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Optimisation-based Framework for Resin Selection Strategies in Biopharmaceutical Purification Process Development

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

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