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

BACKGROUND: While immune globulins for intravenous administration (IGIV) ha ve an excellent record with respect to virus safety, concern regarding thes e preparations has been raised by reports of transmission of hepatitis C vi rus (HCV) to patients treated with IGIV and the presence of genetic materia l for HCV in IGIV preparations. STUDY DESIGN AND METHODS: This in vitro study evaluated the effectiveness o f several manufacturing steps, including ethanol precipitation and pasteuri zation, in reducing HIV and model viruses including encephalomyocarditts (E MC) virus, pseudorabies virus (PRV), bovine viral diarrhea virus (BVDV), Si ndbis 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 (log(10)) 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 log(1 0) and resulted in a log(10) reduction of >6.54 for HIV, >5.39 for PRV, 26. 64 for BVDV, >7.78 for Sindbis virus, >5.84 for vaccinia virus, and >6.99 f or VSV. All viruses except EMC virus were reduced below the limit of detect ion within 6 hours of the beginning of pasteurization. Cohn processing of F raction II + III paste and the 4.5-percent alcohol precipitation step prior to pasteurization provided additional virus removal. Studies using the pol ymerase chain reaction technique found that HCV RNA was detectable in the s tarting fraction of Cohn Fraction II paste, but not in the final IGIV prepa ration. CONCLUSION: These findings strongly support the viral safety of IGIV prepar ed by this method and show a significant added measure of virus safety asso ciated with pasteurization of this preparation.