Process reagent clearance for biopharmaceutical products: A science-based perspective incorporating safety threshold limits and clearance modeling.

Evaluation and demonstration of process reagent clearance (PRC) from drug substance manufacturing process are required to ensure patient safety and regulatory compliance. However, guidance and literature on PRC evaluation strategies are few and inconsistent. In this commentary, we first review current PRC guidelines and safety assessment practices. Then, we discuss new developments using safety threshold limits and clearance modeling for PRC evaluation. Next, we identify gaps and opportunities to improve efficiency, particularly regarding assessment of new reagents. Finally, we propose an end-to-end PRC evaluation strategy that is patient-safety focused, science-based, compliant with regulatory requirements, and achievable.