(36c) Development of Platform Host Cell Protein Enrichment Strategies for Use in Impurity Spike Challenge Studies

Controlling process related impurities is essential for minimizing risk-to-patients, however, for platform processes producing monoclonal antibodies the risk associated with host impurities may be low owing to process refinement over time.  As an alternative to establishing measurement controls with acceptance criteria, ICH Q6B authorities’ state “clearance studies, which could include spiking experiments at the laboratory scale” can be used to demonstrate removal of such impurities.  This paper presents the development and characterization of a platform methodology to enable the enrichment of highly representative and product-specific host cell protein impurities.  These impurities can then be used in high resolution spike challenge studies to monitor host cell protein clearance by successive chromatography steps.  The results of these spike challenge studies provide greater understanding of purity identity, process step redundancy and, correspondingly, the necessity for in-process measurement controls.