Potential contribution of mild pepsin treatment at pH4 to the viral safety of human immunoglobulin products.

Different manufacturers use several different processes for the production of intravenous immunoglobulin. Several manufacturers include a production step where the immunoglobulin is treated with low levels of pepsin at pH 4. A series of experiments were undertaken to assess whether or not pH 4/pepsin treatment could inactivate a range of test viruses. Acid-labile viruses such as vaccinia, herpes simplex, mumps and Semliki Forest virus were found to be susceptible to pH 4/pepsin treatment whereas poliovirus type 2, an acid-stable virus, was completely resistant to this treatment. In immunoglobulin preparations, viral contaminants are likely to be present as antibody/virus complexes and such complexing was found to help protect the test viruses from inactivation by pH 4/pepsin treatment. Despite this protection, at least 99% of the test inoculum of two susceptible viruses (vaccinia and herpes simplex) was found to be inactivated after treatment and the subsequent dissociation of virus/antibody complexes. It is concluded that pH 4/pepsin treatment may contribute to the safety of intravenous IgG by inactivating potential viral contaminants.