Inactivation of retroviruses in biologicals manufactured for human use

Human immunodeficiency virus may occur in human plasma and mammalian retroviruses in established cell lines used for the production of monoclonal antibodies or recombinant proteins. To avoid any risk of retrovirus infections being transmitted to human patients by human plasma proteins or other biologicals obtained from established cell lines, these products must be free of contaminating retroviruses. This can be achieved by excluding contaminated source material and by establishing manufacturing procedures which inactivate and eliminate retroviruses. Some methods were investigated, and it was proved that these methods not only completely inactivate retroviruses, but that they are at the same time mild enough not to destroy the biological activities of the substances to be used as therapeutics. In addition, the clearance of retroviruses by the entire manufacturing process of an immunoglobulin, human plasminogen, a murine monoclonal antibody and a recombinant human protein were studied. In each case cumulative clearance factors of greater than 10(12) were achieved for the retroviruses used in these spiking experiments. It can be concluded that these high clearance factors contribute a very high margin of safety to the biologicals manufactured.