Partitioning and inactivation of viruses during isolation of albumin and immunoglobulins by cold ethanol fractionation.

Albumin solutions invariably transmitted infectious hepatitis viruses before the introduction of pasteurisation in the final container. Immunoglobulin solutions (the older intramuscular as well as the current intravenous ones), on the other hand, only rarely transmitted hepatitis. The apparent safety of the latter was usually attributed to the presence of neutralizing antibodies and to the fractionation process. It was shown that viruses tend to concentrate in those fractions of the cold ethanol precipitation procedure which are used neither for albumin nor for immunoglobulin preparations. Additionally, ethanol alone inactivates some viruses, albeit much less at low temperatures than at room temperature. According to EC-directives, all manufacturers of stable blood products must introduce production steps which inactivate viruses or they have to prove that certain production steps, which are already being used, do inactivate viruses. In either case, the inactivation has to be validated with appropriate experiments. Procedures that are now recognized as virucidal are, e.g., pasteurisation (i.e., heating of the liquid product at 60 degrees C for 10 hours), solvent/detergent (S/D) treatment, photodynamic treatment, or incubation at pH4 with pepsin.