Scaling-down biopharmaceutical production processes via a single multi-compartment bioreactor (SMCB).

Autor: Gaugler L; Institute of Biochemical Engineering University of Stuttgart Stuttgart Germany., Mast Y; Institute of Biochemical Engineering University of Stuttgart Stuttgart Germany., Fitschen J; Institute of Multiphase Flows Hamburg University of Technology Hamburg Germany., Hofmann S; Institute of Multiphase Flows Hamburg University of Technology Hamburg Germany., Schlüter M; Institute of Multiphase Flows Hamburg University of Technology Hamburg Germany., Takors R; Institute of Biochemical Engineering University of Stuttgart Stuttgart Germany.
Jazyk: angličtina
Zdroj: Engineering in life sciences [Eng Life Sci] 2022 Mar 14; Vol. 23 (1), pp. e2100161. Date of Electronic Publication: 2022 Mar 14 (Print Publication: 2023).
DOI: 10.1002/elsc.202100161
Abstrakt: Biopharmaceutical production processes often use mammalian cells in bioreactors larger than 10,000 L, where gradients of shear stress, substrate, dissolved oxygen and carbon dioxide, and pH are likely to occur. As former tissue cells, producer cell lines such as Chinese hamster ovary (CHO) cells sensitively respond to these mixing heterogeneities, resulting in related scenarios being mimicked in scale-down reactors. However, commonly applied multi-compartment approaches comprising multiple reactors impose a biasing shear stress caused by pumping. The latter can be prevented using the single multi-compartment bioreactor (SMCB) presented here. The exchange area provided by a disc mounted between the upper and lower compartments in a stirred bioreactor was found to be an essential design parameter. Mimicking the mixing power input at a large scale on a small scale allowed the installation of similar mixing times in the SMCB. The particularities of the disc geometry may also be considered, finally leading to a converged decision tree. The work flow identifies a sharply contoured operational field comprising disc designs and power input to install the same mixing times on a large scale in the SMCB without the additional shear stress caused by pumping. The design principle holds true for both nongassed and gassed systems.
Competing Interests: The authors have declared no conflicts of interest.
(© 2022 The Authors. Engineering in Life Sciences published by Wiley‐VCH GmbH.)
Databáze: MEDLINE
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