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    Quantitative Host Cell Protein Analysis Using Two Dimensional Data Independent LC–MSE
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    † Characterisation and Comparability Laboratory, NIBRT−The National Institute for Bioprocessing Research and Training, Foster Avenue, Mount Merrion, Blackrock, Co., Dublin, Ireland
    ‡ Department of Analytical Chemistry, University of Granada, Avenue Fuentenueva S/N, 18071 Granada, Spain
    § School of Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland
    *E-mail: [email protected]. Phone: +353 1215 8105. Fax: +353 1215 8116.
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    Analytical Chemistry

    Cite this: Anal. Chem. 2015, 87, 18, 9186–9193
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    https://doi.org/10.1021/acs.analchem.5b01377
    Published August 17, 2015
    Copyright © 2015 American Chemical Society
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    Abstract

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    Host cell proteins (HCPs) are bioprocess-related impurities arising from cell-death or secretion from nonhuman cells used for recombinant protein production. Clearance of HCPs through downstream purification (DSP) is required to produce safe and efficacious therapeutic proteins. While traditionally measured using anti-HCP ELISA, more in-depth approaches for HCP characterization may ensure that risks to patients from HCPs are adequately assessed. Mass spectrometry methods provide rationale for targeted removal strategies through the provision of both qualitative and quantitative HCP information. A high pH, low pH, reversed-phase data independent 2D-LC–MSE proteomic platform was applied to determine HCP repertoires in the Protein A purified monoclonal antibody (mAb) samples as a function of culture harvest time, elution buffer used for DSP and also following inclusion of additional DSP steps. Critical quality attributes (CQAs) were examined for mAbs purified with different Protein A elution buffers to ensure that the selected buffers not only minimized the HCP profile but also exhibited no adverse effect on product quality. Results indicated that an arginine based Protein A elution buffer minimized the levels of HCPs identified and quantified in a purified mAb sample and also demonstrated no impact on product CQAs. It was also observed that mAbs harvested at later stages of cell culture contained higher concentrations of HCPs but that these were successfully removed by the addition of DSP steps complementary to Protein A purification. Taken together, our results showed how mass spectrometry based methods for HCP determination in conjunction with careful consideration of processing parameters such as harvest time, Protein A elution buffers, and subsequent DSP steps can reduce the HCP repertoire of therapeutic mAbs.

    Copyright © 2015 American Chemical Society

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    The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.analchem.5b01377.

    • Additional chromatograms and results and anti-interleukin 8 IgG1 (mAb1) structure (PDF)

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    Analytical Chemistry

    Cite this: Anal. Chem. 2015, 87, 18, 9186–9193
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.analchem.5b01377
    Published August 17, 2015
    Copyright © 2015 American Chemical Society
    Request reuse permissions

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