Long-term surveillance for human anti-murine antibodies of a group of haemophiliacs treated only with immunoaffinity-purified FVIII concentrates

Abstract

An immunoaffinity purified, solvent/detergent virally inactivated factor VIII (FVIII) concentrate (Hemofil® M) has been in clinical use in persons with haemophilia A since March 1987 and under clinical trial prior to licencing in the USA, Europe and Japan. The specification set and consistently met for the monoclonal antibody (mAb) content of the final product is 0.1 ng/IU FVIII. This level was considered non-immunogenic, based upon animal studies, recommendations of the European PHarmacopoeia with ovalbumin contamination of influenza vaccine and also the experience during clinical research studies using aAb for diagnostic or other clinical purpose as reported in the medical literature. This research communication documents the surveillance for human anti-murine antibodies (HAMA) in 13 patients with serve haemophilia A. These patients have been treated with a large amount of product (mean 14,026 IU), numerous different lots of Hemofil M (total 45; mean 17) over a substantial period of time (mean 28 months). The data generated from this group of 13 patients before and during therapeutic Hemofil M administration failed to show the development of any HAMA response at any timepoint. Therefore Hemofil M prepared by mAb resin immunoaffinity column chromatography under the currently set specifications for mAb contaminant of 0.1 ng/IU FVIII or less is a safe therapeutic agent in the management and prevention of bleeding episodes in persons with haemophilia A.

Keywords: antibody; antihaemophilic factor; murine.