(296a) A Biophysical Outlook of Viral Inactivation with Arginine and Common Buffers in Biologics Manufacturing

Joshi, P. U. - Presenter, Michigan Technological University
Meingast, C., Michigan Technological U
Xu, X., Bristol-Myers Squibb
Holstein, M., Bristol-Myers Squibb
Feroz, H., Bristol-Myers Squibb
Ranjan, S., Bristol-Myers Squibb
Ghose, S., Bristol-Myers Squibb
Heldt, C., Michigan Technological University
A need for robust virus inactivation processes and environmentally friendly materials had prompted an exploration of innovative and alternate strategies in biologics manufacturing. A common detergent, Triton X-100, often relied on for inactivation of enveloped viruses, is on the edge of disbarment due to its detrimental effect on the environment. In this interest, two inactivation methods based on arginine and commonly used buffers were explored. Past studies have shown arginine to inactivate certain viruses under various conditions. However, the optimal conditions and mechanisms for fully inactivating all enveloped viruses by arginine is not known. For this reason, we tested a matrix of parameters such as pH, incubation time and buffer type to discern an optimal condition for inactivation of all enveloped viruses. Our results demonstrated that larger viruses - herpes simplex virus (HSV-1) and pseudorabies virus (SuHV-1) were effectively inactivated with > 4 LRV as compared to the smaller sized viruses - bovine viral diarrhea virus (BVDV) and equine arteritis virus (EAV). However, the optimal conditions resulted in different inactivation values between the similar herpes family viruses, HSV-1 and SuHV-1. Mechanistic understanding is being derived from the study of mechanical properties, virus-host interaction, and changes in the virus membrane. The second study explored the efficiency of commonly used buffers in the downstream train. Various buffers such as glycine, acetate, and citrate at pH 4 were explored to determine the inactivation efficacy of the above-mentioned viruses. A similar trend of inactivation based on virus size was observed for all the buffers. The efficiency of the buffers considering both the composition and incubation time was in the order of glycine < acetate ≤ citrate. Overall, this work directs towards the trend in phasing out Triton X-100 inactivation of enveloped viruses during biologics manufacturing and effects of commonly used buffers in the biologic and viral DSP.