(467b) Eco-Friendly Detergent Combo for Viral Inactivation in Protein Manufacturing

Protein viral contaminants can be a major concern in biologics manufacturing. Therefore, most biologics manufacturing processes need to effectively inactivate and remove viruses to comply with regulatory requirements and ensure safe administration of therapeutics to patients. Detergent-based treatment is an effective way to inactivate enveloped viruses, and a widely used commercial detergent is Triton X-100. However, due to environmental concern, the European Chemical Agency has mandated a sunset date of 2021 to replace Triton X-100. Hence, there is an industry-wide initiative ongoing to find eco-friendly Triton X-100 alternatives. The purpose of this study is to propose a novel eco-friendly detergent combo (referred as “OG/DDM”) for viral inactivation in biologics manufacturing.

The OG/DDM was evaluated on three aspects, i.e., viral inactivation effectiveness, impact on product quality, and impact on process robustness. Sets of viral inactivation, detergent incubation, and detergent spike studies were conducted to obtain data on the first, second, and third aspect, respectively. The same studies were also conducted on Triton X-100 and another eco-friendly commercial detergent, i.e., EcoSurf EH9^®, and associated data were used as control groups. The data associated with OG/DDM were compared with the data associated with Triton X-100 and EcoSurf EH9^® to assess its suitability.

First, the OG/DDM provided satisfactory viral inactivation effects, i.e., its log reduction value for two model viruses, i.e., amphotrophic murine leukemia virus and herpes simplex virus, was above 4 under ambient temperature after 15, 30, and 60 minutes of treatment. Second, the detergent combo showed negligible negative impact on product quality. The impurity species in product pool, i.e., high molecular weight, deamidated, and oxidized species, were all within acceptable range after detergent treatment. Besides, the protein sialic acid content, which was an important species to control immune response, was also within acceptable range after detergent treatment. Third, the detergent spike study demonstrated that the detergent level in product pool was below the limit of detection after a protein A chromatography step. Therefore, the OG/DDM can be cleared by subsequent purification steps and will not disturb manufacturing process. In addition, all results associated with OG/DDM are comparable to the results associated with Triton X-100 and EcoSurf EH9^®, which demonstrated that the performance of OG/DDM was comparable to conventional commercial detergents.

The proposed novel eco-friendly detergent combo, OG/DDM, demonstrated effective viral inactivation, negligible negative impact on product quality and process robustness. Besides, the performance of OG/DDM was comparable to Triton X-100 and EcoSurf EH9^®. It is demonstrated that OG/DDM is a suitable eco-friendly alternative for Triton X-100 and can be used for viral inactivation in protein manufacturing.