Recombinant Coagulation Factor IX (BeneFIX®)

Abstract

Coagulation factor IX is a zymogen that is an essential component of the clotting process; deficient factor IX activity results in hemophilia B. To overcome problems associated with plasma-derived blood products, Genetics Institute developed a recombinant coagulation factor IX (rFIX, BeneFrx9 produced using a Chinese hamster ovary cell line. The production cell line includes an rFE expression vector as well as another plasmid expressing PACE-SOL for necessary posttranslational processing. Extensive testing of master cell bank, working cell bank, and end-of-production cells has demonstrated that these plasmids are accurately integrated into the genome of the CHO cell line and that rFIX is correctly and stably expressed across multiple generations. No blood or plasma products are used in the manufacturing process or formulation of rFIX. Additionally, to ensure product purity, the manufacturing process includes four chromatographic separation procedures and two filtration procedures to remove impurities and potential contaminants. The identity, purity, potency, safety, and quality of rFIX drug substance are ensured by a series of test procedures, including gel electrophoresis, size-exclusion chromatography, peptide mapping, carbohydrate fingerprinting, and biological activity in a one-stage clotting assay. Preclinical and clinical testing of rFIX has shown it to be safe and effective for treating hemorrhagic episodes and preventing bleeding during surgery in patients with hemophilia B.