Principles for Management of Extractables and Leachables in Ophthalmic Drug Products
Christopher T. Houston, Andrea Desantis Rodrigues, Brenda Birkestrand Smith, Tao Wang, Mary Richardson
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 (ODPs) 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, ODPs 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 ODPs 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 ODPs at this time. Nevertheless, the ophthalmic industry has developed a number of time-tested practices to manage E&L for ODPs. This article describes those science-based practices and key considerations in the analysis, management, and safety assessment of E&L in ODPs.