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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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
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/19420862.2023.2213365
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author Jia Guo
Regina Kufer
Delia Li
Stefanie Wohlrab
Midori Greenwood-Goodwin
Feng Yang
author_facet Jia Guo
Regina Kufer
Delia Li
Stefanie Wohlrab
Midori Greenwood-Goodwin
Feng Yang
author_sort Jia Guo
collection DOAJ
description 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.
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institution Kabale University
issn 1942-0862
1942-0870
language English
publishDate 2023-12-01
publisher Taylor & Francis Group
record_format Article
series mAbs
spelling doaj-art-273decb2ae694d2098838e32ef9d9bf52025-08-20T03:25:59ZengTaylor & Francis GroupmAbs1942-08621942-08702023-12-0115110.1080/19420862.2023.2213365Technical advancement and practical considerations of LC-MS/MS-based methods for host cell protein identification and quantitation to support process developmentJia Guo0Regina Kufer1Delia Li2Stefanie Wohlrab3Midori Greenwood-Goodwin4Feng Yang5Protein Analytical Chemistry, Genentech, A Member of the Roche Group, South San Francisco, CA, USAPharma Technical Development Analytics, Roche Diagnostics GmbH, Penzberg, GermanyProtein Analytical Chemistry, Genentech, A Member of the Roche Group, South San Francisco, CA, USAPharma Technical Development Analytics, Roche Diagnostics GmbH, Penzberg, GermanyBiological Technologies, Genentech, A Member of the Roche Group, South San Francisco, CA, USAProtein Analytical Chemistry, Genentech, A Member of the Roche Group, South San Francisco, CA, USAHost 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.https://www.tandfonline.com/doi/10.1080/19420862.2023.2213365Host cell protein (HCP)identificationimpuritiesliquid chromatography tandem mass spectrometry (LC-MS/MS)process developmentquantitation
spellingShingle Jia Guo
Regina Kufer
Delia Li
Stefanie Wohlrab
Midori Greenwood-Goodwin
Feng Yang
Technical advancement and practical considerations of LC-MS/MS-based methods for host cell protein identification and quantitation to support process development
mAbs
Host cell protein (HCP)
identification
impurities
liquid chromatography tandem mass spectrometry (LC-MS/MS)
process development
quantitation
title Technical advancement and practical considerations of LC-MS/MS-based methods for host cell protein identification and quantitation to support process development
title_full Technical advancement and practical considerations of LC-MS/MS-based methods for host cell protein identification and quantitation to support process development
title_fullStr Technical advancement and practical considerations of LC-MS/MS-based methods for host cell protein identification and quantitation to support process development
title_full_unstemmed Technical advancement and practical considerations of LC-MS/MS-based methods for host cell protein identification and quantitation to support process development
title_short Technical advancement and practical considerations of LC-MS/MS-based methods for host cell protein identification and quantitation to support process development
title_sort technical advancement and practical considerations of lc ms ms based methods for host cell protein identification and quantitation to support process development
topic Host cell protein (HCP)
identification
impurities
liquid chromatography tandem mass spectrometry (LC-MS/MS)
process development
quantitation
url https://www.tandfonline.com/doi/10.1080/19420862.2023.2213365
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