Technical advancement and practical considerations of LC-MS/MS-based methods for host cell protein identification and quantitation to support process development

Host cell proteins (HCPs) are process-related impurities derived from the manufacturing of recombinant biotherapeutics. Residual HCP in drug products, ranging from 1 to 100 ppm (ng HCP/mg product) or even below sub-ppm level, may affect product quality, stability, efficacy, or safety. Therefore, rem...

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Bibliographic Details
Main Authors: Jia Guo, Regina Kufer, Delia Li, Stefanie Wohlrab, Midori Greenwood-Goodwin, Feng Yang
Format: Article
Language:English
Published: Taylor & Francis Group 2023-12-01
Series:mAbs
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Online Access:https://www.tandfonline.com/doi/10.1080/19420862.2023.2213365
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Summary:Host cell proteins (HCPs) are process-related impurities derived from the manufacturing of recombinant biotherapeutics. Residual HCP in drug products, ranging from 1 to 100 ppm (ng HCP/mg product) or even below sub-ppm level, may affect product quality, stability, efficacy, or safety. Therefore, removal of HCPs to appropriate levels is critical for the bioprocess development of biotherapeutics. Liquid chromatography-mass spectrometry (LC-MS) analysis has become an important tool to identify, quantify, and monitor the clearance of individual HCPs. This review covers the technical advancement of sample preparation strategies, new LC-MS-based techniques, and data analysis approaches to robustly and sensitively measure HCPs while overcoming the high dynamic range analytical challenges. We also discuss our strategy for LC-MS-based HCP workflows to enable fast support of process development throughout the product life cycle, and provide insights into developing specific analytical strategies leveraging LC-MS tools to control HCPs in process and mitigate their potential risks to drug quality, stability, and patient safety.
ISSN:1942-0862
1942-0870