ANNEX 4 WHO RECOMMENDATIONS FOR THE PRODUCTION, CONTROL AND REGULATION OF HUMAN PLASMA FOR FRACTIONATION Adopted by the 56th meeting of the WHO Expert Committee on Biological Standardization, 24-28 October 2005. A definitive version of this document, which will differ from this version in editorial but not scientific detail, will be published in the WHO Technical Report Series. Page 2 TABLE OF CONTENTS Page TABLE OF CONTENTS................................................................................................................. INTRODUCTION............................................................................................................................ 1 INTERNATIONAL BIOLOGICAL REFERENCE PREPARATIONS ............................ 2 LIST OF ABBREVIATIONS AND DEFINITION USED ................................................... 3 GENERAL CONSIDERATIONS........................................................................................... 3.1 Range of products made from human blood and plasma ....................................................... 3.2 Composition of human plasma............................................................................................... 3.3 Pathogens present in blood and plasma.................................................................................. 4 MEASURES TO EXCLUDE INFECTIOUS DONATIONS ............................................... 4.1 Appropriate selection of blood/plasma donors....................................................................... 4.2 Screening of blood/plasma donations for infectious markers ................................................ 4.2.1 Screening tests............................................................................................................. 4.2.2 Other tests.................................................................................................................... 4.2.3 NAT testing ................................................................................................................. 4.2.4 Test kits ....................................................................................................................... 4.2.5 Quality control of screening ........................................................................................ 4.2.6 Look- back................................................................................................................... 4.3 Epidemiological surveillance of donor population ................................................................ 4.4 Strict adherence to Good Manufacturing Practices................................................................ 4.5 Post donation events............................................................................................................... 5 PRODUCTION OF PLASMA FOR FRACTIONATION ................................................... 5.1 Methods used to obtain plasma for fractionation ................................................................... 5.1.1 Recovered plasma........................................................................................................ 5.1.2 Apheresis plasma (source plasma) .............................................................................. 5.2 Characteristics of plasma for fractionation ............................................................................ 5.2.1 Plasma frozen within 24 hours of collection ............................................................... 5.2.2 Plasma frozen after 24 hours of collection .................................................................. 5.2.3 Plasma not meeting the requirement for fractionation ................................................ 5.2.4 Hyper-immune (antibody-specific) plasma................................................................. Page 3 5.2.4.1 Anti-D (anti-Rho).............................................................................................. 5.2.4.2 Anti-HAV.......................................................................................................... 5.2.4.3 Anti-HBs ........................................................................................................... 5.2.4.4 Anti-tetanus ....................................................................................................... 5.2.4.5 Anti-varicella/zoster .......................................................................................... 5.2.4.6 Anti-cytomegalovirus........................................................................................ 5.2.4.7 Anti-rabies......................................................................................................... 5.3 Premises and devices for collection of plasma for fractionation............................................ 5.3.1 Premises....................................................................................................................... 5.3.2 Containers.................................................................................................................... 5.3.3 Anticoagulants............................................................................................................. 5.4 Blood/plasma collection process............................................................................................ 5.4.1 Procedure..................................................................................................................... 5.4.2 Labelling of collection bags ........................................................................................ 5.4.3 Equipment.................................................................................................................... 5.4.4 Laboratory samples ..................................................................................................... 5.4.5 Volume of plasma per unit .......................................................................................... 5.4.6 Secure holding and reconciliation ............................................................................... 5.4.7 Donor call back system ............................................................................................... 5.5 Separation of plasma .............................................................................................................. 5.5.1 Premises....................................................................................................................... 5.5.2 Intermediate storage and transport .............................................................................. 5.5.3 Impact of whole blood holding period ........................................................................ 5.5.4 Centrifugation of whole blood..................................................................................... 5.5.5 Impact of leucoreduction............................................................................................. 5.6 Freezing of plasma ................................................................................................................. 5.6.1 Holding time of plasma ............................................................................................... 5.6.2 Freezing rate and freezing temperature ....................................................................... 5.6.2.1 Freezing conditions ........................................................................................... 5.6.2.2 Impact of containers and equipment ................................................................. 5.6.2.3 Validation of the freezing process..................................................................... 5.7 Storage of plasma ................................................................................................................... 5.7.1 Storage conditions and validation ............................................................................... Page 4 5.7.2 Premises and equipment.............................................................................................. 5.7.3 Segregation procedures ............................................................................................... 5.8 Compliance with plasma fractionator equipment................................................................... 5.9 Release of plasma for fractionation........................................................................................ 5.9.1 Plasma release using electronic information systems ................................................. 5.10 Packaging of plasma............................................................................................................... 5.11 Transportation of plasma........................................................................................................ 5.12 Recall system.......................................................................................................................... 6 QA SYSTEM AND GOOD MANUFACTURING PRACTICES........................................ 6.1 Organisation and personnel.................................................................................................... 6.2 Documentation system ........................................................................................................... 6.3 Premises and equipment......................................................................................................... 6.4 Materials................................................................................................................................