{"title":"Model-based Optimization for Laboratory-Scale Upstream Processing in Monoclonal Antibody Production","authors":"Guilherme A. Pimentel , Camilo Garcia-Tenorio , Radhouane Fekih-Salem , Cédric Toussaint , Ahmed Kanfoud , Thomas Cornet , Thibault Helleputte , Adrien Boes , Riccardo Marega , Alain Vande Wouwer , Laurent Dewasme","doi":"10.1016/j.ifacol.2025.03.069","DOIUrl":null,"url":null,"abstract":"<div><div>The production of monoclonal antibodies (mAbs) is a complex pharmacological process involving upstream and downstream chains, focusing on mAbs production and purification, respectively. This paper presents a process optimization based on an end-to-end mechanistic model for the upstream process chain to enhance the production of mAbs. Upstream processing considers cell expansion, cell production, and primary harvesting steps by filtration. The optimization results offer users the optimal initial concentrations of the medium in the bioreactors, the duration of the cultures, the feed flow rate profiles, and the permeate flow profile in the filtration operation. Simulations incorporating interconnected reactors and process constraints led to optimized initial media concentrations and feed flow profiles, resulting in a 25% increase in mAb production compared to baseline conditions.</div></div>","PeriodicalId":37894,"journal":{"name":"IFAC-PapersOnLine","volume":"59 1","pages":"Pages 403-408"},"PeriodicalIF":0.0000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"IFAC-PapersOnLine","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2405896325002861","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"Engineering","Score":null,"Total":0}
引用次数: 0
Abstract
The production of monoclonal antibodies (mAbs) is a complex pharmacological process involving upstream and downstream chains, focusing on mAbs production and purification, respectively. This paper presents a process optimization based on an end-to-end mechanistic model for the upstream process chain to enhance the production of mAbs. Upstream processing considers cell expansion, cell production, and primary harvesting steps by filtration. The optimization results offer users the optimal initial concentrations of the medium in the bioreactors, the duration of the cultures, the feed flow rate profiles, and the permeate flow profile in the filtration operation. Simulations incorporating interconnected reactors and process constraints led to optimized initial media concentrations and feed flow profiles, resulting in a 25% increase in mAb production compared to baseline conditions.
期刊介绍:
All papers from IFAC meetings are published, in partnership with Elsevier, the IFAC Publisher, in theIFAC-PapersOnLine proceedings series hosted at the ScienceDirect web service. This series includes papers previously published in the IFAC website.The main features of the IFAC-PapersOnLine series are: -Online archive including papers from IFAC Symposia, Congresses, Conferences, and most Workshops. -All papers accepted at the meeting are published in PDF format - searchable and citable. -All papers published on the web site can be cited using the IFAC PapersOnLine ISSN and the individual paper DOI (Digital Object Identifier). The site is Open Access in nature - no charge is made to individuals for reading or downloading. Copyright of all papers belongs to IFAC and must be referenced if derivative journal papers are produced from the conference papers. All papers published in IFAC-PapersOnLine have undergone a peer review selection process according to the IFAC rules.