Virus reduction in the preparation of intravenous immune globulin: in vitro experiments.

BACKGROUND: While immune globulins for intravenous administration (IGIV) have an excellent record with respect to virus safety, concern regarding these preparations has been raised by reports of transmission of hepatitis C virus (HCV) to patients treated with IGIV and the presence of genetic material for HCV in IGIV preparations.

STUDY DESIGN AND METHODS: This in vitro study evaluated the effectiveness of several manufacturing steps, including ethanol precipitation and pasteurization, in reducing HIV and model viruses including encephalomyocarditis (EMC) virus, pseudorabies virus (PRV), bovine viral diarrhea virus (BVDV), Sindbis virus, vaccinia virus, and vesicular stomatitis virus (VSV), as well as HCV RNA, in IGIV.

RESULTS: Ethanol precipitation carried out after pasteurization resulted in virus reductions (log10) of >3.97 for HIV, 1.95 for EMC virus, >5.39 for PRV, and 3.52 for BVDV. Pasteurization inactivated EMC virus by 4.52 log10 and resulted in a log10 reduction of >6.54 for HIV, >5.39 for PRV, >6.64 for BVDV, >7.78 for Sindbis virus, >5.84 for vaccinia virus, and >6.99 for VSV. All viruses except EMC virus were reduced below the limit of detection within 6 hours of the beginning of pasteurization. Cohn processing of Fraction II + III paste and the 4.5-percent alcohol precipitation step prior to pasteurization provided additional virus removal. Studies using the polymerase chain reaction technique found that HCV RNA was detectable in the starting fraction of Cohn Fraction II paste, but not in the final IGIV preparation.

CONCLUSION: These findings strongly support the viral safety of IGIV prepared by this method and show a significant added measure of virus safety associated with pasteurization of this preparation.