Extractables And Leachables Risk Assessment In Pharmaceutical Manufacturing: A Practical USP <1665> And <665> Approach

By Vicki Ward, Ph.D., Director at Pace® Life Sciences

Extractables and leachables (E&L) risk assessment has become increasingly important as pharmaceutical and biopharmaceutical manufacturing relies more heavily on plastic components such as tubing, connectors, filters, and single‑use systems. These materials often contain additives that can migrate into process streams, potentially affecting product safety, efficacy, and stability. USP <1665> provides a structured, risk‑based approach for evaluating which components require assessment, using factors such as contact duration, temperature, process stream chemistry, and material composition to determine characterization levels.

USP <665> then links these risk levels to appropriate testing requirements, ranging from basic screening for low‑risk materials to comprehensive analytical evaluations for higher‑risk components. This approach ensures testing efforts are aligned with true risk while maintaining regulatory compliance. Mitigation factors—such as downstream process clearance or clinical use considerations—can further refine the strategy. By integrating USP <1665> and <665>, manufacturers can develop defensible, science‑driven E&L programs that protect patients and support robust regulatory submissions.