Sichuan Institute for Food and Drug Control and Huzhou Shenke Biotechnology Co., Ltd. (HZSKBIO^®) jointly published the research paper Analysis of Low-Abundance Host Cell Residual Protein Detection in Monoclonal Antibody Drugs by Liquid Chromatography-Tandem Mass Spectrometry in Chinese Journal of Pharmaceutical Analysis (Chin J Pharm Anal), 2025, 45(12).

Monoclonal antibody (mAb) drugs serve as the core segment in the biopharmaceutical field, and their quality and safety are directly correlated with clinical efficacy and patient medication risks. As inevitable trace impurities generated during production, host cell proteins (HCPs) may trigger immune responses and degrade drug components, thus being a key quality attribute under key supervision by global regulatory authorities.

For a long time, enzyme-linked immunosorbent assay (ELISA) has been the mainstream method for HCP detection. Nevertheless, ELISA features limited antibody coverage, fails to identify specific impurity components, and has limitations in risk level assessment, which can hardly meet the increasingly stringent quality control requirements for monoclonal antibody drugs. With the rapid development of biopharmaceuticals including monoclonal antibodies, bispecific antibodies, and antibody-drug conjugates (ADCs) based on antibody structures, regulatory requirements for HCP residual detection in specifications such as the Chinese Pharmacopoeia and the United States Pharmacopeia (USP) have become increasingly strict. Although regulatory authorities worldwide have not established a unified and fixed absolute limit for HCP residues in all biological products, the industry generally recommends that the residue level should be lower than 100 ppm. Therefore, establishing a method with high sensitivity and wide coverage, especially for the detection of low-abundance HCPs, has become an urgent demand in the industry.

The liquid chromatography-tandem mass spectrometry (LC-MS/MS) detection method jointly developed by the research team targets and solves the difficulty in low-abundance HCP detection: by optimizing the sample pretreatment process, mass spectrometry parameters and data analysis methods, this method achieves improved detection sensitivity and can accurately capture low-abundance impurities that may be missed by traditional ELISA; it can not only quantify the total amount of HCPs but also clarify the species and content of individual residual proteins, providing data support for the targeted monitoring of high-risk HCPs (such as proteases, cytokines, etc.); the method has undergone systematic validation, and its reproducibility, limit of detection, precision, accuracy and other indicators comply with the regulatory requirements for methodological validation, which can be directly applied to the whole-process monitoring of monoclonal antibody drug production and finished product release testing.

SHENTEK^® LC-MS Platform

Huzhou Shenke has established a full-process standardized solution for host cell residual protein detection, covering sample pretreatment, mass spectrometry detection and bioinformatics analysis. The solution includes a sample management platform, rigorously validated sample pretreatment kits, protein standards for quantification, quality control products and standard procedures for mass spectrometry detection, as well as validated protein databases and bioinformatics analysis processes for result analysis.

References

[1] Yu Jiejing, Li Yan, Ma Quangang, et al. Analysis of Low-Abundance Host Cell Residual Protein Detection in Monoclonal Antibody Drugs by Liquid Chromatography-Tandem Mass Spectrometry [J]. Chinese Journal of Pharmaceutical Analysis, 2025, 45(12): 2097-2106.