{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T16:30:06Z","timestamp":1759336206616,"version":"build-2065373602"},"reference-count":70,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T00:00:00Z","timestamp":1757462400000},"content-version":"vor","delay-in-days":253,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>This paper presents the Multi Clone Kinetic Model (MCKM), a novel generalized kinetic mechanistic model for fed-batch cultivations of diverse Chinese hamster ovary (CHO) cell lines, producing different recombinant monoclonal antibodies (mAbs). Unlike traditional kinetic models requiring multiple cultures for one parameter regression, MCKM derives a complete set of 13 kinetic parameters from a single fed-batch cell line culture of 49 data points. This enables per-cell-line metabolic characterization during cell line development, as well as direct comparisons of kinetics across clones, passages, and different recombinant mAbs. To enable MCKM to be broadly applicable across many cell lines and mAbs, and to address the high-dimensional challenge of estimating 13 kinetic parameters from a small number of datapoints, the model uniquely incorporates a mechanistic growth constraint, a glucose-dependent lactate switch, and automated parameter balancing. MCKM demonstrated successful regression of 656 fed-batch culture runs of 157 unique CHO cell lines across four passage generations, recombinant for three different mAbs, achieving high accuracy in biomass and mAb titre (average ${\\rm{\\bar{R}}}_{{{{\\rm{X}}}_{\\rm{v}}}}^2$ \u2248 0.96\u00a0\u00b1\u00a00.07 and ${\\rm{\\bar{R}}}_{\\rm{P}}^2$ \u2248 0.97\u00a0\u00b1\u00a00.05, respectively). MCKM could facilitate automated cell line selection, identification of critical process parameters and biomarkers, guide media and feeding strategies, predict metabolite profiles, and support scale-up and quality-by-design studies, delivering overall reduction of experimental workload.<\/jats:p>\n               <jats:p>One-Sentence Summary: This paper presents a novel kinetic model that derives distinct parameter sets from a single fed-batch run, enabling characterization of individual CHO clones across different mAb targets.<\/jats:p>","DOI":"10.1093\/jimb\/kuaf029","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T14:35:21Z","timestamp":1758551721000},"source":"Crossref","is-referenced-by-count":0,"title":["A Multi Clone Kinetic Model for characterizing Chinese hamster ovary cell line variability"],"prefix":"10.1093","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-1904-7696","authenticated-orcid":false,"given":"Devi","family":"Sietaram","sequence":"first","affiliation":[{"name":"University of Cambridge Department of Chemical Engineering and Biotechnology, , Cambridge CB3 0AS ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pavlos","family":"Kotidis","sequence":"additional","affiliation":[{"name":"BioPharm Process Research, GSK , Stevenage SG1 2NY ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary","family":"Finka","sequence":"additional","affiliation":[{"name":"BioPharm Process Research, GSK , Stevenage SG1 2NY ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7621-0889","authenticated-orcid":false,"given":"Alexei A","family":"Lapkin","sequence":"additional","affiliation":[{"name":"University of Cambridge Department of Chemical Engineering and Biotechnology, , Cambridge CB3 0AS ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,9,10]]},"reference":[{"issue":"5","key":"2025100108471806500_bib2","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1007\/s10616-010-9291-z","article-title":"Comparison of viable cell concentration estimation methods for a mammalian cell cultivation process","volume":"62","author":"Aehle","year":"2010","journal-title":"Cytotechnology"},{"key":"2025100108471806500_bib3","doi-asserted-by":"publisher","first-page":"740215","DOI":"10.3389\/fbioe.2021.740215","article-title":"Model transferability and reduced experimental burden in cell culture process development facilitated by hybrid modeling and intensified design of experiments","volume":"9","author":"Bayer","year":"2021","journal-title":"Frontiers in Bioengineering and 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