Biomedical subjects

T Charlebois

Publications and source records attributed to T Charlebois.

3 recordsLinked to original sources

PubMed2001

The manufacturing process for B-domain deleted recombinant factor VIII.

The development of a cell bank used in the routine manufacturing of a B-domain deleted recombinant coagulation factor VIII (BDDrFVIII) molecule involved stable insertion of the human BDDrFVIII gene into Chinese hamster ovary (CHO) cells, selection of a cell line capable of expressing consistent levels of active BDDrFVIII, and the establishment of a cell bank. The manufacturing process begins with the culturing of CHO cells in large bioreactors. Product synthesis is initiated by altering the cell culture conditions, thereby arresting the cells in a stationary growth phase and inducing elevated expression of BDDrFVIII. Harvested culture medium is concentrated by chromatography and then purified through a series of four column chromatography steps and one solvent-detergent virus inactivation step. By eliminating the presence of human serum albumin in the final formulation, the BDDrFVIII-containing coagulant product meets with a high standard of safety against microbial and viral contamination. Extensive studies have shown that BDDrFVIII is a consistent, highly pure factor VIII for the treatment of patients with hemophilia A.

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PubMed1998

The manufacturing process for recombinant factor IX.

Advances in recombinant DNA manufacturing technology have now made possible the production of a highly purified and active recombinant factor IX (rFIX) product. Recombinant factor IX was developed by (1) stable insertion of the genes for both factor IX and PACE-SOL (a truncated, soluble serine protease needed to enhance the capacity of cells to remove the amino-terminal propeptide from rFIX) into Chinese hamster ovary cells; (2) selection of a cell line that was capable of expressing high amounts of active rFIX while growing in bioreactors containing a completely defined culture medium that does not contain blood or plasma products; and (3) inclusion of four independent chromatography steps, none of which require monoclonal antibodies. Furthermore, rFIX has been extensively tested to demonstrate similarity to plasma-derived factor IX and has been shown to be a consistent, high-purity product. For example, a high-specific-activity product (276+/-23 IU/mg) has been consistently produced throughout 65 consecutive batches from five consecutive manufacturing campaigns. Thus, rFIX offers a consistent and high-purity source of factor IX treatment for patients with hemophilia B.

Animals↗

PubMed1998

Viral safety of recombinant factor IX.

The viral safety of Chinese hamster ovary (CHO)-cell-based pharmaceuticals is well established. There have been more than 100 million infusions of CHO-derived pharmaceuticals without a single documented case of viral transmission. The recombinant factor IX (rFIX) process builds on this safety record by using a state-of-the-art multitiered approach to viral safety. This includes extensive testing of the CHO cells used to produce rFIX, routine viral monitoring of the cell culture production process, a manufacturing process and formulation that do not use blood or plasma products, and validation of the viral removal capacity of the purification process. The multifaceted viral safety program for rFIX has sufficient redundancy between approaches to compensate for potential limitations of any single safety measure. Together, the elements of the rFIX multitiered viral safety program offer patients and physicians a product that is inherently free of human blood-borne pathogens, including any risk of human immunodeficiency virus (HIV) hepatitis, parvovirus, and Creutzfeldt-Jakob disease (CJD).

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