Antibody capture process based on magnetic beads from very high cell density suspension. Issue 9 (4th May 2021)

• Record Type: Journal Article
• Authors: Brechmann, Nils A.; Schwarz, Hubert; Eriksson, Per‐Olov; Eriksson, Kristofer; Shokri, Atefeh; Chotteau, Véronique
• Other Names: Warikoo Veena guestEditor.
• Is Part Of: Biotechnology and bioengineering. Volume 118:Issue 9(2021)
• Page Start: 3499
• Page End: 3510
• Publication Date: 2021-05-04
• Subjects: high cell density -- mAb capture -- magnetic beads -- magnetic separation -- process integration; Biotechnology -- Periodicals; Bioengineering -- Periodicals; 660.6
• DOI: 10.1002/bit.27776
• Languages: English
• ISSNs: 0006-3592

Abstract

Abstract: Cell clarification represents a major challenge for the intensification through very high cell density in the production of biopharmaceuticals such as monoclonal antibodies (mAbs). The present report proposes a solution to this challenge in a streamlined process where cell clarification and mAb capture are performed in a single step using magnetic beads coupled with protein A. Capture of mAb from non‐clarified CHO cell suspension showed promising results; however, it has not been demonstrated that it can handle the challenge of very high cell density as observed in intensified fed‐batch cultures. The performances of magnetic bead‐based mAb capture on non‐clarified cell suspension from intensified fed‐batch culture were studied. Capture from a culture at density larger than 100 × 10 6 cells/ml provided an adsorption efficiency of 99% and an overall yield of 93% with a logarithmic host cell protein (HCP) clearance of ≈2–3 and a resulting HCP concentration ≤≈5 ppm. These results show that direct capture from very high cell density cell suspension is possible without prior processing. This technology, which brings significant benefits in terms of operational cost reduction and performance improvements such as low HCP, can be a powerful tool alleviating the challenge of process intensification. Abstract : The authors present a magnetic bead‐based purification for the direct capture of monoclonal antibodies from very high cell density (>100 × 10 6 cell/ml) intensified fed‐batch CHO cell culture. Direct capture from non‐clarified cell suspension showed excellent efficacy regarding absorption, elution, and very low final HCP content, despite a very high cell density. Compared to legacy cell clarifications following mAb capture, this process represents significant savings in operational time, consumables, and workload, while providing very gentle conditions for the cells.