Host Cell Protein Challenges in Antibody Processing: Insights Into Persistence and Mitigation Strategies

Persistence of HCPs remains a major purification challenge in biopharmaceutical manufacturing with direct consequences for product quality, patient safety, and regulatory compliance. Over the last two decades, deeper insights into the mechanisms driving HCP persistence have clarified why certain proteins evade removal during purification. These advances are steering the field away from reactive responses and toward proactive, design-based strategies. This review consolidates current knowledge on the mechanisms underlying HCP persistence with a particular focus on antibody production processes. It examines recent insights into how specific HCP properties contribute to persistence, and how these findings inform the design and assessment of mitigation strategies. Our goal is to provide a comprehensive, yet forward-looking, perspective to help guide future research and development of robust HCP control strategies.