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 factors and intravenous immunoglobulin (IGIV). Iodine/Sephadex delivers iodine to IGIV solutions in a slow, controlled way and allows for inactivation of > or = 4 logs of porcine parvovirus (PPV), a hardy non-enveloped virus, under conditions which do not measurably damage the structural or functional properties of the IGIV, and with essentially no iodination of the protein. All detectable enveloped and non-enveloped viruses were inactivated by this treatment. Gamma irradiation has been successfully used to inactivate viruses at the final vial stage in freeze-dried plasma proteins. Four logs of PPV were inactivated by irradiation in the presence of fibrinogen, factor VIII and alpha 1-proteinase inhibitor (API) at doses of 23, 28 and 30 kiloGray (kGy) respectively, while retaining 93% of fibrinogen solubility, 67% of factor VIII activity and over 80% of API activity. Bovine viral diarrhea virus (BVDV), a lipid-enveloped model for hepatitis C virus, was completely inactivated by radiation doses of 20-30 kGy in these products. Gamma irradiation was less effective in inactivating viruses in freeze-dried IGIV.