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A Framework for Assessing the Solutions in Chromatographic Process Design and Operation for Large Scale Manufacture

Joseph, J; Sinclair, A; Titchener-Hooker, NJ; Zhou, Y; (2006) A Framework for Assessing the Solutions in Chromatographic Process Design and Operation for Large Scale Manufacture. Journal of Chemical Technology and Biotechnology , 81 (6) pp. 1009-1020. 10.1002/jctb.1508. Green open access

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Abstract

Chromatographic separation of biopharmaceuticals is complex and tools for the prediction of performance and the trade-offs necessary for efficient operation are limited and time-consuming. This complexity is due to the large number of possible column aspect ratios that satisfy process and economic needs. This paper demonstrates a framework for the design and analysis of chromatographic steps. The functionalities are illustrated by application to a Protein A separation where the effects of column diameter, bed length and linear flow rate on cost of goods (COG/g) and productivity (g/h) are investigated so as to identify the optimal operating strategy. Results are presented as a series of ‘windows of operation’ to address key design and operating decisions. The tool allows the designer to customise limiting constraints based on product and process specific knowledge. Results indicate the significant impact on COG/g of column over-sizing and how this can be balanced by increased levels of productivity.

Type: Article
Title: A Framework for Assessing the Solutions in Chromatographic Process Design and Operation for Large Scale Manufacture
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/jctb.1508
Publisher version: https://doi.org/10.1002/jctb.1508
Language: English
Additional information: This version is the author accepted manuscrip. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Chromatography, Windows of operation, Feasible space, Decision based modelling
UCL classification: UCL
UCL > Provost and Vice Provost Offices
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
URI: https://discovery.ucl.ac.uk/id/eprint/97072
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