From Failures to Insights: The Role of Surge Tanks in Integrated and Continuous Bioprocessing for Antibody Production

Continuous bioprocessing has great potential to address issues of flexibility, cost, and robustness in pharmaceutical manufacturing. Despite the identified benefits, continuous bioprocessing has not yet been adopted for commercial production owing to the difficulty of integrating the cultivation and purification processes. Surge tanks installed between unit operations play a critical role in integrated bioprocessing, but their role has not been fully understood and defined. In this study, we examined the function of surge tanks in an integrated and continuous bioprocessing (ICB) system. We developed the ICB train equipped with surge tanks, used a 10 L bioreactor to produce monoclonal antibodies, and conducted a 6-day experiment. During the experiment, unexpected issues related to the surge tanks emerged, and they were analyzed using a fault tree diagram. Key findings highlight the surge tanks’ role in balancing flow between upstream and downstream operations and raise considerations about antibody concentration fluctuations and residence time. Proposed improvements based on these findings include optimizing the capacity and placement of surge tanks, strengthening monitoring and control systems, and enabling the flexible adjustment of operating conditions. These measures are expected to further facilitate seamless upstream integration and contribute to the stability of the operation of the ICB system.