[Plasma fractionation. Progress, problems and perspectives].

Abstract

In the last few years, plasma fractionation has been subjected to major technological changes which have contributed to improve the viral safety and overall purity of plasma derivatives. New viral inactivation treatments, primarily solvent-detergent and pasteurization, have been introduced in the manufacturing processes of plasma derivatives to ensure the inactivation of major plasma-borne viruses, including HIV and hepatitis B and C viruses. Concurrently, new highly purified products obtained by chromatographic methods (mainly ion exchange and/or immunopurification) have been developed in the last five years and have replaced former preparations, providing a significantly higher safety level in terms of purity and viral risks. For an example, the new generation of Factor VIII and Factor IX concentrates (to treat hemophilia A and hemophilia B, respectively), which have been introduced in the last five years, are purified over 10,000- to 20,000-fold from plasma, as compared to only 50- to 100-fold for the former products. Similarly, new, standardized, clotting factor or protease inhibitor concentrates have been made available, thus permitting to carry out selective hemotherapy of specific diseases. Examples include the development of von Willebrand factor, factor XI, protein C, or alpha 1-antitrypsin concentrates for the substitutive therapy of congenital or acquired deficiencies. In addition, the concept of good manufacturing practices has been implemented, whereas carefully controlled, validated processes are contributing to the consistency in the quality of those products. Current major problems in plasma fractionation relate to the potential occurrence of new pathogenic agents that could resist present viral inactivation treatments and to the potential effect of given purification technologies on the development of immunogenic properties of proteins. Current trends indicate that significant progress in viral safety of plasma derivatives (for example through the introduction of new concept such as viral filtration) are to be expected very soon. Further research in this very important field is mandatory as plasma should remain the starting material of important therapeutic products in the coming years.