Fred Feldman

Effectiveness of alternative treatments for reducing potential viral contaminants from plasma-derived products

An issue of great importance and continuing concern with regard to all products derived from human plasma is their safety from potential contaminants in the source material from which they are purified. Since viral contaminants are a major safety consideration with these products, a number of different methods, including dry heating, vapor heating, filtration and nanofiltration, ultraviolet and gamma irradiation, pasteurization, solvent/detergent (S/D) treatment, sodium thiocyanate treatment, and chromatography (immunoaffinity, metal chelation, affinity, and ion exchange), have been developed to remove or inactivate potentially contaminating viruses. Pasteurization and S/D treatment have emerged as the dominant viral inactivation methods. Results summarized in this review demonstrate that pasteurization is the broadest and most rigorous currently available method for removal of potential viral contaminants from plasma-derived products. S/D treatment requires control over a large number of manufacturing parameters and has no ability to inactivate nonlipid-enveloped viruses. Pasteurization requires control over only a small number of manufacturing variables, is easily monitored, and remains effective even if deviations are encountered from specified protein and stabilizer concentrations and temperature. In addition, pasteurization is effective against a wide range of lipid- and nonlipid-enveloped viruses.

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.

Improved Safety from Plasma Derivatives: Purification and Viral Elimination Characteristics of Mononine

The occurrence of viral transmission with coagulation factor concentrates treated with a single virus elimination step has resulted in a consensus that multiple virus elimination steps must be incorporated in the processing of these proteins. As an example of this methodology, the steps included in the purification of the factor VIII concentrate Monoclate-P are reviewed and those used to purify the factor IX concentrate Mononine--monoclonal antibody chromatography, sodium thiocyanate incubation, and a novel ultrafiltration system--are described. Rigorous quality control/quality assurance during processing is essential. The ultimate safety of the product used clinically further requires monitoring of long-term stability and verification of the absence of neoantigens that could stimulate unusual levels of antibody formation. Standardization of regulatory compliance will further strengthen the safety of all products. The zeal to add further barriers to viral contamination should not compromise the timely assessment of these additional protections.