Integration of Single Pass Tangential Flow Filtration and High Performance Countercurrent Membrane Purification for Intensification of Monoclonal Antibody Processing

ABSTRACT There is increasing interest in the development of intensified processes that can provide significant reductions in manufacturing costs for monoclonal antibody (mAb) products. This study examines the performance of an integrated membrane process that combines single‐pass tangential flow filtration (SPTFF) with high‐performance countercurrent membrane purification (HPCMP) for the preconditioning of clarified culture fluid (CCF). The SPTFF step was operated with a single‐pass concentration factor of 20x for 24 h filtration, with no evidence of membrane fouling; the transmembrane pressure remained < 30 kPa throughout the process. HPCMP was then performed on the pre‐concentrated feed, resulting in a 60 ± 8% reduction in host cell proteins (HCPs) and more than a 30‐fold removal of DNA while maintaining 94 ± 3% mAb step yield. The HPCMP process operated continuously for 36 h with a slight decline in HCP removal in the latter stages of operation due to membrane fouling. The buffer requirement for the integrated process was only 76 L/kg mAb. These results demonstrate the potential of using an integrated SPTFF‐HPCMP process for preconditioning CCF as part of a highly intensified mAb manufacturing process with much lower cost of goods.