Modeling industrial centrifugation of mammalian cell culture using a capillary based scale-down system

Authors

  • Matthew Westoby,

    Corresponding author
    1. Process Biochemistry, Biopharmaceutical Development, Biogen Idec, Inc., 5200 Research Place, San Diego, CA 92122; telephone: +1-858-401-5995; fax: +1-858-401-2714
    • Process Biochemistry, Biopharmaceutical Development, Biogen Idec, Inc., 5200 Research Place, San Diego, CA 92122; telephone: +1-858-401-5995; fax: +1-858-401-2714.
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  • Jameson K. Rogers,

    1. Process Biochemistry, Biopharmaceutical Development, Biogen Idec, Inc., 5200 Research Place, San Diego, CA 92122; telephone: +1-858-401-5995; fax: +1-858-401-2714
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  • Ryan Haverstock,

    1. Process Biochemistry, Biopharmaceutical Development, Biogen Idec, Inc., 5200 Research Place, San Diego, CA 92122; telephone: +1-858-401-5995; fax: +1-858-401-2714
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  • Jonathan Romero,

    1. Process Biochemistry, Biopharmaceutical Development, Biogen Idec, Inc., 5200 Research Place, San Diego, CA 92122; telephone: +1-858-401-5995; fax: +1-858-401-2714
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  • John Pieracci

    1. Process Biochemistry, Biopharmaceutical Development, Biogen Idec, Inc., 5200 Research Place, San Diego, CA 92122; telephone: +1-858-401-5995; fax: +1-858-401-2714
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Abstract

Continuous-flow centrifugation is widely utilized as the primary clarification step in the recovery of biopharmaceuticals from cell culture. However, it is a challenging operation to develop and characterize due to the lack of easy to use, small-scale, systems that can be used to model industrial processes. As a result, pilot-scale continuous centrifugation is typically employed to model large-scale systems requiring a significant amount of resources. In an effort to reduce resource requirements and create a system which is easy to construct and utilize, a capillary shear device, capable of producing energy dissipation rates equivalent to those present in the feed zones of industrial disk stack centrifuges, was developed and evaluated. When coupled to a bench-top, batch centrifuge, the capillary device reduced centrate turbidity prediction error from 37% to 4% compared to using a bench-top centrifuge alone. Laboratory-scale parameters that are analogous to those routinely varied during industrial-scale continuous centrifugation were identified and evaluated for their utility in emulating disk stack centrifuge performance. The resulting relationships enable bench-scale process modeling of continuous disk stack centrifuges using an easily constructed, scalable, capillary shear device coupled to a typical bench-top centrifuge. Bioeng. 2011; 108:989–998. © 2010 Wiley Periodicals, Inc.

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