ABSTRACT
We report on the viral validation of an industrial purification process which is used to manufacture high purity human albumin from frozen placentas. This process has been used without any modification since 1980 except for a progressive increase in production scale to reach a capacity of 19 tons of placentas per day. The extraction purification process includes five alcohol manufacturing steps, some with strict conditions of alcohol concentration, acid pH, temperature and one including chloroform. These steps are followed by three chromatographies. Albumin is finally submitted to pasteurization both in bulk and in the final container. Selected steps of this process have been tested for their ability to remove or inactivate viruses. Viruses used were HBV, HIV-1, HIV-2 and model viruses poliovirus, avian reovirus, MuLV, Sindbis, SV40 and Aujeszky's. In vitro infectivity titration assays were used for all viruses except for HBV where DNA and antigen titrations were performed. Reduction factors obtained were from 10 to 29 log10 depending on the viral marker. Moreover, testing done on regular production batches demonstrated the absence of HBV, HIV-1 and HCV genomic sequence in the final lots. Viral risk calculation for HBV, HIV-1 and HCV was made considering the maximal theoretically possible contamination of the starting material. This calculation showed the very large safety margin the manufacturing process with respect to virus transmission for these viruses or possibly other unknown ones.
