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  4. Mimicking CHO large-scale effects in the single multicompartment bioreactor: A new approach to access scale-up behavior
 
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Mimicking CHO large-scale effects in the single multicompartment bioreactor: A new approach to access scale-up behavior

Citation Link: https://doi.org/10.15480/882.9094
Publikationstyp
Journal Article
Date Issued
2024-04
Sprache
English
Author(s)
Gaugler, Lena  
Hofmann, Sebastian  orcid-logo
Mehrphasenströmungen V-5  
Schlüter, Michael  orcid-logo
Mehrphasenströmungen V-5  
Takors, Ralf  
TORE-DOI
10.15480/882.9094
TORE-URI
https://hdl.handle.net/11420/45277
Journal
Biotechnology and bioengineering  
Volume
121
Issue
4
Start Page
1244
End Page
1256
Citation
Biotechnology and Bioengineering 121 (4): 1244-1256 (2024)
Publisher DOI
10.1002/bit.28647
Scopus ID
2-s2.0-85181755248
Publisher
John Wiley and Sons Inc
During the scale-up of biopharmaceutical production processes, insufficiently predictable performance losses may occur alongside gradients and heterogeneities. To overcome such performance losses, tools are required to explain, predict, and ultimately prohibit inconsistencies between laboratory and commercial scale. In this work, we performed CHO fed-batch cultivations in the single multicompartment bioreactor (SMCB), a new scale-down reactor system that offers new access to study large-scale heterogeneities in mammalian cell cultures. At volumetric power inputs of 20.4–1.5 W m−3, large-scale characteristics like long mixing times and dissolved oxygen (DO) heterogeneities were mimicked in the SMCB. Compared to a reference bioreactor (REFB) set-up, the conditions in the SMCB provoked an increase in lactate accumulation of up to 87%, an increased glucose uptake, and reduced viable cell concentrations in the stationary phase. All are characteristic for large-scale performance. The unique possibility to distinguish between the effects of changing power inputs and observed heterogeneities provided new insights into the potential reasons for altered product quality attributes. Apparently, the degree of galactosylation in the evaluated glycan patterns changed primarily due to the different power inputs rather than the provoked heterogeneities. The SMCB system could serve as a potent tool to provide new insights into scale-up behavior and to predict cell line-specific drawbacks at an early stage of process development.
Subjects
CHO fed-batch cultivations
gradients
large-scale heterogeneities
multicompartment system
scale-down
SMCB
DDC Class
570: Life Sciences, Biology
Publication version
publishedVersion
Lizenz
https://creativecommons.org/licenses/by/4.0/
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