Shear stress analysis of mammalian cell suspensions for prediction of industrial centrifugation and its verification

Authors

  • N. Hutchinson,

    1. Department of Biochemical Engineering, The Advanced Centre for Biochemical Engineering, University College London, Torrington Place, London, WC1E 7JE, United Kingdom; telephone: 020 7679 7031; fax: 020 7209 0703
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  • N. Bingham,

    1. Lonza Biologics plc, 228 Bath Road, Slough, Berkshire, SL1 4DX, United Kingdom
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  • N. Murrell,

    1. Lonza Biologics plc, 228 Bath Road, Slough, Berkshire, SL1 4DX, United Kingdom
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  • S. Farid,

    1. Department of Biochemical Engineering, The Advanced Centre for Biochemical Engineering, University College London, Torrington Place, London, WC1E 7JE, United Kingdom; telephone: 020 7679 7031; fax: 020 7209 0703
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  • M. Hoare

    Corresponding author
    1. Department of Biochemical Engineering, The Advanced Centre for Biochemical Engineering, University College London, Torrington Place, London, WC1E 7JE, United Kingdom; telephone: 020 7679 7031; fax: 020 7209 0703
    • Department of Biochemical Engineering, The Advanced Centre for Biochemical Engineering, University College London, Torrington Place, London, WC1E 7JE, United Kingdom; telephone: 020 7679 7031; fax: 020 7209 0703
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Abstract

This article describes the use of ultra scale-down studies requiring milliliter quantities of process material to study the clarification of mammalian cell culture broths using industrial-scale continuous centrifuges during the manufacture of a monoclonal antibody for therapeutic use. Samples were pretreated in a small high-speed rotating-disc device in order to mimic the effect on the cells of shear stresses in the feed zone of the industrial scale centrifuges. The use of this feed mimic was shown to predict a reduction of the clarification efficiency by significantly reducing the particle size distribution of the mammalian cells. The combined use of the rotating-disc device and a laboratory-scale test tube centrifuge successfully predicted the separation characteristics of industrial-scale, disc stack centrifuges operating with different feed zones. A 70% reduction in flow rate in the industrial-scale centrifuge was shown to arise from shear effects. A predicted 2.5-fold increase in throughput for the same clarification performance, achieved by the change to a centrifuge using a feed zone designed to give gentler acceleration of the bioprocess fluid, was also verified at large-scale. © 2006 Wiley Periodicals, Inc.

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