NEW METHODS FOR INACTIVATION OF LIPID-ENVELOPED AND NONENVELOPED VIRUSES

Two new methods are described for inactivating lipid-enveloped and non -enveloped viruses in plasma-derived products such as coagulation fact ors and intravenous immunoglobulin (IGIV). Iodine/Sephadex(R) delivers iodine to IGIV solutions in a slow, controlled way and allows for ina ctivation of greater than or equal to 4 logs of porcine parvovirus (PP V), a hardy non-enveloped virus, under conditions which do not measura bly damage the structural or functional properties of the IGIV, and wi th essentially no iodination of the protein. All detectable enveloped and non-enveloped viruses were inactivated by this treatment. Gamma ir radiation has been successfully used to inactivate viruses at the fina l vial stage in freeze-dried plasma proteins. Four logs of PPV were in activated by irradiation in the presence of fibrinogen, factor VIII an d alpha 1-proteinase inhibitor (API) at doses of 23, 28 and 30 kiloGra y (kGy) respectively, while retaining 93% of fibrinogen solubility, 67 % of factor VIII activity and over 80% of API activity. Bovine viral d iarrhea virus (BVDV), a lipid-enveloped model for hepatitis C virus, w as completely inactivated by radiation doses of 20-30 kGy in these pro ducts. Gamma irradiation was less effective in inactivating viruses in freeze-dried IGIV.