Schmitz, F., Saballus, M., Kruse, T., Minceva, M., Kampmann, M. Streamlined Clarification and Capture Process for Monoclonal Antibodies Using Fluidized Bed Centrifugation and Multi-Column Chromatography With Membrane Adsorbers Biotechnology and Bioengineering, 2025, 122(2), pp. 382–394.  doi.org/10.1002/bit.28884

Abstract

Harmonizing unit operations in the downstream process of monoclonal antibodies (mAbs) has a high potential to overcome throughput limitations and reduce manufacturing costs. This study proposes a streamlined clarification and capture (S-CC) process concept for the continuous processing of cell broth harvested from a connected bioreactor. The process was realized with a fluidized bed centrifuge connected to depth and sterile filters, a surge tank, and a multi-column chromatography (MCC) unit. The MCC unit was operated in the rapid cycling simulated moving bed (RC-BioSMB) mode with five convective diffusive membrane adsorbers (MAs). A control strategy and the surge tank were used to adjust the loading flow rate of the MCC unit. The mAb was recovered with a total process yield of 90%, with high removal of the process-related impurities HCP (2.1 LRV) and DNA (2.9 LRV). Moreover, the S-CC process productivity of 4.2 g h⁻¹ was up to 5.3 times higher than for comparable, hypothetical batch MA processes. In addition, the buffer consumption of the capture step could be reduced from 2.0 L g⁻¹ in batch mode to 1.2 L g⁻¹ in the RC-BioSMB mode. These results demonstrate the high potential of streamlined interconnected unit operations to improve the overall mAb downstream process performance.

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