Defining process design space for a hydrophobic interaction chromatography (HIC) purification step: Application of quality by design (QbD) principles

Authors

  • Canping Jiang,

    1. Manufacturing Sciences & Technology, Bristol-Myers Squibb Co., 6000 Thompson Road, East Syracuse, New York 13057, USA, telephone: 315-431-7926; fax: 315-432-2343
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  • Lisa Flansburg,

    1. Manufacturing Sciences & Technology, Bristol-Myers Squibb Co., 6000 Thompson Road, East Syracuse, New York 13057, USA, telephone: 315-431-7926; fax: 315-432-2343
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  • Sanchayita Ghose,

    1. Process Development, Bristol-Myers Squibb Co., East Syracuse, New York
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  • Paul Jorjorian,

    1. Process Development, Bristol-Myers Squibb Co., East Syracuse, New York
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  • Abhinav A. Shukla

    Corresponding author
    1. Manufacturing Sciences & Technology, Bristol-Myers Squibb Co., 6000 Thompson Road, East Syracuse, New York 13057, USA, telephone: 315-431-7926; fax: 315-432-2343
    • Manufacturing Sciences & Technology, Bristol-Myers Squibb Co., 6000 Thompson Road, East Syracuse, New York 13057, USA, telephone: 315-431-7926; fax: 315-432-2343.
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Abstract

The concept of design space has been taking root under the quality by design paradigm as a foundation of in-process control strategies for biopharmaceutical manufacturing processes. This paper outlines the development of a design space for a hydrophobic interaction chromatography (HIC) process step. The design space included the impact of raw material lot-to-lot variability and variations in the feed stream from cell culture. A failure modes and effects analysis was employed as the basis for the process characterization exercise. During mapping of the process design space, the multi-dimensional combination of operational variables were studied to quantify the impact on process performance in terms of yield and product quality. Variability in resin hydrophobicity was found to have a significant influence on step yield and high-molecular weight aggregate clearance through the HIC step. A robust operating window was identified for this process step that enabled a higher step yield while ensuring acceptable product quality. Biotechnol. Bioeng. 2010;107: 985–997. © 2010 Wiley Periodicals, Inc.

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