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A framework for assessing the solutions in chromatographic process design and operation for large-scale manufacture

Authors

  • John R Joseph,

    1. Innovative Manufacturing Research Centre, Advanced Centre for Biochemical Engineering, University College London, Torrington Place, London WC1E 7JE, UK
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  • Andrew Sinclair,

    1. Biopharm Services UK, Lancer House, East Street, Chesham, Bucks HP5 1DG, UK
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  • Nigel J Titchener-Hooker,

    1. Innovative Manufacturing Research Centre, Advanced Centre for Biochemical Engineering, University College London, Torrington Place, London WC1E 7JE, UK
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  • Yuhong Zhou

    Corresponding author
    1. Innovative Manufacturing Research Centre, Advanced Centre for Biochemical Engineering, University College London, Torrington Place, London WC1E 7JE, UK
    • Innovative Manufacturing Research Centre, Advanced Centre for Biochemical Engineering, University College London, Torrington Place, London WC1E 7JE, UK
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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−1) 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 oversizing and how this can be balanced by increased levels of productivity. Copyright © 2006 Society of Chemical Industry

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