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Designing cost-effective biopharmaceutical facilities using mixed-integer optimization.

Liu, S; Simaria, AS; Farid, SS; Papageorgiou, LG; (2013) Designing cost-effective biopharmaceutical facilities using mixed-integer optimization. Biotechnol Prog , 29 (6) 1472 - 1483. 10.1002/btpr.1795. Green open access

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Abstract

Chromatography operations are identified as critical steps in a monoclonal antibody (mAb) purification process and can represent a significant proportion of the purification material costs. This becomes even more critical with increasing product titers that result in higher mass loads onto chromatography columns, potentially causing capacity bottlenecks. In this work, a mixed-integer nonlinear programming (MINLP) model was created and applied to an industrially relevant case study to optimize the design of a facility by determining the most cost-effective chromatography equipment sizing strategies for the production of mAbs. Furthermore, the model was extended to evaluate the ability of a fixed facility to cope with higher product titers up to 15 g/L. Examination of the characteristics of the optimal chromatography sizing strategies across different titer values enabled the identification of the maximum titer that the facility could handle using a sequence of single column chromatography steps as well as multi-column steps. The critical titer levels for different ratios of upstream to dowstream trains where multiple parallel columns per step resulted in the removal of facility bottlenecks were identified. Different facility configurations in terms of number of upstream trains were considered and the trade-off between their cost and ability to handle higher titers was analyzed. The case study insights demonstrate that the proposed modeling approach, combining MINLP models with visualization tools, is a valuable decision-support tool for the design of cost-effective facility configurations and to aid facility fit decisions. 2013.

Type: Article
Title: Designing cost-effective biopharmaceutical facilities using mixed-integer optimization.
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/btpr.1795
Publisher version: http://dx.doi.org/10.1002/btpr.1795
Language: English
Additional information: © 2013 The Authors. Published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: antibody titers, biopharmaceutical facility design, chromatography, mixed integer non-linear programming, monoclonal antibody purification, Antibodies, Monoclonal, Chromatography, Cost-Benefit Analysis, Humans, Models, Theoretical
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
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Chemical Engineering
URI: https://discovery.ucl.ac.uk/id/eprint/1404997
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