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

ABSTRACT

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.

KEYWORDS:

• Host cell protein (HCP)
• identification
• impurities
• liquid chromatography tandem mass spectrometry (LC-MS/MS)
• process development
• quantitation

Acknowledgments

The authors would like to thank Christopher Yu for kindly reviewing our manuscript draft and giving feedback. The authors acknowledge the following colleagues for their support and collaboration: Vikas Sharma, Guoying Jiang, Margaret Lin, Lori O’Connell, Shelley Elvington, Inn Yuk, Amy Shen, and John Stults.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.