Strategic assay deployment as a method for countering analytical bottlenecks in high throughput process development: Case studies in ion exchange chromatography

Authors

  • Spyridon Konstantinidis,

    1. The Advanced Centre for Biochemical Engineering, Dept. of Biochemical Engineering, University College London, London WC1E 7JE, U.K.
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  • Eva Heldin,

    1. GE Healthcare Life Sciences, BioTechnologies R&D, Björkgatan 30, Uppsala 751 84, Sweden
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  • Sunil Chhatre,

    1. The Advanced Centre for Biochemical Engineering, Dept. of Biochemical Engineering, University College London, London WC1E 7JE, U.K.
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  • Ajoy Velayudhan,

    1. The Advanced Centre for Biochemical Engineering, Dept. of Biochemical Engineering, University College London, London WC1E 7JE, U.K.
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    • Effective September 2012

  • Nigel Titchener-Hooker

    Corresponding author
    1. The Advanced Centre for Biochemical Engineering, Dept. of Biochemical Engineering, University College London, London WC1E 7JE, U.K.
    • The Advanced Centre for Biochemical Engineering, Dept. of Biochemical Engineering, University College London, London WC1E 7JE, U.K.
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Abstract

High throughput approaches to facilitate the development of chromatographic separations have now been adopted widely in the biopharmaceutical industry, but issues of how to reduce the associated analytical burden remain. For example, acquiring experimental data by high level factorial designs in 96 well plates can place a considerable strain upon assay capabilities, generating a bottleneck that limits significantly the speed of process characterization. This article proposes an approach designed to counter this challenge; Strategic Assay Deployment (SAD). In SAD, a set of available analytical methods is investigated to determine which set of techniques is the most appropriate to use and how best to deploy these to reduce the consumption of analytical resources while still enabling accurate and complete process characterization. The approach is demonstrated by investigating how salt concentration and pH affect the binding of green fluorescent protein from Escherichia coli homogenate to an anion exchange resin presented in a 96-well filter plate format. Compared with the deployment of routinely used analytical methods alone, the application of SAD reduced both the total assay time and total assay material consumption by at least 40% and 5%, respectively. SAD has significant utility in accelerating bioprocess development activities. © 2012 American Institute of Chemical Engineers Biotechnol. Prog., 2012

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