Principles for Management of Extractables and Leachables in Ophthalmic Drug Products

Abstract

Ophthalmic solutions and suspensions have long been classified into a high risk category with respect to concerns over extractables and leachables (E&L), though specific guidance on the management of leachables in these products is generally absent from regulatory authorities or the scientific literature. As a result, ophthalmic drug products (ODP) were originally included in the scope of the Product Quality Research Institute Leachables and Extractables Working Group for Parenteral and Ophthalmic Drug Products (PQRI-PODP). Relative to other high concern dosage forms such as metered dose inhalers or injectables, ODP possess unique challenges with respect to the nature of impactful E&L as well as the safety assessment of leachables. For example, extensive use of semipermeable low density polyethylene primary packaging for ODP necessitates a strong focus on E&L from secondary packaging sources. For safety assessment, a key challenge is the lack of a sufficient database developed on all relevant ophthalmic toxicity endpoints. As result, the working group is unable to recommend a Safety Concern Threshold (SCT) for ODP at this time. Nevertheless, the ophthalmic industry has developed a number of time-tested practices to manage E&L for ODP. This article describes those science-based practices and key considerations in the analysis, management, and safety assessment of E&L in ODP.