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Model-based workflow for scale-up of process strategies developed in miniaturized bioreactor systems

Arndt, L; Wiegmann, V; Kuchemüller, KB; Baganz, F; Pörtner, R; Möller, J; (2021) Model-based workflow for scale-up of process strategies developed in miniaturized bioreactor systems. Biotechnology Progress 10.1002/btpr.3122. (In press). Green open access

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Abstract

Miniaturized bioreactor (MBR) systems are routinely used in the development of mammalian cell culture processes. However, scale-up of process strategies obtained in MBR- to larger scale is challenging due to mainly non-holistic scale-up approaches. In this study, a model-based workflow is introduced to quantify differences in the process dynamics between bioreactor scales and thus enable a more knowledge-driven scale-up. The workflow is applied to two case studies with antibody-producing Chinese hamster ovary cell lines. With the workflow, model parameter distributions are estimated first under consideration of experimental variability for different scales. Second, the obtained individual model parameter distributions are tested for statistical differences. In case of significant differences, model parametric distributions are transferred between the scales. In case study I, a fed-batch process in a microtiter plate (4 ml working volume) and lab-scale bioreactor (3750 ml working volume) was mathematically modeled and evaluated. No significant differences were identified for model parameter distributions reflecting process dynamics. Therefore, the microtiter plate can be applied as scale-down tool for the lab-scale bioreactor. In case study II, a fed-batch process in a 24-Deep-Well-Plate (2 ml working volume) and shake flask (40 ml working volume) with two feed media was investigated. Model parameter distributions showed significant differences. Thus, process strategies were mathematically transferred, and model predictions were simulated for a new shake flask culture setup and confirmed in validation experiments. Overall, the workflow enables a knowledge-driven evaluation of scale-up for a more efficient bioprocess design and optimization.

Type: Article
Title: Model-based workflow for scale-up of process strategies developed in miniaturized bioreactor systems
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/btpr.3122
Publisher version: https://doi.org/10.1002/btpr.3122
Language: English
Additional information: This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Biochemical Engineering
URI: https://discovery.ucl.ac.uk/id/eprint/10121958
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