An improved manufacturing process for Xyntha/ReFacto AF.

SUMMARY: ReFacto Antihemophilic Factor is a second-generation antihaemophilia A product manufactured using a process that includes therapeutic grade human serum albumin (HSA) in the cell culture medium, but is formulated without HSA as a stabilizer. Even though this second-generation antihaemophilia product has a good safety profile, a programme was implemented to eliminate all animal- and human-derived raw materials from the production process, thus producing a third-generation product. To that end, HSA has been removed from the master and working cell banks and from the culture medium. The hybridoma-derived monoclonal antibody formerly used in the purification process has been replaced by a chemically synthesized affinity peptide, and a virus-retaining filtration step has been added to enhance the clearance of large viruses, such as retroviruses. The purification process has been validated for the removal of a panel of model viruses and provides significant clearance of all viruses tested. Host cell- and process-derived impurity removal validations also were conducted, including host cell DNA and protein, in addition to the affinity peptide. Compared with the product manufactured according to the original process, these changes had no detectable effect on the structural integrity, stability or clinical efficacy of this antihaemophilia A product. The product produced by the improved manufacturing process is named Xyntha/ReFacto AF.