Liu, S;
Gerontas, S;
Gruber, D;
Turner, R;
Titchener-Hooker, NJ;
Papageorgiou, LG;
(2017)
Optimisation-based Framework for Resin Selection Strategies in Biopharmaceutical Purification Process Development.
Biotechnology Progress
, 33
(4)
pp. 1116-1126.
10.1002/btpr.2479.
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Abstract
This work addresses rapid resin selection for integrated chromatographic separations when conducted as part of a high-throughput screening (HTS) exercise during the early stages of purification process development. An optimisation-based decision support framework is proposed to process the data generated from microscale experiments in order to identify the best resins to maximise key performance metrics for a biopharmaceutical manufacturing process, such as yield and purity. A multiobjective mixed integer nonlinear programming (MINLP) model is developed and solved using the ε-constraint method. Dinkelbach's algorithm is used to solve the resulting mixed integer linear fractional programming (MILFP) model. The proposed framework is successfully applied to an industrial case study of a process to purify recombinant Fc Fusion protein from low molecular weight and high molecular weight product related impurities, involving two chromatographic steps with 8 and 3 candidate resins for each step, respectively. The computational results show the advantage of the proposed framework in terms of computational efficiency and flexibility. This article is protected by copyright. All rights reserved.
| Type: | Article |
|---|---|
| Title: | Optimisation-based Framework for Resin Selection Strategies in Biopharmaceutical Purification Process Development |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/btpr.2479 |
| Publisher version: | http://doi.org/10.1002/btpr.2479 |
| Language: | English |
| Additional information: | Copyright © 2017 The Authors Biotechnology Progress published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers. This is an open access article under the terms of the CreativeCommons Attribution License, which permits use, distribution andreproduction in any medium, provided the original work is properlycited. |
| Keywords: | resin selection, purification process development, multiobjective optimization, e-constraint method, Dinkelbach’s algorithm |
| 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 Chemical Engineering |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/1552871 |
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