LC-MS for improving decision making and mitigating risk in process development

BEBPA HCP 2024 -- Host-cell proteins (HCPs) pose a risk both to patient safety by means of immunogenic response, and to drug substance integrity by enzymatic digestion and degradation. Effective removal of the impurities while minimizing loss of the drug substance is a major challenge and milestone in the drug development life-cycle. ELISA offers excellent sensitivity for HCP content but is only able to provide total HCP abundance and is reliant on expensive polyclonal reagents. LC-MS is able to identify and quantify individual HCPs, allowing a purification strategy to be developed around known impurities using a quality-by-design approach in-line with ICH Q14. A phase-appropriate approach to HCP characterisation should be carefully considered in-line with the phase of product development for efficient process development and risk mitigation.