Continuous In‐Line Virus Inactivation for Next Generation Bioprocessing

Viral inactivation plays a critical role in assuring the safety of monoclonal antibody (mAb) therapeutics. Traditional viral inactivation involves large holding tanks in which product is maintained at a target low pH for a defined hold time, typically 30–60 min. The drive toward continuous processing and improved facility utilization has provided motivation for development of a continuous viral inactivation process. To this end, a lab‐scale prototype viral inactivation system was designed, built, and characterized. Multiple incubation chamber designs are evaluated to identify the optimal design that enables narrow residence time distributions in continuous flow systems. Extensive analysis is conducted supporting rapid low pH viral inactivation and included evaluations with multiple viruses, a range of pH levels, buffer compositions, mAb concentrations, and temperatures. Multiple test conditions are evaluated using the in‐line system and results compared to traditional batch‐mode viral inactivation. Comparability in kinetics of virus inactivation suggests equivalency between the two approaches. Virus clearance in monoclonal antibody processing is critical, where an inactivation step contributes significantly to the overall viral reduction in a process. In this work, the transition of the low pH viral inactivation step from a batch process to a continuous flow process that requires control of two critical pieces, namely virus inactivation kinetics, which were evaluated as a function of different solution conditions, and the incubation chamber, where conditions are maintained to ensure exposure of the process fluid to the inactivation conditions for a set time is evaluated. This work demonstrates the feasibility of transitioning from a traditional batch inactivation process to a fully continuous process enabling the development of a fully continuous downstream process for monoclonal antibodies.