An alternative to Triton X-100 for use in viral inactivation for recombinant factor VIII /

Abstract

Solvent detergent combinations for viral inactivation have long been used in the manufacture of Biopharmaceutical products due their proven safety record for inactivating viruses. Triton X-100, a non-ionic detergent, has been the detergent of choice within the modern Biopharma industry. However, this detergent, when broken down has environmental hazards proving it toxic to aquatic species. Because of this, Triton X-100 has been assessed by the European Chemicals Agency and has formally been placed on the REACH authorisation list. This has resulted in companies who employ Triton X-100 within their manufacturing process to perform an analysis of alternatives in an attempt to move away from the use of Triton X-100. The basic aim of this research was to identify an alternative chemical to Triton X-100 for use in viral inactivation of recombinant factor FVIII. This research project was based on an extensive literature review followed by a series of practical research studies. From this research, 6 alternative candidates were identified and evaluated through bench scales studies for impact to a recombinant factor VIII protein. This allowed for the elimination of candidates based on their bench scale results and also the progression of 2 candidates to further design of experiments (DOE) studies. The DOE studies showed that the 2 candidates had no negative impact to product quality or stability. It also allowed for optimal process conditions to be determined using the 2 candidates which were carried forward to a proof of concept virus inactivation study at a third party laboratory. This viral inactivation study employed the use of two model viruses, MuLV and PRV. Both candidates showed their robustness at inactivating the two viruses with a LRV >5 log, providing sufficient certainty that the two candidates are viable alternatives to Triton X-100.