Host cell proteins in monoclonal antibody processing: Control, detection, and removal.

Area of Science:

• Biopharmaceutical Manufacturing
• Protein Chemistry
• Process Engineering

Background:

• Host cell proteins (HCPs) are critical impurities in therapeutic proteins produced via cell culture.
• Monoclonal antibody (mAb) production often involves high cell density cultures, increasing HCP levels.
• Effective HCP clearance is essential for ensuring the safety and quality of biotherapeutics.

Purpose of the Study:

• To review industry trends in HCPs during mAb bioprocessing.
• To assess HCP clearance capabilities of downstream unit operations.
• To identify best practices for HCP reduction in biomanufacturing.

Main Methods:

• Comprehensive assessment of implemented and emerging HCP management technologies.
• Meta-analysis of published downstream processing data to identify trends.
• Review of analytical methods and understanding of high-risk HCPs.

Main Results:

• Higher cell density cultures increase both mAb expression and HCP levels.
• Improved downstream operations can significantly reduce HCP concentrations to ~10 ppm.
• No significant difference in HCP clearance performance between enhanced and traditional downstream processing.

Conclusions:

• Advances in analytical methods and HCP understanding enhance process robustness.
• Effective HCP reduction is achievable despite challenges from modern cell culture techniques.
• Best practices for process development are crucial for minimizing HCPs in biotherapeutics.