Improvement in Anti-hemophilic Factor Concentrates

Abstract

Lyophilized, heat-treated, factor VIII and IX concentrates are the predominantly prescribed treatment for bleeding in hemophiliacs. Two major drawbacks currently identified with pooled-plasma concentrates are the risk of viral transmission upon infusion and immunosuppression thought to be due to alloantigen stimulation. Two new AHF manufacturing processes have been recently developed that may eliminate these problems. One process uses monoclonal antibody to purity AHF from plasma; the other uses gene recombination techniques to prepare rDNA AHF. The first method includes purification of F VIII or F VIII/vWF from the cryoprecipitate by immunoaffinity chromatography using mouse monoclonal antibodies raised against F VIII or F VIII/vWF. The specific activity of the resulting F VIII concentrate (Method M, MONOCLATE^®) is high (1,500∼3,000 u/mg protein) because it is virtually free of éxtraneous proteins and completely free of alloantigen. rDNA preparations are being developed by several firms. The one developed by Genetics Institute is still in the experimental stage, but phase I studies begun with two patients showed good hemostatic efficiency without side effects. Encouraged by this success, it is expected that the production of rDNA AHF will move from the laboratory to full-scale manufacturing.