Viral safety of haemophilia treatment products

Abstract

The epidemics of HIV and hepatitis C in treated haemophiliacs spurred rapid technological advances in the viral safety of clotting factor concentrates produced from large donor pools. Sequential steps are now employed to minimize infectious risks. The initial viral burden is reduced by screening donors and by testing individual donations and plasma pools for antivirus antibodies, viral antigens, and nucleic acid. These techniques are supplemented by nonspecific viral reduction steps based on physical partitioning and inactivation of pathogens by physical (eg, heat) or chemical (eg, solvent-detergent) means. Although these processes have virtually eliminated the transmission of HIV and hepatitis B and C, there is still evidence that concentrates can transmit small nonenveloped viruses, such as parvovirus B19 and hepatitis A virus. Furthermore, new agents which may not be susceptible to current viral inactivation procedures continue to be identified. Concerns such as these have also given impetus to the development of recombinant clotting factor proteins. Recombinant factor IX concentrate is now produced without the use of human plasma proteins at any step in the manufacturing or formulation process. In practice, the risk of viral transmission by clotting factor concentrates is now so remote that any manipulations to further reduce this risk may be counter-productive, by enhancing cost (hence compromising availability) and potentially promoting other adverse effects such as immunogenicity.