Partitioning and Inactivation of Viruses by Cold Ethanol Fractionation and Pasteurization during Manufacture of Albumin from Human Plasma

Abstract

The purpose of the present study was to examine the efficacy and mechanism of the fraction IV cold ethanol fractionation and pasteurization (60°C heat treatment for 10 h) steps, involved in the manufacture of albumin from human plasma, in the removal and/or inactivation of blood-born viruses. A variety of experimental model viruses for human pathogenic viruses, including the Bovine viral diarrhoea virus (BVDV), Bovine herpes virus (BHV), Murine encephalomyocarditis virus (EMCV), and Porcine parvovirus (PPV), were selected for this study. Samples from the relevant stages of the production process were spiked with the viruses, and the amount of virus in each fraction was then quantified using a 50% tissue culture infectious dose (TCID 50 ). The mechanism of reduction for the enveloped viruses (BHV and BVDV) during fraction IV fractionation was inactivation rather than partitioning, however, it was partitioning in the case of the non-enveloped viruses (EMCV and PPV). The log reduction factors achieved during fraction IV fractionation were ≥6.9 for BHV, ≥5.2 for BVDV, 4.9 for EMC, and 4.0 for PPV. Pasteurization was found to be a robust and effective step in inactivating the enveloped viruses as well as EMCV. The log reduction factors achieved during pasteurization were ≥7.0 for BHV, ≥6.1 for BVDV,≥6.3 for EMCV, and 1.7 for PPV. These results indicate that the production process for albumin has sufficient virus-reducing capacity to achieve a high margin of virus safety.