Strengthening Extractable & Leachable Study Submissions: Best Practices to Avoid Regulatory Deficiencies

Abstract

The assessment of extractable and leachables (E&L) has become a cornerstone of pharmaceutical product safety, yet no unified global standards currently exist to quantify or report E&L from container closure systems. While initially limited to primary packaging, E&L evaluations now encompass secondary packaging, manufacturing equipment, and medical devices. Key milestones include the FDA’s 1999 guidance on container closure systems and more recent frameworks from USP chapters < 1661 >, < 1663 >, and < 1664 >, as well as PQRI recommendations. These guidelines have set the foundation for conducting E&L studies, especially for high-risk dosage forms, and are complemented by the forthcoming ICH Q3E, which aims to standardize E&L considerations across dosage forms. This article outlines a structured procedure for E&L assessments, integrating regulatory expectations with practical insights.