Lab-Scale Continuous Biomanufacturing: A Tool for Process Development With Adaptive Strategies for Capture and Virus Inactivation.

Monoclonal antibodies (mAbs) are nowadays fundamental in treating a wide range of severe diseases, including cancer, infections, or autoimmune disorders. Due to their high specificity, potent activity, and fewer side effects compared to small molecular drugs, the market for mAbs is growing continuously. Consequently, there is an increasing demand for process intensification technologies to increase the mAb throughput. This study introduces a novel integrated continuous biomanufacturing (ICB) process at lab-scale as a tool for process development. The ICB comprises a perfusion cultivation as an upstream process (USP) as well as a continuous multi-column chromatography capture step using membrane adsorbers (RC-BioSMB) and a continuous virus inactivation (VI) approach for the subsequent downstream processing. The process was continuously operated for 4 days. USP variations, like changes in titer and permeate flow rate, were successfully addressed by an adaptive control of the flow rates through all unit operations. The small-scale ICB was used to establish an adaptive control of the RC-BioSMB loading volume. A novel approach for the subsequent continuous VI was developed to enable processing at lab-scale with the associated very low flow rates. Throughout the lab-scale ICB process, a high overall yield of 88% was obtained with simultaneous high removal of process-related impurities like host cell proteins (3.4 log removal to 73 ppm) and DNA (2.9 log removal to 0.8 ppm).