Intravenous immunoglobulin and hepatitis C virus: an overview of transmission episodes with emphasis on manufacturing data.

A number of episodes of non-A, non-B hepatitis (NANB) have been associated in the recent past with the administration of intravenous immunoglobulin (IGIV). It now appears that hepatitis C virus (HCV) is the cause of NANB, although not all the factors leading to HCV transmission by IGIV are completely understood. Nevertheless, based on a retrospective analysis of two episodes of HCV transmitted by anti-Rh D immunoglobulin (anti-D), cold ethanol fractionation clearly is important in ensuring viral safety; both of these intravenous anti-D preparations were manufactured without benefit of this purification step. Other episodes of HCV transmission have been associated with IGIV produced using chromatography (particularly DEAE-Sephadex chromatography), which has been used after cold ethanol fractionation to further purify immunoglobulin G. DEAE-Sephadex chromatography may have only a marginal partitioning capacity, such that infective HCV virions are not further fractionated into waste fractions. All IGIV preparations associated with HCV transmission were formulated as lyophilized preparations, which may be important in stabilizing HCV before administration to patients. The role of anti-HCV screening in improving the viral safety of IGIV preparations remains unclear, but additional viral inactivation steps, such as solvent-detergent treatment or incubation at pH 4.0, probably are required for IGIV manufactured using chromatographic procedures.