Influence of cell death and metabolite inhibition on the performance of fed-batch and perfusion bioreactors: insights from mathematical modelling

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dc.contributor.authorFitzpatrick, John J.
dc.contributor.authorO'leary, Fionn
dc.contributor.authorHill, Ali
dc.contributor.authorDaly, James
dc.contributor.authorLalor, Fergal
dc.contributor.authorByrne, Edmond P.
dc.date.accessioned2026-09-16T12:54:01Z
dc.date.available2026-09-16T12:54:01Z
dc.date.issued2026-07-30
dc.description.abstractBoth 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.en
dc.description.versionPublished Version
dc.format.extent27
dc.format.mimetypeapplication/pdfen
dc.identifier.authororcidFitzpatrick, John J.
dc.identifier.authororcidO'leary, Fionn
dc.identifier.authororcidHill, Ali
dc.identifier.authororcidDaly, James
dc.identifier.authororcidLalor, Fergal
dc.identifier.authororcidByrne, Edmond P.
dc.identifier.citationFitzpatrick, 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
dc.identifier.doi10.1515/cppm-2026-0008
dc.identifier.endpage27
dc.identifier.issn1934-2659
dc.identifier.journaltitleChemical Product and Process Modeling
dc.identifier.startpage1
dc.identifier.urihttps://hdl.handle.net/10468/19260
dc.language.isoen
dc.publisherWalter de Gruyter GmbH
dc.relation.urihttps://www.scopus.com/pages/publications/105046156905
dc.rights© 2026 the author(s), published by De Gruyter, Berlin/Boston. This work is licensed under the Creative Commons Attribution 4.0 International License.
dc.rights.accessrightsopen access
dc.rights.licensenameAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.statusPeer reviewed
dc.subjectBiopharmaceutical
dc.subjectBioreactor performance
dc.subjectFed-batch
dc.subjectPerfusion
dc.subject[EngineeringArchitecture]
dc.titleInfluence of cell death and metabolite inhibition on the performance of fed-batch and perfusion bioreactors: insights from mathematical modellingen
dc.typeArticle (peer-reviewed)
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