Work

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

Year: 2024

Type: article

Abstract: 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.

Source: Biotechnology and Bioengineering

DOI: 10.1002/bit.28884

Authors: Fabian Schmitz, Martin Saballus, Thomas Kruse, Mirjana Minceva, Markus Kampmann

Institutions: Sartorius (Germany), Technical University of Munich

Language: English

Topic: Protein purification and stability

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Responsible consumption and production

Open Access status: hybrid

Estimated APC paid: $5,010