Advanced mass spectrometry techniques for monitoring biopharmaceutical host cell proteins.

Abstract

Residual host cell proteins (HCPs) in biologic drug products can compromise safety or stability and must be carefully monitored. While traditional immunoassays remain essential, they often lack specificity or coverage. Mass spectrometry (MS) offers a complementary approach by enabling direct identification and quantification of individual HCPs throughout development. This review highlights recent advances in MS technologies and workflows relevant to HCP detection, including new data acquisition strategies, software tools, and artificial intelligence applications. We also discuss regulatory perspectives and considerations for implementing MS in controlled environments. By integrating analytical innovations with risk-based strategies, MS-based approaches are becoming key components of modern biopharmaceutical quality control.