Continuous precipitation-filtration process for initial capture of a monoclonal antibody product using a four-stage countercurrent hollow fiber membrane washing step.

Autor:	Minervini M; Department of Chemical Engineering, The Pennsylvania State University, State College, Pennsylvania, USA., Mergy M; Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, New York, USA., Zhu Y; Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, New York, USA., Gutierrez Diaz MA; Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, New York, USA., Pointer C; ChromaTan, Inc., Gwynedd, Pennsylvania, USA., Shinkazh O; ChromaTan, Inc., Gwynedd, Pennsylvania, USA., Oppenheim SF; Takeda Pharmaceuticals, Cambridge, Massachusetts, USA., Cramer SM; Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, New York, USA., Przybycien TM; Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, New York, USA., Zydney AL; Department of Chemical Engineering, The Pennsylvania State University, State College, Pennsylvania, USA.
Jazyk:	angličtina
Zdroj:	Biotechnology and bioengineering [Biotechnol Bioeng] 2024 Aug; Vol. 121 (8), pp. 2258-2268. Date of Electronic Publication: 2023 Aug 10.
DOI:	10.1002/bit.28525
Abstrakt:	The significant increase in product titers, coupled with the growing focus on continuous bioprocessing, has renewed interest in using precipitation as a low-cost alternative to Protein A chromatography for the primary capture of monoclonal antibody (mAb) products. In this work, a commercially relevant mAb was purified from clarified cell culture fluid using a tubular flow precipitation reactor with dewatering and washing provided by tangential flow microfiltration. The particle morphology was evaluated using an inline high-resolution optical probe, providing quantitative data on the particle size distribution throughout the precipitation process. Data were obtained in both a lab-built 2-stage countercurrent washing system and a commercial countercurrent contacting skid that provided 4 stages of continuous washing. The processes were operated continuously for 2 h with overall mAb yield of 92 ± 3% and DNA removal of nearly 3 logs in the 4-stage system. The high DNA clearance was achieved by selective redissolution of the mAb using a low pH acetate buffer. Host cell protein clearance was 0.59 ± 0.08 logs, comparable to that based on model predictions. The process mass intensity was slightly better than typical Protein A processes and could be significantly improved by preconcentration of the antibody feed material. (© 2023 The Authors. Biotechnology and Bioengineering published by Wiley Periodicals LLC.)
Databáze:	MEDLINE
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