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

Area of Science:

• Biopharmaceutical Manufacturing
• Protein Chemistry
• Process Development

Background:

• Host cell proteins (HCPs) pose a significant challenge in biopharmaceutical purification, impacting product quality, patient safety, and regulatory adherence.
• Recent advancements have elucidated the mechanisms behind HCP persistence, enabling a shift from reactive to proactive control strategies.

Purpose of the Study:

• To review current knowledge on HCP persistence mechanisms, specifically within antibody production.
• To examine how HCP properties influence persistence and inform mitigation strategies.
• To offer a forward-looking perspective for developing robust HCP control strategies.

Main Methods:

• Literature review and synthesis of current research on HCP persistence.
• Analysis of specific HCP properties contributing to their evasion of removal during purification.
• Examination of design-based strategies for HCP mitigation.

Main Results:

• Insights into HCP mechanisms clarify why certain proteins resist removal during purification processes.
• Understanding specific HCP properties is crucial for designing effective removal strategies.
• Proactive, design-based approaches are emerging as superior to reactive methods.

Conclusions:

• A deeper understanding of HCP persistence mechanisms is essential for improving biopharmaceutical purification.
• Future research should focus on leveraging these insights to develop robust, proactive HCP control strategies.
• This review provides a foundation for guiding future development in HCP management for enhanced biomanufacturing.