LAPSE:2019.1074
Published Article
LAPSE:2019.1074
Accelerating Biomanufacturing by Modeling of Continuous Bioprocessing—Piloting Case Study of Monoclonal Antibody Manufacturing
Martin Kornecki, Axel Schmidt, Lara Lohmann, Maximilian Huter, Fabian Mestmäcker, Leon Klepzig, Mourad Mouellef, Steffen Zobel-Roos, Jochen Strube
September 30, 2019
An experimental feasibility study on continuous bioprocessing in pilot-scale of 1 L/day cell supernatant, that is, about 150 g/year product (monoclonal antibody) based on CHO (Chinese hamster ovary) cells for model validation is performed for about six weeks including preparation, start-up, batch, and continuous steady-state operation for at least two weeks stable operation as well as final analysis of purity and yield. A mean product concentration of around 0.4 g/L at cell densities of 25 × 106 cells/mL was achieved. After perfusion cultivation with alternating tangential flow filtration (ATF), an aqueous two-phase extraction (ATPE) followed by ultra-/diafiltration (UF/DF) towards a final integrated counter-current chromatography (iCCC) purification with an ion exchange (IEX) and a hydrophobic interaction (HIC) column prior to lyophilization were successfully operated. In accordance to prior studies, continuous operation is stable and feasible. Efforts of broadly-qualified operation personal as well as the need for an appropriate measurement and process control strategy is shown evidently.
Keywords
antibodies, continuous bioprocessing (CBP), model validation, process analytical technology (PAT), quality-by-design (QbD)
Suggested Citation
Kornecki M, Schmidt A, Lohmann L, Huter M, Mestmäcker F, Klepzig L, Mouellef M, Zobel-Roos S, Strube J. Accelerating Biomanufacturing by Modeling of Continuous Bioprocessing—Piloting Case Study of Monoclonal Antibody Manufacturing. (2019). LAPSE:2019.1074
Author Affiliations
Kornecki M: Institute for Separation and Process Technology, Clausthal University of Technology, Leibnizstr. 15, 38678 Clausthal-Zellerfeld, Germany
Schmidt A: Institute for Separation and Process Technology, Clausthal University of Technology, Leibnizstr. 15, 38678 Clausthal-Zellerfeld, Germany [ORCID]
Lohmann L: Institute for Separation and Process Technology, Clausthal University of Technology, Leibnizstr. 15, 38678 Clausthal-Zellerfeld, Germany
Huter M: Institute for Separation and Process Technology, Clausthal University of Technology, Leibnizstr. 15, 38678 Clausthal-Zellerfeld, Germany
Mestmäcker F: Institute for Separation and Process Technology, Clausthal University of Technology, Leibnizstr. 15, 38678 Clausthal-Zellerfeld, Germany
Klepzig L: Institute for Separation and Process Technology, Clausthal University of Technology, Leibnizstr. 15, 38678 Clausthal-Zellerfeld, Germany
Mouellef M: Institute for Separation and Process Technology, Clausthal University of Technology, Leibnizstr. 15, 38678 Clausthal-Zellerfeld, Germany
Zobel-Roos S: Institute for Separation and Process Technology, Clausthal University of Technology, Leibnizstr. 15, 38678 Clausthal-Zellerfeld, Germany
Strube J: Institute for Separation and Process Technology, Clausthal University of Technology, Leibnizstr. 15, 38678 Clausthal-Zellerfeld, Germany
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Journal Name
Processes
Volume
7
Issue
8
Article Number
E495
Year
2019
Publication Date
2019-08-01
Published Version
ISSN
2227-9717
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PII: pr7080495, Publication Type: Journal Article
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LAPSE:2019.1074
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doi:10.3390/pr7080495
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Sep 30, 2019
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Calvin Tsay
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