Increasing parvovirus filter throughput of monoclonal antibodies using ion exchange membrane adsorptive pre-filtration

Authors

  • Arick Brown,

    Corresponding author
    1. Process Research & Development, Genentech, 1 DNA Way, South San Francisco, California 94080; telephone: 650-225-2682; fax: 650-225-4049
    • Process Research & Development, Genentech, 1 DNA Way, South San Francisco, California 94080; telephone: 650-225-2682; fax: 650-225-4049.
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  • Charity Bechtel,

    1. Process Research & Development, Genentech, 1 DNA Way, South San Francisco, California 94080; telephone: 650-225-2682; fax: 650-225-4049
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  • Jerome Bill,

    1. Process Research & Development, Genentech, 1 DNA Way, South San Francisco, California 94080; telephone: 650-225-2682; fax: 650-225-4049
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  • Hui Liu,

    1. Process Research & Development, Genentech, 1 DNA Way, South San Francisco, California 94080; telephone: 650-225-2682; fax: 650-225-4049
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  • Jun Liu,

    1. Process Research & Development, Genentech, 1 DNA Way, South San Francisco, California 94080; telephone: 650-225-2682; fax: 650-225-4049
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  • Dan McDonald,

    1. Process Research & Development, Genentech, 1 DNA Way, South San Francisco, California 94080; telephone: 650-225-2682; fax: 650-225-4049
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  • Satyan Pai,

    1. Process Research & Development, Genentech, 1 DNA Way, South San Francisco, California 94080; telephone: 650-225-2682; fax: 650-225-4049
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  • Asha Radhamohan,

    1. Process Research & Development, Genentech, 1 DNA Way, South San Francisco, California 94080; telephone: 650-225-2682; fax: 650-225-4049
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  • Ryan Renslow,

    1. Process Research & Development, Genentech, 1 DNA Way, South San Francisco, California 94080; telephone: 650-225-2682; fax: 650-225-4049
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  • Brooke Thayer,

    1. Process Research & Development, Genentech, 1 DNA Way, South San Francisco, California 94080; telephone: 650-225-2682; fax: 650-225-4049
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  • Stefan Yohe,

    1. Process Research & Development, Genentech, 1 DNA Way, South San Francisco, California 94080; telephone: 650-225-2682; fax: 650-225-4049
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  • Chris Dowd

    1. Process Research & Development, Genentech, 1 DNA Way, South San Francisco, California 94080; telephone: 650-225-2682; fax: 650-225-4049
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Abstract

Pre-filtration using ion exchange membrane adsorbers can improve parvovirus filter throughput of monoclonal antibodies (mAbs). The membranes work by binding trace foulants, and although some antibody product also binds, yields ≥99% are easily achieved by overloading. Results show that foulant adsorption is dependent on pH and conductivity, but independent of scale and adsorber brand. The ability to use ion exchange membranes as pre-filters is significant because it provides a clean, well defined, chemically stable option for enhancing throughput. Additionally, ion exchange membranes facilitate characterization of parvovirus filter foulants. Examination of adsorber elution samples using sedimentation velocity analysis and SEC-MALS/QELS revealed the presence of high molecular weight species ranging from 8 to 13 nm in hydrodynamic radius, which are similar in size to parvoviruses and thus would be expected to plug the pores of a parvovirus filter. A study of two identical membranes in-series supports the hypothesis that the foulants are soluble, trace level aggregates in the feed. This study's significance lies in a previously undiscovered application of membrane chromatography, leading to a more cost effective and robust approach to parvovirus filtration for the production of monoclonal antibodies. Biotechnol. Bioeng. 2010;106: 627–637. © 2010 Wiley Periodicals, Inc.

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