The recently released USP chapter <1664.3> represents an important extension of the US Pharmacopeia Extractables and Leachables (E&L) framework, providing guidance specifically tailored to topical ophthalmic drug products. It applies to a wide range of formulations, including solutions, suspensions, emulsions and ointments, and addresses the unique E&L risks associated with these dosage forms. In particular, the chapter focuses on interactions between ophthalmic formulations, manufacturing equipment, and container-closure systems over the full product shelf life.
Ophthalmic drug products present distinctive leachables assessment challenges due to the extreme sensitivity of the ocular route of administration and the very low dosing volumes typically involved. Even trace levels of leachable compounds may pose a potential safety risk, requiring a more refined and scientifically justified approach than that used for many other dosage forms.
At the same time, manufacturers must ensure that E&L programmes remain proportionate and efficient throughout development and commercialisation.
USP addresses these challenges by building upon the principles established in the existing series while introducing safety-based thresholds specific to ophthalmic use. These thresholds support a risk-based determination of study scope, analytical sensitivity, and overall programme complexity.
By clearly linking toxicological considerations with analytical expectations, the chapter provides practical direction for designing fit-for-purpose leachables studies aligned with regulatory expectations.
The chapter also fits within a broader, evolving regulatory landscape. Alignment with frameworks such as ICH Q3E supports the development of globally acceptable, regulator-ready E&L strategies that balance patient safety with development efficiency. More broadly, USP reflects its ongoing efforts to promote harmonised, risk-based E&L practices across dosage forms. These efforts are further reinforced by the planned revision of the USP subchapters across 2025 and 2026, which aim to refine and clarify dosage form-specific expectations and strengthen consistency across the compendial framework.
Eurofins BioPharma Product Testing can support testing and mitigate challenges, drawing on over 20 years of experience in E&L, through risk-based study design, selection of relevant extraction conditions, and development of sensitive, validated analytical methods (e.g. LC-MS, GC-MS, ICP-MS) for reliable identification and quantification of leachables in line with USP and ICH expectations. For more information, contact us at: information@bpt.eurofinseu.com or watch the webinar here: www.attendee.gotowebinar.com/