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Design and characterization of a novel perfusion reactor for biopharmaceuticals production

Tregidgo, Molly; Dorn, Marie; Lucas, Ciara; Micheletti, Martina; (2023) Design and characterization of a novel perfusion reactor for biopharmaceuticals production. Chemical Engineering Research and Design , 194 pp. 344-357. 10.1016/j.cherd.2023.04.066. Green open access

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Abstract

The demand for commercially valuable biopharmaceuticals able to treat different immunopathological diseases has accelerated in the last few decades. In recent years the industry has shifted the preferred mode of operation towards continuous strategies and has favoured the adoption of perfusion approaches for the cell culture step. In this mode successful perfusion process examples have reached up to 10-fold higher cell densities and product titres than fed-batch, while maintaining product quality at reduced costs. Perfusion processes are operated at high cell densities where cells are retained, while product and waste are continuously removed. This leads to different requirements in flow and mixing in comparison to lower cell density operations, potentially influencing the cellular production performance and therefore product quality. As the pharmaceutical industry is highly regulated, ensuring homogeneity in the bulk throughout the process is critical, while oxygen and mixing requirements of high cell density cultures must be continuously met. This paper presents the design and characterization of a novel 250 mL stirred tank reactor (STR) developed to work in perfusion mode. The results presented include the experimental measurement of the power consumption, the mixing analysis of the flow within the bioreactor which informs design consideration and scaling efforts and the biological data of the perfusion stage with an industrially relevant cell line producing an IgG monoclonal antibody. The characterization allows the operating window of the reactor to be established, resulting in increased productivity of intensified cultures.

Type: Article
Title: Design and characterization of a novel perfusion reactor for biopharmaceuticals production
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.cherd.2023.04.066
Publisher version: https://doi.org/10.1016/j.cherd.2023.04.066
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: Process intensification, Mixing, Fluid flow, Stirred-tank reactor, Perfusion, Scale-down models
UCL classification: UCL
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/10169558
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