Streamlined Clarification and Capture Process for Monoclonal Antibodies Using Fluidized Bed Centrifugation and Multi‐Column Chromatography With Membrane Adsorbers

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.