Label-free shotgun proteomics: Exploiting a reliable and sensitive method to monitor residual host-cell proteins in monoclonal antibody products

The removal of host cell proteins (HCPs) remains a challenge in the downstream processing of monoclonal antibodies (mAbs). It is critical to monitor residual HCPs since they can have an impact on product stability and safety. The enzyme-linked immunosorbent assay (ELISA) only quantifies the total am...

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Bibliographic Details
Main Authors: Somar Khalil, Adeline Wychowski, Cyrille Chéry, Annick Gervais
Format: Article
Language:English
Published: Elsevier 2023-06-01
Series:Journal of Pharmaceutical and Biomedical Analysis Open
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Online Access:http://www.sciencedirect.com/science/article/pii/S2949771X23000129
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Summary:The removal of host cell proteins (HCPs) remains a challenge in the downstream processing of monoclonal antibodies (mAbs). It is critical to monitor residual HCPs since they can have an impact on product stability and safety. The enzyme-linked immunosorbent assay (ELISA) only quantifies the total amount of HCPs and does not indicate the identity or quantity of any specific HCP. Mass spectrometry-based proteomics applications demonstrate an advantage in quantitatively profiling individual HCPs. However, technical reproducibility, dynamic range, and ensuring an acceptable statistical significance of scoring measurements are critical hurdles that ought to be overcome. In this paper, we describe a sensitive and reproducible shotgun proteomics approach that includes an efficient mAb depletion strategy and addresses the shortcomings of such workflows. Our methodology is potentially a valuable complement or alternative to ELISA. Additionally, it can facilitate the purification process development and the evaluation of ELISA kits upon process changes.
ISSN:2949-771X