Evolving perspectives in product safety for haemophilia.
The past decade has seen a consolidation of the safety measures built into the manufacture of coagulation factor concentrates for people with haemophilia. The scientific developments of the 1980s have been fully reflected in the manufacturing principles and the regulatory control of concentrate production, so that the safety of concentrate therapy now exceeds the safety of normal blood transfusion. A clear understanding of the epidemiology of the transfusion-transmitted viruses allows the selection of donors with a satisfactory safety profile. Source material for plasma-derived concentrates is now screened with sensitive tests that detect viral infection in donors at a very early phase in the viral life cycle. This decreases the potential viral load to levels that are easily eliminated by well-accredited viral inactivation procedures. These measures have ensured a high level of assurance regarding the safety of products from the traditional transfusion-transmitted infections. However, testing for some transfusion-transmitted viruses does not yet form part of mainstream blood screening; alternative strategies based upon the particular needs of pooled plasma product recipients may be more feasible. Whereas the risk of emerging pathogens has to be kept constantly under review, four such viruses identified over the 1990s have proven to be of little relevance to plasma product recipients and the need for measures specifically directed against them is debatable. The risk of variant Creuzfeldt-Jakob Disease (vCJD) is a special case of an emerging infection that is insufficiently well characterized to allow a conclusive assessment of its role in the safety of concentrates; however, data regarding the capacity of concentrate manufacturing methods to clear the putative agent are encouraging. The relative uncertainty surrounding vCJD has caused the influential regulatory authorities of North America to take a precautionary approach regarding the selection of blood donors. This is having an effect on the supply of factor VIII concentrates and has possibly affected the rate at which developed countries have switched to recombinant products. The safety of recombinant products continues to be supported through patient monitoring, and the new generation of plasma protein-free products will further enhance the role of these products as the treatment of choice with people with haemophilia. However, their cost-effectiveness relative to the current generation of plasma-derived products makes it unlikely that they will be accessible by developing countries. The dependence of most of the world's population of people with haemophilia on a safe and sufficient blood supply will therefore continue into the foreseeable future, and with it the need to maintain constant vigilance on blood safety matters.
Farrugia
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Manager Blood and Tissue Services, Therapeutic Goods Administration, Australian Commonwealth Department of Health and Aged Care, Adviser on Blood Safety, World Federation of Hemophilia, Australia. albert.farrugia@health.gov.au
D001782:Blood Donors; D003257:Consumer Product Safety / Q000592:standards*; D006467:Hemophilia A / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D017096:Prion Diseases / Q000517:prevention & control / Q000635:transmission; D013242:Sterilization; D014777:Virus Diseases / Q000517:prevention & control / Q000635:transmission