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Aggregation of a monoclonal antibody induced by adsorption to stainless steel

Authors

  • Jared S. Bee,

    1. Department of Chemical and Biological Engineering, University of Colorado, Room: ECCH 111, Campus Box 0424, 1111 Engineers Dr, Boulder, Colorado 80309-0424; telephone: 303-492-4776; fax: 303-492-4341
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  • Michele Davis,

    1. Department of Chemical and Biological Engineering, University of Colorado, Room: ECCH 111, Campus Box 0424, 1111 Engineers Dr, Boulder, Colorado 80309-0424; telephone: 303-492-4776; fax: 303-492-4341
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  • Erwin Freund,

    1. Drug Product & Device Development, Amgen, Inc., Thousand Oaks, California
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  • John F. Carpenter,

    1. Department of Pharmaceutical Sciences, University of Colorado, Aurora, Colorado
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  • Theodore W. Randolph

    Corresponding author
    1. Department of Chemical and Biological Engineering, University of Colorado, Room: ECCH 111, Campus Box 0424, 1111 Engineers Dr, Boulder, Colorado 80309-0424; telephone: 303-492-4776; fax: 303-492-4341
    • Department of Chemical and Biological Engineering, University of Colorado, Room: ECCH 111, Campus Box 0424, 1111 Engineers Dr, Boulder, Colorado 80309-0424; telephone: 303-492-4776; fax: 303-492-4341.
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Abstract

Stainless steel is a ubiquitous surface in therapeutic protein production equipment and is also present as the needle in pre-filled syringe biopharmaceutical products. Stainless steel microparticles can cause the aggregation of a monoclonal antibody (mAb). The initial rate of mAb aggregation was second order in steel surface area and zero order in mAb concentration, generally consistent with a bimolecular surface aggregation being the rate-limiting step. Polysorbate 20 (PS20) suppressed the aggregation yet was unable to desorb the firmly bound first layer of protein that adsorbs to the stainless steel surface. Also, there was no exchange of mAb from the first adsorbed layer to the bulk phase, suggesting that the aggregation process actually occurs on subsequent adsorption layers. No oxidized Met residues were detected in the mass spectrum of a digest of a highly aggregated mAb, although there was a fourfold increase in carbonyl groups due to protein oxidation. Biotechnol. Bioeng. 2010;105: 121–129. © 2009 Wiley Periodicals, Inc.

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