare in-
stances;
• transmission of other pathogens that are not tested for or recog-
nised;
• citrate toxicity in neonates and in patients with impaired liver
function;
• metabolic imbalance in massive transfusion (e.g. hyperkalae-
mia);
• transfusion-associated circulatory overload;
• iron overload.
2. Whole Blood, Leucocyte-Depleted

Whole Blood, Leucocyte-Depleted (LD) is a component derived from
Whole Blood by removing the leucocytes to a maximum residual
content.
Whole Blood, LD contains a minimum haemoglobin content of 43 g.
Whole Blood, LD normally contains less than 1.0 × 106 leucocytes.
283
Preparation
Generally a filtration technique is used to produce Whole Blood, LD.
Pre-storage leucocyte depletion within 48 hours after donation is the
standard.

Table 5A-2 lists the requirements. Additional testing may be required
to comply with national requirements (see also Chapter 9, Standards
for screening for infectious markers).
Table 5A-2

screening test
HbsAg Negative by approved All units
screening test
screening test
Volume a 450 ± 50 mL volume as determined by SPC
(excluding anticoagulant
A non-standard donation should
be labelled accordingly
Residual leucocytes content a < 1 × 106 per unit by count as determined by SPC
284

Whole Blood, LD must be kept at a controlled temperature between
+ 2 °C and + 6 °C. The storage time depends on the anticoagulant/
preservative solution used. For example, the storage time is 35 days in
CPDA-1.
Validated transport systems must ensure that at no time during
a maximum transit time of 24 hours did the temperature exceed
+ 10 °C.
Labelling
appropriate:
ate);
285
Warnings
Compatibility of Whole Blood, LD with the intended recipient must be
verified by suitable pre-transfusion testing.
should not be transfused with red cells from RhD-positive donors.
Whole Blood, LD is not recommended in cases of:
• anaemia without blood volume loss;
• plasma intolerance.
urticaria);
• anaphylaxis;
stances;
nised;
function;
286

mia);
• circulatory overload;
• iron overload.
287
Part B. Red cell components
289
1. Red Cells

Red Cells is a component obtained by removal of a major part of the
plasma from Whole Blood.
Red Cells also contain the greater part of the Whole Blood leucocytes
(about 2.5 to 3.0 × 109 cells) and a variable content of platelets, depend-
ing on the method of centrifugation.
Preparation
For the preparation of Red Cells, plasma is removed from Whole Blood
by centrifugation.

Table 5B-1 lists the requirements. Additional testing may be required
Table 5B-1

screening test
screening test
screening test
Volume a 280 mL ± 50 mL as determined by SPC
Haematocrit a 0.65 – 0.75 as determined by SPC
290
Haemoglobina Minimum 45 g per unit as determined by SPC


Red Cells must be kept at a controlled temperature between + 2 °C and
+ 6 °C. The storage time depends on the anticoagulant/preservative
solution used. For example, the storage time is 35 days in CPDA-1.
Validated transport systems must ensure that at no time during a
maximum transit time of 24 hours did the temperature exceed + 10 °C.
Labelling
appropriate:
ate);
291

Warnings
Compatibility of Red Cells with the intended recipient must be verified
by suitable pre-transfusion testing.
should not be transfused with Red Cells from RhD-positive donors.
Red Cells are not recommended in cases of:
• intolerance due to allo-immunisation against leucocyte antigens;
• exchange transfusion in newborns, unless supplementary plasma
is added.
urticaria);
• anaphylaxis;
292

stances;
nised;
function;
mia);
• iron overload.
2. Red Cells, Buffy Coat Removed

Red Cells, Buffy Coat Removed (BCR) is a red cell component prepared
by the removal of a major part of the plasma and the buffy coat layer
from Whole Blood.
Red Cells, BCR contains a minimum haemoglobin content of 43 g. The
haematocrit is 0.65 to 0.75.
Red Cells, BCR normally contains less than 1.2 × 109 leucocytes
and a variable content of platelets, depending on the method of
centrifugation.
Preparation
Red Cells, BCR is derived from Whole Blood by centrifugation. The
plasma and 20 to 60 mL of the buffy coat layer are removed from
Whole Blood after centrifugation, resulting in the loss of 10 to 30 mL
of the red cells from the donated Whole Blood. Sufficient plasma is
retained to give a haematocrit of 0.65-0.75.
293

Table 5B-2

screening test
screening test
screening test
Volume a 250mL ± 50 mL as determined by SPC
Haematocrit a 0.65 – 0.75 as determined by SPC
Residual leucocyte content a < 1.2 × 109 per unit as determined by SPC

Red Cells, BCR must be kept at a controlled temperature between
+ 2 °C and + 6 °C. The storage time depends on the anticoagulant/
preservative solution used. For example, the storage time is 35 days in
CPDA-1.
+ 10 °C.
294
Labelling
appropriate:
ate);
Warnings
Compatibility of Red Cells, BCR with the intended recipient must be
Red Cells, BCR is not recommended in cases of:
• plasma intolerance (may not concern units with a low plasma
content, unless IgA incompatibility is present);
295
• exchange transfusions in newborns, unless supplementary

plasma is added.
urticaria);
• anaphylaxis;
stances;
nised;
function;
mia);
• iron overload.
296
3. Red Cells, in Additive Solution

Red Cells, in Additive Solution (AS) is a red cell component prepared
by the removal of the plasma from Whole Blood with subsequent addi-
tion of an appropriate additive solution.
Red Cells, AS contains a minimum haemoglobin content of 45 g. The
haematocrit is 0.50-0.70.
Red Cells, AS also contains the greater part of the Whole Blood leuco-
cytes (about 2.5 to 3.0 × 109 cells) and a variable content of platelets,
depending on the method of centrifugation.
Preparation
Whole Blood is collected, using CPD as the anticoagulant solution.
After centrifugation of Whole Blood, plasma is removed and the addi-
tive solution is added immediately to red cells and mixed carefully.

Table 5B-3

screening test
screening test
screening test
297
Volume a To be defined for the system used as determined by SPC

Haematocrit a 0.50-0.70 as determined by SPC

Red Cells, AS must be kept at a controlled temperature between + 2
and + 6 °C during storage. Depending on the anticoagulant/additive
system, the storage time may be extended up to the approved limit of
the additive solution system.
+ 10 °C.
Labelling
appropriate:
298
• the name and volume of the additive solution;

ate);
Warnings
Compatibility of Red Cells, AS with the intended recipient must be
should not be transfused with Red Cells, AS from RhD-positive
donors.
Red Cells, AS is not recommended in cases of:
• intolerance due to allo-immunisation against leucocyte antigens;
• exchange transfusion in newborns, unless used within 5 days
of donation and only if the additive solution is replaced by fresh
frozen plasma on the day of use.
urticaria);
• anaphylaxis;
299

stances;
nised;
function;
mia);
• iron overload.
4. Red Cells, Buffy Coat Removed, in Additive Solution

Red Cells, Buffy Coat Removed, in Additive Solution (BCR-AS) is a red
cell component prepared by the removal of a major part of the plasma
and the buffy coat layer from Whole Blood, with subsequent addition
of an appropriate nutrient solution.
Red Cells, BCR-AS contains a minimum haemoglobin content of 43 g.
The haematocrit is 0.50 to 0.70.
Red Cells, BCR-AS contains less than 1.2 × 109 leucocytes and a varia-
ble platelet content, depending on the method of centrifugation.
300
Preparation
Red Cells, BCR-AS is derived from Whole Blood by centrifugation. For
preparation, the plasma and 20 to 60 mL of the buffy coat layer are
removed, resulting in the loss of 10 to 30 mL of the red cells from the
donated Whole Blood. The additive solution is immediately added to
the red cells and carefully mixed.

Table 5B-4

screening test
screening test
screening test
Residual leucocyte content a < 1.2 × 109 per unit as determined by SPC
301

Red Cells, BCR-AS must be kept at a controlled temperature between
+ 2 and + 6 °C during storage. Depending on the anticoagulant/addi-
tive system, storage time may be extended up to the approved limit of
+ 10 °C.
Labelling
appropriate:
ate);
302

Warnings
Compatibility of Red Cells, BCR-AS with the intended recipient must
be verified by suitable pre-transfusion testing.
Red Cells, BCR-AS is not recommended in cases of:
• intolerance due to allo-immunisation against leucocyte antigens.
urticaria);
• anaphylaxis;
• syphilis can be transmitted if component is stored for less than
96 hours at + 4 °C;
stances;
nised;
303

function;
mia);
• iron overload.
5. Red Cells, Leucocyte-Depleted

Red Cells, Leucocyte-Depleted (LD) is a red cell component derived
from Whole Blood donation, Red Cells or Red Cells, BCR by removing
the leucocytes.
Red Cells, LD contains a minimum haemoglobin content of 40 g. The
haematocrit is 0.65-0.75.
Red Cells, LD contains less than 1.0 × 106 leucocytes.
Preparation
Generally a filtration technique is used to produce Red Cells, LD. Leu-
cocyte depletion within 48 hours after donation is the standard.
Red Cells, LD can be produced:
• by leucocyte filtration of Whole Blood, with subsequent centrifu-
gation and removal of the plasma;
• by leucocyte filtration of a red cell component.

304
Table 5B-5

screening test
screening test
screening test
Residual leucocyte content a < 1 × 106 per unit as determined by SPC

Red Cells, LD must be kept at a controlled temperature between + 2
+ 10 °C.
Labelling
appropriate:
305

• the name and volume of the additive solution (if appropriate);
ate);
Warnings
Compatibility of Red Cells, LD with the intended recipient must be
Red Cells, LD is not recommended in the case of:
Potential adverse reactions include:
306
• anaphylaxis;
urticaria);
• allo-immunisation against red cell and HLA (very rarely) anti-
gens;
stances;
nised;
function;
mia);
• iron overload.
6. Red Cells, Leucocyte-Depleted in Additive Solution

Red Cells, Leucocyte depleted in Additive Solution (LD-AS) is a red cell
component derived from Whole Blood donation, from Red Cells, AS or
Red Cells, BCR-AS by removing the leucocytes to a maximum residual
content.
307
Red Cells, LD-AS contains a minimum haemoglobin content of 40 g.

The haematocrit is 0.50 to 0.70.
Red Cells, LD-AS contains less than 1.0 × 106 leucocytes.
Preparation
Generally, a filtration technique is used to produce Red Cells, LD-AS.
Leucocyte depletion within 48 hours after donation is the standard.
Red Cells, LD-AS can be produced:
• by leucocyte filtration of Whole Blood, with subsequent centrifu-
gation and removal of the plasma and immediate addition of the
additive solution, followed by careful mixing;
• by leucocyte filtration of Red Cells, AS or Red Cells, BCR-AS.

Table 5B-6

screening test
screening test
screening test
308


Red Cells, LD-AS must be kept at a controlled temperature between
+ 2 and + 6 °C during storage. Depending on the anticoagulant/addi-
tive system, the storage time may be extended up to the approved limit
of the additive solution system.
+ 10 °C.
Labelling
appropriate:
309

ate);
Warnings
Compatibility of Red Cells, LD-AS with the intended recipient must be
Red Cells, LD-AS is not recommended in the case of:
• plasma intolerance (may not apply to units with a low plasma
content).
urticaria);
• anaphylaxis;
gens;
310

stances;
nised;
function;
mia);
• iron overload.
7. Red Cells, Apheresis

Red Cells, Apheresis (Aph) is a red cell component obtained by aphere-
sis of a single donor using automated cell-separation equipment.
Red Cells, Aph contains a minimum haemoglobin content of 40 g. The
haematocrit is 0.65 to 0.75 (0.50 to 0.70 if an additive solution is used).
The leucocyte content of Red Cells, Aph can vary. When leucocyte- de-
pleted, Red Cells, Aph normally contains less than 1.0 × 106 leucocytes.
Preparation
For preparation of Red Cells, Aph, Whole Blood is removed by an ap-
propriate apheresis machine from the donor and anti-coagulated with
a citrate-containing solution. The plasma is returned to the donor.
Either one or two units of Red Cells, Aph can be collected during a
single procedure.
311
Red Cells, Aph can be used either unmodified or can undergo further
processing, e.g. leucocyte depletion or addition of an additive solution.

Table 5B-7

screening test
screening test
screening test
Haematocrit a (if additive solution) 0.50-0.70 as determined by SPC

Red Cells, Aph must be kept at a controlled temperature between + 2
312
Red Cells, Aph to be stored must be collected and prepared in a func-

tionally closed system. If prepared or filtered by methods under an
open system, the storage time is limited to 24 hours at + 2 and + 6 °C.
+ 10 °C.
Labelling
appropriate:
• the unique identity number. If 2 or more units are collected from
the donor in one session, each component must have a unique
component identity number;
• the name and volume of the additive solution (if appropriate);
ate);
313

Warnings
Compatibility of Red Cells, Aph with the intended recipient must be
Red Cells, Aph is not recommended in the case of:
• plasma intolerance (may not apply to units with a low plasma
content unless IgA incompatibility is present).
• anaphylaxis;
urticaria);
• allo-immunisation against red cell and HLA (very rarely after
leucocyte-depletion) antigens;
stances;
314

nised;
function;
mia);
• iron overload.
8. Red Cells, Washed

Red Cells, Washed (W) is derived from secondary processing of a red
cell component or Whole Blood involving sequential washing and
re-suspension of red cells in an additive solution.
Most of the plasma, leucocytes and platelets are removed. The amount
of residual plasma depends upon the washing protocol. The haemat-
ocrit can be varied according to clinical need.
Preparation
After centrifugation of the primary component and removal of the
plasma or additive solution (and, if applicable, the buffy coat layer),
the red cells are washed by sequential addition and removal of an
additive solution. Centrifugation must be performed at a controlled
temperature.

315
Table 5B-8

screening test
screening test
screening test
Protein content of final < 0.5 g per unit as determined by SPC
supernatant a

Red Cells, W must be kept at a controlled temperature between + 2 °C
and + 6 °C during storage.
When an open system is used for washing, the storage time should be
as short as possible after washing and must never exceed 24 hours.
If a closed system and a suitable additive solution are used, storage
times may be prolonged, subject to validation.
Validated transport systems must ensure that at no time does the tem-
perature exceed + 10 °C.
316
Labelling
appropriate:
• the date and time of expiry;
• the name and volume of the washing solution;
ate);
Warnings
Compatibility of Red Cells, W with the intended recipient must be
317

urticaria);
• anaphylaxis;
gens;
stances;
nised;
mia);
• iron overload.
9. Red Cells, Cryopreserved

Red Cells, Cryopreserved (Cryo) is a red cell component derived by
secondary processing of a red cell component or Whole Blood. Red
cells are frozen (preferably within 7 days of collection) using a cryo-
protectant and stored at – 60 °C to – 80 °C or below, depending on the
method of cryopreservation.
318
A reconstituted unit of Red Cells, Cryo contains low amounts of

protein, leucocytes and platelets. Each unit of Red Cells, Cryo contains
a minimum haemoglobin content of 36 g. The haematocrit is 0.35-0.70.
Preparation
Two methods are generally used for the preparation of Red Cells,
Cryo. One is a high glycerol, the other a low glycerol technique. Both
methods require a washing/de-glycerolisation procedure.

Table 5B-9

screening test
screening test
screening test
Volume a > 185 mL as determined by SPC
Haemoglobin (supernatant) b < 0.2 g per unit as determined by SPC
a If different from ‘All units’, the frequency of control is an indication of minimal frequency but, where SPC is used
to minimise the risk of process deviation, this frequency may be adjusted accordingly.
b Final suspending solution.
c These requirements are deemed to have been met if 90 % of the tested units fall within the values indicated.
319
Osmolarity c Maximum 20 mOsm/L above

osmolarity of resupending fluid
Sterility a Sterile as determined by SPC
a If different from ‘All units’, the frequency of control is an indication of minimal frequency but, where SPC is used
to minimise the risk of process deviation, this frequency may be adjusted accordingly.
b Final suspending solution.
c These requirements are deemed to have been met if 90 % of the tested units fall within the values indicated.
Since cryopreservation allows prolonged storage, serum and/or

plasma samples obtained at collection must also be stored to enable
future testing for newly discovered markers of transmissible diseases
when components are thawed for use.

Red Cells, Cryo in frozen state
Red Cells, Cryo in the frozen state must be constantly maintained
between:
• – 60 °C to – 80 °C if stored in an electric freezer and when a high
glycerol method is used;
• – 140 °C to – 150 °C if stored in vapour-phase liquid nitrogen and
when a low glycerol method is used.
Red Cells, Cryo in the frozen state can be stored for 30 years.
Thawed reconstituted Red Cells, Cryo

Thawed and reconstituted Red Cells, Cryo must be stored between + 2
and + 6 °C. The storage time must be validated but should be as short
as possible after washing, and must never exceed 24 hours when an
open system is used.
If transport in the frozen state is unavoidable, storage conditions must
be maintained. Transport of thawed, reconstituted red cells is limited
320
by the short storage time. Storage conditions must be maintained

during transport.
Labelling
international agreements.
The following information must be traceable for each frozen unit:
• the name and volume of the cryoprotective solution;
• additional component information (if appropriate);
• the storage temperature.
Labelling of reconstituted components

After thawing and reconstitution (washing), the date of expiry must be
changed to the date (and time) of expiry. Also, the name and volume
of the cryoprotective solution must be changed to the name and
volume of the additive solution (if any). The following information
must be shown on the label of the reconstituted component or must
be contained in the component information leaflet, as appropriate:
321

• additional component information (if appropriate);
Warnings
Compatibility of Red Cells, Cryo with the intended recipient must be
When Red Cells, Cryo are processed in an open system, the risk of
bacterial contamination is increased and therefore extra vigilance is
required during transfusion.
• anaphylaxis;
gens;
stances;
322

nised;
• iron overload.
323
Part C. Platelet components
325
1. Platelets, Recovered, Single Unit

Platelets, Recovered, Single Unit (Rec, SU) is a platelet component
derived from a single Whole Blood donation. It contains the majority
of the original Whole Blood platelet content, suspended in plasma.
Platelets, Rec, SU contains more than 60 × 109 platelets.
Platelets, Rec, SU contains up to 0.2 × 109 leucocytes if prepared by the
platelet-rich plasma method, and up to 0.05 × 109 leucocytes if pre-
pared by the buffy coat method.
Platelets, Rec, SU can be used for neonatal and infant transfusion. In
order to achieve a ‘standard adult dose’, 4 to 6 units of Platelets, Rec,
SU have to be transfused.
Preparation
Preparation from platelet-rich plasma (PRP)
A unit of Whole Blood, stored for up to 24 hours in conditions vali-
dated to maintain the temperature between + 20 °C and + 24 °C, is
centrifuged so that an optimal number of platelets remain in the
plasma and the number of leucocytes and red cells are reduced to a
defined level. Platelets from PRP are sedimented by hard-spin cen-
trifugation; the supernatant platelet-poor plasma is removed, leaving
50-70 mL of it with the platelets. The platelets are allowed to disaggre-
gate and are then resuspended in the remnant plasma.
Preparation from buffy coat

A Whole Blood unit, stored for up to 24 hours in conditions validated
to maintain the temperature between + 20 and + 24 °C, is centrifuged
so that platelets are primarily sedimented to the buffy coat layer to-
gether with the leucocytes. The buffy coat is separated and processed
further to obtain a platelet concentrate. Single buffy coats diluted with
plasma are centrifuged so that the platelets remain in the supernatant,
but red cells and leucocytes are sedimented to the bottom of the bag.
326

Table 5C-1 lists the requirements. Additional testing may be required
to comply with national requirements (see also Chapter 9, Chapter 9,
Standards for screening for infectious markers).
Demonstration of the swirling phenomenon, which is based on light
scattering by platelets in motion and of normal morphology, must be
carried out prior to the issue and transfusion of this component. This
is best done as soon as possible before transfusion.
Table 5C-1

screening test
screening test
screening test
Volume a > 40 mL per 60 × 109 of platelets as determined by SPC
Platelet content per final unit a > 60 × 109 as determined by SPC
Residual leucocytes per final unit a as determined by SPC
a. prepared from buffy-coat
b. prepared from PRP a. < 0.05 × 109
b. < 0.2 × 109
pH measured (+ 22 °C) at the end > 6.4 as determined by SPC
of the recommended shelf-life b

b All tested units must comply. Measurement of the pH in a closed system is preferable to prevent CO2 escape.
Measurement may be made at another temperature and then corrected.
327

Platelets, Rec, SU must be stored under conditions which guarantee
that their viability and haemostatic activities are optimally preserved.
The storage temperature must be between + 20 and + 24 °C, under
constant agitation.
The maximum storage time for Platelets, Rec, SU is 5 days. Storage
may be extended to 7 days, in conjunction with appropriate detection
or reduction of bacterial contamination.
During transportation, the temperature of Platelets, Rec, SU must be
kept as close as possible to the recommended storage temperature and,
upon receipt, unless intended for immediate therapeutic use, they
must be transferred to storage under the recommended conditions.
Labelling
appropriate:
• the unique identity number; if platelets are pooled the original
donations must be traceable;
ate);
• the volume of the blood component;
• the number of platelets (average or actual, as appropriate);
328

Warnings
should preferably not be transfused with platelets from RhD-positive
donors. If this is unavoidable, administration of anti-D immunoglob-
ulin should be considered.
Platelets, Rec, SU are not recommended in cases of:
• haemolytic reaction due to transfusion of ABO-incompatible
plasma in the component;
urticaria);
• anaphylaxis;
• allo-immunisation against HLA and red cell antigens;
• allo-immunisation against HPA antigens;
• syphilis transmission;
stances;
329

nised;
function;
• transfusion-associated circulatory overload.
2. Platelets, Recovered, Pooled

Platelets, Recovered, Pooled (Rec, Pool) is a platelet component derived
from 4 to 6 fresh Whole Blood donations, which contains the major-
ity of the original platelet content in a therapeutically effective dose,
suspended in plasma.
Platelets, Rec, Pool contain a minimum content of 2 × 1011 platelets.
Platelets, Rec, Pool contain a maximum of 1 × 109 leucocytes.
Preparation
Platelets, Rec, Pool can be produced:
• directly from Whole Blood-derived buffy coats, which is the
method of choice;
• by secondary processing, after pooling of 4-6 units of Platelets,
Rec, SU.

A Whole Blood unit, stored in conditions validated to maintain the
temperature between + 20 and + 24 °C, for up to 24 hours, is centri-
fuged so that the platelets are primarily sedimented to the buffy coat
layer, together with the leucocytes. The buffy coat is separated and
further processed so that, usually, 4 to 6 blood group-compatible buffy
coats are pooled in a sterile manner and re-suspended with plasma.
After careful mixing, the buffy coat pool is centrifuged (soft- spin)
so that the platelets remain in the supernatant, but the red cells and
leucocytes are effectively sedimented to the bottom of the bag. The
330
platelet-containing supernatant is immediately transferred into a suit-

able platelet storage bag in a sterile manner.
Preparation from Platelets, Recovered, Single Units (PRP method)

Four to six units of Platelets, Rec, SU prepared by the PRP method are
connected and pooled. If storage for longer than 6 hours is intended,
pooling must be undertaken in a sterile manner.

Table 5C-2

screening test
screening test
screening test
Residual leucocyte content b < 1 × 109 per final unit as determined by SPC
pH measured (+22°C) at the end > 6.4 as determined by SPC
of the recommended shelf-life c

b These requirements are deemed to have been met if 90 % of the tested units fall within the values indicated.
c All tested units must comply. Measurement of the pH in a closed system is preferable to prevent CO2 escape.
331

scattering by platelets in motion and of normal morphology, may
be carried out either as a separate quality-control procedure or as a
routine part of the issue and transfusion of this component. This is
best done just before transfusion.

Platelets, Rec, Pool must be stored under conditions which guarantee
The storage temperature must be between + 20 and + 24 °C, under
constant agitation.
The maximum storage time for Platelets, Rec, Pool is 5 days. Storage
may be extended to 7 days, in conjunction with appropriate detection
or reduction of bacterial contamination.
When an open system has been used for the preparation of Platelets,
Rec, Pool, the storage time must not exceed 6 hours.
During transportation, the temperature of Platelets, Rec, Pool must
be kept as close as possible to the recommended storage temperature
and, upon receipt, unless intended for immediate therapeutic use, the
component must be transferred to storage under the recommended
conditions.
Labelling
appropriate:
• the unique identity number; if platelets are pooled the original
332

• additional component information: irradiated, number of dona-
tions combined to make the pool, etc. (if appropriate);
Warnings
donors. If unavoidable, administration of anti-D immunoglobulin
should be considered.
Platelets, Rec, Pool are not recommended in the case of:
• anaphylaxis;
urticaria);
333

stances;
nised;
function.
3. Platelets, Recovered, Pooled, Leucocyte-Depleted

Platelets, Recovered, Pooled, Leucocyte-Depleted (Rec, Pool, LD) is a
leucocyte-depleted platelet component derived from 4 to 6 donations
of fresh Whole Blood and which contains most of the original platelet
content in a therapeutically effective dose suspended in plasma.
Platelets, Rec, Pool, LD contains a minimum content of 2 × 1011
platelets.
Platelets, Rec, Pool, LD contains a maximum leucocyte content of
1.0 × 106 cells.
Preparation
Platelets, Rec, Pool, LD is leucocyte-depleted by filtration. Pre-storage
leucocyte filtration is recommended in preference to filtration during
or shortly before transfusion.
Platelets, Rec, Pool, LD can be produced:
• directly from Whole Blood-derived buffy coats, which is the
method of choice;
334
• by secondary processing, after pooling 4-6 units of Platelets, Rec,

SU.

A Whole Blood unit, stored in conditions validated to maintain a tem-
perature between + 20 and + 24 °C for up to 24 hours, is centrifuged
so that the platelets are primarily sedimented to the buffy coat layer,
together with the leucocytes. The buffy coat is separated and further
processed so that, usually, 4 to 6 blood group-compatible buffy coats
are pooled in a sterile manner and re-suspended with plasma. After
careful mixing, the buffy coat pool is centrifuged (soft-spin) so that
the platelets remain in the supernatant, but the red cells and leuco-
cytes are sedimented to the bottom of the bag. The platelet-containing
supernatant is immediately filtered and transferred into a suitable
platelet storage bag in a sterile manner.
Preparation from Platelets, Recovered, Single Units (PRP method)

Four to six units of Platelets, Rec, SU, prepared by the PRP method,
are connected, pooled, immediately filtered and transferred into a
suitable platelet storage bag. If storage for longer than 6 hours is in-
tended, preparation must be undertaken in a sterile manner.

Table 5C-3 lists the requirements for the final component. Additional
testing may be required to comply with national requirements (see
also Chapter 9, Standards for screening for infectious markers).
335
Table 5C-3

screening test
screening test
screening test
Residual leucocytes per final unit a < 1 × 106 as determined by SPC
of the recommended shelf-life b

b All tested units must comply. Measurement of the pH in a closed system is preferable to prevent CO2 escape.

Platelets, Rec, Pool, LD must be stored under conditions which
guarantee that its viability and haemostatic activities are optimally
preserved.
The storage temperature must be + 20 and + 24 °C, under constant
agitation.
The maximum storage time for Platelets, Rec, Pool, LD is 5 days.
Storage may be extended to 7 days, in conjunction with detection or
reduction of bacterial contamination.
When an open system has been used for the preparation of Platelets,
Rec, Pool, LD, the storage time must not exceed 6 hours.
336
During transportation, the temperature of Platelets, Rec, Pool, LD

must be kept as close as possible to the recommended storage tem-
perature and, on receipt, unless intended for immediate therapeutic
use, the component must be transferred to storage under the recom-
mended conditions.
Labelling
appropriate:
• the unique identity number. If platelets are pooled, the original
Warnings
337

Platelets, Rec, Pool, LD are not recommended in the case of:
• anaphylaxis;
urticaria);
• allo-immunisation against HLA (very rarely after leucocyte-
depletion) and red cell antigens;
stances;
nised;
function.
338
4. Platelets, Recovered, Pooled, in Additive Solution

Platelets, Recovered, Pooled, in Additive Solution (Rec, Pool, AS) is
a platelet component derived from 4 to 6 donations of fresh Whole
Blood which contains most of the original platelet content in a thera-
peutically effective dose suspended in a mixture of plasma (30-40 %)
and an additive solution (60-70 %).
Platelets, Rec, Pool, AS contains a minimum content of 2 × 1011
platelets.
Platelets, Rec, Pool, AS contains a maximum of 0.3 × 109 leucocytes.
Preparation
Platelets, Rec, Pool, AS is prepared from Whole Blood-derived buffy
coats.
A Whole Blood unit, stored in conditions validated to maintain a tem-
perature between + 20 and + 24 °C for up to 24 hours, is centrifuged
so that the platelets are primarily sedimented to the buffy coat layer,
together with the leucocytes. The buffy coat is separated and further
are pooled in a sterile manner and suspended in an additive solution.
After careful mixing, the buffy coat pool is centrifuged (soft-spin) so
that the platelets remain in the supernatant, but the red cells and leu-
cocytes are effectively sedimented to the bottom of the bag.
The platelet-containing supernatant is immediately transferred into a
suitable platelet storage bag in a sterile manner.

339
Table 5C-4

screening test
screening test
screening test
Residual leucocyte content b < 0.3 × 109 per final unit as determined by SPC

c Measurement of the pH in a closed system is preferable to prevent CO2 escape. Measurement may be made at
another temperature and then corrected.

be carried out either as a separate quality control procedure or as a

Platelets, Rec, Pool, AS must be stored under conditions which guaran-
tee that its viability and haemostatic activities are optimally preserved.
The storage temperature must be + 20 and + 24 °C, under constant
agitation.
The maximum storage time for Platelets, Rec, Pool, AS is 5 days.
340
reduction of bacterial contamination and depending on the type of

additive solution. When an open system has been used for preparation
of Platelets, Rec, Pool, AS, the storage time must not exceed 6 hours.
During transportation, the temperature of Platelets, Rec, Pool, AS
must be kept as close as possible to the recommended storage temper-
ature and, on receipt and unless intended for immediate therapeutic
mended conditions.
Labelling
appropriate:
341
Warnings
Platelets, Rec, Pool, AS is not recommended in the case of:
• haemolytic reaction due to anti-A, -B in case of incompatible
transfusions;
• anaphylaxis;
urticaria);
stances;
nised;
function.
342
5. Platelets, Recovered, Pooled, Leucocyte-Depleted, in

Additive Solution
Platelets, Recovered, Pooled, Leucocyte-Depleted, in Additive Solution
(Rec, Pool, LD-AS) is a leucocyte-depleted platelet component derived
from 4 to 6 fresh Whole Blood donations, which contains the major-
ity of the original platelet content in a therapeutically effective dose,
suspended in a mixture of plasma (30-40 %) and an additive solution
(60-70 %).
Platelets, Rec, Pool, LD-AS contains a minimum content of 2 × 1011
platelets.
Platelets, Rec, Pool, LD-AS contains a maximum of 1.0 × 106
leucocytes.
Preparation
Platelets, Rec, Pool, LD-AS is prepared from Whole Blood-derived
buffy coats and is then leucocyte-depleted by filtration. Pre-storage
leucocyte filtration within 6 hours of preparation is recommended.
A Whole Blood unit, stored in conditions validated to maintain a
temperature between + 20 and + 24 °C for up to 24 hours, is centri-
fuged so that the platelets are primarily sedimented to the buffy coat
layer, together with leucocytes. The buffy coat is separated and further
are pooled in a sterile manner and suspended in an additive solution.
After careful mixing, the buffy coat pool is centrifuged (soft-spin)
so that the platelets remain in the supernatant, but the red cells and
leucocytes are effectively sedimented to the bottom of the bag. The
platelet-containing supernatant is immediately filtered and transferred
into a suitable platelet storage bag in a sterile manner.
343

best done as soon as possible before transfusion.
Table 5C-5

screening test
screening test
screening test

344

Platelets, Rec, Pool, LD-AS must be stored under conditions which
guarantee that their viability and haemostatic activities are optimally
preserved.
The storage temperature must be + 20 and + 24 °C under constant
agitation.
The maximum storage time for Platelets, Rec, Pool, LD-AS is 5 days.
reduction of bacterial contamination and depending on the type of
additive solution.
During transportation, the temperature of Platelets, Rec, Pool, LD-AS
must be kept as close as possible to the recommended storage tem-
perature and, on receipt, unless intended for immediate therapeutic
mended conditions.
Labelling
appropriate:
345

Warnings
Platelets, Rec, Pool, LD, AS is not recommended in the case of:
transfusions;
• anaphylaxis;
• non-haemolytic transfusion reactions (mainly chills, fever and
urticaria). The incidence is reduced by the use of pre-storage
leucocyte-depleted platelets;
346

stances;
nised;
function.
6. Platelets, Pooled, Pathogen-reduced

Platelets, Pooled, Pathogen Reduced (Pool, PR) is a leucocyte-depleted
platelet component derived from 4 to 6 fresh Whole Blood dona-
tions, which contains the majority of the original platelet content in
a therapeutically effective dose suspended in plasma or a mixture of
plasma (30-40 %) and an additive solution (60-70 %). Subsequently, the
component is subjected to treatment with an approved and validated
pathogen reduction technology (PRT) before storage.
Platelets, Pool, PR contains a minimum content of 2 × 1011 platelets.
Platelets, Pool, PR contains a maximum leucocyte content of 1.0 × 106
cells.
The PRT typically reduces the risk of infection with enveloped viruses
(e.g. HBV, HCV, HIV) and with most bacteria (with the exception of
bacterial spores) by at least one-thousand-fold.
Depending on the procedure, some PRT have been shown to inacti-
vate lymphocytes and, if this is the case, irradiation to prevent trans-
fusion-associated TA-GvHD is not required.
347
Preparation
Platelets, Pool, PR is prepared by pooling several Whole Blood dona-
tions as described for Platelets, Recovered, Pooled, Leucocyte- Depleted
and Platelets, Recovered, Pooled, Leucocyte-Depleted, in Additive
Solution.
The PRT is undertaken according to manufacturers’ instructions.

The parameters listed in Table 5C-6 must be checked with the given
frequency. A technical procedure must be in place to ensure that the
illumination of the PRT has been performed correctly. Additional
testing might be necessary to comply with national requirements (see
Chapter 9, Standards for screening for infectious markers).
Table 5C-6

screening test
screening test
screening test
348


Platelets, Pool, PR must be stored under conditions which guarantee
Storage temperature must be between + 20 °C to + 24 °C under con-
stant agitation.
The maximum storage time for Platelets, Pool, PR may be extended to
7 days depending on the PRT and on the type of additive solution.
During transportation the temperature of Platelets, Pool, PR must be
kept as close as possible to recommended storage temperature and, on
receipt, unless intended for immediate therapeutic use, they should be
transferred to storage under recommended conditions.
Labelling
The labelling must comply with the relevant national legislation
and international agreements. The following information must be
shown on the label or contained in the product information leaflet, as
appropriate:
• the unique identity number (the original donations contributing
to the pool must be traceable);
349
• the name of the blood component ;

• the name of the PRT used;
• the ABO and RhD group;
• additional component information: leucocyte-depleted, number
of donations combined to make the pool;
• the temperature of storage;
Warnings
RhD negative female recipients of child-bearing age or younger should
preferably not be transfused with platelets from RhD positive donors.
If unavoidable, administration of anti-D immunoglobulin should be
considered.
Platelets, Pool, PR is not recommended:
• in a patient with intolerance to plasma proteins;
• when prepared by amotosalen treatment in neonates undergoing
phototherapy with devices that emit a peak energy wavelength
less than 425 nm, and/or have a lower bound of the emission
bandwidth < 375 nm;
• in a patient with known allergy to the compounds used for, or
generated by, the PRT.
Adverse effects include:
350
• transfusion associated circulatory overload;

• haemolytic reactions due to anti-A, -B in case of incompatible
transfusions;
• non-haemolytic transfusion reactions may occur (mainly chills,
fever and urticaria). The incidence is reduced by the use of
pre-storage leucocyte-depleted platelets;
• transfusion related acute lung injury (TRALI);
• viral transmission and bacterial contamination (other than bac-
terial spores) is highly unlikely. Transmission of other pathogens
that are not sensitive to PRT is possible;
• citrate toxicity in patients with impaired liver function;
• anaphylaxis and allergic reactions (including allergy to the com-
pounds used for, or generated by, PRT).
7. Platelets, Apheresis

Platelets, Apheresis (Aph) is a component obtained by platelet aphere-
sis of a single donor using automated cell separation equipment, which
contains platelets in a therapeutically effective dose suspended in
plasma.
Platelets, Aph contains a minimum content of 2 × 1011 platelets.
Platelets, Aph contains a maximum leucocyte content of 0.3 × 109 cells.
Preparation
For preparation of Platelets, Aph, Whole Blood is removed from the
donor by the apheresis machine, anti-coagulated with a citrate solu-
tion and then the platelets are harvested.
351
For use in neonates and infants, Platelets, Aph can be divided into
satellite units under sterile conditions.

Table 5C-7

screening test
screening test
screening test
Platelet content a Standard unit: as determined by SPC
minimum 2 × 1011 per unit
For use in neonates or infants:
minimum 0.5 × 1011 per unit
Residual leucocyte content b < 0.3 × 109 per unit as determined by SPC


352
routine part of the issuance and transfusion of this component. This is


Platelets, Aph must be stored under conditions which guarantee that
their viability and haemostatic activities are optimally preserved.
The storage temperature must be between + 20 to + 24 °C, under con-
stant agitation.
Platelets, Aph to be stored for more than 6 hours must be collected
and prepared in a functionally closed system. The maximum storage
time for Platelets, Aph is 5 days. Storage may be extended to 7 days, in
conjunction with detection or reduction of bacterial contamination.
During transportation, the temperature of Platelets, Aph must be kept
as close as possible to the recommended storage temperature and, on
receipt, unless intended for immediate therapeutic use, the component
must be transferred to storage under the recommended conditions.
Labelling
appropriate:
• the unique identity number. If two or more units are collected
from the donor in one session, each component must have a
unique component identity number;
353

ate);
• the relevant HLA and/or HPA type, if determined;
Warnings
RhD-negative female recipients of child- bearing age or younger
Platelets, Aph is not recommended in the case of:
• anaphylaxis;
urticaria);
354

stances;
nised;
function.
8. Platelets, Apheresis, Leucocyte-Depleted

Platelets, Apheresis, Leucocyte-Depleted (Aph, LD) is a leucocyte-
depleted platelet component obtained by platelet apheresis of a single
donor using automated cell separation equipment, which contains
platelets in a therapeutically effective dose suspended in plasma.
Platelets, Aph, LD contains a minimum content of 2 × 1011 platelets.
Platelets, Aph, LD normally contains a maximum content of 1.0 × 106
leucocytes.
Preparation
To prepare Platelets, Aph, LD, Whole Blood is removed from the donor
by the apheresis machine, anti-coagulated with a citrate solution and
the platelets are then harvested. Centrifugation, filtration or other
in-process steps are included in the process to reduce the number of
contaminating leucocytes. Pre-storage leucocyte depletion is recom-
mended (within 6 hours after preparation if performed by filtration).
For use in neonates and infants, Platelets, Aph, LD can be divided into
355

Table 5C-8

screening test
screening test
screening test
Residual leucocyte content b < 1 × 106 per unit as determined by SPC

356

Platelets, Aph, LD must be stored under conditions which guarantee
stant agitation.
Platelets, Aph, LD to be stored for more than 6 hours must be col-
lected and prepared in a functionally closed system. The maximum
storage time for Platelets, Aph, LD is 5 days. Storage may be extended
to 7 days, in conjunction with detection or reduction of bacterial
contamination.
During transportation, the temperature of Platelets, Aph, LD must
and, upon receipt, unless intended for immediate therapeutic use, the
conditions.
Labelling
appropriate:
357

ate);
Warnings
Platelets, Apheresis, LD is not recommended in the case of:
• anaphylaxis;
urticaria). The incidence is reduced by the use of pre-storage
leucocyte-depleted platelets;
• allo-immunisation against HLA (very rarely) and red cell anti-
gens;
358

stances;
nised;
function.
9. Platelets, Apheresis, in Additive Solution

Platelets, Apheresis, in Additive Solution (Aph, AS) is a component
obtained by platelet apheresis of a single donor using automated cell
separation equipment, which contains platelets in a therapeutically
effective dose suspended in a mixture of plasma (30-40 %) and an
additive solution (60-70 %).
Platelets, Aph, AS contains a minimum content of 2 × 1011 platelets.
Platelets, Aph, AS contains a maximum leucocyte content of 0.3 × 109
cells.
Preparation
To prepare Platelets, Aph, AS, Whole Blood is removed from the donor
by the apheresis machine, anti-coagulated with a citrate solution and
then the platelets are harvested. Platelets are stored in a combination
of plasma and an appropriate additive solution.
For use in neonates and infants, Platelets, Aph, AS can be divided into
359

Table 5C-9

screening test
screening test
screening test
Residual leucocyte content b < 0.3 × 109 per final unit as determined by SPC


360

Platelets, Aph, AS must be stored under conditions which guarantee
The storage temperature must be + 20 to + 24 °C, under constant
agitation.
Platelets, Aph, AS to be stored for more than 6 hours must be collected
and prepared in a functionally closed system. The maximum storage
time for Platelets, Aph, AS is 5 days. Storage may be extended to
7 days, in conjunction with detection or reduction of bacterial con-
tamination and depending on the type of additive solution.
During transportation, the temperature of Platelets, Aph, AS must
and, on receipt, unless intended for immediate therapeutic use, the
conditions.
Labelling
appropriate:
361

ate);
Warnings
Platelets, Apheresis, AS is not recommended in the case of:
transfusions;
• anaphylaxis;
urticaria);
362

stances;
nised;
function.
10. Platelets, Apheresis, Leucocyte-Depleted, in

Additive Solution
Platelets, Apheresis, Leucocyte-Depleted, in Additive Solution (Aph,
LD-AS) is a leucocyte-depleted platelet component obtained by platelet
apheresis of a single donor using automated cell-separation equipment,
which contains platelets in a therapeutically effective dose suspended
in a mixture of plasma (30-40 %) and an additive solution (60-70 %).
Platelets, Aph, LD-AS contains a minimum content of 2 × 1011 platelets.
Platelets, Aph, LD-AS contains a maximum of 1.0 × 106 leucocytes.
Preparation
To prepare Platelets, Aph, LD-AS, Whole Blood is removed from
the donor by the apheresis machine, anti-coagulated with a citrate
solution and then the platelets are harvested. Platelets are stored in a
combination of plasma and an appropriate nutrient solution. Centrif-
ugation, filtration or other in-process steps are included in the process
to reduce the number of contaminating leucocytes. Pre-storage leu-
cocyte depletion is recommended (within 6 hours after preparation if
performed by filtration).
For use in neonates and infants, Platelets, Aph, LD-AS can be divided
into satellite units under sterile conditions.
363

Table 5C-10

screening test
screening test
screening test
HLA and/or HPA As required All units


364


Platelets, Aph, LD-AS must be stored under conditions which guar-
antee that their viability and haemostatic activities are optimally
preserved.
stant agitation.
Platelets, Aph, LD-AS to be stored for more than 6 hours must be
collected and prepared in a functionally closed system. The maximum
storage time for Platelets, Aph, LD-AS is 5 days. Storage may be
extended to 7 days, in conjunction with detection or reduction of bac-
terial contamination and depending on the type of additive solution.
During transportation, the temperature of Platelets, Aph, LD-AS must
and, on receipt, unless intended for immediate therapeutic use, the
conditions.
Labelling
appropriate:
365

ate);
Warnings
Platelets, Aph, LD-AS is not recommended in the case of:
transfusions;
• anaphylaxis;
urticaria);
• allo-immunisation against HLA (very rarely after pre-storage
leucocyte-depletion) and red cell antigens;
366

• viral transmission (hepatitis, HIV, etc.) is possible despite careful
donor selection and screening procedures;
stances;
nised;
function.
11. Platelets, Apheresis, Pathogen-reduced

Platelets, Apheresis, Pathogen Reduced (Aph, PR) is a platelet compo-
nent obtained by platelet apheresis of a single donor using automated
cell separation equipment, which contains platelets in a therapeu-
tically effective dose suspended in plasma or a mixture of plasma
(30-50 %) and an additive solution (50-70 %). Subsequently, the com-
ponent is subjected to treatment with an approved and validated PRT
before storage. Pools of two to three platelet components obtained
from the same platelet apheresis donation can be made prior to PRT if
validated.
Platelets, Aph, PR contains a minimum content of 2 × 1011 platelets.
Platelets, Aph, PR contains a maximum leucocyte content of 1.0 × 106
cells.
The PRT typically reduces the risk of infection by enveloped viruses
(e.g. HBV, HCV, HIV) and most bacteria (with the exception of bacte-
rial spores) by at least one-thousand-fold.
367
Depending on the procedure, some PRT have been shown to inac-

tivate lymphocytes and, if so, irradiation to prevent transfusion-
associated TA-GvHD is not required.
Preparation
To prepare Platelets, Aph, PR, Whole Blood is removed from the donor
by the apheresis machine, anti-coagulated with a citrate solution
and then the platelets are harvested. Platelets are stored in plasma
or a mixture of plasma (30-50 %) and an additive solution (50-70 %).
Centrifugation, filtration or other in-process steps are included in the
process to reduce the number of contaminating leucocytes.
The PRT is undertaken according to manufacturer instructions.

The parameters listed in Table 5C-11 must be checked according to the
reported frequency. A technical procedure must be in place to ensure
that the illumination of the PRT has been performed correctly. Ad-
ditional testing might be necessary to comply with national require-
ments (see Chapter 9, Standards for screening for infectious markers).
368
Table 5C-11

screening test
screening test
screening test
Platelet content a minimum 2 × 1011 per unit as determined by SPC



Platelets, Aph, PR must be stored under conditions which guarantee
stant agitation.
The maximum storage time for Platelets, Aph, PR may be extended to
7 days depending on the type of additive solution and the PRT.
During transportation, the temperature of Platelets, Aph, PR must be
kept as close as possible to the recommended storage temperature and,
on receipt, unless intended for immediate therapeutic use, they should
be transferred to storage under the recommended conditions.
369
Labelling
The labelling must comply with the relevant national legislation
and international agreements. The following information must be
shown on the label or contained in the product information leaflet, as
appropriate:
• additional component information: leucocyte-depleted, number
of donations combined to make the pool, etc. (as appropriate);
Warnings
Platelets, Aph, PR is not recommended in cases of:
370

bandwidth <375 nm;
• haemolytic reactions due to anti-A, -B in case of incompatible
transfusions;
• non-haemolytic transfusion reactions may occur (mainly chills,
fever and urticaria). The incidence is reduced by the use of
pre-storage leucocyte-depleted platelets;
• allo-immunisation against HLA (very rarely after leucocyte- de-
pletion) and red cell antigens;
• viral transmission and bacterial contamination (other than bac-
terial spores) is highly unlikely. Transmission of other pathogens
that are not sensitive to PRT is possible;
• citrate toxicity in patients with impaired liver function;
• anaphylaxis and allergic reactions, including allergy to the com-
pounds used for, or generated by, the PRT.
12. Platelets, Cryopreserved

Platelets, Cryopreserved (Cryo) is a component prepared by the freez-
ing of platelet components within 24 hours of collection, using a
cryoprotectant.
371
Reconstituted Platelets, Cryo contain more than 40 % of the original

component.
The method facilitates extended storage of platelets from selected
donors and of autologous platelets.
Preparation
Platelets, Cryo are prepared by secondary processing of Platelets, Aph,
LD. The component is cryopreserved within 24 hours of collection
using a cryoprotectant. Two methods are, in general, used for prepa-
ration of Platelets, Cryo: DMSO (6% w/v) and a very low glycerol (5%
w/v) technique.
Before use, the platelets are thawed, washed and resuspended in (au-
tologous) plasma or in a suitable additive solution.

As indicated for Platelets, Aph (see Table 5C-7), with the following
additions and changes:
Table 5C-12
Volume 50-200 mL All units

Platelet content > 40 % of the pre-freeze All units
platelet content
Platelets, Cryo when thawed will not swirl.

Platelets in the frozen state must be constantly maintained at:
• – 80 °C, if stored in an electric freezer;
• – 150 °C, if stored in vapour-phase liquid nitrogen.
If storage will be extended for more than one year, storage at – 150 °C
is preferred.
372
If transport in the frozen state is unavoidable, storage conditions must

be maintained during transportation.
Thawed platelets must be used as soon as possible after thawing. If
short-to-intermediate storage is required, the component must be kept
between + 20 °C to + 24 °C.
Transportation of thawed platelets is limited by the short shelf-life of
this component. During transportation, the temperature of Platelets,
Cryo must be kept as close as possible between + 20 to + 24 °C.
Labelling
international agreements.
The following information must be shown on the label or contained in
the component information leaflet, as appropriate and must be tracea-
ble for each frozen unit:
• additional component information if appropriate;
• the storage temperature.
Labelling of the reconstituted component

After thawing and reconstitution (washing), the date of expiry must be
changed to the date (and time) of expiry, and the name and volume of
the cryoprotective solution must be changed to the name and volume
of the additive solution (if any).
The following information must be shown on the label or contained in
the component information leaflet, as appropriate:
373

• the unique identity number. If 2 or more units are collected from
the donor in one session, each component must have a unique
component identity number;
• the date of preparation;
• additional component information: Leucocyte depleted, irradi-
ated, etc. (if appropriate);
• the date of expiry (and time of expiry when required);
• the HLA and/or HPA type (if determined);
Warnings
Residual cryoprotectant (e.g. DMSO) can be toxic.
transfusions when thawed platelets are re-suspended in plasma;
urticaria);
374
• allo-immunisation against HLA (very rarely) and red cell anti-

gens;
• graft versus host disease (TA-GVHD);
stances;
nised.
375
Part D. Plasma components
377
1. Plasma, Fresh Frozen

Plasma, Fresh Frozen (FFP) is a component for transfusion or for frac-
tionation, prepared either from Whole Blood or from plasma collected
by apheresis, frozen within a period of time and to a temperature that
adequately maintains the labile coagulation factors in a functional
state.
FFP used as Human plasma for fractionation must comply with the
specifications of the European Pharmacopoeia monograph Human
plasma for fractionation (0853).
FFP used for clinical transfusion must comply with the specifications
as given in this section (Chapter 5, Part D).
It must contain, on average, 70 % or more of the value of Factor VIII of
the freshly collected plasma unit and at least similar quantities of the
other labile coagulation factors and naturally occurring inhibitors.
It must not contain irregular antibodies of clinical significance. If
leucocyte-depleted, the component must contain less than 1 × 106
leucocytes.
Preparation
From Whole Blood
Plasma is separated from Whole Blood that has been collected using
a blood bag with integral transfer packs employing hard-spin cen-
trifugation with freezing commenced within 6 hours of collection or
within a timeframe validated to result in a component meeting spec-
ification. An intermediate step involving preparation of platelet-rich
plasma is also permissible.
Alternatively, plasma may be separated from Whole Blood that, im-
mediately after donation, has been cooled rapidly by a special device
validated to maintain the temperature between + 20 °C and + 24 °C
and is held at that temperature for up to 24 hours.
378
Freezing must take place in a system that allows complete freez-

ing within one hour to a temperature below – 25 °C. If FFP is to be
prepared from a single-pack Whole Blood donation, adequate sterility
precautions must be adopted.
By apheresis
FFP may be collected by apheresis. Freezing must commence either
within 6 hours of collection or within a timeframe validated to result
in a component meeting specification. Freezing must take place in a
system that allows complete freezing within one hour to a tempera-
ture below – 25 °C.
Quarantine FFP
Quarantine FFP can be released once the donor has been re-tested, at
least for HBsAg, anti-HIV and anti-HCV, with negative results after a
defined period of time that is designed to exclude the risk associated
with the window period. A period of six months is generally applied.
This may be reduced if NAT testing is performed.

Table 5D-1 lists the requirements. Additional testing may be required
Table 5D-1
ABO, RhD a, b Grouping only for clinical FFP All units

Anti-HIV 1 & 2 a Negative by approved All units
screening test
HbsAg a Negative by approved All units
screening test
a Unless performed on the source whole blood.

b A minimum of 90 % of units tested should meet the required value.
379
Anti-HCV a Negative by approved All units

screening test
Volume b Stated volume ± 10 % as determined by SPC
Factor VIII b Average (after freezing and as determined by SPC
thawing): not less than 70 IU on units in the first
Factor VIII per 100 mL month of storage a
Residual cells b Red cells: < 6.0 × 109/L as determined by SPC
Leucocytes: < 0.1 × 109/L
Platelets: < 50 × 109/L
If leucocyte-depleted: as determined by SPC
< 1 × 106 per unit
Leakage No leakage in any part of All units
container. Requires visual
inspection after pressure in a
plasma extractor before freezing
Visual changes No abnormal colour or visible clots All units


The following storage times and temperatures are permitted:
• 36 months at below – 25 °C;
• 3 months at – 18 °C to – 25 °C.
The storage temperature must be maintained during transport. Unless
for immediate use, the packs must be transferred at once to storage at
the recommended temperature.
Once thawed, the component must not be refrozen and should be
transfused as soon as possible. If delay is unavoidable, the component
may be stored and should be used within 4 hours if maintained at
22 ± 2 °C or 24 hours if stored at 4 ± 2 °C. For management of major
bleeding, thawed FFP that has been stored at 4 ± 2 °C can be used for
380
up to 5 days, but it should be borne in mind that extended post-thaw

storage will result in a decline in the content of labile coagulation
factors.
Labelling
appropriate:
• the ABO and RhD groups (only for clinical FFP);
• additional component information: leucocyte-depleted, irradi-
ated, quarantined, etc. (if appropriate);
After thawing, the date of expiry must be changed to the appropri-
ate date (and time) of expiry. The storage temperature must also be
changed accordingly.
Warnings
Transfusion of ABO blood group-incompatible plasma may result in
haemolytic transfusion reaction.
381
FFP must not be used in a patient with an intolerance to plasma

proteins.
Before use, the component must be thawed in a properly controlled
environment and the integrity of the pack must be verified to exclude
any defects or leakages. No insoluble cryoprecipitate must be visible
on completion of the thaw procedure.
urticaria);
nised;
function;
• anaphylaxis and allergic reactions.
2. Plasma, Fresh Frozen, Pathogen Reduced

Plasma, Fresh Frozen, Pathogen Reduced (PR) is a component for
transfusion prepared from plasma derived from Whole Blood or
apheresis plasma which is subjected to treatment with an approved
and validated PRT and subsequent freezing within a period of time to
a temperature that adequately maintains the labile coagulation factors
in a functional state.
Plasma, Fresh Frozen, PR may be prepared from small pools of up to
12 individual donations if in accordance with the specifications of the
manufacturer of the PR system used.
382
Plasma, Fresh Frozen, PR used for clinical transfusion must comply

with the specifications given in this monograph.
It contains, on average, about 50 to 70 % of the labile coagulation
factors and naturally occurring inhibitors present in fresh unfrozen/
thawed plasma.
(e.g. HBV, HCV, HIV) by at least one-thousand-fold.
Plasma, Fresh Frozen, PR must not contain irregular antibodies of
clinical significance.
If leucocyte-depleted, the component must contain less than 1 × 106
leucocytes.
Preparation
Plasma, Fresh Frozen, PR is prepared from plasma obtained from
Whole Blood or collected by apheresis as described for Plasma, Fresh
Frozen. The PRT can be applied either before or after freezing and
thawing of the plasma.

Table 5D-2
ABO, RhD a Grouping All units

Only for clinical FFP
screening test

383
HBsAg a Negative by approved All units

screening test
screening test
Volume b Stated volume ± 10 % All units
Factor VIII b Average: not less than 50 as determined by SPC
IU Factor VIII per 100 mL on units in the first
month of storage
Fibrinogen b Average (after freezing and as determined by SPC
thawing) = 60 % of the potency of on units in the first
the freshly collected plasma unit month of storage
Residual cells b Red cells: < 6.0 × 109/L as determined by SPC
Leucocytes: < 0.1 × 109L
Platelets: < 50 × 109/L
If leucocyte-depleted: as determined by SPC
< 1 × 106 per unit
Leakage No leakage in any part of container. All units
Requires visual inspection after
pressure in a plasma extractor,
before freezing and after thawing
Visual changes No abnormal colour or visible clots All units


The following storage times and temperatures are permitted:
• 36 months at or below – 25 °C;
• 3 months at – 18 °C to – 25 °C.
The storage temperature must be maintained during transport. Unless
for immediate use, the packs must be transferred at once to storage at
the recommended temperature.
384
In order to preserve labile factors, Plasma, Fresh Frozen, PR must be

used as soon as possible following thawing. It must not be re-frozen.
Labelling
appropriate:
ated, etc. (if appropriate);
Warnings
385
Plasma Fresh Frozen, PR must not be used in cases of:

• patients with intolerance to plasma proteins;
bandwidth < 375 nm;
generated by, the PRT;
• patients with G6PD deficiency when the plasma is prepared by
the methylene blue procedure;
• patients with a known allergy to the compounds used for, or
urticaria);
• viral transmission (hepatitis B and C, HIV) is highly unlikely,
but transmission of other pathogens that are not tested for or are
not sensitive to PRT is possible;
function;
386
3. Cryoprecipitate
Cryoprecipitate is a component containing the cryoglobulin fraction
of plasma obtained by further processing of Plasma, Fresh Frozen and
then concentrated.
It contains a major portion of the Factor VIII, von Willebrand factor,
fibrinogen, Factor XIII and fibronectin present in freshly drawn and
separated plasma.
Preparation
Plasma, Fresh Frozen is thawed, either overnight between + 2 to
+ 6 °C or by the rapid thaw-siphon thaw technique. After thawing, the
component is re-centrifuged using a hard spin at the same temper-
ature. The supernatant cryoprecipitate-poor plasma is then partially
removed. The sedimented cryoprecipitate is then rapidly frozen.
When Cryoprecipitate is prepared from Whole Blood-derived plasma,
the maximal final volume of the component is 40 mL.
Alternatively, Plasma, Fresh Frozen obtained by apheresis may be used
as the starting material and the final component can be prepared
using the same freezing/thawing/refreezing technique.
Leucocyte depletion of the starting material and/or virus inactivation,
and/or quarantine is a requirement in some countries.

387
Table 5D-3a
ABO, RhD a, b Grouping All units

Only for clinical FFP
screening test
HBsAg a Negative by approved All units
screening test
screening test
a Unless performed on whole blood used as the source.

b Unless intended only for fractionation.
Table 5D-3b
Volume a 30-40 mL All units

Factor VIII b ≥ 70 IU per unit Every 2 months:
a. pool of 6 units of mixed
blood groups during their
first month of storage
b. pool of 6 units of mixed
last month of storage
Fibrinogen ≥ 140 mg per unit 1 % of all units
with a minimum of
4 units per month
a This table is designed for quality control of cryoprecipitate obtained from FFP derived from one unit of whole
blood. In the event that apheresis FFP is used as a starting material, the volume may be different.
b Only required if component used for treatment of haemophilia and/or vWD patients respectively.
388
Von Willebrand Factor b > 100 IU per unit Every 2 months:

b. pool of 6 units of mixed
a This table is designed for quality control of cryoprecipitate obtained from FFP derived from one unit of whole
blood. In the event that apheresis FFP is used as a starting material, the volume may be different.
b Only required if component used for treatment of haemophilia and/or vWD patients respectively.

The stability of Cryoprecipitate on storage is dependent on the storage
temperature. The optimal storage temperature is below – 25 °C.
Recommended storage times are:
• 3 months at – 18 °C to – 25 °C.
The storage temperature must be maintained during transport. The
receiving hospital blood bank must ensure that the Cryoprecipitate has
remained frozen during transit. Unless for immediate use, the Cryo-
precipitate must be transferred at once to storage at the temperature
stated above.
Before use, Cryoprecipitate must be thawed in a properly controlled
environment at + 37 °C immediately after removal from storage.
Dissolution of the precipitate must be encouraged by careful manipu-
lation during the thawing procedure.
In order to preserve labile factors, Cryoprecipitate must be used as
soon as possible following thawing. It must not be re-frozen.
389
Labelling
appropriate:
• the ABO group;
ated, quarantined, etc. (if appropriate);
Warnings
Before use the component must be thawed in a properly controlled
any defects or leakages.
Cryoprecipitate is not recommended for patients with an intolerance
to plasma proteins.
390

urticaria);
• possibility of development of inhibitors to Factor VIII in patients
with haemophilia;
• in rare instances, haemolysis of recipient red blood cells due to
high titre allo-agglutinins in the donor has been recorded;
nised;
function.
4. Cryoprecipitate, Pathogen Reduced

Cryoprecipitate, Pathogen Reduced is a component containing the cry-
oglobulin fraction of plasma obtained by further processing of Plasma,
Fresh Frozen which is then concentrated.
It is subjected to treatment with an approved and validated Patho-
gen Reduction Technique (PRT) and subsequent freezing within a
period of time to a temperature that adequately maintains the labile
coagulation factors in a functional state. It contains a major portion
of the Factor VIII, von Willebrand factor, fibrinogen, Factor XIII and
fibronectin present in freshly drawn and separated plasma.
(e.g. HBV, HCV, HIV) by at least one to ten-thousand-fold.
Cryoprecipitate, PR used for clinical transfusion must comply with
the specifications given in this monograph.
391
Preparation
Plasma, Fresh Frozen is thawed, either overnight between + 2 °C to
+ 6 °C or by the rapid thaw-siphon thaw technique. After thawing, the
component is re-centrifuged using a hard spin at the same temper-
ature. The supernatant cryoprecipitate-poor plasma is then partially
removed. The sedimented cryoprecipitate is then either rapidly frozen
and kept at < − 25°C until processing by the pathogen reduction
method or subject to the PRT process and then frozen.
Cryoprecipitate, PR is prepared from Whole Blood-derived plasma or
from apheresis-derived plasma.
For the PR step, units may be treated singly or pooled.

Table 5D-4a and 4b list the requirements. Additional testing may be
required to comply with national requirements (see also Chapter 9,
Standards for screening for infectious markers).
Table 5D-4a
ABO, RhD a Grouping All units

screening test
HbsAg a Negative by approved All units
screening test
screening test
a Unless performed on donor sample of whole blood donation or apheresis donation used as the source.
392
Table 5D-4b
Volume as per system used All units

Factor VIII > 50 IU per single unit Every 2 months
b pool of 6 units of mixed
Fibrinogen > 140 mg per single unit 1 % of all units with
a minimum of 4
units per month
Von Willebrand Factor > 100 IU per single unit Every batch for
accurate labelling
Every 2 months
a. 4 units of small
bags during their first
month of storage
b. 4 units of small
bags during their last
month of storage
The exact number of units to be tested could be determined by statistical process control.

The stability of Cryoprecipitate, PR on storage is dependent on the
storage temperature. The optimal storage temperature is below – 25 °C.
Recommended storage times are:
• 3 months at – 18 °C to – 25 °C.
receiving hospital blood bank must ensure that the Cryoprecipitate,
393
PR has remained frozen during transit. Unless for immediate use, the
Cryoprecipitate, PR must be transferred immediately to storage at the
temperature stated above.
Before use, Cryoprecipitate, PR must be thawed in a properly con-
trolled environment at + 37 °C immediately after removal from
storage. Dissolution of the precipitate must be encouraged by careful
manipulation during the thawing procedure.
In order to preserve labile factors, Cryoprecipitate, PR must be used as
soon as possible following thawing. It must not be re-frozen.
Labelling
appropriate:
• additional component information: pathogen reduced (indicat-
ing the name of the PRT used);
• the ABO group;
394
Warnings
Cryoprecipitate, PR is not recommended for patients with an intoler-
ance to plasma proteins.
urticaria);
• development of inhibitors to Factor VIII in patients with haemo-
philia;
• haemolysis of recipient red blood cells due to high titre allo-ag-
glutinins in the donor viral transmission of lipid enveloped
viruses (such as hepatitis B, C, HIV, etc.) is highly unlikely after
PR but transmission of non-lipid enveloped viruses (such as
hepatitis A, Parvovirus B19) is possible, despite careful donor
selection and screening procedures;
nised;
function;
• transfusion associated circulatory overload (TACO);
bandwidth < 375 nm;
395
5. Plasma, Fresh Frozen, Cryoprecipitate-Depleted

Plasma, Fresh Frozen, Cryoprecipitate-Depleted is a component pre-
pared from Plasma, Fresh Frozen by the removal of the cryoprecipitate.
Its content of albumin, immunoglobulins and coagulation factors is
the same as that of Plasma, Fresh Frozen, except that the levels of the
labile Factors V and VIII are markedly reduced. The fibrinogen con-
centration is also reduced in comparison to Plasma, Fresh Frozen.
Preparation
Plasma, Fresh Frozen, Cryoprecipitate-Depleted is the by-product of
the preparation of Cryoprecipitate from Plasma, Fresh Frozen.
Leucocyte depletion of the starting material and/or virus inactivation,
and/or quarantine, is a requirement in some countries.

As indicated for Plasma, Fresh Frozen (see Table 5D-1 above), with the
additional requirement given in Table 5D-5 below. Additional testing
may be required to comply with national requirements (see also
Chapter 9, Standards of screening for infectious markers).
Table 5D-5
Volume Stated volume ± 10 % All units

The stability of Plasma, Fresh Frozen, Cryoprecipitate-Depleted on
storage is dependent on the storage temperature. The optimal storage
temperature is below – 25 °C. Approved storage times are:
• 3 months at – 18 °C to – 25 °C.
396

receiving hospital blood bank must ensure that Plasma, Fresh Frozen,
Cryoprecipitate-Depleted has remained frozen during transit. Unless
for immediate use, the units must be transferred at once to storage at
the temperature stated above.
In order to preserve labile factors, Plasma Fresh Frozen, Cryoprecipi-
tate-Depleted must be used as soon as possible following thawing. It
must not be re-frozen.
Labelling
appropriate:
• the ABO group;
ated, quarantined, pathogen-reduced, etc. (if appropriate);
397

Warnings
Plasma Fresh Frozen, Cryoprecipitate-Depleted is not recommended
for patients with an intolerance to plasma proteins.
urticaria);
nised;
function;
398
Part E. White cell components
399
1. Granulocytes, Apheresis

Granulocytes, Apheresis is a component that contains granulocytes
suspended in plasma and is obtained by apheresis of a single donor
using automated cell separation equipment.
An adult therapeutic dose of Granulocytes, Apheresis contains between
1.5 × 108 and 3.0 × 108 granulocytes/kg body weight of the designated
recipient.
Granulocytes, Apheresis has a significant content of red blood cells,
lymphocytes and platelets.
Granulocytes, Apheresis must be irradiated.
IMPORTANT NOTICE
The clinical efficacy, indication and dosage of granulocyte transfu-
sions have not been established. Potential donors of granulocytes need
to receive medication before collection, and sedimenting agents are
required during the apheresis procedure, both of which have poten-
tially severe side-effects that are described below. Thus, it is essential
to secure the informed consent of the donor. In addition to the rec-
ognised complications of routine donor apheresis (see Chapters 2
and 3), the following side-effects may occur.
• Hydroxyethyl starch (HES): acts as a volume expander. Donors
who have received HES may experience headaches or peripheral
oedema because of an expanded circulatory volume. HES may
accumulate (which can result in pruritus) and allergic reactions
are possible.
• Corticosteroids: may cause, for example, hypertension, diabetes,
cataracts and peptic ulcer.
• G-CSF: The most common short-term complication after G-CSF
administration in peripheral blood stem cell (PBSC) donors is
bone pain though, on very rare occasions, splenic rupture or
lung injury may occur. Concerns over acute myeloid leukaemia
400
(AML)/myelodysplasia (MDS) development following G-CSF

administration are based primarily on reports of increased rates
of AML/MDS among women with breast cancer who received
chemotherapy or patients with severe chronic neutropenia (SCN)
who received G-CSF support. To date, registry data from Europe
and the United States have not identified any increased risk of
AML/MDS (including those based on the data of over 100 000
healthy individuals who donated PBSC and received G-CSF as
pre-treatment). However, the median follow-up of these studies
is less than 5 years.
Preparation
Donors of Granulocytes, Apheresis require pre-treatment with corti-
costeroids and/or growth factors. Granulocytes, Apheresis are collected
from a single donor by apheresis. Optimal collection yields require
the use of a sedimenting agent, such as HES, low molecular weight
dextran or modified fluid gelatine.

Table 5E-1 lists the requirements. Additional testing may be required
Table 5E-1

screening test
screening test
screening test
401
HLA (when required) Typing As required

Volume < 500 mL All units
Granulocyte content Achieve clinical dose: e.g. adult All units
patient of 60 kg = 0.9-1.8 × 1010
granulocytes per unit

Granulocytes, Apheresis are not suitable for storage and must be trans-
fused as soon as possible after collection. If unavoidable, storage must
be limited to the shortest possible period.
The unit must be transported to the user in a suitable container
between + 20 and + 24 °C, but without agitation.
Labelling
appropriate:
• the name of the anticoagulant solution, additive solutions and/or
other agents;
• additional component information: irradiated, etc. (as appropri-
ate);
• the date of expiry (and time of expiry, when required);
402
• the number of granulocytes;

• HLA type, if determined;
Warnings
Because of the possibility of severe adverse effects associated with the
collection (donor side-effects) and transfusion of granulocytes (recipi-
ent side-effects), the goals of granulocyte transfusion must be defined
clearly before a course of therapy is initiated.
As there is a significant content of red blood cells, compatibility of
donor red cells with the designated recipient must be verified by
suitable pre-transfusion testing. RhD-negative female recipients of
child-bearing potential must not be transfused with Granulocyte
Concentrates from RhD-positive donors; if RhD-positive concentrates
have to be used, the prevention of RhD immunisation by use of RhD-
immunoglobulin must be considered.
Attention to HLA compatibility is also required for allo-immunised
recipients.
Granulocytes, Apheresis must be irradiated.
CMV-seronegative components for CMV-seronegative recipients must
be considered.
Administration through a micro-aggregate or leucocyte-reduction
filter is contraindicated.
The risk of adverse reactions is increased with concomitant adminis-
tration of Amphotericin B.
urticaria);
403
• allo-immunisation against red cell antigens, HLA, HPA and

HNA;
• protozoal transmission (e.g. malaria, toxoplasmosis) may occur
in rare instances;
nised;
• citrate intoxication in neonates and in patients with impaired
liver function;
• accumulation of HES in multi-exposed patients.
2. Granulocytes, Pooled

Granulocytes, Pooled is a component that contains granulocytes
obtained by pooling of up to 12 buffy coats, suspended in either
plasma or a mixture of platelet additive solution and plasma. Granu-
locytes, Pooled contains on average 11.0 × 109 granulocytes per unit.
The recommended dose for an adult is 1-2 units daily and for a child
0.3 × 109 granulocytes/kg.
Granulocytes, Pooled has a significant content of red blood cells, lym-
phocytes and platelets.
Granulocytes, Pooled must be irradiated.
Preparation
One method of preparation involves pooling of up to 12 ABO matched
buffy coats within 18 hours of donation and platelet additive solution
404
added prior to centrifugation. The red cell residue, supernatant and

granulocyte rich layer (buffy coat) are separated. The buffy coat is
then mixed with 70 mL of ABO matched plasma from one of the
donations.
An alternative method of preparation involves the use of the remain-
ing cellular residue after preparation of Platelets, Recovered, Pooled
from buffy coats. Two ABO matched residues are combined and
diluted with saline prior to centrifugation. The red cell residue, super-
natant and granulocyte rich layer (buffy coat) are separated. The buffy
coat is used as such.
The component must be stored in a pack that allows gas exchange (i.e.
a platelet pack).

Table 5E-2 lists the requirements. Additional testing may be required
Table 5E-2

screening test
screening test
screening test
Volume As defined locally All units
Granulocyte content > 5 × 109/unit All units
405

Granulocytes, Pooled are not suitable for storage and must be trans-
fused as soon as possible after collection. If unavoidable, storage must
be limited to the shortest possible period. At the very latest, transfu-
sion should commence by midnight on the day following donation
(day 1).
The unit must be transported to the user in a suitable container
between + 20 and + 24 °C, but without agitation.
Labelling
appropriate:
• the name of the anticoagulant solution, additive solutions and/or
other agents;
ate);
• the date of expiry (and time of expiry, when required);
Warnings
Because of the possibility of severe adverse effects associated with
the transfusion of granulocytes (recipient side-effects), the goals of
406
granulocyte transfusion must be defined clearly before a course of

therapy is initiated.
As there is a significant content of red blood cells, compatibility of
donor red cells with the designated recipient must be verified by
suitable pre-transfusion testing. RhD-negative female recipients of
child-bearing potential must not be transfused with Granulocyte
Concentrates from RhD-positive donors; if RhD-positive concentrates
have to be used, the prevention of RhD immunisation by administra-
tion of anti-D immunoglobulin should be considered.
Caution is advised for patients with HLA antibodies.
CMV-seronegative components for CMV-seronegative recipients must
be considered.
Administration through a micro-aggregate or leucocyte-reduction
filter is contraindicated.
The risk of adverse reactions is increased with concomitant adminis-
tration of Amphotericin B.
urticaria);
• allo-immunisation against red cell antigens, HLA, HPA and
HNA;
• protozoal transmission (e.g. malaria, toxoplasmosis) may occur
in rare instances;
nised;
407
• citrate intoxication in neonates and in patients with impaired

liver function.
408
Chapter 6
Standards for blood components for

intrauterine, neonatal and infant use
Specially designed blood components are required for intrauterine,
neonatal and infant transfusion.
These recipients are particularly prone to the complications of cyto-
megalovirus infection and transfusion-associated graft versus host
disease and appropriate steps are required to minimise these risks.
Methods of preparation, storage and administration of these compo-
nents should be validated to ensure that the delivered potassium load
is within acceptable limits.
If components are split for use in neonates and infants, each satellite
pack must have a unique unit identity number that allows traceability
to the source donation and to other subunits prepared from the same
component.
Part A. Components for intrauterine transfusions
1. Red Cells, Leucocyte-Depleted for Intrauterine Transfusion, 412
2. Platelets, Leucocyte-Depleted for Intrauterine Transfusion, 414
Part B. Components for neonatal exchange transfusion
1. Whole Blood, Leucocyte-Depleted for Exchange Transfusion, 418
409
2. Whole Blood, Leucocyte-Depleted, Plasma Reduced for Exchange

Transfusion, 419
3. Red Cells, Leucocyte-Depleted, suspended in Fresh Frozen Plasma,
for Exchange Transfusion, 421
Part C. Components (small volume) for neonatal and infant transfusion
1. Red Cells for Neonatal and Infant Small Volume Transfusion, 426
410
Standards for blood components
for intrauterine, neonatal
and infant use
Part A. Components
for intrauterine transfusions
411
1. Red Cells, Leucocyte-Depleted for Intrauterine

Transfusion
Red Cells, Leucocyte-Depleted for Intrauterine Transfusion (IUT) is a
red cell component for intrauterine transfusion.
Red Cells, IUT has a haematocrit (Ht) of 0.70 to 0.85.
Red Cells, IUT contains less than 1 × 106 leucocytes per original
source component.
Preparation
Red Cells IUT is prepared by the secondary processing of Whole Blood
LD, Red Cells LD or Red Cells LD-AS. In order to achieve the required
haematocrit, the storage medium is partly removed and/or exchanged
for another appropriate solution.
Red Cells, IUT must be compatible with both mother and foetus. In
the event that the foetal blood group is not known, a type O RhD-
negative donation must be selected unless the mother has blood
group antibodies that necessitate the use of another blood group.
The red cells must be antigen-negative for any relevant maternal
allo-antibodies.
The component must not contain irregular antibodies of clinical
significance.
Red Cells, IUT must be used within five days of donation.
Red Cells, IUT must be irradiated and used within 24 hours of
irradiation.

As indicated for the source component with the following additional
changes given in Table 6A-1.
412
Chapter 6 Standards for blood components for intrauterine, neonatal and infant use
Table 6A-1
Haematocrit 0.70-0.85 All units

The storage and transport conditions are as for the source components.
The storage time must not be longer than 24 hours after concentra-
tion and irradiation. The component must be used within five days of
donation.
Labelling
The additional and/or amended labelling requirements to those of the
source component are:
• the relevant blood group phenotype if the maternal antibody is
other than anti-RhD;
• the modified date and time of preparation;
• the modified date and time of expiry;
• the name of the anticoagulant or additive solution;
ate);
• the haematocrit of the blood component.
Warnings
Compatibility of this component with maternal serum/plasma must
be verified by suitable pre-transfusion testing.
The rate of transfusion should be controlled to avoid excessive fluctua-
tions in blood volume.
As the foetus is at increased risk of graft versus host disease, the com-
ponent must be irradiated.
413
Adverse reactions:
Note: Although the component is given to the foetus, because of pla-
cental transfer adverse reactions may also affect the mother.
The general adverse reactions are outlined in the relevant source com-
ponent monograph.
In addition, the foetus is especially vulnerable to:
• CMV infection;
• citrate toxicity;
• metabolic imbalance (e.g. hyperkalaemia);
2. Platelets, Leucocyte-Depleted for Intrauterine

Transfusion
Platelets, Leucocyte-Depleted for Intrauterine Transfusion (IUT) is a
platelet component for intrauterine transfusion obtained from a single
donor either by apheresis or from whole blood.
Platelets, IUT must be leucocyte-depleted, irradiated and may be
hyper-concentrated.
Platelets, IUT contains from 45-85 × 109 platelets (on average, 70 × 109)
in 50-60 mL of suspension medium.
Preparation
Platelets, IUT is prepared either from Platelets, Apheresis, LD or by
leucocyte-depletion of Platelets, Recovered and, where appropriate, the
donation is from an HPA-compatible donor.
The component can be concentrated if necessary by removing part of
the supernatant solution by centrifugation. This must be followed by a
1-hour rest period.
If platelets obtained from the mother are to be transfused, then these
must be depleted of plasma and re-suspended in an additive solution.
414
Platelets, IUT must be irradiated.

As indicated for the source component, with the following additional
standards given in Table 6A-2.
Table 6A-2
HPA a Typing When required

Volume 50-60 mL All units
Platelet content 45-85 × 109 per unit All units
a HPA typing of the selected donor, not of the individual component.

Storage and transport requirements are as defined for the source
component, but Platelets, IUT must be used within 6 hours after any
secondary concentration process.
Labelling
source component Platelets, IUT are:
• if components are split for use in neonates and infants, each split
must have a unique unit identity number that allows traceability
to the source donation and to other subunits prepared from the
same component;
• additional component information: irradiated, plasma- or super-
natant-reduced, etc. (if appropriate);
• the platelet count;
• the date and time of expiry.
415
Warnings
As the foetus is at increased risk of graft versus host disease, the com-
ponent must be irradiated.
The rate of transfusion must be controlled to avoid excessive fluctua-
tions in blood volume and possible bleeding after puncture must be
monitored.
Adverse reactions:
Note: Although the component is given to the foetus, because of pla-
cental transfer adverse reactions may also affect the mother.
The general adverse reactions are outlined in the relevant source com-
ponent monograph.
In addition, the foetus is especially vulnerable to:
• CMV infection;
416
Standards for blood components
and infant use
Part B. Components for neonatal
exchange transfusion
417
1. Whole Blood, Leucocyte-Depleted for Exchange

Transfusion
Whole Blood, Leucocyte-Depleted for Exchange Transfusion (ET)
corresponds to Whole Blood, LD with the properties as defined in the
relevant monograph, selected for neonatal exchange transfusion to be
transfused within five days of donation.
Preparation
If the maternal antibody is anti-RhD, the component is prepared from
type O RhD-negative red cells. If the maternal antibody is other than
anti-RhD, red cells are selected that are antigen-negative for any rele-
vant maternal allo-antibodies.
Whole Blood, ET must be irradiated:
• if there is a prior history of intrauterine transfusion;
• for all other patients, unless compelling clinical circumstances
indicate that delay would compromise the clinical outcome.
Whole Blood, ET must be used within 24 hours of irradiation.

As indicated for Whole Blood, LD.

The storage and transport of Whole Blood, ET is as described in the
monograph for Whole Blood, LD.
The storage time must not be longer than 24 hours after irradiation
and five days from donation.
Labelling
Additional and/or amended labelling requirements to those of Whole
Blood, LD are:
• blood group phenotype, if the antibody is other than anti-RhD;
418

ate).
Warnings
Blood group compatibility with any maternal allo-antibodies is es-
sential. The rate of transfusion must be controlled to avoid excessive
Adverse reactions:
In addition to the adverse reactions identified for Whole Blood, LD,
particular concerns in the context of newborns undergoing exchange
transfusion are:
• metabolic imbalance including: citrate toxicity, hypocalcaemia,
hyperkalaemia, hypoglycaemia, hypokalaemia;
• thrombocytopaenia;
• cytomegalovirus infection;
• graft versus host disease, unless irradiated;
• hypothermia.
2. Whole Blood, Leucocyte-Depleted, Plasma Reduced

for Exchange Transfusion
Whole Blood, Leucocyte-Depleted, Plasma Reduced for Exchange
Transfusion (PR, ET) is Whole Blood, ET with a proportion of the
plasma removed.
419
Preparation
Whole Blood, LD is selected within five days from donation and a
proportion of the plasma is removed to achieve a clinically prescribed
haematocrit.
If the maternal antibody is anti-RhD, the component is prepared from
a type O RhD-negative donation. If the maternal antibody is other
than anti-RhD, red cells are selected that are antigen negative for any
relevant maternal allo-antibodies.
Whole Blood, PR, ET must be irradiated:
• if there is a prior history of intrauterine transfusion;
Whole Blood, PR, ET must be used within 24 hours of irradiation.

As indicated for Whole Blood, LD, with the following additional
standards.
Table 6B-2
Haematocrit As clinically prescribed All units

or locally defined

The storage and transport of Whole Blood, PR, ET is as in the mono-
graph described for Whole Blood, LD.
The storage time must not be longer than 24 hours after irradiation
and 5 days from donation.
420
Labelling
Additional and/or amended labelling requirements to those of Whole
Blood, LD are:
• additional component information: irradiated, haematocrit, etc.
(as appropriate).
Warnings
Blood group compatibility with any maternal allo-antibodies is es-
sential. The rate of transfusion must be controlled to avoid excessive
Adverse reactions:
In addition to the adverse reactions identified for Whole Blood, LD,
particular concerns in the context of newborns undergoing exchange
transfusion are:
• hypothermia.
3. Red Cells, Leucocyte-Depleted, suspended in Fresh

Frozen Plasma, for Exchange Transfusion
Red Cells, Leucocyte-Depleted, suspended in Fresh Frozen Plasma,
for Exchange Transfusion (Red Cells, in FFP, ET) is a reconstituted
421
component derived from Red Cells, LD or Red Cells, LD-AS to which

Plasma, Fresh Frozen is added.
Preparation
Red Cells, LD or Red Cells, LD-AS are selected within 5 days from
collection for secondary processing. The supernatant containing the
additive solution and/or plasma is removed after centrifugation, and
then thawed fresh frozen plasma is added to reach the clinically re-
quired haematocrit.
If the maternal antibody is anti-RhD, the component is prepared
from type O RhD-negative red cells. If the maternal antibody is other
than anti-RhD, red cells are selected that are antigen-negative for any
relevant maternal allo-antibodies. The red cells and FFP must be ABO-
compatible with both mother and infant.
Red Cells, in FFP, ET must be irradiated:
• if there is a prior history of prior intrauterine transfusion;
Red Cells, in FFP, ET must be used within 24 hours of irradiation.

As indicated for the source components (Red Cells, LD; Red Cells,
LD-AS and FFP), with the following additional standards given below
(Table 6B-3).
Table 6B-3
Parameter to be checked Requirement Frequency of control
Haematocrit As clinically prescribed All units

or locally defined
422

The storage and transport of Red Cells, in FFP, ET is as in the mono-
graph described for Red Cells, LD or Red Cells, LD-AS.
In addition, storage time must not be longer than 24 hours after re-
constitution and irradiation and 5 days from the red cell donation.
Labelling
reconstituting components are:
• a new unique identity number by which the source donation
identity numbers must be traceable;
• the ABO and RhD group of the red cells;
• the date and time of preparation;
• the new date and time of expiry;
• additional component information: irradiated, haematocrit, etc.
(as appropriate).
Warnings
Compatibility of Red Cells, in FFP, ET with the intended recipient
must be verified by suitable pre-transfusion testing. Blood group com-
patibility with any maternal antibodies is essential.
The rate of transfusion must be controlled to avoid excessive fluctua-
tions in blood volume.
Adverse reactions:
The side-effects correspond to those of the two constituting
components.
Particular concerns in the context of newborns undergoing exchange
transfusion are:
423

• hypothermia.
424
Standards of blood components
and infant use
Part C. Components (small volume)
for neonatal and infant transfusion
425
1. Red Cells for Neonatal and Infant Small Volume

Transfusion
Red Cells for Neonatal and Infant Small Volume Transfusion is a red
cell component derived from Red Cells, BCR; Red Cells, BCR-AS; Red
Cells, LD; or Red Cells, LD-AS, which is divided into satellite units.
The properties are those of the source component.
Preparation
Red Cells for Neonatal and Infant Small Volume Transfusion are
prepared by the secondary processing of Red Cells, BCR; Red Cells,
BCR-AS; Red Cells, LD; or Red Cells, LD-AS. The selected component
is divided into 3 to 8 satellite packs by using a closed or functionally
closed system.
The component may be irradiated where clinically indicated.
Quality control
Quality control of the primary source component is described in the
relevant component monograph standards. Additional quality control
of the final component is given in Table 6C-1.
Table 6C-1
Volume 25-100 mL per unit All units

Storage and transport requirements are as described for the primary
source red cell component.
The storage time must not exceed that of the original component.
426
The component may be irradiated at any time up to 28 days following

collection so long as the component is transfused immediately fol-
lowing irradiation. If the irradiated component is to be stored then
irradiation may be undertaken up to 14 days following collection and
the component stored for up to 48 hours. This period may be extended
to 14 days when effective mechanisms are in place to avoid such units
being transfused in large volume and / or rapid transfusion clinical
settings.
Labelling
primary red cell component are:
• if components are split for use in neonates and infants, each
satellite pack must have a unique unit identity number which
allows traceability to the source donation and to other subunits
prepared from the same component;
ate);
• the volume or weight of the component;
• the date and time of expiry.
Warnings
Transfusion rates must be carefully controlled.
Red Cells for Neonatal and Infant Small Volume Transfusion must not
be used for rapid transfusion or large volume transfusion, unless used
within 5 days from the source red cell donation.
Adverse reactions:
Adverse reactions are those of the primary component selected for
secondary processing.
In addition, of particular concern for infants and neonates are:
427
• metabolic imbalance (e.g. hyperkalaemia in massive transfusion

or if rapidly transfused);
• graft versus host disease, unless the component is irradiated.
428
Chapter 7
Standards for autologous pre-deposit

transfusion
1. Overview
Pre-deposit autologous donation (PAT) means blood and blood com-
ponents collected from an individual and intended solely for subse-
quent autologous transfusion or other human application in that same
individual, i.e. a transfusion in which the donor and the recipient are
the same person.
The Standards for allogeneic whole blood and component donations
also apply to PAT and derived components, with the following exemp-
tions for donor selection:
• age and body weight;
• haemoglobin level;
• protein level;
• donor platelet level.
Autologous donation must be performed in or under the control of a
blood establishment.
429
2. Selection of patients for PAT and blood collection

Role of the physician in charge of collection
The physician in charge of blood collection has ultimate responsibility
for ensuring that the patient’s clinical condition allows pre-operative
blood donation.
Where autologous donation is contraindicated, the physician in
charge of blood collection must inform the patient and the physician
in charge of the patient.
Information for donors

Written informed consent must be obtained from the patient by the
physician in charge of the blood collection, who must provide the
patient with the following information:
• the reasons for requiring a medical history;
• the nature of the procedure and its risks and benefits;
• the possibility of deferral and the reasons why this might occur;
• the tests that are performed and why, and that a positive test for
mandatory microbiological markers results in the destruction of
the collected unit;
• the significance of ‘informed consent’;
• the possibility that the pre-deposit donations may not suffice and
that allogeneic transfusion may be additionally required;
• that unused blood is discarded and is not transfused to other
patients and why this is the case.
In the case of a paediatric patient, the information must be provided
both to the child and the parents, and the parents must give written
informed consent.
Contraindications or deferral criteria

Active bacterial infection is an absolute contraindication.
430
Chapter 7 Standards for autologous pre-deposit transfusion
Serious cardiac disease, depending on the clinical setting of blood

collection, is a relative contraindication (see Principles).
Patients positive for infectious disease markers (as for allogeneic dona-
tions) must not be included in a PAT donation programme unless no
compatible allogeneic blood is available.
3. Preparation, storage and distribution of pre-deposit

autologous blood components
Blood typing and microbiological screening
Blood typing and microbiological screening must be carried out
according to the minimum requirements for the equivalent allogeneic
components.
Patients positive for infectious disease markers must not be included
in pre-deposit autologous programmes, unless no compatible alloge-
neic blood is available.
Preparation
Autologous blood must be processed as for the equivalent allogeneic
components.
Labelling
In addition to the labelling information described for allogeneic com-
ponents, labels on pre-deposit autologous donations must have:
• the statement: autologous donation;
• the statement: strictly reserved for;
• family name and first name;
• date of birth;
• identity number of the patient.
431
Storage and handling

Pre-deposit autologous blood components must be stored, transported
and distributed under the same conditions as, but clearly separated
from, the equivalent allogeneic components.
Warnings
Release procedures must include a confirmation of identity:
• on the component labels;
• on the prescription document;
• and at the bedside.
Pre-transfusion infectious disease marker tests must be carried out as
described for allogeneic components.
Untransfused autologous blood components must not be used for
allogeneic transfusion or for plasma for fractionation.
432
Chapter 8
Standards for immunohaematology
1. Overview
Standards in this chapter apply to the immunohaematology testing of
donors, donations and patients, whether by serological or molecular
methods.
2. Selection and validation of reagents and methods

All laboratory testing procedures must be validated before use (Directive 2005/62/EC Annex 6.3.1).
There must be data confirming the suitability of any laboratory reagents used in the testing of
donor samples and blood component samples (Directive 2005/62/EC Annex 6.3.4).
Only test reagents that have been licensed or evaluated and considered
suitable by a responsible National Health Authority must be used. In
the EU, such reagents are considered as in vitro diagnostic devices and
must be CE marked. In-house manufactured reagents may be used for
rare occasions (e.g. blood group genotyping of high- or low-frequency
antigens where commercial CE-marked reagents are not available).
EU Directive 98/79/EC classifies ABO, Rh (C, c, D, E, e) anti-Kell
reagents in list A of Annex II. The manufacturer of such reagents must
have a full quality system certified by an authorised body and must
submit an application containing all the control results for each lot.
433
Blood group testing must be undertaken in accordance with the in-

structions provided by the manufacturer of the reagents and kits.
All techniques and modifications to techniques in use must be
validated.
The validation of reagents must detect deviations from the established
minimal quality requirements (specifications).
Prospective purchasers must require potential suppliers to provide
them with full validation data for all lots of reagents. Each lot of
reagent must be qualified by the purchaser to demonstrate suitability
for its intended purpose within the system used for testing.
There must be a reliable process in place for transcribing, collating and
interpreting results.
3. Quality control

The quality of the laboratory testing must be regularly assessed by the participation in a formal
system of proficiency testing, such as an external quality assurance programme (Directive 2005/62/
EC Annex 6.3.5).
Quality-control procedures must be implemented for the equipment,

reagents and techniques used for ABO, RhD and other blood-group
antigen typing and detection and identification of antibodies. The
frequency of the control is dependent on the method used.
4. Blood group testing of blood donors and donations

Each donation must be tested in conformity with the requirements laid down in Annex IV to
Directive 2002/98/EC (Directive 2005/62/EC Annex 6.3.2).
Blood group serology testing must include procedures for testing specific groups of donors (e.g.
first-time donors, donors with a history of transfusion) (Directive 2005/62/EC Annex 6.3.6).
ABO and RhD

The ABO and RhD labelling of blood components of all first-time
donors must be based upon the results of two independent ABO and
434
Chapter 8 Standards for immunohaematology
RhD tests with two independent reagents. At least one of the ABO
tests must include reverse grouping.
A positive RhD test must lead to labelling of the unit as ‘RhD positive’.
Components must be labelled as ‘RhD negative’ only if the donor has
tested negative for RhD using appropriate reagents or tests specifically
selected to detect weak D and D variants.
ABO and RhD testing must be performed on all donations excepted
for plasma intended only for fractionation.
The ABO and RhD blood group must be verified on each subsequent
donation and a comparison must be made with the historically deter-
mined blood group.
If a discrepancy is found, the applicable blood components must not
be released until the discrepancy is unequivocally resolved.
Additional typing
If additional typing is performed then, before the result of the con-
firmed phenotype is printed on the label, a test must be done at least
twice from two different samples collected from two different dona-
tions. In the absence of historic information, two tests carried out
independently on the current donation allow the phenotype to be
printed on the label of that donation – but not on subsequent dona-
tions without further testing. The results should be linked to the donor
record.
Irregular antibody testing

All first-time donors as well as repeat and regular donors with a
history of pregnancy or transfusions since the last donation must be
tested for clinically significant irregular red cell antibodies.
5. Testing of patient samples

The ABO and RhD blood group and, when needed, other blood types
must be determined on the patient’s blood sample before issuing
components for transfusion. In an emergency situation, when a delay
may be life-threatening, components may be issued before all results
435
of grouping and antibody screening are completed. In these situations,

testing must be completed as soon as possible.
A sample of the patient’s plasma/serum used for compatibility testing
and/or antibody screening must be retained for a defined period of
time.
Blood grouping and antibody detection

The laboratory must have a reliable and validated procedure for blood
grouping and antibody detection that includes an effective mechanism
to verify the accuracy of the data at the time of issuing a report on
the blood group and other test findings for inclusion in the patient’s
record.
Sufficiently sensitive techniques for the detection of clinically sig-
nificant red cell allo-antibodies must be used, including reagent red
cells that cover all appropriate antigens, preferably with homozygous
expression for the most clinically significant allo-antibodies.
Compatibility testing
Compatibility between red cell components and the recipient’s
plasma/serum must be assured for transfusions. Sufficiently sensitive
techniques for the detection of clinically significant red cell allo-
antibodies must be used. Laboratory records of the tests performed
and of the destination of all units handled (including patient identifi-
cation) must be kept.
Compatibility testing must be carried out on a sample taken no more
than 3 days before the proposed transfusion for patients who have
been transfused or have become pregnant during the last 3 months.
Serological compatibility testing

Serological compatibility testing must be performed if clinically
significant red cell allo-antibodies are suspected or have been iden-
tified by current or previous testing. Whenever possible, red cell
components that lack the corresponding antigens must be selected for
transfusion, and a serological compatibility test between donor red
436
Chapter 8 Standards for immunohaematology
cells and recipient plasma/serum must be undertaken before issuing

red cell components for transfusion.
Type and screen

A type and screen procedure may be used as replacement for sero-
logical compatibility testing if antibody screening has not detected
clinically significant red cell antibodies. The process must include:
• reagent red cells that cover all clinically significant antigens
(preferably with homozygous expression) must be used for anti-
body detection;
• a reliable and validated procedure (preferably by computer) that
ensures compatibility between the donor red blood cells and
recipient plasma.
437
Chapter 9
Standards for screening for infectious

markers
1. Selection and validation of infectious marker tests

All laboratory testing procedures must be validated before use (Directive 2005/62/EC Annex 6.3.1).
Each donation must be tested, in conformity with the requirements laid down in Annex IV to
Directive 2002/98/EC (Directive 2005/62/EC Annex 6.3.2).
There must be data confirming the suitability of any laboratory reagents used in the testing of
donor samples and blood component samples (Directive 2005/62/EC Annex 6.3.4).
The quality of the laboratory testing must be regularly assessed by participation in a formal system
of proficiency testing, such as an external quality assurance programme (Directive 2005/62/EC
Annex 6.3.5).
Only tests that have been licensed or evaluated and considered suita-
ble by the responsible health authorities can be used. In the EU, these
reagents are considered as in vitro diagnostic devices and must be CE
marked. EU Directive 98/79/EC classifies the HIV, HTLV, hepatitis B
and hepatitis C screening tests in list A. The manufacturer must have
a full quality system certified by an authorised body and must submit
an application containing all the control results for each lot.
439
Screening tests for infectious markers must be performed in ac-

cordance with the instructions provided by the manufacturer of the
reagents and test kits.
All laboratory assays and test systems for infectious disease marker
screening, including any upgrades from the manufacturer, used by
blood establishments must be validated before introduction to ensure
compliance with the intended use of the test.
Correct determination of negative and positive controls, as provided
by and in accordance with the manufacturer’s instructions, is a
minimum requirement.
2. Mandatory serological screening tests

The minimum mandatory serological blood donor screening tests are:
• antibody to HIV-1 (anti-HIV-1) and HIV-2 (anti-HIV-2), includ-
ing outlying types (e.g. HIV-1 type O);
• antibody to hepatitis C virus (anti-HCV);
• a hepatitis B surface antigen (HBsAg) assay, which will detect at
least 0.13 IU/mL of HBsAg.
Appropriate quality control measures must be in place when screening
for infectious markers. Specific requirements are shown in Table 9.1.
Table 9.1. Quality control of mandatory

serological screening tests
Anti-HIV 1/2 screening sensitivity Detection of weak positive serum a Each plate/run
Anti-HCV screening sensitivity Detection of weak positive serum a Each plate/run
HBsAg screening test Detection of 0.5 IU/mL standard Each plate/run
a Where possible, the weak positive control should not be the one provided by the manufacturer.
440
Chapter 9 Standards for screening for infectious markers
Laboratories undertaking infectious disease testing of blood do-

nations must participate in a regular external quality assurance
programme.
3. Additional serological screening tests

National authorities may also require additional screening tests for
donations resulting in blood components for direct clinical use such
as: Treponema pallidum haemagglutination assay (TPHA); IA for
syphilis; antibody to human T-cell lymphotropic virus types I (anti-
HTLV-1) and II (anti-HTLV-II); antibody to hepatitis B core antigen
(anti-HBc). These tests are not required for plasma for fractionation.
Table 9.2. Quality control of additional serological screening
Syphilis: TPHA or another IA Detection of weak positive serum a Each plate/run

Anti-HTLV I/II screening test Detection of weak positive serum a Each plate/run
Anti-HBc screening test Detection of weak positive serum a Each plate/run
a Where possible, the weak positive control should not be the one provided by the manufacturer.
4. Management of reactive results in serological

screening tests
There must be clearly defined procedures to resolve discrepant results and ensure that blood and
blood components that have a repeatedly reactive result in a serological screening test for infection
with the viruses mentioned in Annex IV to Directive 2002/98/EC must be excluded from therapeutic
use and be stored separately in a dedicated environment. Appropriate confirmatory testing must
take place. In case of confirmed positive results, appropriate donor management must take place,
including the provision of information to the donor and follow-up procedures (Directive 2005/62/
EC Annex 6.3.3).
Initially reactive donations must be retested in duplicate. If any of

the repeat tests are reactive, then the donation is deemed repeatedly
441
reactive. The donation must not be used for transfusion or the man-
ufacture of medicinal products. Confirmatory testing must be per-
formed by a certified/accredited laboratory.
Algorithms to enable consistent resolution of repeatedly reactive
donations must be in place. In the event that a repeatedly reactive do-
nation is confirmed positive, the donor must be notified and a further
sample must be obtained to reconfirm the results and the identity of
the donor. The results of confirmatory testing that present evidence of
on-going infection must be discussed with the donor and the donor
must be deferred from donation and referred for appropriate care.
The above rules do not necessarily apply to all donations found repeat-
edly reactive for anti-HBc. Additional testing, e.g. for HBs-antibody
and/or HBV-DNA might enable some repeatedly reactive donations to
be used clinically.
If a confirmed infection by HBV, HCV or HIV is shown in a repeat
donor, the blood establishment must undertake a look-back procedure
to identify previous potentially infectious donations. If so, the look-
back procedure must ensure that:
• the blood establishment informs the hospital in writing about
the incident and advises the hospital to trace the recipient(s) of
the implicated blood component(s) and to inform the treating
physician about the potentially infectious transfusion;
• the relevant organisation that carried out plasma fractionation is
notified;
• if the recipient is confirmed to be positive for the given infection,
the incident is reported to the national haemovigilance system
and/or Competent Authority.
5. Nucleic acid screening

If screening of blood donations by Nucleic Acid Amplification Tech-
niques (NAT) is required by national authorities for the release
of blood components, the NAT assays must be validated to detect
5 000 IU/mL for HCV-RNA, 10 000 IU/mL for HIV-RNA and
442
Chapter 9 Standards for screening for infectious markers
100 IU/mL for HBV-DNA in single donations. Appropriate quality

control measures must be in place. The specific requirements are
shown in Table 9.3.
Table 9.3. Quality control of HBV, HCV and HIV

nucleic acid amplification techniques
Parameter to Requirement Frequency of control

be checked
HBV-NAT Detection of 100 IU/mL HBV-DNA per donation Internal control for each NAT
reaction
HCV-NAT Detection of 5 000 IU/mL HCV-RNA per donation Internal control for each NAT
reaction
HIV-NAT Detection of 10 000 IU/mL HIV RNA per donation Internal control for each NAT
reaction
6. Selective screening of donations

Screening of selected donations for antibodies to cytomegalovirus
(anti-CMV) may be undertaken. When performed the assay and test
system must be fully validated. Confirmation of reactive results and
notification of reactive donors is not necessary.
Screening for additional infectious agents, such as malaria antibody,
T. Cruzi antibody and West Nile Virus NAT or others may be ap-
propriate to reduce the risk of transfusion-transmitted infections in
selected donor populations.
When selective screening is in place the assay and test system must be
fully validated.
443
Table 9.4. Quality control of selective screening tests
Parameter Requirement Frequency

to be checked of control
Anti-CMV screening test Detection of weak positive serum a Each plate/run

Malaria antibody test Detection of weak positive serum a Each plate/run
T. Cruzi antibody test Detection of weak positive serum a Each plate/run
West Nile virus NAT Detection of 250 copies WNV RNA per mL in Internal control for
each donation each NAT reaction
a Where possible the weak positive control should not be the one provided by the manufacturer.
444
Chapter 10
Standards for haemovigilance
1. Overview
Haemovigilance procedures must be in place to ensure the organised
surveillance of serious adverse or unexpected events or reactions in
recipients of blood and blood components and for the epidemiological
assessment of infections in donors.
The results of haemovigilance analyses must be fed back periodically
to the providers of haemovigilance data and communicated to the
field and to the relevant Competent Authorities, together with recom-
mendations for preventive or corrective measures.
2. Prerequisites for implementation of a

haemovigilance network
Haemovigilance must be the shared responsibility of the professionals
in the field and the Competent Authorities for blood safety.
Traceability of blood components

There must be procedures in place to ensure full traceability, allowing
the tracing of each individual unit of blood (or any blood components
derived from it), from the donor to its final destination (whether this
445
is a patient, a manufacturer of medicinal products or disposal) and

vice versa.
Traceability must also cover cases in which the blood unit or compo-
nent is not transfused to a patient, but is used for the manufacturing
of medicinal products or for research and investigational purposes, or
if it is disposed of.
of blood components has a serious adverse reaction, indicating that a
blood component may have been the cause.
Confidentiality of haemovigilance data

Any database of haemovigilance reports must operate in compli-
ance with applicable regulations on the confidentiality of individ-
ual medical patient and donor data. Individual reports must be
anonymised.
3. Device defects

When a causality assessment suggests that a medical device (including
in vitro diagnostics) had a possible role in causing an adverse reaction/
event, the manufacturer or his authorised representative must be noti
fied at the same time as the national health authority, even if at the
time of reporting full causality has not necessarily been established.
When haemovigilance and medical device vigilance are the respon-
sibility of separate entities, both the health authority responsible for
haemovigilance and the health authority responsible for medical
device vigilance must be notified.
4. Post-transfusion infection reported to the blood

establishment
of blood components develops laboratory tests results and/or disease
symptoms, indicating that a blood component may have been infec-
tious for hepatitis (B or C), HIV or other transmissible agents.
446
Chapter 10 Standards for haemovigilance
The blood establishment must request relevant information from the

hospital about the infection and the course of disease in the recipient
and possible risk factors in the recipient for the infection.
The blood establishment’s physician must establish a plan of investiga-
tion, the results of which must be recorded.
The incident must be reported to the Competent Authorities.
447
APPENDIX 1.
KEY CRITERIA FOR DONOR
ELIGIBILITY
449
The Standards require medical assessment to be undertaken on all

prospective donors using a combination of interview, questionnaire
and, if necessary, further direct questions. The questionnaire must
be designed to elicit information on the health and lifestyle on the
donor that may adversely affect the safety of both the recipient and the
donor.
Blood establishments should develop a questionnaire that is
appropriate for local circumstances. Therefore, it is not possible to
provide a generic questionnaire in this Guide.
Instead, key eligibility topics for donor inclusion in the questionnaire
or direct questions in an interview have been developed and are
included in the table below.
Key eligibility topics identified as being critical for the safety of donors
and recipients are labelled as ‘core’. It is recommended that countries
include a question which meets the described intent of the core topics
for donor eligibility in their donor questionnaire. Examples of such
questions are included, but the wording may be changed provided the
question still meets the described intent.
A number of key eligibility topics have also been identified that
may be considered to be important for the safety of donors and
recipients dependent on local arrangements and circumstances in
blood establishments. These are labelled as ‘optional’. The blood
establishment may choose to include or not include such questions.
Core and optional sample questions have been categorised into those
which apply only to first-time and repeat donors, and those which also
apply to regular donors.
Blood establishments may also choose to include additional questions.
These recommendations are intended as a guide. Final responsibility
for the content of the donor questionnaire lies with the blood
establishment and Competent Authorities.
450
Key evaluative topic Intent of question Core sample question Optional sample First-time Regular
for donor eligibility question & repeat donors
donors
GENERAL – health To assess general health and Are you in good health? Y Y
provide the donor with an
opportunity to volunteer
health issues that may not be
addressed by specific questions.
GENERAL – previous A donor who has previously Have you ever volunteered Y N
donation history volunteered to donate should to donate blood before?
have a record, which may contain If yes: where/when?
important information regarding
their ongoing eligibility.
Appendix 1. Key criteria for donor eligibility

Countries with more than one
blood establishment could
also have donors who present
at different establishments.
GENERAL – pre- To identify people who have Have you previously been Y N
vious deferral been permanently deferred from told not to give blood?
donating blood previously.
451
452
donors
GENERAL – weight Total blood volume is pro- Is your weight over 50 kg? Y Y
portional to donor weight.
Donors must weigh at least 50
kg to safely donate blood.
GENERAL – donor Efficacy of the donor interview Have you read and under- Y Y
comprehension process requires the donor to stood the above questions
firstly understand the questions and do you affirm that you
being asked of him/her and have answered the questions
then to truthfully and accurately truthfully and to the best
complete the questionnaire to of your knowledge?
the best of his/her knowledge.
NOTE: If not included as
an optional question, then
Blood Establishments should
include as part of the donor
declaration to assist gaining
written informed consent.
donors
SERIOUS ILLNESS To capture any history of Have you ever suffered from any Y N
– examples serious illness, using examples serious illness? Examples include:
of common and important • jaundice, malaria, tuber-
serious illnesses that have culosis, rheumatic fever?
implications for donor and/or
recipient safety. Each example • heart disease, high or
listed would require deferral or low blood pressure?
further assessment of eligibility. • severe allergy, asthma?
• convulsions or diseases
of the nervous system?

• chronic diseases such as
diabetes or malignancies?
SERIOUS ILLNESS – phy- Illness that is serious enough to Since your last donation, N Y
sician and hospital visits require medical consultation may have you been to see a
be relevant to donor selection. doctor or to hospital?
453
454
donors
HAZARDOUS OCCUPA- To identify donors with Do you have a hazardous Y Y

TIONS & HOBBIES occupations or hobbies occupation or hobby such
that may put them or other as driving public trans-
people at risk in the event of port, operating heavy
a delayed vasovagal reaction machinery, underwater
following blood donation. diving and piloting a plane
or other activities?
donors
PREGNANCY To protect donors from iron For women: Are you or have Y Y
depletion +/- risk of vasovagal you become pregnant in
reaction in late pregnancy. the previous 6 months?
Donors who have recently
become pregnant should be
deferred temporarily to allow
time for iron stores to replenish.
To identify donors whose Have you ever been Y N
blood donations may contain pregnant?
HLA or granulocyte anti-

bodies and thereby pose a
higher risk of TRALI. These
antibodies may develop in
response to exposure to foetal
antigens during pregnancy.
455
456
donors
MEDICATIONS – general Medications may render blood Have you taken any med- Y Y
donations partly or completely ications recently?
unsuitable for use. This question
also serves as an additional
prompt for underlying disease,
and therefore the indications
for each medication should
also be determined.
MEDICATIONS Some medications affect In the last 48 hours have Y Y
Platelet affecting drugs platelet function. This ques- you taken any aspirin,
tion can also serve to capture pain killers or anti‑inflam
chronic pain or inflammation. matory medications?
donors
MEDICATIONS Medications with known tera- Have you ever had Y Y

– teratogenic togenic potential require donor medication with:
deferral to cover the maximum • isotretinoin (eg Accutane R)
potential period that the drug
will circulate in the donor’s • etretinate (eg Tigason R)
peripheral blood, with a subse- • acitretin (eg Neotigason R)
quent risk if the donation is trans-
fused to a pregnant recipient. • finasteride (eg Pros-
car R, Propecia R)
• dutasteride (eg Avodart R)

MEDICATIONS Recent vaccination may harm Have you had any vaccina- Y Y
– vaccinations immunocompromised blood tions in the last 8 weeks?
recipients through the trans-
mission of live/attenuated path-
ogens, and may also interfere
with the interpretation of donor
screening tests, such as HBsAg.
BLOOD-BORNE RISKS – Injecting drug use is an Have you ever used needles to Y Y
intravenous use of drugs important route of transmission take drugs, steroids, or anything
for blood-borne infections not prescribed by your doctor?
including HIV, hepatitis B and C.
457
458
donors
SEXUAL ACTIVITY In many countries, sex workers Have you ever received payment Y Y
– sex worker have a significantly higher (gifts, money or drugs) for sex?
prevalence of blood-borne and
sexually transmitted infections
than the general population.
SEXUAL ACTIVITY – Male to male sex is associated For men: have you had Y Y
male to male sex with a higher risk of HIV. This male to male sex in the
group also has a higher risk [specified time period]?
of syphilis, gonorrhoea, as (For the purpose of this question,
well as infection by hepatitis sex is defined as oral or anal inter-
B and hepatitis A viruses. course with or without a condom.)
SEXUAL ACTIVITY – Men who have sex with men For women: to the best of your Y Y
female partner of man have a higher risk of HIV infection knowledge, has any man with
who has sex with men and other sexually transmitted whom you have had sex in
diseases. Therefore, women who the [specified time period] ever
have sexual contact with men in had sex with another man?
this group have a higher risk of (For the purpose of this ques-
such diseases than other women. tion, sex is defined as oral,
vaginal or anal intercourse
with or without a condom.)
donors
SEXUAL ACTIVITY – A donor with a known his- In the past [specified time Y Y
at-risk sexual partner tory of sexual contact with period] have you had sexual
persons in these risk groups contact with someone who:
has a higher risk of infection • is HIV positive or has hepatitis?
by HIV and/or hepatitis.
• has ever used needles to take
drugs, steroids, or anything not
prescribed by his/her doctor?
• receives or has received
payment (gifts, money

or drugs) for sex?
Donors who have had sex with Have you had sex with Y Y
a new sexual partner may a new partner within
be at higher risk of infection the past 4 months?
by HIV and other sexually
transmitted diseases.
Some countries have a high Since your last donation (or, Y Y
prevalence of HIV. Sexual if a new donor, in the last
contact with residents or former 12 months) have you had
residents of those countries is sex with a new partner who
a risk factor for HIV exposure. currently lives or previously
lived in another country?
459
460
donors
TRAVEL – entry question Several infectious diseases Were you born or have you Y Y
relevant to blood safety are lived and/or travelled abroad?
restricted to certain geographical
regions. These include variant
Creutzfeldt-Jakob disease (vCJD),
malaria, Chagas disease, and
other vector-borne diseases
such as West Nile virus, dengue
fever and chikungunya.
TRAVEL – malaria A country without endemic Have you ever spent a Y Y
semi-immunity malaria can use this ques- continuous period of 6
tion to flag for possible months or more abroad?
malaria semi-immunity. If so, check whether the
donor spent any continuous
period of 6 months or more
in a malaria-endemic area.
donors
TRAVEL – malaria A donor who visits a malaria risk Have you been abroad since Y Y
exposure area could harbour asympto- your last donation (or, for new
matic infection after returning donors, in the last 12 months)?
to their country of residence. If so, check whether the
donor visited any malaria-
endemic areas.
TRAVEL – unex- A donor who visits a malaria risk Have you ever had an Y Y
plained fever area could harbour asympto- unexplained fever after
matic infection after returning travelling abroad?

to their country of residence. If so, check whether it was
within 6 months of visiting
a malaria-endemic area.
TRAVEL – Cha- To identify donors who were born What was your country of birth? Y N
gas’ exposure in a Chagas-endemic country,
and hence are suitable only for
plasma derivative production.
461
462
donors
TRAVEL – vCJD exposure The core geographical risk of From 1980 to 1996 inclusive, Y N
variant Creutzfeldt-Jakob disease did you spend 6 months or
(vCJD) has been defined as more (cumulative) in the UK?
extending from 1980 to 1996
in the United Kingdom. In each
individual blood establishment,
risk assessment should define the
appropriate cumulative period
and whether additional countries
should be added to the risk zone.
OTHER BLOOD-BORNE To identify donors with occupa- Have you been exposed to Y Y
RISKS – hepatitis tional or household exposure to hepatitis or jaundice(via
hepatitis, and trigger appropriate family, household or occupa-
clearance/immunity testing. tion) in the past 6 months?
OTHER BLOOD-BORNE Some countries have reported an Have you had an endos- Y Y
RISKS – flexible association between procedures copy or gastroscopy in
endoscopy employing flexible endoscopy the last 4 months?
and hepatitis C infection. If so, was a flexible
instrument used and was
any biopsy performed?
donors
OTHER BLOOD-BORNE Tooth extraction and other dental Have you had any dental Y Y
RISKS – dental procedures can be associated treatment in the last week?
with transient bacteraemia,
which can theoretically cause
bacterial contamination of
fresh blood components.
OTHER BLOOD-BORNE Invasive procedures can be a Since your last donation or in the Y Y
RISKS – invasive source of blood-borne infec- previous 6 months have you had:
procedures tion. The donor may require • an operation or med-
temporary deferral to exclude

ical investigations?
window period transmission
of infectious disease. • any body piercing and/or tattoo?
• acupuncture treatment
by anyone other than a
registered practitioner?
• an accidental injury involving a
needle and/or mucous membrane
exposure to human blood?
OTHER BLOOD-BORNE Classical CJD (CJD) may Have you been told of a Y Y
RISKS – familial CJD potentially be transmitted family history of Creutzfeldt-
by blood transfusion. Jakob disease (CJD)?
463
464
donors
OTHER BLOOD-BORNE Most reported cases of iatrogenic Have you ever had treatment Y N
RISKS – pituitary extracts CJD have been associated with human pituitary extracts?
with human-derived pitui-
tary hormone treatment.
OTHER BLOOD-BORNE Transplantation may result in Have you ever had a transplant Y Y
RISKS – transplantation the transmission of a range of or graft (organ, bone marrow,
infectious diseases, and corneal cornea, dura mater, bone, etc)?
transplantation and dura mater
grafts have been reported as
causes of iatrogenic CJD?
OTHER BLOOD- Broken or inflamed skin is a Do you have any cuts, Y Y
BORNE RISKS – cuts potential source of bacterial abrasions or sores?
and abrasions contamination. A rash may be
a sign of underlying disease.
OTHER BLOOD-BORNE Gastrointestinal symptoms In the past week, have you Y Y
RISKS – gastrointes- could be associated with had any diarrhoea, abdom-
tinal symptoms conditions which impact both inal pain or vomiting?
recipient safety (e.g. Yersinia
enterocolitica) and donor safety
(e.g. hypokalaemia secondary
to vomiting and diarrhoea).
donors
OTHER BLOOD-BORNE Blood transfusion may cause Have you ever received a blood Y Y
RISKS – transfusion transmission of blood-borne transfusion or injection of blood
infections, including geograph- products? If so, where and when?
ically restricted infections such
as vCJD and Chagas’ disease.
OTHER BLOOD-BORNE HIV, hepatitis B, hepatitis C and Are you or is your partner Y Y
RISKS – positive infec- HTLV are transfusion-transmissi- positive for HIV, hepatitis
tious disease testing ble infectious agents, and all may B, hepatitis C or HTLV?
be transmitted between partners
by sexual or blood contact.

465
APPENDIX 2.
TABLES FOR CALCULATION
OF BLOOD VOLUMES
467
Table 1. Blood volume of women in mL

as calculated according to the ICSH formula1
The weights and heights corresponding to the minimum acceptable
blood volumes of 3 233 mL, 3 400 mL and 3 567 mL are indicated with
grey backgrounds.
kg 50 51 52 53 54 55 56 57 58 59
145 cm 3 141 3 167 3 193 3 219 3 244 3 269 3 294 3 319 3 343 3 367
146 cm 3 157 3 183 3 209 3 235 3 260 3 285 3 310 3 335 3 359 3 384
147 cm 3 172 3 199 3 225 3 251 3 276 3 301 3 327 3 351 3 376 3 400
148 cm 3 187 3 214 3 240 3 266 3 292 3 318 3 343 3 368 3 392 3 417
149 cm 3 203 3 230 3 256 3 282 3 308 3 334 3 359 3 384 3 409 3 433
150 cm 3 218 3 245 3 272 3 298 3 324 3 350 3 375 3 400 3 425 3 450
151 cm 3 234 3 261 3 287 3 314 3 340 3 366 3 391 3 416 3 441 3 466
152 cm 3 249 3 276 3 303 3 329 3 356 3 381 3 407 3 433 3 458 3 483
153 cm 3 264 3 291 3 318 3 345 3 371 3 397 3 423 3 449 3 474 3 499
154 cm 3 279 3 307 3 334 3 361 3 387 3 413 3 439 3 465 3 490 3 515
155 cm 3 295 3 322 3 349 3 376 3 403 3 429 3 455 3 481 3 506 3 532
156 cm 3 310 3 337 3 365 3 392 3 418 3 445 3 471 3 497 3 523 3 548
157 cm 3 325 3 353 3 380 3 407 3 434 3 461 3 487 3 513 3 539 3 564
158 cm 3 340 3 368 3 396 3 423 3 450 3 476 3 503 3 529 3 555 3 581
159 cm 3 355 3 383 3 411 3 438 3 465 3 492 3 519 3 545 3 571 3 597
160 cm 3 370 3 399 3 426 3 454 3 481 3 508 3 535 3 561 3 587 3 613
161 cm 3 385 3 414 3 442 3 469 3 497 3 524 3 550 3 577 3 603 3 629
162 cm 3 400 3 429 3 457 3 485 3 512 3 539 3 566 3 593 3 619 3 645
163 cm 3 416 3 444 3 472 3 500 3 528 3 555 3 582 3 609 3 635 3 661
164 cm 3 430 3 459 3 487 3 515 3 543 3 571 3 598 3 625 3 651 3 677
165 cm 3 445 3 474 3 503 3 531 3 559 3 586 3 613 3 640 3 667 3 693
166 cm 3 460 3 489 3 518 3 546 3 574 3 602 3 629 3 656 3 683 3 709
167 cm 3 475 3 504 3 533 3 561 3 589 3 617 3 645 3 672 3 699 3 726
168 cm 3 490 3 519 3 548 3 577 3 605 3 633 3 660 3 688 3 715 3 741
1 Pearson TC, Guthrie DL, Simpson J, Chinn C, Barosi G, Ferrant A, Lewis

SM, Najean Y; Interpretation of measured red cell mass and plasma volume
in adults: Expert Panel on Radionuclides of the International Council for
Standardisation in Haematology. Br. J. Haem. 1995, 89:748-56.
468
Appendix 2. Tables for calculation of blood volumes
kg 50 51 52 53 54 55 56 57 58 59
169 cm 3 505 3 534 3 563 3 592 3 620 3 648 3 676 3 703 3 731 3 757
170 cm 3 520 3 549 3 578 3 607 3 636 3 664 3 692 3 719 3 746 3 773
171 cm 3 535 3 564 3 593 3 622 3 651 3 679 3 707 3 735 3 762 3 789
172 cm 3 550 3 579 3 608 3 637 3 666 3 695 3 723 3 750 3 778 3 805
173 cm 3 564 3 594 3 624 3 653 3 681 3 710 3 738 3 766 3 794 3 821
174 cm 3 579 3 609 3 638 3 668 3 697 3 725 3 754 3 782 3 809 3 837
175 cm 3 594 3 624 3 653 3 683 3 712 3 741 3 769 3 797 3 825 3 853
176 cm 3 608 3 639 3 668 3 698 3 727 3 756 3 784 3 813 3 841 3 868
177 cm 3 623 3 653 3 683 3 713 3 742 3 771 3 800 3 828 3 856 3 884
178 cm 3 638 3 668 3 698 3 728 3 757 3 786 3 815 3 844 3 872 3 900
179 cm 3 652 3 683 3 713 3 743 3 772 3 802 3 831 3 859 3 887 3 916
180 cm 3 667 3 698 3 728 3 758 3 788 3 817 3 846 3 875 3 903 3 931
181 cm 3 682 3 712 3 743 3 773 3 803 3 832 3 861 3 890 3 919 3 947
182 cm 3 696 3 727 3 758 3 788 3 818 3 847 3 877 3 905 3 934 3 962
183 cm 3 711 3 742 3 772 3 803 3 833 3 862 3 892 3 921 3 950 3 978
184 cm 3 725 3 756 3 787 3 818 3 848 3 878 3 907 3 936 3 965 3 994
185 cm 3 740 3 771 3 802 3 832 3 863 3 893 3 922 3 952 3 981 4 009
kg 60 61 62 63 64 65 66 67 68 69
145 cm 3 391 3 414 3 438 3 461 3 484 3 507 3 529 3 552 3 574 3 596
146 cm 3 408 3 431 3 455 3 478 3 501 3 524 3 547 3 569 3 591 3 613
147 cm 3 424 3 448 3 472 3 495 3 518 3 541 3 564 3 587 3 609 3 631
148 cm 3 441 3 465 3 489 3 512 3 535 3 558 3 581 3 604 3 627 3 649
149 cm 3 458 3 482 3 505 3 529 3 552 3 576 3 599 3 622 3 644 3 667
150 cm 3 474 3 498 3 522 3 546 3 570 3 593 3 616 3 639 3 662 3 684
151 cm 3 491 3 515 3 539 3 563 3 587 3 610 3 633 3 656 3 679 3 702
152 cm 3 507 3 532 3 556 3 580 3 604 3 627 3 650 3 674 3 697 3 719
153 cm 3 524 3 548 3 573 3 597 3 621 3 644 3 668 3 691 3 714 3 737
154 cm 3 540 3 565 3 589 3 614 3 638 3 661 3 685 3 708 3 731 3 754
155 cm 3 557 3 581 3 606 3 630 3 654 3 678 3 702 3 725 3 749 3 772
156 cm 3 573 3 598 3 623 3 647 3 671 3 695 3 719 3 743 3 766 3 789
157 cm 3 590 3 615 3 639 3 664 3 688 3 712 3 736 3 760 3 783 3 807
158 cm 3 606 3 631 3 656 3 681 3 705 3 729 3 753 3 777 3 801 3 824
469
kg 60 61 62 63 64 65 66 67 68 69
159 cm 3 622 3 647 3 672 3 697 3 722 3 746 3 770 3 794 3 818 3 841
160 cm 3 639 3 664 3 689 3 714 3 739 3 763 3 787 3 811 3 835 3 859
161 cm 3 655 3 680 3 705 3 730 3 755 3 780 3 804 3 828 3 852 3 876
162 cm 3 671 3 697 3 722 3 747 3 772 3 797 3 821 3 845 3 869 3 893
163 cm 3 687 3 713 3 738 3 764 3 789 3 813 3 838 3 862 3 886 3 910
164 cm 3 703 3 729 3 755 3 780 3 805 3 830 3 855 3 879 3 903 3 928
165 cm 3 720 3 746 3 771 3 797 3 822 3 847 3 872 3 896 3 921 3 945
166 cm 3 736 3 762 3 788 3 813 3 838 3 864 3 888 3 913 3 938 3 962
167 cm 3 752 3 778 3 804 3 830 3 855 3 880 3 905 3 930 3 955 3 979
168 cm 3 768 3 794 3 820 3 846 3 872 3 897 3 922 3 947 3 972 3 996
169 cm 3 784 3 810 3 837 3 862 3 888 3 914 3 939 3 964 3 988 4 013
170 cm 3 800 3 827 3 853 3 879 3 905 3 930 3 955 3 981 4 005 4 030
171 cm 3 816 3 843 3 869 3 895 3 921 3 947 3 972 3 997 4 022 4 047
172 cm 3 832 3 859 3 885 3 911 3 937 3 963 3 989 4 014 4 039 4 064
173 cm 3 848 3 875 3 901 3 928 3 954 3 980 4 005 4 031 4 056 4 081
174 cm 3 864 3 891 3 918 3 944 3 970 3 996 4 022 4 047 4 073 4 098
175 cm 3 880 3 907 3 934 3 960 3 987 4 013 4 039 4 064 4 090 4 115
176 cm 3 896 3 923 3 950 3 977 4 003 4 029 4 055 4 081 4 106 4 132
177 cm 3 912 3 939 3 966 3 993 4 019 4 046 4 072 4 097 4 123 4 148
178 cm 3 927 3 955 3 982 4 009 4 036 4 062 4 088 4 114 4 140 4 165
179 cm 3 943 3 971 3 998 4 025 4 052 4 078 4 105 4 131 4 156 4 182
180 cm 3 959 3 987 4 014 4 041 4 068 4 095 4 121 4 147 4 173 4 199
181 cm 3 975 4 003 4 030 4 057 4 084 4 111 4 137 4 164 4 190 4 216
182 cm 3 991 4 018 4 046 4 073 4 100 4 127 4 154 4 180 4 206 4 232
183 cm 4 006 4 034 4 062 4 089 4 117 4 143 4 170 4 197 4 223 4 249
184 cm 4 022 4 050 4 078 4 105 4 133 4 160 4 187 4 213 4 239 4 266
185 cm 4 038 4 066 4 094 4 121 4 149 4 176 4 203 4 229 4 256 4 282
kg 70 71 72 73 74 75 76 77 78 79
145 cm 3 618 3 639 3 661 3 682 3 703 3 724 3 745 3 765 3 786 3 806
146 cm 3 635 3 657 3 679 3 700 3 721 3 742 3 763 3 784 3 804 3 825
147 cm 3 653 3 675 3 697 3 718 3 739 3 761 3 782 3 802 3 823 3 844
148 cm 3 671 3 693 3 715 3 736 3 758 3 779 3 800 3 821 3 842 3 862
149 cm 3 689 3 711 3 733 3 754 3 776 3 797 3 818 3 839 3 860 3 881
470
kg 70 71 72 73 74 75 76 77 78 79
150 cm 3 706 3 729 3 751 3 772 3 794 3 816 3 837 3 858 3 879 3 900
151 cm 3 724 3 746 3 769 3 790 3 812 3 834 3 855 3 876 3 897 3 918
152 cm 3 742 3 764 3 786 3 808 3 830 3 852 3 873 3 895 3 916 3 937
153 cm 3 759 3 782 3 804 3 826 3 848 3 870 3 892 3 913 3 934 3 956
154 cm 3 777 3 800 3 822 3 844 3 866 3 888 3 910 3 931 3 953 3 974
155 cm 3 795 3 817 3 840 3 862 3 884 3 906 3 928 3 950 3 971 3 993
156 cm 3 812 3 835 3 858 3 880 3 902 3 924 3 946 3 968 3 990 4 011
157 cm 3 830 3 853 3 875 3 898 3 920 3 942 3 964 3 986 4 008 4 029
158 cm 3 847 3 870 3 893 3 916 3 938 3 960 3 982 4 004 4 026 4 048
159 cm 3 865 3 888 3 911 3 933 3 956 3 978 4 001 4 023 4 044 4 066
160 cm 3 882 3 905 3 928 3 951 3 974 3 996 4 019 4 041 4 063 4 085
161 cm 3 899 3 923 3 946 3 969 3 992 4 014 4 037 4 059 4 081 4 103
162 cm 3 917 3 940 3 963 3 986 4 009 4 032 4 055 4 077 4 099 4 121
163 cm 3 934 3 958 3 981 4 004 4 027 4 050 4 072 4 095 4 117 4 139
164 cm 3 951 3 975 3 998 4 022 4 045 4 068 4 090 4 113 4 135 4 158
165 cm 3 969 3 992 4 016 4 039 4 062 4 085 4 108 4 131 4 153 4 176
166 cm 3 986 4 010 4 033 4 057 4 080 4 103 4 126 4 149 4 171 4 194
167 cm 4 003 4 027 4 051 4 074 4 098 4 121 4 144 4 167 4 189 4 212
168 cm 4 020 4 044 4 068 4 092 4 115 4 139 4 162 4 185 4 207 4 230
169 cm 4 037 4 062 4 086 4 109 4 133 4 156 4 179 4 203 4 225 4 248
170 cm 4 055 4 079 4 103 4 127 4 150 4 174 4 197 4 220 4 243 4 266
171 cm 4 072 4 096 4 120 4 144 4 168 4 192 4 215 4 238 4 261 4 284
172 cm 4 089 4 113 4 137 4 162 4 185 4 209 4 233 4 256 4 279 4 302
173 cm 4 106 4 130 4 155 4 179 4 203 4 227 4 250 4 274 4 297 4 320
174 cm 4 123 4 147 4 172 4 196 4 220 4 244 4 268 4 291 4 315 4 338
175 cm 4 140 4 165 4 189 4 213 4 238 4 262 4 285 4 309 4 333 4 356
176 cm 4 157 4 182 4 206 4 231 4 255 4 279 4 303 4 327 4 350 4 374
177 cm 4 174 4 199 4 223 4 248 4 272 4 297 4 321 4 344 4 368 4 392
178 cm 4 191 4 216 4 241 4 265 4 290 4 314 4 338 4 362 4 386 4 409
179 cm 4 207 4 233 4 258 4 282 4 307 4 331 4 356 4 380 4 403 4 427
180 cm 4 224 4 250 4 275 4 300 4 324 4 349 4 373 4 397 4 421 4 445
181 cm 4 241 4 266 4 292 4 317 4 341 4 366 4 390 4 415 4 439 4 463
182 cm 4 258 4 283 4 309 4 334 4 359 4 383 4 408 4 432 4 456 4 480
183 cm 4 275 4 300 4 326 4 351 4 376 4 401 4 425 4 450 4 474 4 498
471
kg 70 71 72 73 74 75 76 77 78 79
184 cm 4 291 4 317 4 343 4 368 4 393 4 418 4 443 4 467 4 491 4 516
185 cm 4 308 4 334 4 360 4 385 4 410 4 435 4 460 4 485 4 509 4 533
kg 80 81 82 83 84 85 86 87 88 89 90
145 cm 3 826 3 846 3 866 3 886 3 906 3 925 3 944 3 964 3 983 4 002 4 021
146 cm 3 845 3 865 3 885 3 905 3 925 3 944 3 964 3 983 4 002 4 021 4 040
147 cm 3 864 3 884 3 904 3 924 3 944 3 964 3 983 4 003 4 022 4 041 4 060
148 cm 3 883 3 903 3 923 3 943 3 963 3 983 4 003 4 022 4 042 4 061 4 080
149 cm 3 902 3 922 3 942 3 963 3 983 4 002 4 022 4 042 4 061 4 081 4 100
150 cm 3 920 3 941 3 961 3 982 4 002 4 022 4 041 4 061 4 081 4 100 4 119
151 cm 3 939 3 960 3 980 4 001 4 021 4 041 4 061 4 081 4 100 4 120 4 139
152 cm 3 958 3 979 3 999 4 020 4 040 4 060 4 080 4 100 4 120 4 139 4 159
153 cm 3 977 3 997 4 018 4 039 4 059 4 079 4 099 4 119 4 139 4 159 4 178
154 cm 3 995 4 016 4 037 4 057 4 078 4 098 4 119 4 139 4 159 4 178 4 198
155 cm 4 014 4 035 4 056 4 076 4 097 4 117 4 138 4 158 4 178 4 198 4 218
156 cm 4 032 4 053 4 074 4 095 4 116 4 136 4 157 4 177 4 197 4 217 4 237
157 cm 4 051 4 072 4 093 4 114 4 135 4 155 4 176 4 196 4 217 4 237 4 257
158 cm 4 069 4 091 4 112 4 133 4 154 4 174 4 195 4 215 4 236 4 256 4 276
159 cm 4 088 4 109 4 130 4 152 4 173 4 193 4 214 4 235 4 255 4 275 4 295
160 cm 4 106 4 128 4 149 4 170 4 191 4 212 4 233 4 254 4 274 4 295 4 315
161 cm 4 125 4 146 4 168 4 189 4 210 4 231 4 252 4 273 4 293 4 314 4 334
162 cm 4 143 4 165 4 186 4 208 4 229 4 250 4 271 4 292 4 312 4 333 4 353
163 cm 4 161 4 183 4 205 4 226 4 248 4 269 4 290 4 311 4 332 4 352 4 373
164 cm 4 180 4 202 4 223 4 245 4 266 4 288 4 309 4 330 4 351 4 371 4 392
165 cm 4 198 4 220 4 242 4 263 4 285 4 306 4 328 4 349 4 370 4 390 4 411
166 cm 4 216 4 238 4 260 4 282 4 304 4 325 4 346 4 368 4 389 4 410 4 430
167 cm 4 234 4 257 4 279 4 300 4 322 4 344 4 365 4 386 4 408 4 429 4 450
168 cm 4 253 4 275 4 297 4 319 4 341 4 362 4 384 4 405 4 427 4 448 4 469
169 cm 4 271 4 293 4 315 4 337 4 359 4 381 4 403 4 424 4 445 4 467 4 488
170 cm 4 289 4 311 4 334 4 356 4 378 4 400 4 421 4 443 4 464 4 486 4 507
171 cm 4 307 4 329 4 352 4 374 4 396 4 418 4 440 4 462 4 483 4 505 4 526
172 cm 4 325 4 348 4 370 4 392 4 415 4 437 4 459 4 480 4 502 4 523 4 545
173 cm 4 343 4 366 4 388 4 411 4 433 4 455 4 477 4 499 4 521 4 542 4 564
174 cm 4 361 4 384 4 407 4 429 4 451 4 474 4 496 4 518 4 540 4 561 4 583
472
kg 80 81 82 83 84 85 86 87 88 89 90
175 cm 4 379 4 402 4 425 4 447 4 470 4 492 4 514 4 536 4 558 4 580 4 602
176 cm 4 397 4 420 4 443 4 466 4 488 4 511 4 533 4 555 4 577 4 599 4 620
177 cm 4 415 4 438 4 461 4 484 4 506 4 529 4 551 4 574 4 596 4 618 4 639
178 cm 4 433 4 456 4 479 4 502 4 525 4 547 4 570 4 592 4 614 4 636 4 658
179 cm 4 451 4 474 4 497 4 520 4 543 4 566 4 588 4 611 4 633 4 655 4 677
180 cm 4 468 4 492 4 515 4 538 4 561 4 584 4 607 4 629 4 651 4 674 4 696
181 cm 4 486 4 510 4 533 4 556 4 579 4 602 4 625 4 648 4 670 4 692 4 714
182 cm 4 504 4 528 4 551 4 574 4 598 4 621 4 643 4 666 4 689 4 711 4 733
183 cm 4 522 4 546 4 569 4 592 4 616 4 639 4 662 4 684 4 707 4 729 4 752
184 cm 4 540 4 563 4 587 4 610 4 634 4 657 4 680 4 703 4 725 4 748 4 770
185 cm 4 557 4 581 4 605 4 628 4 652 4 675 4 698 4 721 4 744 4 767 4 789
Table 2. Blood volume of men in mL as calculated

according to the ICSH formula
kg 50 51 52 53 54 55 56 57 58 59
160 cm 3 774 3 813 3 852 3 890 3 927 3 965 4 001 4 038 4 074 4 110
161 cm 3 795 3 834 3 873 3 911 3 949 3 986 4 023 4 060 4 096 4 132
162 cm 3 816 3 855 3 894 3 932 3 970 4 008 4 045 4 082 4 118 4 154
163 cm 3 837 3 876 3 915 3 954 3 992 4 030 4 067 4 104 4 140 4 177
164 cm 3 858 3 897 3 936 3 975 4 013 4 051 4 089 4 126 4 162 4 199
165 cm 3 878 3 918 3 957 3 996 4 035 4 073 4 110 4 148 4 184 4 221
166 cm 3 899 3 939 3 978 4 017 4 056 4 094 4 132 4 169 4 206 4 243
167 cm 3 919 3 960 3 999 4 038 4 077 4 116 4 154 4 191 4 228 4 265
168 cm 3 940 3 980 4 020 4 060 4 098 4 137 4 175 4 213 4 250 4 287
169 cm 3 961 4 001 4 041 4 081 4 120 4 158 4 197 4 235 4 272 4 309
170 cm 3 981 4 022 4 062 4 102 4 141 4 180 4 218 4 256 4 294 4 331
171 cm 4 002 4 042 4 083 4 123 4 162 4 201 4 240 4 278 4 316 4 353
172 cm 4 022 4 063 4 103 4 144 4 183 4 222 4 261 4 300 4 338 4 375
173 cm 4 042 4 084 4 124 4 164 4 204 4 244 4 283 4 321 4 359 4 397
174 cm 4 063 4 104 4 145 4 185 4 225 4 265 4 304 4 343 4 381 4 419
175 cm 4 083 4 125 4 166 4 206 4 246 4 286 4 325 4 364 4 403 4 441
176 cm 4 103 4 145 4 186 4 227 4 267 4 307 4 347 4 386 4 424 4 463
473
kg 50 51 52 53 54 55 56 57 58 59
177 cm 4 124 4 166 4 207 4 248 4 288 4 328 4 368 4 407 4 446 4 484
178 cm 4 144 4 186 4 228 4 269 4 309 4 349 4 389 4 429 4 468 4 506
179 cm 4 164 4 206 4 248 4 289 4 330 4 371 4 410 4 450 4 489 4 528
180 cm 4 184 4 227 4 269 4 310 4 351 4 392 4 432 4 471 4 511 4 550
181 cm 4 205 4 247 4 289 4 331 4 372 4 413 4 453 4 493 4 532 4 571
182 cm 4 225 4 267 4 310 4 351 4 393 4 433 4 474 4 514 4 554 4 593
183 cm 4 245 4 288 4 330 4 372 4 413 4 454 4 495 4 535 4 575 4 614
184 cm 4 265 4 308 4 350 4 393 4 434 4 475 4 516 4 556 4 596 4 636
185 cm 4 285 4 328 4 371 4 413 4 455 4 496 4 537 4 578 4 618 4 657
186 cm 4 305 4 348 4 391 4 434 4 476 4 517 4 558 4 599 4 639 4 679
187 cm 4 325 4 368 4 412 4 454 4 496 4 538 4 579 4 620 4 660 4 700
188 cm 4 345 4 389 4 432 4 475 4 517 4 559 4 600 4 641 4 682 4 722
189 cm 4 365 4 409 4 452 4 495 4 537 4 579 4 621 4 662 4 703 4 743
190 cm 4 385 4 429 4 472 4 515 4 558 4 600 4 642 4 683 4 724 4 764
191 cm 4 405 4 449 4 492 4 536 4 578 4 621 4 663 4 704 4 745 4 786
192 cm 4 424 4 469 4 513 4 556 4 599 4 641 4 683 4 725 4 766 4 807
193 cm 4 444 4 489 4 533 4 576 4 619 4 662 4 704 4 746 4 787 4 828
194 cm 4 464 4 509 4 553 4 597 4 640 4 683 4 725 4 767 4 808 4 849
195 cm 4 484 4 529 4 573 4 617 4 660 4 703 4 746 4 788 4 829 4 871
196 cm 4 503 4 549 4 593 4 637 4 681 4 724 4 766 4 809 4 850 4 892
197 cm 4 523 4 568 4 613 4 657 4 701 4 744 4 787 4 829 4 871 4 913
198 cm 4 543 4 588 4 633 4 677 4 721 4 765 4 808 4 850 4 892 4 934
199 cm 4 562 4 608 4 653 4 698 4 742 4 785 4 828 4 871 4 913 4 955
200 cm 4 582 4 628 4 673 4 718 4 762 4 806 4 849 4 892 4 934 4 976
kg 60 61 62 63 64 65 66 67 68 69
160 cm 4 145 4 180 4 215 4 249 4 283 4 317 4 350 4 384 4 417 4 449
161 cm 4 168 4 203 4 238 4 272 4 306 4 340 4 374 4 407 4 440 4 473
162 cm 4 190 4 225 4 260 4 295 4 329 4 363 4 397 4 431 4 464 4 497
163 cm 4 212 4 248 4 283 4 318 4 352 4 387 4 421 4 454 4 488 4 521
164 cm 4 235 4 270 4 306 4 341 4 375 4 410 4 444 4 478 4 511 4 544
165 cm 4 257 4 293 4 328 4 364 4 398 4 433 4 467 4 501 4 535 4 568
474
kg 60 61 62 63 64 65 66 67 68 69
166 cm 4 279 4 315 4 351 4 386 4 421 4 456 4 490 4 525 4 558 4 592
167 cm 4 302 4 338 4 374 4 409 4 444 4 479 4 514 4 548 4 582 4 615
168 cm 4 324 4 360 4 396 4 432 4 467 4 502 4 537 4 571 4 605 4 639
169 cm 4 346 4 383 4 419 4 454 4 490 4 525 4 560 4 594 4 629 4 663
170 cm 4 368 4 405 4 441 4 477 4 513 4 548 4 583 4 618 4 652 4 686
171 cm 4 390 4 427 4 464 4 500 4 535 4 571 4 606 4 641 4 675 4 710
172 cm 4 413 4 449 4 486 4 522 4 558 4 594 4 629 4 664 4 699 4 733
173 cm 4 435 4 472 4 508 4 545 4 581 4 617 4 652 4 687 4 722 4 756
174 cm 4 457 4 494 4 531 4 567 4 603 4 639 4 675 4 710 4 745 4 780
175 cm 4 479 4 516 4 553 4 590 4 626 4 662 4 698 4 733 4 768 4 803
176 cm 4 501 4 538 4 575 4 612 4 649 4 685 4 721 4 756 4 792 4 826
177 cm 4 522 4 560 4 598 4 635 4 671 4 708 4 744 4 779 4 815 4 850
178 cm 4 544 4 582 4 620 4 657 4 694 4 730 4 766 4 802 4 838 4 873
179 cm 4 566 4 604 4 642 4 679 4 716 4 753 4 789 4 825 4 861 4 896
180 cm 4 588 4 626 4 664 4 701 4 739 4 775 4 812 4 848 4 884 4 919
181 cm 4 610 4 648 4 686 4 724 4 761 4 798 4 835 4 871 4 907 4 942
182 cm 4 632 4 670 4 708 4 746 4 783 4 820 4 857 4 894 4 930 4 966
183 cm 4 653 4 692 4 730 4 768 4 806 4 843 4 880 4 916 4 953 4 989
184 cm 4 675 4 714 4 752 4 790 4 828 4 865 4 902 4 939 4 975 5 012
185 cm 4 697 4 736 4 774 4 812 4 850 4 888 4 925 4 962 4 998 5 035
186 cm 4 718 4 757 4 796 4 834 4 872 4 910 4 947 4 984 5 021 5 058
187 cm 4 740 4 779 4 818 4 856 4 895 4 932 4 970 5 007 5 044 5 080
188 cm 4 761 4 801 4 840 4 878 4 917 4 955 4 992 5 030 5 067 5 103
189 cm 4 783 4 822 4 862 4 900 4 939 4 977 5 015 5 052 5 089 5 126
190 cm 4 804 4 844 4 883 4 922 4 961 4 999 5 037 5 075 5 112 5 149
191 cm 4 826 4 866 4 905 4 944 4 983 5 021 5 060 5 097 5 135 5 172
192 cm 4 847 4 887 4 927 4 966 5 005 5 044 5 082 5 120 5 157 5 194
193 cm 4 869 4 909 4 949 4 988 5 027 5 066 5 104 5 142 5 180 5 217
194 cm 4 890 4 930 4 970 5 010 5 049 5 088 5 126 5 165 5 202 5 240
195 cm 4 911 4 952 4 992 5 032 5 071 5 110 5 149 5 187 5 225 5 263
196 cm 4 933 4 973 5 014 5 053 5 093 5 132 5 171 5 209 5 247 5 285
197 cm 4 954 4 995 5 035 5 075 5 115 5 154 5 193 5 232 5 270 5 308
198 cm 4 975 5 016 5 057 5 097 5 137 5 176 5 215 5 254 5 292 5 330
199 cm 4 997 5 038 5 078 5 119 5 158 5 198 5 237 5 276 5 315 5 353
475
kg 60 61 62 63 64 65 66 67 68 69
200 cm 5 018 5 059 5 100 5 140 5 180 5 220 5 259 5 298 5 337 5 375
kg 70 71 72 73 74 75 76 77 78 79
160 cm 4 482 4 514 4 545 4 577 4 608 4 639 4 670 4 701 4 731 4 761
161 cm 4 506 4 538 4 570 4 601 4 633 4 664 4 695 4 726 4 756 4 787
162 cm 4 530 4 562 4 594 4 626 4 657 4 689 4 720 4 751 4 782 4 812
163 cm 4 553 4 586 4 618 4 650 4 682 4 713 4 745 4 776 4 807 4 837
164 cm 4 577 4 610 4 642 4 675 4 706 4 738 4 770 4 801 4 832 4 862
165 cm 4 601 4 634 4 667 4 699 4 731 4 763 4 794 4 826 4 857 4 887
166 cm 4 625 4 658 4 691 4 723 4 755 4 787 4 819 4 850 4 882 4 913
167 cm 4 649 4 682 4 715 4 747 4 780 4 812 4 844 4 875 4 906 4 938
168 cm 4 673 4 706 4 739 4 772 4 804 4 836 4 868 4 900 4 931 4 963
169 cm 4 696 4 730 4 763 4 796 4 828 4 861 4 893 4 925 4 956 4 988
170 cm 4 720 4 753 4 787 4 820 4 852 4 885 4 917 4 949 4 981 5 012
171 cm 4 744 4 777 4 811 4 844 4 877 4 909 4 942 4 974 5 006 5 037
172 cm 4 767 4 801 4 835 4 868 4 901 4 934 4 966 4 998 5 030 5 062
173 cm 4 791 4 825 4 858 4 892 4 925 4 958 4 990 5 023 5 055 5 087
174 cm 4 814 4 848 4 882 4 916 4 949 4 982 5 015 5 047 5 080 5 112
175 cm 4 838 4 872 4 906 4 940 4 973 5 006 5 039 5 072 5 104 5 136
176 cm 4 861 4 896 4 930 4 963 4 997 5 030 5 063 5 096 5 129 5 161
177 cm 4 885 4 919 4 953 4 987 5 021 5 054 5 088 5 121 5 153 5 186
178 cm 4 908 4 943 4 977 5 011 5 045 5 079 5 112 5 145 5 178 5 210
179 cm 4 931 4 966 5 001 5 035 5 069 5 103 5 136 5 169 5 202 5 235
180 cm 4 955 4 990 5 024 5 059 5 093 5 127 5 160 5 193 5 227 5 259
181 cm 4 978 5 013 5 048 5 082 5 116 5 150 5 184 5 218 5 251 5 284
182 cm 5 001 5 036 5 071 5 106 5 140 5 174 5 208 5 242 5 275 5 308
183 cm 5 024 5 060 5 095 5 129 5 164 5 198 5 232 5 266 5 300 5 333
184 cm 5 047 5 083 5 118 5 153 5 188 5 222 5 256 5 290 5 324 5 357
185 cm 5 071 5 106 5 142 5 177 5 211 5 246 5 280 5 314 5 348 5 381
186 cm 5 094 5 129 5 165 5 200 5 235 5 270 5 304 5 338 5 372 5 406
187 cm 5 117 5 153 5 188 5 224 5 259 5 293 5 328 5 362 5 396 5 430
188 cm 5 140 5 176 5 212 5 247 5 282 5 317 5 352 5 386 5 420 5 454
189 cm 5 163 5 199 5 235 5 270 5 306 5 341 5 376 5 410 5 444 5 478
190 cm 5 186 5 222 5 258 5 294 5 329 5 364 5 399 5 434 5 468 5 503
476
kg 70 71 72 73 74 75 76 77 78 79
191 cm 5 209 5 245 5 281 5 317 5 353 5 388 5 423 5 458 5 492 5 527
192 cm 5 231 5 268 5 304 5 340 5 376 5 412 5 447 5 482 5 516 5 551
193 cm 5 254 5 291 5 327 5 364 5 400 5 435 5 470 5 506 5 540 5 575
194 cm 5 277 5 314 5 351 5 387 5 423 5 459 5 494 5 529 5 564 5 599
195 cm 5 300 5 337 5 374 5 410 5 446 5 482 5 518 5 553 5 588 5 623
196 cm 5 323 5 360 5 397 5 433 5 470 5 506 5 541 5 577 5 612 5 647
197 cm 5 345 5 383 5 420 5 456 5 493 5 529 5 565 5 600 5 636 5 671
198 cm 5 368 5 405 5 443 5 479 5 516 5 552 5 588 5 624 5 660 5 695
199 cm 5 391 5 428 5 466 5 503 5 539 5 576 5 612 5 648 5 683 5 719
200 cm 5 413 5 451 5 488 5 526 5 562 5 599 5 635 5 671 5 707 5 742
kg 80 81 82 83 84 85 86 87 88 89
160 cm 4 791 4 821 4 851 4 880 4 909 4 938 4 967 4 995 5 024 5 052
161 cm 4 817 4 847 4 876 4 906 4 935 4 964 4 993 5 022 5 050 5 078
162 cm 4 842 4 872 4 902 4 932 4 961 4 990 5 019 5 048 5 076 5 105
163 cm 4 868 4 898 4 928 4 957 4 987 5 016 5 045 5 074 5 103 5 131
164 cm 4 893 4 923 4 953 4 983 5 013 5 042 5 071 5 100 5 129 5 158
165 cm 4 918 4 948 4 979 5 009 5 038 5 068 5 097 5 127 5 155 5 184
166 cm 4 943 4 974 5 004 5 034 5 064 5 094 5 123 5 153 5 182 5 211
167 cm 4 968 4 999 5 030 5 060 5 090 5 120 5 149 5 179 5 208 5 237
168 cm 4 994 5 024 5 055 5 085 5 116 5 145 5 175 5 205 5 234 5 263
169 cm 5 019 5 050 5 080 5 111 5 141 5 171 5 201 5 231 5 260 5 290
170 cm 5 044 5 075 5 106 5 136 5 167 5 197 5 227 5 257 5 286 5 316
171 cm 5 069 5 100 5 131 5 162 5 192 5 223 5 253 5 283 5 312 5 342
172 cm 5 094 5 125 5 156 5 187 5 218 5 248 5 278 5 309 5 338 5 368
173 cm 5 119 5 150 5 181 5 212 5 243 5 274 5 304 5 334 5 364 5 394
174 cm 5 144 5 175 5 206 5 238 5 269 5 299 5 330 5 360 5 390 5 420
175 cm 5 168 5 200 5 232 5 263 5 294 5 325 5 355 5 386 5 416 5 446
176 cm 5 193 5 225 5 257 5 288 5 319 5 350 5 381 5 412 5 442 5 472
177 cm 5 218 5 250 5 282 5 313 5 345 5 376 5 407 5 437 5 468 5 498
178 cm 5 243 5 275 5 307 5 338 5 370 5 401 5 432 5 463 5 494 5 524
179 cm 5 267 5 300 5 332 5 363 5 395 5 426 5 458 5 488 5 519 5 550
180 cm 5 292 5 324 5 357 5 388 5 420 5 452 5 483 5 514 5 545 5 576
181 cm 5 317 5 349 5 381 5 414 5 445 5 477 5 508 5 540 5 571 5 601
477
kg 80 81 82 83 84 85 86 87 88 89
182 cm 5 341 5 374 5 406 5 438 5 470 5 502 5 534 5 565 5 596 5 627
183 cm 5 366 5 399 5 431 5 463 5 495 5 527 5 559 5 590 5 622 5 653
184 cm 5 390 5 423 5 456 5 488 5 521 5 553 5 584 5 616 5 647 5 678
185 cm 5 415 5 448 5 481 5 513 5 545 5 578 5 610 5 641 5 673 5 704
186 cm 5 439 5 472 5 505 5 538 5 570 5 603 5 635 5 667 5 698 5 730
187 cm 5 464 5 497 5 530 5 563 5 595 5 628 5 660 5 692 5 724 5 755
188 cm 5 488 5 521 5 555 5 588 5 620 5 653 5 685 5 717 5 749 5 781
189 cm 5 512 5 546 5 579 5 612 5 645 5 678 5 710 5 742 5 774 5 806
190 cm 5 537 5 570 5 604 5 637 5 670 5 703 5 735 5 767 5 800 5 831
191 cm 5 561 5 595 5 628 5 662 5 695 5 728 5 760 5 793 5 825 5 857
192 cm 5 585 5 619 5 653 5 686 5 719 5 752 5 785 5 818 5 850 5 882
193 cm 5 609 5 643 5 677 5 711 5 744 5 777 5 810 5 843 5 875 5 907
194 cm 5 633 5 668 5 702 5 735 5 769 5 802 5 835 5 868 5 900 5 933
195 cm 5 658 5 692 5 726 5 760 5 793 5 827 5 860 5 893 5 925 5 958
196 cm 5 682 5 716 5 750 5 784 5 818 5 851 5 885 5 918 5 951 5 983
197 cm 5 706 5 740 5 775 5 809 5 842 5 876 5 909 5 943 5 976 6 008
198 cm 5 730 5 764 5 799 5 833 5 867 5 901 5 934 5 968 6 001 6 033
199 cm 5 754 5 788 5 823 5 857 5 891 5 925 5 959 5 992 6 026 6 059
200 cm 5 778 5 813 5 847 5 882 5 916 5 950 5 984 6 017 6 051 6 084
kg 90 91 92 93 94 95 96 97 98 99
160 cm 5 080 5 107 5 135 5 163 5 190 5 217 5 244 5 271 5 297 5 324
161 cm 5 106 5 134 5 162 5 190 5 217 5 244 5 271 5 298 5 325 5 352
162 cm 5 133 5 161 5 189 5 217 5 244 5 272 5 299 5 326 5 353 5 379
163 cm 5 160 5 188 5 216 5 244 5 271 5 299 5 326 5 353 5 380 5 407
164 cm 5 186 5 215 5 243 5 271 5 298 5 326 5 353 5 381 5 408 5 435
165 cm 5 213 5 241 5 270 5 298 5 325 5 353 5 381 5 408 5 435 5 462
166 cm 5 239 5 268 5 296 5 324 5 353 5 380 5 408 5 436 5 463 5 490
167 cm 5 266 5 295 5 323 5 351 5 379 5 407 5 435 5 463 5 490 5 518
168 cm 5 292 5 321 5 350 5 378 5 406 5 434 5 462 5 490 5 518 5 545
169 cm 5 319 5 348 5 376 5 405 5 433 5 461 5 489 5 517 5 545 5 573
170 cm 5 345 5 374 5 403 5 432 5 460 5 488 5 517 5 545 5 572 5 600
171 cm 5 371 5 400 5 429 5 458 5 487 5 515 5 544 5 572 5 600 5 627
172 cm 5 398 5 427 5 456 5 485 5 514 5 542 5 571 5 599 5 627 5 655
478
kg 90 91 92 93 94 95 96 97 98 99
173 cm 5 424 5 453 5 482 5 511 5 540 5 569 5 597 5 626 5 654 5 682
174 cm 5 450 5 479 5 509 5 538 5 567 5 596 5 624 5 653 5 681 5 709
175 cm 5 476 5 506 5 535 5 564 5 594 5 622 5 651 5 680 5 708 5 736
176 cm 5 502 5 532 5 561 5 591 5 620 5 649 5 678 5 707 5 735 5 764
177 cm 5 528 5 558 5 588 5 617 5 647 5 676 5 705 5 734 5 762 5 791
178 cm 5 554 5 584 5 614 5 644 5 673 5 702 5 732 5 760 5 789 5 818
179 cm 5 580 5 610 5 640 5 670 5 700 5 729 5 758 5 787 5 816 5 845
180 cm 5 606 5 636 5 666 5 696 5 726 5 756 5 785 5 814 5 843 5 872
181 cm 5 632 5 662 5 693 5 723 5 752 5 782 5 811 5 841 5 870 5 899
182 cm 5 658 5 688 5 719 5 749 5 779 5 808 5 838 5 867 5 897 5 926
183 cm 5 684 5 714 5 745 5 775 5 805 5 835 5 865 5 894 5 923 5 953
184 cm 5 709 5 740 5 771 5 801 5 831 5 861 5 891 5 921 5 950 5 979
185 cm 5 735 5 766 5 797 5 827 5 857 5 888 5 917 5 947 5 977 6 006
186 cm 5 761 5 792 5 823 5 853 5 884 5 914 5 944 5 974 6 003 6 033
187 cm 5 786 5 818 5 848 5 879 5 910 5 940 5 970 6 000 6 030 6 060
188 cm 5 812 5 843 5 874 5 905 5 936 5 966 5 997 6 027 6 057 6 086
189 cm 5 838 5 869 5 900 5 931 5 962 5 992 6 023 6 053 6 083 6 113
190 cm 5 863 5 895 5 926 5 957 5 988 6 019 6 049 6 079 6 110 6 140
191 cm 5 889 5 920 5 952 5 983 6 014 6 045 6 075 6 106 6 136 6 166
192 cm 5 914 5 946 5 977 6 009 6 040 6 071 6 101 6 132 6 162 6 193
193 cm 5 940 5 971 6 003 6 034 6 066 6 097 6 128 6 158 6 189 6 219
194 cm 5 965 5 997 6 029 6 060 6 092 6 123 6 154 6 185 6 215 6 246
195 cm 5 990 6 022 6 054 6 086 6 117 6 149 6 180 6 211 6 241 6 272
196 cm 6 016 6 048 6 080 6 112 6 143 6 175 6 206 6 237 6 268 6 298
197 cm 6 041 6 073 6 105 6 137 6 169 6 200 6 232 6 263 6 294 6 325
198 cm 6 066 6 099 6 131 6 163 6 195 6 226 6 258 6 289 6 320 6 351
199 cm 6 091 6 124 6 156 6 188 6 220 6 252 6 284 6 315 6 346 6 377
200 cm 6 117 6 149 6 182 6 214 6 246 6 278 6 310 6 341 6 372 6 403
kg 100 101 102 103 104 105 106 107 108 109
160 cm 5 350 5 376 5 402 5 428 5 454 5 479 5 505 5 530 5 555 5 580
161 cm 5 378 5 404 5 430 5 456 5 482 5 508 5 534 5 559 5 584 5 609
162 cm 5 406 5 432 5 459 5 485 5 511 5 536 5 562 5 588 5 613 5 638
163 cm 5 434 5 460 5 487 5 513 5 539 5 565 5 591 5 616 5 642 5 667
479
kg 100 101 102 103 104 105 106 107 108 109
164 cm 5 462 5 488 5 515 5 541 5 567 5 593 5 619 5 645 5 671 5 696
165 cm 5 489 5 516 5 543 5 569 5 596 5 622 5 648 5 674 5 699 5 725
166 cm 5 517 5 544 5 571 5 597 5 624 5 650 5 676 5 702 5 728 5 754
167 cm 5 545 5 572 5 599 5 625 5 652 5 678 5 704 5 731 5 757 5 782
168 cm 5 572 5 600 5 626 5 653 5 680 5 706 5 733 5 759 5 785 5 811
169 cm 5 600 5 627 5 654 5 681 5 708 5 735 5 761 5 787 5 814 5 840
170 cm 5 628 5 655 5 682 5 709 5 736 5 763 5 789 5 816 5 842 5 868
171 cm 5 655 5 682 5 710 5 737 5 764 5 791 5 818 5 844 5 870 5 897
172 cm 5 682 5 710 5 737 5 765 5 792 5 819 5 846 5 872 5 899 5 925
173 cm 5 710 5 738 5 765 5 793 5 820 5 847 5 874 5 901 5 927 5 954
174 cm 5 737 5 765 5 793 5 820 5 848 5 875 5 902 5 929 5 955 5 982
175 cm 5 765 5 793 5 820 5 848 5 875 5 903 5 930 5 957 5 984 6 010
176 cm 5 792 5 820 5 848 5 876 5 903 5 930 5 958 5 985 6 012 6 039
177 cm 5 819 5 847 5 875 5 903 5 931 5 958 5 986 6 013 6 040 6 067
178 cm 5 846 5 875 5 903 5 931 5 958 5 986 6 014 6 041 6 068 6 095
179 cm 5 873 5 902 5 930 5 958 5 986 6 014 6 041 6 069 6 096 6 123
180 cm 5 901 5 929 5 957 5 986 6 014 6 041 6 069 6 097 6 124 6 151
181 cm 5 928 5 956 5 985 6 013 6 041 6 069 6 097 6 125 6 152 6 180
182 cm 5 955 5 983 6 012 6 040 6 069 6 097 6 125 6 152 6 180 6 208
183 cm 5 982 6 010 6 039 6 068 6 096 6 124 6 152 6 180 6 208 6 236
184 cm 6 009 6 038 6 066 6 095 6 123 6 152 6 180 6 208 6 236 6 263
185 cm 6 035 6 065 6 093 6 122 6 151 6 179 6 207 6 236 6 264 6 291
186 cm 6 062 6 092 6 121 6 149 6 178 6 207 6 235 6 263 6 291 6 319
187 cm 6 089 6 118 6 148 6 177 6 205 6 234 6 263 6 291 6 319 6 347
188 cm 6 116 6 145 6 175 6 204 6 233 6 261 6 290 6 318 6 347 6 375
189 cm 6 143 6 172 6 202 6 231 6 260 6 289 6 317 6 346 6 374 6 403
190 cm 6 169 6 199 6 229 6 258 6 287 6 316 6 345 6 373 6 402 6 430
191 cm 6 196 6 226 6 255 6 285 6 314 6 343 6 372 6 401 6 430 6 458
192 cm 6 223 6 253 6 282 6 312 6 341 6 370 6 399 6 428 6 457 6 486
193 cm 6 249 6 279 6 309 6 339 6 368 6 398 6 427 6 456 6 485 6 513
194 cm 6 276 6 306 6 336 6 366 6 395 6 425 6 454 6 483 6 512 6 541
195 cm 6 302 6 333 6 363 6 392 6 422 6 452 6 481 6 510 6 539 6 568
196 cm 6 329 6 359 6 389 6 419 6 449 6 479 6 508 6 538 6 567 6 596
197 cm 6 355 6 386 6 416 6 446 6 476 6 506 6 535 6 565 6 594 6 623
480
kg 100 101 102 103 104 105 106 107 108 109
198 cm 6 382 6 412 6 443 6 473 6 503 6 533 6 562 6 592 6 621 6 651
199 cm 6 408 6 439 6 469 6 500 6 530 6 560 6 589 6 619 6 649 6 678
200 cm 6 434 6 465 6 496 6 526 6 556 6 587 6 616 6 646 6 676 6 705
kg 110 111 112 113 114 115 116 117 118 119 120
160 cm 5 605 5 630 5 655 5 679 5 704 5 728 5 752 5 776 5 800 5 824 5 848
161 cm 5 634 5 659 5 684 5 709 5 733 5 758 5 782 5 806 5 830 5 854 5 878
162 cm 5 664 5 689 5 713 5 738 5 763 5 787 5 812 5 836 5 860 5 884 5 908
163 cm 5 693 5 718 5 743 5 767 5 792 5 817 5 841 5 866 5 890 5 914 5 938
164 cm 5 721 5 747 5 772 5 797 5 822 5 846 5 871 5 895 5 920 5 944 5 968
165 cm 5 750 5 776 5 801 5 826 5 851 5 876 5 901 5 925 5 950 5 974 5 998
166 cm 5 779 5 805 5 830 5 855 5 880 5 905 5 930 5 955 5 979 6 004 6 028
167 cm 5 808 5 834 5 859 5 884 5 910 5 935 5 960 5 984 6 009 6 034 6 058
168 cm 5 837 5 863 5 888 5 913 5 939 5 964 5 989 6 014 6 039 6 063 6 088
169 cm 5 866 5 891 5 917 5 943 5 968 5 993 6 018 6 043 6 068 6 093 6 118
170 cm 5 894 5 920 5 946 5 972 5 997 6 022 6 048 6 073 6 098 6 123 6 147
171 cm 5 923 5 949 5 975 6 001 6 026 6 052 6 077 6 102 6 127 6 152 6 177
172 cm 5 951 5 978 6 004 6 029 6 055 6 081 6 106 6 132 6 157 6 182 6 207
173 cm 5 980 6 006 6 032 6 058 6 084 6 110 6 135 6 161 6 186 6 211 6 236
174 cm 6 009 6 035 6 061 6 087 6 113 6 139 6 165 6 190 6 215 6 241 6 266
175 cm 6 037 6 063 6 090 6 116 6 142 6 168 6 194 6 219 6 245 6 270 6 295
176 cm 6 065 6 092 6 118 6 145 6 171 6 197 6 223 6 248 6 274 6 300 6 325
177 cm 6 094 6 120 6 147 6 173 6 200 6 226 6 252 6 278 6 303 6 329 6 354
178 cm 6 122 6 149 6 175 6 202 6 228 6 255 6 281 6 307 6 332 6 358 6 384
179 cm 6 150 6 177 6 204 6 231 6 257 6 283 6 310 6 336 6 362 6 387 6 413
180 cm 6 179 6 206 6 232 6 259 6 286 6 312 6 338 6 365 6 391 6 417 6 442
181 cm 6 207 6 234 6 261 6 288 6 314 6 341 6 367 6 394 6 420 6 446 6 472
182 cm 6 235 6 262 6 289 6 316 6 343 6 370 6 396 6 422 6 449 6 475 6 501
183 cm 6 263 6 290 6 317 6 345 6 371 6 398 6 425 6 451 6 478 6 504 6 530
184 cm 6 291 6 318 6 346 6 373 6 400 6 427 6 454 6 480 6 507 6 533 6 559
185 cm 6 319 6 347 6 374 6 401 6 428 6 455 6 482 6 509 6 535 6 562 6 588
186 cm 6 347 6 375 6 402 6 430 6 457 6 484 6 511 6 538 6 564 6 591 6 617
187 cm 6 375 6 403 6 430 6 458 6 485 6 512 6 539 6 566 6 593 6 620 6 646
188 cm 6 403 6 431 6 458 6 486 6 513 6 541 6 568 6 595 6 622 6 649 6 675
481
kg 110 111 112 113 114 115 116 117 118 119 120
189 cm 6 431 6 459 6 487 6 514 6 542 6 569 6 596 6 624 6 650 6 677 6 704
190 cm 6 459 6 487 6 515 6 542 6 570 6 597 6 625 6 652 6 679 6 706 6 733
191 cm 6 486 6 515 6 543 6 570 6 598 6 626 6 653 6 681 6 708 6 735 6 762
192 cm 6 514 6 542 6 570 6 598 6 626 6 654 6 682 6 709 6 736 6 763 6 791
193 cm 6 542 6 570 6 598 6 626 6 654 6 682 6 710 6 737 6 765 6 792 6 819
194 cm 6 569 6 598 6 626 6 654 6 683 6 710 6 738 6 766 6 793 6 821 6 848
195 cm 6 597 6 626 6 654 6 682 6 711 6 739 6 766 6 794 6 822 6 849 6 877
196 cm 6 625 6 653 6 682 6 710 6 739 6 767 6 795 6 823 6 850 6 878 6 905
197 cm 6 652 6 681 6 710 6 738 6 767 6 795 6 823 6 851 6 879 6 906 6 934
198 cm 6 680 6 709 6 737 6 766 6 794 6 823 6 851 6 879 6 907 6 935 6 962
199 cm 6 707 6 736 6 765 6 794 6 822 6 851 6 879 6 907 6 935 6 963 6 991
200 cm 6 735 6 764 6 793 6 821 6 850 6 879 6 907 6 935 6 963 6 991 7 019
482
APPENDIX 3.
DATA PROCESSING SYSTEMS
1. Planning of a system

There are a variety of computer systems and software programs
available and each has different functions. Prior to purchase, the user
should:
• establish a list of requirements that will meet the needs of
the user, including the duration of record keeping (in general
15 years in EU member states) and the duration of data keeping
for traceability (30 years are required under EU Directive
2002/98/EC);
• evaluate the different computer systems and choose the one that
meets the established requirements;
• audit the developer/manufacturer to ensure that they are able to
provide a product that meets regulatory requirements;
• establish responsibility between the user and the developer/
supplier/manufacturer to define roles and responsibilities
with regard to testing, user instructions, maintenance, system
improvements and access to source codes.
These steps ensure that the user has all the necessary information
about the purchased system and has an established relationship with
the developer. This course of action also minimises the need for
‘workarounds’ by the user, which can be a source of error.
2. Defining the system

The computer system of a blood establishment or hospital blood bank
includes: hardware, software, peripheral devices and documentation
(e.g. manuals and SOPs). To define the system, in co-operation with
the vendor or developer, the user should generate a written descrip-
tion of the system, the functions that it is designed to perform and all
human interactions. The documentation should be current, effectively
updated, accurate and as detailed as necessary to ensure proper opera-
tion of the system. The documentation should include:
484
Appendix 3. Data processing systems
• a detailed specification (inventory) of the hardware, software and

peripheral devices, including their environmental requirements
and limitations;
• diagrams or flow charts of the system’s operations that describe
all component interfaces, a network diagram (if applicable) and
all database structures, e.g. file sizes, input and output formats,
etc.;
• SOPs that describe how the system is used. The user should
develop the SOPs based on the instructions for use provided by
the software developer and the internal procedures of the blood
establishment or hospital blood bank. In particular, SOPs should
address all manual and automated interactions with the system
including:
– routine back-up, maintenance and diagnostic procedures,
including assignment of responsibilities;
– ‘workarounds’ for system limitations;
– procedures for handling errors, including assignment of
responsibilities;
– procedures for handling disasters and contingency planning,
including assignment of responsibilities;
– procedures for supervised changes to incorrect data;
– procedures for validation of a change;
– a training system including training manuals, documentation
and procedures for training.
3. Implementation and validation

Provisions of the Good Practice Guidelines for blood establishments
and hospital blood banks must be taken into account.
Validation documents and the results of tests performed and approved
by the supplier/vendor/developer of the system should be presented
to the user. The user can then perform tests according to a pre-de-
fined and documented test plan. Types of risk to consider include:
485
inadequate design of the system, errors that may occur in use (user
error or system defects), and loss/compromise of data. Testing should
involve the entire system, and in the manner it is expected to perform
in the blood facility. Testing may be performed by a third party but,
in that case, must also include personnel from the blood facility. The
following types of basic testing should be conducted:
Functional testing of components

The system components are presented with all types of expected in-
teraction, including normal value, boundary, invalid and special case
inputs. The system must produce the correct outputs, including error
messages by control programs. It is useful to perform this testing in
parallel with a reference or standard system.
Each test case should include the input, expected output, acceptance
criteria and whether the test passed or failed. For traceability purposes
and to facilitate quality assurance review and follow-up, it is recom-
mended that any supporting documentation, such as print- screens, be
included to verify the specific test case.
Data migration
The process for data migration should be defined, documented and
appropriately tested. This should ensure full maintenance of traceabil-
ity, including archiving of data where necessary.
Environmental testing
All qualification steps and results should be documented and ap-
proved before routine use of the system.
In the actual operating environment, functional tests are performed to
demonstrate that:
• the software systems work properly with the hardware;
• all applications of the software perform properly with the
operating system software;
486
• proper information passes correctly through system interfaces,

including appropriate data transfer to or from other laboratory
and automated (e.g. apheresis machine) systems, if applicable;
• accessories, such as barcode scanners, perform as expected with
the blood establishment’s barcode symbols;
• printed reports are appropriately and correctly formatted;
• personnel are trained and use the system correctly;
• the system performs properly at peak production times and with
the maximum number of concurrent users;
• back-ups restore data in a correct way;
• if the system includes wireless radio frequency (RF) technology,
it should be evaluated for electromagnetic compatibility (EMC)
and electromagnetic interference (EMI) in the setting in which it
is used.
Change control
In case of changes in the software, the validation status must be re-es-
tablished. If a revalidation analysis is needed, it should be based on
risk assessment and conducted not only for validation of the individ-
ual change, but also to determine the extent and impact of that change
on the entire computerised system.
Maintenance of the system

The database should be checked periodically and systematically to
identify and remove unwanted data such as duplicate records, and
to ensure that data entries are accurate and stored correctly. Manual
entry of critical data requires independent verification by a second
authorised person.
Security of the database should be maintained by:
• an adequate change history of the system, including both
software and hardware (when necessary);
487
• periodically altering electronic passwords (without reuse) and by

removing unnecessary or outdated access;
• creating records of all data changes, i.e. an audit trail, including
a retained record of the previous data and the reason for the
change;
• the appropriate use of programs to detect and remove computer
viruses;
• the control of administrative security access to ensure that only
authorised personnel can make changes to the software, to the
system configuration and to the data;
• regular testing to verify the proper integrity and accuracy of
backed up data.
Data should be archived periodically using a long-term stable medium
and placed ‘off-site’ at a location other than that of the hardware to
ensure safety. Such archives should be challenged at least annually to
verify data retrieval.
Procedures should be defined for:
• investigation and correction of discrepancies in the database;
• corrective actions to be taken when validation testing yields
unexpected results;
• handling, reporting, documenting and, if needed, correcting
real-time problems, errors and alarms;
• manual operations (contingency planning) in the event of any
system outage (even partial).
Quality assurance
The quality assurance programme should exercise oversight of the
electronic data processing systems that affect product quality. At a
minimum, such oversight should include:
488
• ensuring the ongoing accuracy and completeness of all

documentation on equipment, software maintenance and
operator training;
• performing periodic audits to verify proper accomplishment of
all performance tests, routine maintenance, change procedures,
data integrity checks, error investigations and operator
competency evaluations.
4. Electronic signature

Strict rules must be defined on using electronic signatures to docu-
ment or track required activities when collecting, processing, testing,
transporting, holding, distributing or issuing blood components.
Many member states have specific requirements for the use of elec-
tronic signatures in specific documentation or points of the transfu-
sion chain.
When in use, electronic signatures must be compliant with the
community framework for the use of electronic signatures and must
guarantee full compliance with the standards on traceability and doc-
umentation established by the EU Directives 2005/61 & 62. Member
states must ensure that electronic signatures can be used as evidence
in legal proceedings in all member states.
The ‘advanced electronic signature’ defines a process that does not
describe a particular technology, but rather a process that creates an
enforceable electronic signature if the signature:
• is uniquely linked to the signatory;
• is capable of identifying the signatory;
• is created using means that the signatory can maintain under
their sole control;
• is linked to the data to which it relates in such a manner that any
subsequent change in the data is detectable.
An advanced signature is generally taken to be a specific type of elec-
tronic signature that meets an additional set of criteria for signatory
489
identification. The main purpose of an advanced electronic signature

is authentication, i.e. to give added assurance that the individual
signing the message really is the person that he or she claims to be.
General requirements
Each electronic signature should be unique to one individual and
should not be reused by, or reassigned to, anyone else.
Before an organisation establishes, assigns, certifies or otherwise
sanctions an individual’s electronic signature, or any element of such
electronic signature, the organisation should verify the identity of the
individual.
Signature manifestations
Signed electronic records should contain information associated with
the signing that clearly indicates all of the following:
• the printed name of the signatory;
• the date and time when the signature was executed;
• the meaning (such as review, approval, responsibility, or
authorship) associated with the signature.
Signature/record linking
Electronic signatures should be linked to their respective electronic
records to ensure that the signatures cannot be excised, copied or
otherwise transferred so as to falsify an electronic record by ordinary
means.
Controls for identification codes/passwords/biometrics

Persons who use electronic signatures based upon use of identifica-
tion codes in combination with passwords should employ controls to
ensure their security and integrity. Such controls shall include:
• maintaining the uniqueness of each combined identification
code and password, such that no two individuals have the same
combination of identification code and password;
490
• ensuring that identification code and password issuances are

periodically checked, recalled, or revised (e.g., to cover such
events as password ageing);
• following loss management procedures to electronically
unauthorise lost, stolen, missing, or otherwise potentially
compromised tokens, cards, and other devices that bear or
generate identification code or password information, and to
issue temporary or permanent replacements using suitable,
rigorous controls;
• use of transaction safeguards to prevent unauthorised use of
passwords and/or identification codes, and to detect and report
in an immediate and urgent manner any attempts at their
unauthorised use to the system security unit, and, as appropriate,
to organisational management;
• initial and periodic testing of devices, such as tokens or
cards, that bear or generate identification code or password
information, to ensure that they function properly and have not
been altered in an unauthorised manner.
491
APPENDIX 4.
STATISTICAL PROCESS CONTROL
493
1. Introduction
Statistical Process Control (SPC) is a tool that enables an organisa-
tion to detect changes in the processes and procedures it carries out
by monitoring data collected over a period of time in a standardised
fashion. SPC became mandatory in 2005 for blood establishments
in the EU (Directive 2004/33/EC). Methods and standards for the
application of SPC to quality assurance of blood components need to
be continuously studied and further developed. The technique can be
applied to all activities in a blood facility, including administrative/
clerical, scientific and technical processes. It is important that the
processes to which SPC are to be applied are prioritised due to the
amount of work involved. Currently, SPC is proving most beneficial in
monitoring the performance of infectious markers and leucocyte-de-
pletion testing. SPC is one of the few methods that can show how an
improvement to a process has achieved the desired result, and enables
decision-making to be placed on a much more rational and scientific
basis.
2. Implementation of SPC

As for all other aspects of quality, implementation of SPC demands
understanding and commitment on the part of the management of
the blood facility. It must be included in the quality system of the
facility, and a training programme should be introduced for senior
management as well as operational staff. Plans must be made for data
collection, including of control charts, and all matters dealing with
changes detected in processes, especially sudden situations. Regular
reviews of processes against SPC data should take place, with the spe-
cific objective of continuous improvement.
3. Strategy for statistical sampling

As much as possible, the number and frequency of components
sampled for quality control and the number of test failures per sample
that trigger an appropriate response (e.g. investigation or re-validation
of materials and procedures) should be based on the considerations
detailed below.
494
Appendix 4. Statistical Process Control
Tolerance of failure
A ‘target failure rate’ should be established as the failure rate that
should not be exceeded. This ensures that monitoring of aspects of
quality is continuous and that a failure rate exceeding target values
triggers appropriate corrective action.
Confidence level
A confidence level should be set for the detection of an actual failure
rate that lies above the ‘target failure rate’.
A valid method of statistical analysis should be used to determine
either actual failure rate lies above the ‘target failure rate’.
4. Frequency of control sampling

A number of challenges arise in framing statistically based quality
control testing programs for labile blood components. Due to the
complexity of the transfusion system, blood facilities should consult
statistical experts when designing process control systems. Issues
include the: very large variation in volumes of blood components
at different blood establishments; need to minimise losses in blood
components through testing at small centres; very low expected rate of
non-conformance for some processes, and the number of discrete con-
ditions that arise in the manufacture of otherwise similar components.
These may include:
• number of sites, operators and work shifts;
• different collection and processing systems and equipment;
• use of multiple reagent lots;
• alternative preparation times and temperatures;
• donor-related variables may affect the final quality of the blood
component, even in a fully controlled process (e.g. for HbS donor
blood with poor leucofiltration properties);
495
• the fact that blood components may be used for more than one
clinical indication and require different levels of control (e.g.
leucocyte-depleted RBCs for neonates vs for general transfusion).
Additionally, in many cases, the medical basis for currently accepted
quality standards has not been rigorously established, making it
difficult to determine the level of deviation from the expected level of
conformance that can be tolerated. Nevertheless, to implement SPC,
blood establishments need to establish the ‘target failure rate’ that
should not be exceeded for each control test.
It is also desirable that the criterion for non-conformance should have
at least a power of 80 per cent to detect the target failure rate, while
giving a false-positive result in fewer than 5 % of determinations.
Consideration must also be given to the strategy for representative
sampling of units for control testing. Because similar components
are prepared under a variety of conditions, it is important that the
sample set should include representative units prepared in all possible
ways. Sampling may need to be stratified accordingly (i.e. to include a
minimum number of samples from each condition).
The sample numbers specified for statistically valid process controls
are minimum samples. In circumstances in which there are multi-
ple processing conditions, and in blood establishments with large
volumes of blood components, quality-control testing should be
increased above the statistically determined minimum. This should be
done in a controlled manner through the application of more rigorous
statistical parameters, such as an increase in the expected proportion
of samples that conform to a defined standard.
Additional considerations that may apply to the design of a quality
control strategy include:
• the public-health importance of the standard being controlled
(i.e. the period of time during which a process deviation could be
tolerated before detection and correction);
• the overall blood component volume;
496
• the capacity for sampling and quality-control testing of the

facility, including whether the quality-control testing is ablative
(i.e. destructive of the processed blood component);
• the target failure rate of a process that is in control;
• a pre-defined strategy for managing non-process failures, e.g. a
failed leucocyte-depletion procedure where further evaluation
determined that the donor was HbS positive.
Three methods of statistical process control are provided below as
examples.1
Example 1. Use of control charts

By plotting historical and prospective data on specially constructed
charts, signs of process change can often be detected at an early stage,
enabling remedial action to be taken. Steps for the construction of
SPC charts are the same for all applications:
• collection of historical data;
• calculation of ‘location and variation statistics’ (see below);
• calculation of statistical control limits for the location and
variation statistics;
• construction of the chart;
• plotting of prospective data.
Two types of data are conventionally collected:
• variable data, appropriate to anything that is measured directly
such as cell count, pH, time taken for a process, etc.;
• attribute data, appropriate to anything that is counted on a ‘yes
or no’ basis.
The type of SPC chart used depends on the type of data collected.
1 Beckman N, Nightingale MJ, Pamphilon D. Practical guidelines for applying

statistical process control to blood component blood component. Transfus
Med 2009; 19: 329-39.
497
Control charts for variable data

Major applications in a blood establishment are likely to be Individ-
ual/Moving Range charts and Average/Range charts.
Individual/Moving Range charts are used where a process is monitored
by a single measurement on the sample, of the parameter in question
e.g. residual leucocyte count on a platelet preparation. The steps for
constructing an SPC chart are as follows:
• historical data are collected by measuring a random sample each
day, and the moving range established by taking the difference
between each sample and its predecessor;
• the location statistic is the average of the individual counts,
whereas the variation statistic is the average moving range;
• the natural variation in a process is defined as the process
average, plus or minus 3 standard deviations. Hence, the Upper
Control Limit (UCL) and the Lower Control Limit (LCL) for
the location and variation statistics are determined as the
appropriate average, plus and minus 3 standard deviations;
• SPC charts conventionally have two distinct parts: one for the
location statistic, which appears above the other for the variation
statistic. For each part, the average is drawn as a solid line
between two dotted lines that signify the UCL and LCL.
Prospective data are plotted on SPC charts in a similar way.
Average/Range charts are used in a situation where an early statistical
response to a small process change is required, and where multiple
control samples (up to 10) are subjected to the process. A typical
example might be repeated use of a control sample during the daily
use of a cytometer. In this situation, the average daily count on the
control sample is calculated, the location statistic being the average of
the averages. Each day shows a range in the control counts; the varia-
tion statistic is the average of these ranges. The Average/Range chart
is then constructed in a similar manner to the Individual/Moving
Range chart, except that the LCL for the Range part of the chart is, by
definition, zero.
498
Control charts for attribute data

Attribute data, in general, fall into one of two categories: those
counting the number of units sampled which are defective, and
those counting the incidence of non-conformance to a requirement
(each non-conformance in this case being classified as a defect). For
example, a completed form is classified as ‘defective’ even if it contains
only one non-conformance (though it may, in fact, contain multiple
defects).
Attribute charts for the proportion of defective units (sometimes known
as p-charts) are based on the calculation of the proportion of units
found to be defective, i.e. having one or more defects per unit sampled,
in sets of units sampled at intervals. The location statistic for the
attribute is calculated by dividing the total number of defective units
by the total number of units sampled, unless the sets of samples are
always the same size, in which case the average of the proportion of
defective units in each set may be taken. Since the data stem from yes/
no criteria, attribute charts do not have a variation statistic.
UCL and LCL are determined as described above. In this system, it
is possible to arrive at a negative value for the LCL, in which case it
defaults to zero.
It should be noted that the calculation of standard deviation in a yes/
no system such as this depends on the sample size. Hence, an increase
or decrease in the set of units sampled necessitates re-establishing
the UCL and LCL. An increase in sampling size generally results in
convergence of UCL and LCL, making the system more sensitive to
changes in the process.
Construction of the chart is carried out as described above.
Attribute charts for defects (sometimes known as u-charts) are gener-
ally useful when the object under investigation often has more than
one non-conformance with requirements. They are well-suited to the
control of clerical procedures. Collection of historical data involves
counting the number of defects in each unit of a set of samples, re-
peated at intervals.
499
The location statistic is the average number of defects per unit, calcu-
lated by dividing the total number of defects in the total number of
historical samples. As before, there is no variation statistic for attrib-
ute data.
Once again, UCL and LCL are calculated on the basis of the location
statistic, plus and minus 3 standard deviations. Standard deviation
in this system again depends on sample size, and any prospective
increase requires re-establishment of the UCL and LCL.
The likely result is a convergence on the average, facilitating the detec-
tion of smaller changes in the process.
Construction of the u-chart follows the convention set for all SPC
charts.
Interpretation of control charts

In general, if prospective data are plotted on the control chart and
they follow the pattern established using historical data, the process
may be assumed to be ‘in control’. Changes in the pattern area reliable
and sensitive means of detecting that a change has taken place in the
process, warranting investigations into the cause. Rules have been es-
tablished to give guidance to users as to when a change has occurred:
• rule 1: any point outside one of the control limits;
• rule 2: seven consecutive points all above or all below the average
line;
• rule 3: seven consecutive points all increasing or all decreasing (a
particular indicator of drift in the process average or range).
In addition, any unusual pattern or trend within the control lines may
be an indicator of change.
Should information from the charts indicate that unplanned change
is taking place within the process, action should be taken to identify
any specific or common cause of the change. Application of SPC is
the most reliable way of confirming that measures taken to improve
the efficiency of a process are giving the desired results, by showing
500
reduction in variation around the mean (for measured data) or a trend

toward zero defects (for counted data).
Example 2. Method of scan statistics

The method of scan statistics provides a suitable model for determin-
ing the frequency of control testing.2 In this method, the number
of non-conforming test results in a fixed sample size is determined.
However, the sample set is regarded as a ‘window’ of observations that
‘moves’ progressively as test results are accumulated. For example, if
the ‘window size’ is set at 60 observations, the first test set includes
observations 1 through to 60; the second test set includes observations
2 through to 61; the third test set includes observations 3 through to
62. Progression of the ‘window’ can also be done a few samples at a
time, such as by addition of daily test results as a group. To apply this
method, the blood facility must identify a reasonably large ‘uni-
verse’ of ultimate test samples, typically representing a year or more
of testing, or a period after which routine re-validation might be
expected to occur because of process modifications (e.g. equipment
replacement, software upgrades). The size of the moving window can
then be determined based on the expected rate of failed tests for a
conforming process (as defined in the Quality Control tables of each
component described in Chapter 5), the size of the test universe, and
the target failure rate to be detected as indicating a non-conforming
process. The table below shows the minimum failure rate that can
be detected at 80 per cent or greater power in any single window of
control tests for test criteria with false-positive rates below 5 %.
Requiring that the number of control tests in the ‘window’ should
take place in the desired time interval yields the frequency of control
testing.
The following example illustrates how the method of scan statistics
can be used.
2 Glaz J, Naus J, Wallenstein S, Scan Statistics. 2001; Springer, New York.
501
A blood facility seeks to monitor the failure rate of Leucocyte-

Depleted. The expected failure rate (rate of non-conforming tests
for a conforming process) is taken to be 0.1 %. The facility sets an
action trigger at 5 % as a means to detect a defective lot of filters. The
quality-control standard is established to ensure, with at least 80 %
confidence, that a true failure rate of 5 % would be detected, but at a
false-positive rate below 5 % for a declaration of non-conformance.
For a blood facility with 400 quality-control tests per year (approx-
imately 34 per month), a non-conforming process can be declared
if, in any ‘moving window’ of 60 consecutive such tests, two or more
non-conforming test results are found (i.e. the trigger is greater than
one non-conforming test in any window of 60 tests). This model has a
power of 80.8 % to detect a true rate of non-conformance of 5 % in any
window of 60 tests, and near certainty to detect this rate over 1 year.
Based on scan statistics, the false-positive rate of such declarations is
only 2.0 %.
If the number of quality control tests is 1 200 per year (100 per month),
a non-conforming process can be declared if in any ‘moving window’
of 120 sequential quality control tests, three or more non-conforming
test results are found. The false-positive rate of such declarations is
only 0.7 %. The power is 80.7 % to detect a non-conformance rate of
4.6 % (the power is 85.6 % to detect a 5 % failure rate) for any window
of 120 tests, and near certainty over 1 year.
502
Table 1. Sample size (‘window’) and maximum number of failed

tests allowed for a conforming process based on scan statistics
Allowed Number Sample Maxi- False Minimum failure rate of a

failure of tests size (i.e. mum positive non-conforming process
rate for a in the fixed allowed rate detectable at > 80 % power
con- ‘universe’ number number of test in any single ‘window’
forming (e.g. the of tests of failed criterion
process number in a tests in Minimum Power to
of tests moving window ‘target fail- detect non-
per year) ‘win- ure rate’ for conforming
dow’) a non-con- process in
forming any window
process of quality
control tests
25 % 400 30 16 2.5 % 63 % 81.9 %

60 26 2.9 % 50 % 81.7 %
1 200 30 17 2.0 % 66 % 81.3 %
60 27 3.8 % 52 % 83.0 %
10 % 400 30 9 3.5 % 40 % 82.4 %
60 14 2.7 % 30 % 83.8 %
1 200 30 10 2.8 % 43 % 81.1 %
5 % 400 30 6 3.7 % 29 % 81.0 %
60 9 2.3 % 21 % 83.7 %
1 200 30 7 2.2 % 33 % 82.3 %
1 % 400 30 3 1.0 % 18 % 81.4 %
60 4 0.9 % 11 % 80.3 %
1 200 60 4 2.7 % 11 % 80.3 %
503
Allowed Number Sample Maxi- False Minimum failure rate of a

failure of tests size (i.e. mum positive non-conforming process
rate for a in the fixed allowed rate detectable at > 80 % power
con- ‘universe’ number number of test in any single ‘window’
forming (e.g. the of tests of failed criterion
process number in a tests in Minimum Power to
of tests moving window ‘target fail- detect non-
per year) ‘win- ure rate’ for conforming
dow’) a non-con- process in
forming any window
process of quality
control tests
0.1 % 400 30 1 1.1 % 10 % 81.6 %

60 1 2.0 % 5 % 80.8 %
1 200 30 1 3.2 % 10 % 81.6 %
120 2 0.7 % 4.6 % 80.7 %
Example 3. Statistical process control

for dichotomous outcomes: an approach based
upon hypergeometric/binomial distributions
A hypergeometric distribution is based upon random sampling
(without replacement) of a factor that has a dichotomous outcome.
This distribution is applicable for the assessment of quality control
measures related to blood components for which the outcome is pass/
fail. A binomial distribution is very similar to a hypergeometric distri-
bution, but it is based upon sampling with replacement. At sampling
levels of n ≥ 59 to meet the 95 % criterion, these two distributions are
essentially identical.
For statistical quality control using the hypergeometric/binomial
approach, a cycle is defined as the blood-component volume that is
being subject to quality assessment within a defined time period. The
appropriate size for a quality-control cycle is determined based upon
504
the desired frequency of control sampling as described above and the

selected proportion of conforming samples.3
Statistical quality control based upon a hypergeometric distribution
is applicable for cycle sizes between n = 30 and n = 4 500.4 Successful
control requires that predetermined random sample sizes be assessed
with an outcome of 0, 1 or 2 failures, depending on the cycle size.
For cycle sizes above n = 4 500, the hypergeometric distribution
approaches the binomial distribution and the traditional binomial ap-
proach can be applied, i.e. assessing n = 60 random samples per cycle
with an outcome of zero failures; n = 93 with one failure or n = 124
with 2 failures.
3 For example, 95 % conformance (and the resulting high level of quality-con-
trol testing) would be appropriate for a safety-related blood component
standard such as residual leucocytes in a Leucocyte-Depleted component.
However, 75 % conformance may be acceptable for a standard such as compo-
nents content, where standardisation is desirable, but is not directly related to
recipient safety.
4 For a cycle size of 30, greater than 95 % conformance is reflected by, at most,
one non-conforming unit because 29/30 = 96.7 % and 28/30 = 93.3 %. To
define this conformance statistically, it is necessary to be able to conclude with
95 % confidence that greater than 95 % of the units are conforming (i.e. ≤ n = 1
non-conforming unit for a cycle size of n = 30). Using a null hypothesis that
there are at least two non-conforming units among the 30 units, the alterna-
tive hypothesis is that there are fewer than two non-conforming units among
the 30 units. Under this null hypothesis, the probability that the first 22 units
are all good is 6.4 %, which is calculated as:
28 × 27 × 26 … 9 × 8 × 7 = 8 × 7 = 0.064
30 29 28 11 10 9 30 × 29
So the null hypothesis cannot be rejected at the 5 % significance level, which
corresponds to ‘with 95 % confidence’.
Under the null hypothesis stated above, the probability that the first 23 units
are all good is 4.8 %:
28 × 27 × 26 … 8 × 7 × 6 = 7 × 6 = 0.048
30 29 28 10 9 8 30 × 29
So the null hypothesis can be rejected at the 5 % significance level which
corresponds to ‘with 95 % confidence’. Thus, 23 samples without a non-
conformance are needed to conclude with 95 % confidence that greater than
95 % of the units are conforming.
505
The table below provides random sample sizes across a range of cycle
sizes. With a larger cycle size, 1 or 2 occurrences of non-conformance
are allowed in conjunction with a larger pre-specified sample size.
For example, if the cycle size is 65 (95 %/95 %), there are three options
that need to be pre-determined: a sample size of 34 without any
failure, a sample size of 49 with 1 failure, or a sample size of 59 with 2
failures. If (i) a sample size of 34 and observation of one failure, or (ii)
a sample size of 49 and observation of two failures is chosen, 100 per
cent quality control can still be done to make the final determination,
whether or not greater than 95 per cent of the components meet the
standard.
After the cycle size reaches 7 000 for 95 %/95 % and 13 000 for
95 %/75 %, the results based on the hypergeometric distribution are
same as those based on a binomial distribution.
506
Table 2. Sizes of random samples needed at various quality control cycle sizes to
assess 95 %, 90 % or 75 % conformance to a standard with 95 % confidence
95 %/95 % 95 %/90 % 95 %/75 %

95 % confidence that > 95 % of the 95 % confidence that > 90 % of the 95 % confidence that > 75 % of the
components meet the standard components meet the standard components meet the standard
Lot size Failures Sample size Failures Sample size Failures Sample size
allowed allowed allowed
in lot No failure 1 failure 2 failures in lot No failure 1 failure 2 failures in lot No failure 1 failure 2 failures
allowed allowed allowed allowed allowed allowed
30 1 23 30 N/A 2 19 26 30 7 9 13 17
31 1 24 31 N/A 3 16 23 28 7 9 14 18

32 1 25 32 N/A 3 17 24 29 7 9 14 18
33 1 26 33 N/A 3 17 25 30 8 9 13 17
34 1 26 34 N/A 3 18 25 31 8 9 14 18
35 1 27 35 N/A 3 18 26 32 8 9 14 18
36 1 28 36 N/A 3 19 27 33 8 9 15 19
37 1 29 37 N/A 3 19 28 33 9 9 14 18
507
508
95 %/95 % 95 %/90 % 95 %/75 %

38 1 30 38 N/A 3 20 28 34 9 9 14 18
39 1 30 39 N/A 3 20 29 35 9 9 15 19
40 1 31 39 N/A 3 21 30 36 9 10 15 19
45 2 28 39 45 4 20 29 36 11 9 14 19
50 2 31 43 50 4 22 33 40 12 9 15 19
55 2 35 48 55 5 21 32 40 13 10 15 20
60 2 38 52 60 5 23 34 43 14 10 16 21
65 3 34 49 59 6 22 33 42 16 10 15 20
70 3 37 52 63 6 24 36 46 17 10 16 20
75 3 39 56 68 7 23 35 44 18 10 16 21
95 %/95 % 95 %/90 % 95 %/75 %
80 3 42 60 72 7 24 37 47 19 10 16 21
85 4 38 56 69 8 23 36 46 21 10 16 21
90 4 40 59 73 8 25 38 49 22 10 16 21

95 4 42 62 77 9 24 37 47 23 10 16 21
100 4 45 65 81 9 25 39 50 24 10 16 22
120 5 47 69 87 11 26 40 52 29 10 17 22
140 6 48 72 92 13 26 41 53 34 11 17 22
160 7 49 75 95 15 27 41 54 39 11 17 22
180 8 50 77 98 17 27 42 55 44 11 17 22
200 9 51 78 101 19 27 42 55 49 11 17 23
509
510
95 %/95 % 95 %/90 % 95 %/75 %

220 10 52 79 103 21 27 42 56 54 11 17 23
240 11 52 80 104 23 27 43 56 59 11 17 23
260 12 53 81 106 25 27 43 57 64 11 17 23
280 13 53 82 107 27 28 43 57 69 11 17 23
300 14 54 83 108 29 28 43 57 74 11 17 23
320 15 54 83 109 31 28 44 57 79 11 17 23
340 16 54 84 110 33 28 44 58 84 11 17 23
360 17 54 85 111 35 28 44 58 89 11 17 23
380 18 55 85 111 37 28 44 58 94 11 17 23
400 19 55 85 112 39 28 44 58 99 11 17 23
95 %/95 % 95 %/90 % 95 %/75 %
450 22 54 84 111 44 28 44 59 112 11 17 23

500 24 56 87 114 49 28 44 59 124 11 17 23
550 27 55 86 113 54 28 45 59 137 11 17 23

600 29 56 88 116 59 28 45 59 149 11 17 23
650 32 56 87 115 64 28 45 59 162 11 17 23
700 34 57 89 117 69 28 45 60 174 11 17 23
750 37 56 88 116 74 28 45 60 187 11 17 23
800 39 57 89 118 79 28 45 60 199 11 17 23
850 42 56 89 117 84 28 45 60 212 11 17 23
900 44 57 90 119 89 28 45 60 224 11 17 23
511
512
95 %/95 % 95 %/90 % 95 %/75 %

950 47 57 89 118 94 29 45 60 237 11 17 23

1000 49 57 90 119 99 29 45 60 249 11 17 23
1500 74 58 91 121 149 29 45 60 374 11 17 23
2000 99 58 92 122 199 29 46 61 499 11 17 23
2500 124 58 92 122 249 29 46 61 624 11 17 23
3000 149 58 92 123 299 29 46 61 749 11 17 23
3500 174 58 93 123 349 29 46 61 874 11 17 23
4000 199 58 93 123 399 29 46 61 999 11 17 23
4500 224 59 93 123 449 29 46 61 1124 11 17 23
5000 249 59 93 123 499 29 46 61 1249 11 17 23
95 %/95 % 95 %/90 % 95 %/75 %
6000 299 59 93 123 599 29 46 61 1499 11 17 23

7000 349 59 93 124 699 29 46 61 1749 11 17 23
8000 399 59 93 124 799 29 46 61 1999 11 17 23

9000 449 59 93 124 899 29 46 61 2249 11 17 23
10000 499 59 93 124 999 29 46 61 2499 11 17 23
11000 549 59 93 124 1099 29 46 61 2749 11 17 23
12000 599 59 93 124 1199 29 46 61 2999 11 17 23
13000 649 59 93 124 1299 29 46 61 3249 11 18 23
14000 699 59 93 124 1399 29 46 61 3499 11 18 23
15000 749 59 93 124 1499 29 46 61 3749 11 18 23
513
APPENDIX 5.
HEALTH ECONOMICS IN
BLOOD TRANSFUSION
515
1. Overview
Providing blood is expensive and the heavy burden that it places on
national health budgets may continue to grow as it becomes necessary
to implement further safety measures, including extra screening tests,
new pathogen reduction technologies and additional quality require-
ments. Under these circumstances, costs throughout the blood trans-
fusion chain from donor to recipient are bound to come under intense
scrutiny as funders seek to economise and increasingly demand value
for money.
The objective for blood establishments responsible for preparing, con-
trolling and issuing blood components should be to use appropriate
means in order to economise and reduce capital and recurrent costs in
the blood transfusion service, but without compromising the quality,
effectiveness and safety of their therapeutic blood components for the
benefit of patients in need of transfusion.
Therefore, healthcare managers and professionals in blood transfusion
and quality management should be aware of cost structures in the
blood transfusion chain, in conjunction with efforts to optimise the
use of blood components and minimise relative costs.
2. Investing in quality

Evidence-based data and research on the economics of blood are
limited. Standard methods for costing and financial planning should
be established to enable the calculation of total economic costs associ-
ated with blood services, bench-marking, budget planning, financial
accountability, purchasing and logistics.
Competent Authorities for blood transfusion should define prior-
ities and decide on the data and indicators that must be collected.
The blood supply chain from donor to patient should be analysed to
identify opportunities for cost reductions. Best practices should be
implemented using effective bench-marking procedures. The contri-
bution of management tools towards controlling costs and improving
the efficiency of blood transfusion should be evaluated.
516
Appendix 5. Health economics in blood transfusion
3. Costing analysis

The criteria used for cost analysis and realistic cost-effectiveness pro-
jections at national, regional and local level should comply with WHO
guidelines for costing blood transfusion services.
An important step towards a cost-effectiveness analysis is to define
the regulatory framework in order to allow the estimation of costs
and outputs of specific activities. An activity-based cost procedure
should identify major groups of activities in the blood service, with
cost-output measurable indicators defined for each area (e.g. blood
collection, blood processing, blood storage and distribution, haemo
vigilance). The total costs for each activity include both capital (build-
ing, equipment, training, furniture, vehicles, etc.) and recurrent costs
(personnel, supplies, transportation, utilities, administration, insur-
ance, etc.).
Managers of blood transfusion services (BTS) should define the ob-
jectives of cost analyses for the purposes of budget planning, financial
accountability and evaluation, and cost effectiveness analysis. In this
way, cost information can be used to monitor the efficiency of the
components of BTS, and for resource mobilisation and other tasks.
4. Modelling cost-effectiveness analysis in transfusion

BTS managers need to collect data to support analyses of cost-
effectiveness based on the following rules:
• the central element is the activity, defined as a set of inter-linked
tasks resulting in the production of goods and services;
• activities are not isolated, but are part of a process;
• each activity has a supplier and a client (internal and external)
and contributes to the creation of value.
The BTS manager should perform for each activity:
• calculation of blood component costs;
• calculation of selling prices;
517
• calculation of margins between selling prices and costs;

• cost accounting with a view to benchmarking;
• decision-making regarding the possible introduction of an
innovation and the choice between alternative methods.
5. Economic aspects of the clinical use of blood

The economic aspects of the clinical use of blood should also be eval-
uated in relation to outcomes and effectiveness, taking into account
parameters such as the amount of blood component administered,
duration of treatment, length of hospital stay and quality adjusted life
years (QALYs). Inappropriate use of blood (i.e. in terms of having un-
expected adverse reactions and a direct bearing on healthcare budgets)
should be investigated in order to substantiate the cost-benefit and the
cost-effectiveness of transfusion.
Carrying out an economic evaluation of expenditures related to the
use of blood and blood components involves the identification of the
therapeutic use of blood components and the costs from the initiation
of treatment to its completion.
Assessing the economic implications and effectiveness of therapeutic
interventions would be facilitated by measuring outcomes and effec-
tiveness. Therefore, it is necessary to record data both before and after
the use of blood components, in order to substantiate the benefits that
accrue.
Alternative treatment strategies using blood components need to be
examined with respect to therapeutic outcomes and in relation to
cost-benefit, cost-effectiveness and cost utility.
Methods for evaluating a more expensive therapy (e.g. leucocyte-
depleted cells) against a cheaper one should be considered, given that
the former may result in a shorter hospital stay and as a consequence
reduced hospital charges.
Inappropriate use of blood has a direct bearing on healthcare budgets.
Over and under-use of blood components may harm the patient.
Misuse of blood may also result in an unexpected adverse outcome.
518
DEFINITIONS
Additive solution Solution specifically formulated to maintain beneficial properties of

cellular components during storage.
Advanced electronic An electronic signature which meets the following requirements: (a)
signature it is uniquely linked to the signatory; (b) it is capable of identifying the
signatory; (c) it is created using means that the signatory can maintain
under their sole control; and (d) it is linked to the data to which it relates
in such a manner that any subsequent change of the data is detectable.
Adverse event Any untoward occurrence associated with the collecting, testing, pro-
cessing, storage and distribution of blood and blood components that
might lead to an adverse reaction in blood recipients or blood donors.
Adverse reaction Any unintended response in a donor or patient associated with the
collection or transfusion of blood or blood components.
Affected area An area with ongoing transmission of an infection to humans. This
means that there has been at least one autochthonous case as a result
of local transmission in the area according to the agreed, standardised
and disease-specific case definition. Under exceptional circumstances, a
probable case can be used to determine transmission but only in specific
and agreed situations when case confirmation cannot be performed
within a reasonable time.
Allogeneic donation Blood and blood components collected from an individual and intended
for transfusion to another individual, for use in medical devices or
as starting material/raw material for manufacturing into medicinal
products.
Antibody quantitation Technique routinely used to measure the level of antibody, i.e. anti-RhD
(or anti-c) antibody in maternal sera.
Antiglobulin testing The direct antiglobulin test (direct Coombs’ test) and the indirect
technique antiglobulin test. It detects antibody or complement bound to red cells
in vivo.
Anti-IgA antibodies IgG or occasionally IgM anti-IgA produced by an IgA- deficient patient.
Severe anaphylactoid transfusion reactions can occur in such patients.
Apheresis Method of obtaining one or more blood components by machine pro-
cessing of whole blood, in which the residual components of the blood
are returned to the donor during or at the end of the process.
520
Definitions
Audit programme A systematic and independent examination to determine whether

quality activities and related results comply with planned arrangements
and whether these arrangements are implemented effectively and are
suitable to achieve objectives.
Autologous collection Autologous collection means blood and blood components collected
from an individual and intended solely for subsequent autologous
transfusion or other human application to that same individual.
Autologous donors Individuals who give blood for their own use if the need for blood can be
anticipated and a collection plan developed.
Autologous transfusion Transfusion in which the donor and the recipient are the same person
and in which pre-deposited blood and blood components are used.
Automated system A broad range of systems including, but not limited to, automated pro-
cessing equipment, automated laboratory equipment, process control,
processing execution, laboratory information management, processing
resource planning and document management systems. The automated
system consists of the hardware, software and network components,
together with the controlled functions and associated documentation.
Biometrics A method of verifying an individual's identity based on measurement
of the individual's physical feature(s) or repeatable action(s) where
those features and/or actions are both unique to that individual and
measurable.
Blood component Therapeutic components of blood (red cells, white cells, platelets,
plasma) that can be prepared by centrifugation, filtration and freezing
using conventional methodologies in blood establishment.
Blood component Procedure which enables a blood component to be released from a
release quarantine status by the use of systems and procedures to ensure that
the finished product meets its release specifications.
Blood establishment Any structure or body that is responsible for any aspect of the collection
and testing of human blood or blood components, whatever their
intended purpose, and their processing, storage and distribution if
intended for transfusion. This does not include hospital blood banks.
Blood product Any therapeutic product derived from human blood or plasma.
Buffy coat Blood component prepared by centrifugation of a unit of whole
blood, which contains a considerable proportion of the leucocytes and
platelets.
521
Buoyant density Technique for separation based on density differences between cells.
centrifugation
Calibration Set of operations that establish, under specified conditions, the relation-
ship between values indicated by a measuring instrument/system or
values represented by a material measure and the corresponding known
values of a reference standard.
Case A particular disease, health disorder, or condition under investigation
found in an individual or within a population or study group.
Cell free plasma Plasma obtained by cross-flow filtration, when blood flows along a
membrane with a pore size allowing free passage of plasma proteins,
but not of blood cells.
Cell separator An instrument for apheresis.
Change control A formal system by which qualified representatives of appropriate disci-
plines review proposed or actual changes that might affect the validated
status of facilities, systems, equipment or processes. The intent is to
determine the need for action that would ensure and document that the
system is maintained in a validated state.
Complaint An act of expressing customer dissatisfaction with the quality of prod-
ucts or services provided by the responsible organisation.
Computerised system A system comprising the input of data, electronic processing and the
output of information to be used either for reporting, automatic control
or documentation.
Consent To give assent or approval, such as consent to be transfused
Counter-current Technique where cells subjected simultaneously to a liquid flow and a
centrifugation centrifugal force in opposite directions tend to be separated according
(elutriation) to their size.
CPD-Adenine (CPDA) Citrate-Phosphate-Dextrose with Adenine is a preservative-anticoagu-
lant solution used for whole blood collection.
Cryopreservation Prolongation of the storage life of blood components by freezing.
Cytapheresis An apheresis procedure intended for the collection of a cellular compo-
nent of blood, such as red cells, leucocytes or platelets.
522
Definitions
Depth and surface Technique of filtration using a filter bed of fibres: owing to the specific
filtration properties of platelets and granulocytes, as well as the low flexibility of
lymphocytes, these cells are more easily trapped in such filters than are
red cells.
Distribution Act of delivery of blood and blood components to other blood estab-
lishments, hospital blood banks, and manufacturers of blood- and
plasma-derived products. It does not include issuing blood or blood
components for transfusion.
Donor A person in normal health with a good medical history who voluntarily
gives blood or blood components for therapeutic use.
Donor deferral Suspension of the eligibility of an individual to donate blood or blood
components; such suspension being either permanent or temporary.
Emergency A serious, unexpected, and potentially dangerous situation requiring
immediate action.
Endemic area A risk area where an infectious disease lingers at around the same
incidence for a long time.
Epidemiological The continuous gathering, analysing, and interpreting data about
surveillance diseases, and disseminating conclusions of the analyses to relevant
organisations and audiences.
Facilities Hospitals, clinics, manufacturers and biomedical research institutions to
which blood or blood components may be delivered.
Febrile transfusion A febrile response associated with the administration of blood or blood
reactions components.
First-time donor Someone who has never donated either blood or a blood component.
Full blood count Analysis of haematological parameters including Hb and RBC indices as
well as counts of RBCs, white cells and platelets.
Glycerol Propanetriol, used as a cell-cryoprotective agent for the storage of red
cells in the frozen state.
Good practice All elements in established practice that collectively lead to final blood
or blood components that consistently meet pre-defined specifications
and compliance with defined regulations.
523
Haematocrit Result obtained by the measurement of the volume of red cells in blood,
after centrifugation, expressed as a percentage or as a ratio in the SI
system.
Haematopoietic HPC are primitive pluripotent cells capable of self-renewal as well as
progenitor cells differentiation and maturation into all haematopoietic lineages. They
are found in bone marrow (bone marrow cells (BMC)), in the mononu-
clear cells of circulating blood (peripheral blood stem cells (PBSC)) and in
umbilical cord blood (umbilical stem cells (USC)).
Haemovigilance Organised surveillance procedures related to serious adverse or unex-
pected events or reactions in donors or recipients, and the epidemiolog-
ical follow-up of donors.
Hospital blood bank Hospital unit which stores and distributes and may perform compatibil-
ity tests on blood and blood components exclusively for use within the
hospital facilities, including hospital-based transfusion activities.
Imputability The likelihood that a serious adverse reaction in a recipient can be
attributed to the blood or blood component transfused or that a serious
adverse reaction in a donor can be attributed to the donation process.
Inspection Formal and objective control according to adopted standards to assess
compliance with a given directive and other relevant legislation and to
identify problems.
Issue The provision of blood or blood components by a blood establishment or
a hospital blood bank for transfusion to a recipient. (Dir.2005/61/EC)
Leucocyte depletion The removal of leucocytes from blood.
Medicinal product Any substance or combination of substances presented as having
properties for treating or preventing disease in human beings (Directive
2001/83/EC, 2003/94/EC)
Mobile site A temporary or movable place used for the collection of blood and blood
components which is in a location outside of, but under the control of
the blood establishment.
Open system A system in which a breach has occurred but every effort is made to
prevent microbial contamination by operating in a clean environment
using sterilised materials and aseptic handling techniques.
Pathogen reduced (PR) A term applied to a blood component that has been prepared following
the use of PRT.
524
Definitions
Pathogen reduction Procedures that irreversibly impede proliferation of pathogens, either by

technologies (PRT) removal or inactivation with physical and/or chemical methods.
Peripheral blood Primitive pluripotent cells capable of self-renewal as well as differentia-
stem cells (PBSC) tion and maturation into all haematopoietic line ages, and found in the
mononuclear cells of circulating blood (see haematopoietic progenitor
cells).
Plasma The liquid portion of the blood in which the cells are suspended. Plasma
may be separated from the cellular portion of whole blood for thera-
peutic use as fresh frozen plasma or further processed to cryoprecipitate
and cryoprecipitate-depleted plasma for transfusion. It may be used for
the manufacture of medicinal products derived from human blood and
human plasma or used in the preparation of pooled platelets, or pooled
leucocyte-depleted platelets. It may also be used for resuspension of red
cell preparations for exchange transfusion or perinatal transfusion.
Platelet standard A dose of platelets derived from 4-6 whole blood donations or obtained
adult dose by apheresis, with a minimum platelet content of 200 × 109 platelets.
Prescription form A form on which the clinician prescribes a medicine or a blood compo-
nent to be transfused to the patient.
Preservation The use of chemical agents, alterations in environmental conditions or
other means during processing to prevent or retard biological or physical
deterioration of blood or blood components
Pre-transfusion Procedure for taking blood samples from the patient requiring a trans-
sampling fusion, for compatibility investigation.
Procedure A procedure controls a distinct process or activity, including the asso-
ciated inputs and outputs. A series of tasks usually performed by one
person according to instructions.
Process A set of related tasks and activities that accomplish a work goal.
Processing Any step in the preparation of a blood component that is carried out
between the collection of blood and the issuing of a blood component.
Procurement A process by which blood or blood components are made available
(Directive 2004/33/EC).
Proficiency testing The evaluation of participant performance against pre-established cri-
teria by means of external quality assessment scheme, inter-laboratory
comparisons by use of externally sourced samples or panels.
525
Qualification Part of validation: the action of verifying that any personnel, premises,
equipment or material works correctly and delivers the expected result.
Quality Totality of characteristics of an entity that bear on its ability to satisfy
stated and implied needs. Consistent and reliable performance of
services or products in conformity with specified standards.
Quality assurance All the activities from blood collection to distribution carried out with
the objective of ensuring that blood and blood components are of the
quality required for their intended use.
Quality control Part of a quality system focussed on fulfilling quality requirements.
Quality management The co-ordinated activities to direct and control an organisation with
regard to quality at all levels within the blood establishment.
Quality monitoring That part of a quality assurance programme concerned with main-
tenance and improvement of quality which deals with the identifi-
cation and use of indicators to detect variations from standards or
specifications.
Quality system The organisational structure, responsibilities, procedures, processes, and
resources for implementing quality management.
Quarantine The physical isolation of blood components or incoming materials/rea-
gents over a variable period of time while awaiting acceptance, issuance
or rejection of the blood components or incoming materials/reagents.
Recipient Someone who has been transfused with blood or blood components.
Reconciliation Comparison and assessment of any discrepancy between the amount of
material entering and leaving a given operation or series of operations.
Record Written or electronically captured evidence that an event has occurred
or an outcome has been achieved. A document that contains objective
evidence which shows how well activities are being performed or what
kind or results are being achieved.
Regular donor Someone who routinely donates their blood or plasma (i.e. within the
last 2 years), in accordance with minimum time intervals, in the same
donation centre.
Repeat donor Someone who has donated before, but not within the last two years in
the same donation centre.
Replacement donor Donor recruited by a patient to enable them to undergo elective surgery.
526
Definitions
Reporting The blood establishment, the hospital blood bank or facilities where the
establishment transfusion takes place that reports serious adverse reactions and/or
serious adverse events to the competent authority.
Resources Include people, money, information, knowledge, skills, energy, facilities,
machines, tools, equipment, technologies and techniques.
RhD Immunoglobulin Immunoglobulin specific for RhD antigen is given routinely to
RhD-negative mothers bearing RhD- positive infants to protect them
from red cell exposure during pregnancy and delivery, and so prevent
allo-immunisation.
Risk area An area where individuals are exposed to the risk (which can be small
or large) of being infected with a locally-acquired infection. This is a
generalised use of the term ’risk area,’ to prevent the imprecision linked
to this term due to its use to signify a specific level of risk in an area.
Risk assessment Method to assess and characterise the critical parameters in the func-
tionality of equipment, systems or processes.
Self-inspection An audit carried out by people from within the organisation to ensure
compliance with GPG and regulatory requirements.
Serious adverse event Any untoward occurrence associated with the collecting, testing,
processing, storage and distribution of blood and blood components
that might lead to death or life-threatening, disabling or incapacitating
conditions for donors or recipients or which results in, or prolongs,
hospitalisation or morbidity.
Serious adverse Unintended response in donor or in recipient associated with the
reaction collection or transfusion of blood or blood components that is fatal,
life-threatening, disabling, incapacitating, or which results in, or
prolongs hospitalisation or morbidity.
Signatory A person who holds a signature creation device and acts either on their
own behalf or on behalf of the natural or legal person or entity they
represent.
Specification Description of the criteria that must be fulfilled in order to achieve the
required quality standard.
Standard The requirements that serve as the basis for comparison.
Standard operating Detailed written procedures that give direction for performing certain
procedures (SOPs) operations.
527
Statistical process Method of quality control of a product or a process that relies on a

control system of analysis of an adequate sample size, without the need to
measure every product of the process.
Sterile connecting A device that connects two tubes without breaching the sterility of their
device interior.
Storage Maintaining the product under appropriate controlled conditions until
distribution or issue.
Surveillance Systematic and continuous collection, analysis, and interpretation of
data, closely integrated with the timely and coherent dissemination of
the results and assessment to those who have the right to know so that
action can be taken.
Traceability The ability to trace each individual unit of blood or blood component
derived thereof from the donor to its final destination, whether this is
a recipient, a manufacturer of medicinal products or disposal, and vice
versa.
Trace-back The process of investigating a report of a suspected transfusion-
associated adverse reaction in a recipient to identify a potentially
implicated donor.
Validation Refers to establishment of documented and objective evidence that
the pre-defined requirements for a specific procedure or process can be
fulfilled consistently.
Validation plan Description of validation activities, responsibilities and procedures. It
describes specifically how a certain validation is to be done.
Washed A process of removing plasma or storage medium from cellular com-
ponents by centrifugation, decanting of the supernatant liquid from
the cells and addition of an isotonic suspension fluid, which in turn is
generally removed and replaced following further centrifugation of the
suspension. The centrifugation, decanting, replacing process may be
repeated several times.
Washed red cells A component derived from whole blood by centrifugation and removal
of plasma, with subsequent washing of the red cells in an isotonic
solution.
Whole blood Blood collected from a single donor and processed either for transfusion
or further manufacturing.
528
Definitions
Written procedures Controlled documents that describe how specified operations are to be
carried out.
Xenotransplantation Any procedure that involves transplantation or infusion into a human
recipient of live animal cells, tissues or organs, or human body fluids,
cells, tissues or organs that have ex vivo contact with live animal cells,
tissues or organs.
529
ABBREVIATIONS
531
Ag Antigen
AIDS Acquired Immune Deficiency Syndrome
ALT Alanine Amino Transferase
AML Acute Myeloid Leukaemia
AS Additive Solution
AS-BCR Additive Solution-Buffy Coat Removed
BCR Buffy Coat Removed
BPAT Batch Pre-Acceptance Testing
BSE Bovine Spongiform Encephalopathy
BTS Blood Transfusion Services
CAPA Corrective and Preventative Action
CD-P-TS European Committee on Blood Transfusion
CETS Council of Europe Treaty Series (formerly ETS: European Treaty Series)
CJD Creutzfeldt–Jakob disease
CMV Cytomegalovirus
DMSO Dimethylsulfoxide
DQ Design Qualification
EC European Commission
EDQM European Directorate for the Quality of Medicines & HealthCare
ELISA Enzyme-linked immuno-sorbent assay
EMA European Medicines Agency
EU European Union
FFP Fresh Frozen Plasma
FTA Fluorescent Treponemal Antibody
532
Abbreviations
GCSF Granulocyte Colony Stimulating Factor

GMP Good Manufacturing Practice
GPG Good Practice Guidelines
GTS Ad hoc working group on the guide to the preparation, use and quality
assurance of blood components
ECV Extracorporeal volume
Hb Haemoglobin
HBc Hepatitis B core antigen
HBsAg Hepatitis B surface antigen
HCV Hepatitis C virus
Hct Haematocrit
HES Hydroxyethyl starch
HIV Human Immunodeficiency virus
HLA Human Leucocyte Antigen
HPA Human Platelet Antigen
HTLV Human T-cell lymphotropic virus
INR International Normalised Ratio
IQ Installation Qualification
ISBT International Society of Blood Transfusion
IU International Unit
JACIE Joint Accreditation Committee-ISCT (Europe) & EBMT
LD Leucocyte-Depleted
LISS Low Ionic Strength (Salt) Solution
MDS Myelodysplasia
533
NAT Nucleic Acid Amplification Techniques

OQ Operational Qualification
PAT Pre-deposit Autologous Donation
Ph. Eur. European Pharmacopoeia
PQ Performance Qualification
PR Pathogen Reduced
PRP Platelet-rich Plasma
PRT Pathogen Reduction Technology
QA Quality Assurance
QC Quality Control
RBC Red Blood Cells
SAGM Saline Adenine Glucose Mannitol solution
SOPs Standard Operating Procedures
SPC Statistical Process Control
T. cruzi Trypanosoma cruzi
TA Transfusion-Associated
TA-GVHD Transfusion-Associated Graft-Versus-Host disease
TACO Transfusion-Associated Circulatory Overload
TPHA Treponema pallidum Haemagglutination Assay
TRALI Transfusion-Related Acute Lung Injury
TTI Transfusion-Transmitted Infection
TTP Thrombotic Thrombocytopenic Purpura
vCJD Variant Creutzfeld–Jakob disease
VMP Validation Master Plan
534
REFERENCES
535
Recommendations and resolutions of the Council

of Europe in the field of blood transfusion
Resolution (78) 29 on harmonisation of legislations of member states relating to

removal, grafting and transplantation of human substances
Recommendation No. R (79) 5 concerning international exchange and transportation of human
substances
Recommendation No. R (80) 5 on blood products for the treatment of haemophiliacs
Recommendation No. R (81) 5 concerning antenatal administration of anti-D immunoglobulin
Recommendation No. R (81) 14 on preventing the transmission of infectious diseases in the inter-
national transfer of blood, its components and derivatives
Recommendation No. R (83) 8 on preventing the possible transmission of acquired immune defi-
ciency syndrome (AIDS) from affected blood donors to patients
receiving blood or blood products
Resolution 812 (1983) of the Parliamentary Assembly on acquired immune deficiency
syndrome (AIDS)
Recommendation No. R (84) 6 on the prevention of the transmission of malaria by blood
transfusion
Recommendation No. R (85) 5 on a model curriculum for the training of specialists in blood
transfusion
Recommendation No. R (85) 12 on the screening of blood donors for the presence of AIDS markers
Recommendation No. R (86) 6 on guidelines for the preparation, quality control and use of fresh
frozen plasma (FFP)
Recommendation No. R (87) 25 concerning a common European public health policy to fight the
acquired immunodeficiency syndrome (AIDS)
Recommendation No. R (88) 4 on the responsibilities of health authorities in the field of blood
transfusion
Recommendation No. R (90) 3 concerning medical research on human beings
Recommendation No. R (90) 9 on plasma products and European self-sufficiency
Recommendation No. R (93) 4 concerning clinical trials involving the use of components and
fractionated products derived from human blood or plasma
536
References
Recommendation No. R (95) 14 on the protection of health of donors and recipients in the area of
blood transfusion
Recommendation No. R (95) 15 On the preparation, use and quality assurance of blood
components
Recommendation No. R (96) 11 on documentation and record-keeping to guarantee the traceabil-
ity of blood and blood products , especially in hospital
Recommendation No. R (98) 2 on provision of haematopoietic progenitor cells
Recommendation No. R (98) 10 on the use of human red blood cells for the preparation of oxy-
gen-carrying substances
Recommendation Rec (2001) 4 on the prevention of the possible transmission of variant
Creutzfeldt–Jakob disease (vCJD) by blood transfusion
Recommendation Rec (2002) 11 on the hospital’s and clinician’s role in the optimal use of blood
and blood products
Recommendation Rec (2003) 11 on the introduction of pathogen inactivation procedures for blood
components
Recommendation Rec (2004) 8 on autologous cord blood banks
Recommendation Rec 2004) 18 on teaching transfusion medicine to nurses
Resolution Res (2008) 5 on donor responsibility and limitation of donation of blood and
blood components
Resolution CM/Res (2013) 3 on sexual behaviours of blood donors that have an impact on
transfusion safety
Resolution CM/Res (2015) 2 on principles concerning human immunoglobulin therapies for
immunodeficiency and other diseases
Resolution CM/Res (2015) 3 on principles concerning haemophilia therapies
N.B. The figure in parentheses indicates the year of adoption.
537
Council of Europe publications in the field of blood transfusion
1976 Production and use of cellular blood components for transfusion. Study Director: B. Bucher
with M. Benbunan, H. Heisto, U. Reesink
1978 Indications for the use of albumin, plasma protein solutions and plasma substitutes. Study
Director: J. O’Riordan with M. Aebischer, J. Darnborough and I. Thoren
1980 Preparation and use of coagulation factors VIII and IX for transfusion. Study Director:
R. Masure with G. Myllyla, I. Temperley and K. Stampli
1981 Assessment of the risks of transmitting infectious diseases by international transfer of
blood, its components and derivatives. Study Director: W. Weise with T. Nielsen, P. Skinhot,
J. P. Saleun
1982 European Co-operation in the field of blood: miscellany reports on the occasion of the 20th
anniversary of the Committee of Experts on Blood Transfusion and Immuno-haematology
1962–1982. P. Cazal, A. André, P. Lundsgaard-Hansen, W. Weise, R. Butler, C. P. Engelfriet,
and A. Hässig
1983 Essential aspects of tissue typing. B. Bradley and S. Gore
1985 Study on the current position of training programmes for future specialists in blood trans-
fusion in Council of Europe member states and in Finland. Study Director: E. Freiesleben
with A. André, A. Franco, B. Baysal, J. Cash
1986 Quality control in blood transfusion services. Study Director: E. Freiesleben, R. Butler, C.
Hogman, W. Wagstaff
1987 Renal transplantation: sense and sensitisation. B. Bradley and S. Gore, Martinus Nijhoff
Publishers
1988 First European Symposium on quality in blood transfusion Résumé of lectures (publication
of the Health Division of the Council of Europe)
1989 European Course on Blood transfusion (Athens, March 1988) Compendium of lecturers
(publication of the Health Division of the Council of Europe)
1990 Blood transfusion: 2nd European Course (Madrid 1990) Compendium of lecturers (publica-
tion of the Health Division of the Council of Europe)
1992 Impact of the Aids epidemic on health care services and planning in Europe (publication of
the Health Division of the Council of Europe)
Plasma products and European self-sufficiency: collection, preparation and use. Study
Director: J. Leikola with W. van Aken, C. Hogman, D. Lee, M. Muglia, H. Schmitt
538
References
1993 Blood transfusion in Europe: a ‘white paper’. Safe and sufficient blood in Europe by Piet J.
Hagen
Survey of blood transfusion services of central and eastern European countries and their
co-operation with western transfusion services. Report by H. T. Heiniger
The collection and use of human blood and plasma in Europe. Prof. Dr W.G. van Aken
1995 Guide on the preparation, use and quality assurance in blood components (appendix to
Recommendation No. R (95) 15)
1997 Collection and use of blood and plasma in Europe (member States of the Council of Europe
not members of the European Union). Study 1995, report by Dr Rejman
Activities of blood banks in relation to bone marrow transplantations. Study Director:
I.M. Francklin; Group members S. Koskimies, R. Kroczek, M. Reti, L. de Waal, R. Arrieta, F.
Carbonell-Uberos
1998 Blood transfusion: half a century of contribution by the Council of Europe. Report by Prof.
Dr B. Genetet
2000 Collection and use of human blood and plasma in the non-European Union Council of
Europe member states in 1997. Report by Dr Rejman
Autologous blood donation and transfusion in Europe – 1997 data. Report by Prof. Politis
2001 Pathogen inactivation of labile blood products. Study Director: Prof. A. Morell
2002 Autologous blood donation and transfusion in Europe – 2000 data. Report by Prof. Politis
2004 Collection, testing and use of blood and blood products in Europe – 2001 data. Report by
Drs C.L. van der Poel, M.P. Janssen and M.E. Behr-Gross
539
2011 Trends and observations on the collection, testing and use of blood and blood compo-
nents in Europe – 2001-2005 data. Report by Drs C.L. van der Poel, M.P. Janssen and
M.E. Behr-Gross
Collection, testing and use of blood and blood products in Europe – 2006 data. Report by
2013 Trends and observations on the collection, testing and use of blood and blood compo-
nents in Europe – 2001-2008 data. Report by Drs C.L. van der Poel, M.P. Janssen and
M.E. Behr-Gross
Drs L.R. van Hoeven, M.P. Janssen and G. Rautmann
2015 Trends and observations on the collection, testing and use of blood and blood components
in Europe – 2001–2011 data. Report by Drs L.R. van Hoeven, M.P. Janssen and G. Rautmann
Drs M.P. Janssen and G. Rautmann
540
The use of blood components represents the only therapy
available for many seriously ill patients who suffer from acute
or chronic diseases.
To provide all those working in the field of transfusion
medicine – from blood services to hospital departments
to regulators – with a compendium of measures designed
to ensure the safety, quality and efficacy of blood
components, the Council of Europe has developed a guide
as a technical annex to its Recommendation No. R (95) 15
on the preparation, use and quality assurance of blood
components. The Guide contains recommendations for blood
establishments on blood collection, blood components,
technical procedures, transfusion practices and quality
systems. It represents the basis for a large number of national
regulations, as well as for the blood directives of the European
Commission.
This is the 19th Edition of the Guide, compiled by leading
European experts under the aegis of the European Committee
(Partial Agreement) on Blood Transfusion (CD-P-TS).
For matters dealing with the use of organs and tissues and
cells, see the Council of Europe Guide to the quality and safety
of organs for transplantation and Guide to the quality and safety
of tissues and cells for human application, respectively.
ENG
The Council of Europe is the continent’s leading human rights organisation.

It comprises 47 member states, 28 of which are members of the
European Union. The European Directorate for the Quality of Medicines
www.edqm.eu
& HealthCare (EDQM) is a directorate of the Council of Europe. Its mission
is to contribute to the basic human right of access to good quality
medicines and healthcare and to promote and protect public health.
www.edqm.eu/store
ISBN 978-92-871-8415-3
9 789287 184153 € 30
19th Edition Guide to the preparation, use and quality assurance of blood components EDQM

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Guide to the

preparation, use and

European Committee EDQM

Recommendation No. R (95) 15

European Directorate for the Quality of Medicines & HealthCare

Page layout and cover: EDQM

Supported by the European Union.

EUROPEAN COMMITTEE (PARTIAL AGREEMENT)

MEMBERS OF THE AD HOC GROUP (GTS) . . . . . . . . . . . . . . . . 39

GOOD PRACTICE GUIDELINES . . . . . . . . . . . . . . . . . . . . . . . . . . . 50

12. Bacterial safety of blood components . . . . . . . . . . . . . . . . . . . . . 174

3. Components for neonatal exchange transfusion . . . . . . . . . . . . 188

2. Algorithm for infectious marker screening and

5. Contracts between blood establishments and hospitals for

3. Release of blood components . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 271

Requirements and quality control . . . . . . . . . . . . . . . . . . . . . . . . . . 294

Requirements and quality control . . . . . . . . . . . . . . . . . . . . . . . . . . 312

Definition and properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 334

8. Platelets, Apheresis, Leucocyte-Depleted . . . . . . . . . . . . . . . . . . . 355

Storage and transport . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 396

Requirements and quality control . . . . . . . . . . . . . . . . . . . . . . . . . . 415

3. Additional serological screening tests . . . . . . . . . . . . . . . . . . . . . 441

Controls for identification codes/passwords/biometrics . . . . . . . 490

1 Albania, Andorra, Armenia, Austria, Azerbaijan, Belgium, Bosnia and

remunerated blood donation, mutual assistance, optimal use of blood

principles relating to the preparation, use and quality assurance of

assurance of blood components through education and the provision

2 EDQM is a Directorate of the Council of Europe, created in 1964 on the legal

The elaboration of the 19th Edition of the Guide included a large

OGINSKIENE Rasa (substitute) Netherlands

Romania Irena RAZBORSEK (substitute)

STROM Helena (substitute) Turkey

‘The former Yugoslav

Republic of Belarus USA

World Health Organization

CASTREN Johanna ERTUGRUL ORUC Nigar

DOBROTA Alina Mirella FLESLAND Oystein

FONTANA Stefano KAMMER Winfried

GARRAUD Olivier KLUTER Harald

MEGESSIER Pascal POLITIS Constantina

ROSOCHOVA Jana SORENSEN Betina

SÄFWENBERG Jan VASILJEVIC Nada

on the preparation, use and quality

(Adopted by the Committee of Ministers

No. R (85) 12 on the screening of blood donors for the presence

Considering that this guide will be regularly updated by the

for standards and specifications

Member States shall ensure that, in order to implement the

Good Practice Guidelines

1. General principles

Quality System incorporating Good Practice and

1.2. Quality system

appropriate regulations as set out in the chapters on

of the Quality System (including management

1.2.13. A formal system for the handling of deviations and

1.2.17. A product quality review may also be considered as

1.3. Good practice

generic term ‘preparation’) and quality control. The

1.3.1.1.7. records of preparation (including distribution) that

1.3.1.2.4. records are made, manually and/or by recording in-

1.4. Quality risk management

should incorporate the principles of Quality Risk

2. Personnel and organisation

2.3.1. a ‘Responsible Person’ following Article 9 of Directive