Development of scale-down platforms for the continuous production of mammalian cell derived biopharmaceuticals

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Development of scale-down platforms for the continuous production of mammalian cell derived biopharmaceuticals

Lucas, Ciara; (2025) Development of scale-down platforms for the continuous production of mammalian cell derived biopharmaceuticals. Doctoral thesis (Eng.D), UCL (University College London). Green open access

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Abstract

The use of biopharmaceuticals as revolutionary therapeutics is increasing due to their success in treating cancer and other diseases. As market demand for these is increasing, industry efforts focus on scaling up mammalian cell culture production, whilst simultaneously maintaining product quality and reducing cost. Historically, this has been achieved in industries such as petrochemical and automotive by switching from batch to continuous production. This results in smaller plant footprints, higher efficiency and higher product quality due to the possibility to ensure a steady state environment. The move to continuous mode for mammalian cell culture is now being implemented in the biopharmaceutical industry. For the upstream cell culture this involves maintaining a constant viable cell density (VCD) using a perfusion bioreactor. However, for perfusion reactors to reach their full potential, tools to resolve key challenges are required. High-throughput, small-scale platforms allow to conduct several experiments in parallel while reducing process development time and minimising cost. At UCL, two scale-down platforms have been developed, which can be used for the optimisation of perfusion processes. A microwell plate (MWP) methodology was first used to optimise medium blends for two suspension mammalian cell lines (i) Chinese hamster ovary (CHO) cells producing monoclonal antibodies (mAbs) and (ii) human embryonic kidney (HEK) cells producing lentiviral vectors (LV). The MWP optimisation results were then scaled into a 250 mL custom-made perfusion mini bioreactor (MBR). The 250 mL perfusion bioreactor was characterised, assessing the impact of probes, baffles, impellers’ configuration and recirculation flowrate on dimensionless mixing time. By using a combined methodology, where the MWP platform is used for screening and the MBR for detailed optimisation based on a fewer number of conditions, resources can be significantly reduced, thus leading to an overall cost reduction for the upstream process step.

Type:	Thesis (Doctoral)
Qualification:	Eng.D
Title:	Development of scale-down platforms for the continuous production of mammalian cell derived biopharmaceuticals
Open access status:	An open access version is available from UCL Discovery
Language:	English
Additional information:	Copyright © The Author 2025. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
UCL classification:	UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Biochemical Engineering
URI:	https://discovery.ucl.ac.uk/id/eprint/10204709