Theoretical and technical concerns in inactivation/elimination of viruses in plasma derivatives.

To know the virus eliminating/inactivating capacity of the manufacturing process of a plasma protein, it is essential to analyse it by adding virus to the source material or to different materials obtained at various stages of the manufacturing procedure and then to determine the elimination/inactivation of this virus. To carry out such experiments properly, three prerequisites have to be fulfilled: (i) the manufacturing procedure must be scaled down as exactly as possible; (ii) relevant test viruses have to be selected for the spiking experiments and (iii) the resulting samples must be assayed properly for infectious virus. The successful reduction of a manufacturing procedure to a more than 1000-fold smaller scale has to be validated to prove that it corresponds to the production scale. The most important viruses of risk in human plasma are hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV). HIV is the only one of these viruses which can be tested in vitro. A decision has therefore to be made concerning which other viruses should be used. The selection of test viruses depends on (i) the relationship of these candidates to the viruses of risk; (ii) the possibility of growing them to high titres in vitro and (iii) the availability of accurate infectivity assays. The use of highly sensitive assays is necessary to be able to determine small amounts of residual viruses. Since such assays are based on a 7 to 28 day incubation of the virus samples on cell cultures, these samples must be sterile and non-cytotoxic.(ABSTRACT TRUNCATED AT 250 WORDS)