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

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 sen...

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Published inEngineering in life sciences Vol. 23; no. 1; pp. e2100161 - n/a
Main Authors Gaugler, Lena, Mast, Yannic, Fitschen, Jürgen, Hofmann, Sebastian, Schlüter, Michael, Takors, Ralf
Format Journal Article
LanguageEnglish
Published Germany John Wiley & Sons, Inc 01.01.2023
John Wiley and Sons Inc
Wiley-VCH
Subjects
Acids
Biopharmaceuticals
Bioreactors
Carbon dioxide
cell culture
Cell lines
compartment discs
Decision trees
Design
Design parameters
Dissolved oxygen
Mammalian cells
mixing times
multi‐compartment system
Pumping
R&D
Research & development
scale‐down
Shear stress
Stainless steel
Substrates
Velocity
Workflow
Germany
scale‐down
multi‐compartment system
cell culture
compartment discs
mixing times
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Summary: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.
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content type line 23
ISSN:1618-0240
1618-2863
DOI:10.1002/elsc.202100161