Influence of cell death and metabolite inhibition on the performance of fed-batch and perfusion bioreactors: insights from mathematical modelling
Loading...
Date
2026-07-30
Authors
Fitzpatrick, John J.
O'leary, Fionn
Hill, Ali
Daly, James
Lalor, Fergal
Byrne, Edmond P.
Journal Title
Journal ISSN
Volume Title
Publisher
Walter de Gruyter GmbH
Published Version
Abstract
Both fed-batch and perfusion bioreactors are used in biopharmaceutical production. This study applies mathematical modelling to investigate the influence of cell death, metabolite inhibition, bioreaction time and cell/metabolite control on bioreactor performance. The performance parameters are titre, productivity, product yield, wasted substrate and mean product residence time (tres). Cell death and metabolite inhibition both impact on cell growth and the evolution of viable cell concentration. Major impacts are potential for significantly reducing productivity and increasing tres. Higher values of substrate concentration in media added (Sm) tends to improve bioreactor performance, however higher Sm leads to higher metabolite concentrations, which may contribute to greater metabolite inhibition and reduced bioreactor performance. Consequently, there may exist an optimal Sm. Bioreaction time is very important. For perfusion, there exists a bioreaction time where productivity is maximised and tres is minimised. For fed-batch, sufficient bioreaction time is required to increase titre, yield and productivity, however too long a time leads to major progressive reduction in productivity and possibly very long tres. Overall, with inclusion of cell death and metabolite inhibition, perfusion still has an advantage over fed-batch in terms of higher productivities and shorter tres, while obtaining comparable titres and yields.
Description
Keywords
Biopharmaceutical , Bioreactor performance , Fed-batch , Perfusion , [EngineeringArchitecture]
Citation
Fitzpatrick, J J, O'leary, F, Hill, A, Daly, J, Lalor, F & Byrne, E P 2026, 'Influence of cell death and metabolite inhibition on the performance of fed-batch and perfusion bioreactors : insights from mathematical modelling', Chemical Product and Process Modeling, pp. 1-27. https://doi.org/10.1515/cppm-2026-0008