Viral safety of solvent-detergent treated blood products.

Abstract

Laboratory research commencing in 1982 led to licensing in the United States in 1985 of a solvent/detergent (SD)-treated anti-haemophilic factor (AHF) concentrate. Licensing was based on (a) studies demonstrating the inactivation of several marker viruses [vesicular stomatitis virus (VSV), Sindbis virus, Sendai virus], human immunodeficiency virus (HIV), hepatitis B virus (HBV), and non-A, non-B hepatitis virus [NANBHV; now known to be principally hepatitis C virus (HCV)] added to AHF just before treatment, (b) the realization that the principal viruses of concern in a transfusion setting (e.g. HIV, HBV, NANBHV) were all lipid-enveloped, and (c) laboratory, preclinical and clinical evidence indicating that AHF and other proteins present in the preparation were unaffected. The applicability of the SD method to a wide range of products and preparations, high process recoveries, and a growing body of viral safety information linked with the failure of several other virus inactivation methods to eliminate hepatitis transmission fostered the adoption of SD technology by more than 50 organizations world-wide. SD mixtures are now used in the preparation of products as diverse as intermediate purity and monoclonal antibody purified AHF and other coagulation factor concentrates, fibrin glue, normal and hyperimmune IgG and IgM preparations including those derived from tissue culture, plasma for transfusion, and various diagnostic controls. Over four million doses of SD-treated products have been administered, and numerous laboratory and clinical studies designed to assess virus safety have been conducted. SD treatment has been shown to inactivate > or = 10(9.2) tissue culture infectious doses (TCID50) of VSV, > or = 10(8.8) TCID50 of Sindbis virus, > or = 10(6.0) TCID50 of Sendai virus, > or = 10(7.3) duck infectious doses of duck HBV, > or = 10(11.0) degrees TCID50 of HIV-1, > or = 10(6.0) TCID50 of HIV-2, > or = 10(6.0) chimpanzee infectious doses (CID50) of HBV, > or = 10(5.0) CID50 of HCV, > or = 10(6.0) TCID50 of cytomegalovirus, > or = 10(5.8) TCID50 of herpes simplex virus type 1, > or = 10(4.0) TCID50 of PI-1, > or = 10(6.0) TCID50 of murine leukemia virus (Mov-3), > or = 10(4.0) TCID50 of murine xenotropic virus, and > or = 10(2.0) TCID50 of Rauscher murine leukemia ecotropic virus. Moreover, in ten prospective clinical studies, 0/53, 0/427, and 0/455 patients susceptible to HBV, NANBHV (HCV), and HIV became infected on follow-up.(ABSTRACT TRUNCATED AT 400 WORDS)