Host cell protein risks, detection, and control in vaccine manufacturing
Host cell proteins (HCPs) are critical process-related impurities in vaccine manufacturing that can affect product safety, efficacy, and regulatory compliance. Challenges persist in detecting and controlling HCPs due to their diverse properties and interactions with vaccine components across viral vector, recombinant protein, and nucleotide vaccine platforms. This review provides a comprehensive analysis of HCP risks, detection technologies, including ELISA and advanced mass spectrometry, and control strategies encompassing upstream cell line engineering and downstream purification processes. Regulatory expectations from global authorities are discussed, emphasizing risk-based, case-by-case specification setting rather than universal numeric limits. The review further explores the operational and analytical challenges faced by manufacturers, particularly in low- and middle-income countries, and advocates for harmonized guidelines and decentralized analytical capacity to support rapid, equitable vaccine deployment. By integrating risk-informed control strategies, advanced analytics, and lifecycle monitoring, the field can ensure robust vaccine production and global access, supporting both pandemic preparedness and long-term public health.