Demonstrating the Effectiveness of an Alternative to Triton X-100 for Detergent-Mediated Viral Inactivation in Biomanufacturing

Abstract

Detergent-mediated viral inactivation is an important process step for ensuring viral safety of parenteral biotherapeutics, including plasma proteins and monoclonal antibodies (mAb). The conventional Triton X-100 detergent has ecological toxicity concerns and REACH classification that mandate replacement in the biopharmaceutical industry. Criteria for a replacement detergent include viral inactivation efficacy, acceptable safety and biodegradation profile, process removal, and quality suitable for parenteral drug product manufacturing. A non-ionic, C11-15 secondary alcohol ethoxylate, Deviron 13-S9 detergent, has been demonstrated to meet the necessary requirements for detergent performance. Benchmarking studies with Triton X-100 detergent demonstrate comparable performance with a panel of enveloped viruses in multiple matrices, including human IgG, clarified cell culture harvest, and fractionated plasma. Deviron 13-S9 detergent demonstrated viral inactivation efficiency comparable to or better than Triton X-100 detergent, achieving > 5 log reduction values. Critical micelle concentration was determined across different temperatures and media. Deviron 13-S9 detergent was demonstrated to be readily biodegradable according to OECD 301B guidelines. The absence of detergent binding to typical chromatography resins used in downstream purification was confirmed. The process removal of Deviron 13-S9 detergent from a protein-containing matrix was demonstrated using a protein A resin. These findings support Deviron 13-S9 detergent as a viable alternative to Triton X-100 detergent, ensuring robust viral inactivation, environmental compatibility, and alignment with regulatory requirements.