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Multiobjective evolutionary optimization in antibody purification process design

Paper ID Volume ID Publish Year Pages File Format Full-Text
3133 151 2014 15 PDF Available
Title
Multiobjective evolutionary optimization in antibody purification process design
Abstract

•A computational framework for antibody purification process design is proposed.•The framework comprises a multiobjective EA linked to a process economics model.•Process design is affected by the objectives optimized and uncertainty settings.•Framework is validated for several USP:DSP train ratios, impurity levels and demands.•Purification processes discovered outperform the industrial standard.

To contribute towards designing more cost-efficient, robust and flexible downstream processes for the manufacture of monoclonal antibodies (mAbs), a framework consisting of an evolutionary multiobjective optimization algorithm (EMOA) linked to a biomanufacturing process economics model is presented. The EMOA is tuned to discover sequences of chromatographic purification steps and column sizing strategies that provide the best trade-off with respect to multiple objectives including cost of goods per gram (COG/g), robustness in COG/g, and impurity removal capabilities. Additional complexities accounted for by the framework include uncertainties and constraints. The framework is validated on industrially relevant case studies varying in upstream and downstream processing train ratios, annual demands, and impurity loads. Results obtained by the framework are presented using a range of visualization tools, and indicate that the performance impact of uncertainty is a function of both the level of uncertainty and the objective being optimized, and that uncertainty can cause otherwise optimal processes to become suboptimal. The optimal purification processes discovered outperform the industrial standard with, e.g. savings in COG/g of up to 10%. Guidelines are provided for choosing an optimal purification process as a function of the objectives being optimized and impurity levels present.

Keywords
Biopharmaceutical manufacture; Monoclonal antibodies; Downstream processing; Modeling; Optimisation; Evolutionary multiobjective optimisation
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biochemical Engineering Journal - Volume 91, 15 October 2014, Pages 250–264
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us