LAPSE:2024.0659
Published Article

LAPSE:2024.0659
Scaling Fed-Batch and Perfusion Antibody Production Processes in Geometrically Dissimilar Stirred Bioreactors
June 6, 2024
Modern production processes for biopharmaceuticals often work with very high cell densities. Moreover, there is a trend towards moving from fed-batch to continuous perfusion processes; a development that is influencing the requirements for bioreactor design and process control. In this study, the transfer of fed-batch and perfusion experiments between different cylindrical stirred lab-scale bioreactors and Thermo Scientific’sTM (Waltham, MA, USA) cubical HyPerformaTM DynaDriveTM Single-Use Bioreactor was investigated. Different scaling parameters were used, which were selected based on the requirements of the respective processes. Peak cell densities of up to 49 × 106 cells mL−1 and antibody titers of up to 5.2 g L−1 were achieved in 15- to 16-day fed-batch experiments. In 50-day perfusion cultivations, a viable cell volume of >100 mm3 mL−1 was maintained and more than 1 g L−1 d−1 of antibodies were harvested. The perfusion processes were automated with both cell bleed control and glucose concentration control. Cell retention was performed using Repligen’s (Waltham, MA, USA) XCell® ATF perfusion systems and single-use devices. In summary, approaches for successfully scaling highly productive fed-batch and perfusion processes between geometrically dissimilar lab and pilot scale bioreactors were demonstrated. The advantages of perfusion in comparison to fed-batch processes were also observed.
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Keywords
automation, Chinese hamster ovary cells, monoclonal antibodies, perfusion, Process Intensification, upstream process
Subject
Suggested Citation
Ott V, Ott J, Eibl D, Eibl R. Scaling Fed-Batch and Perfusion Antibody Production Processes in Geometrically Dissimilar Stirred Bioreactors. (2024). LAPSE:2024.0659
Author Affiliations
Ott V: School of Life Sciences and Facility Management, Institute of Chemistry and Biotechnology, ZHAW Zurich University of Applied Sciences, 8820 Wädenswil, Switzerland [ORCID]
Ott J: School of Life Sciences and Facility Management, Institute of Chemistry and Biotechnology, ZHAW Zurich University of Applied Sciences, 8820 Wädenswil, Switzerland [ORCID]
Eibl D: School of Life Sciences and Facility Management, Institute of Chemistry and Biotechnology, ZHAW Zurich University of Applied Sciences, 8820 Wädenswil, Switzerland
Eibl R: School of Life Sciences and Facility Management, Institute of Chemistry and Biotechnology, ZHAW Zurich University of Applied Sciences, 8820 Wädenswil, Switzerland
Ott J: School of Life Sciences and Facility Management, Institute of Chemistry and Biotechnology, ZHAW Zurich University of Applied Sciences, 8820 Wädenswil, Switzerland [ORCID]
Eibl D: School of Life Sciences and Facility Management, Institute of Chemistry and Biotechnology, ZHAW Zurich University of Applied Sciences, 8820 Wädenswil, Switzerland
Eibl R: School of Life Sciences and Facility Management, Institute of Chemistry and Biotechnology, ZHAW Zurich University of Applied Sciences, 8820 Wädenswil, Switzerland
Journal Name
Processes
Volume
12
Issue
4
First Page
806
Year
2024
Publication Date
2024-04-17
ISSN
2227-9717
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Original Submission
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PII: pr12040806, Publication Type: Journal Article
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LAPSE:2024.0659
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https://doi.org/10.3390/pr12040806
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Jun 6, 2024
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Jun 6, 2024
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