@article {Houston278, author = {Christopher T. Houston and Andrea Desantis Rodrigues and Brenda Birkestrand Smith and Tao Wang and Mary Richardson}, title = {Principles for Management of Extractables and Leachables in Ophthalmic Drug Products}, volume = {76}, number = {3}, pages = {278--294}, year = {2022}, doi = {10.5731/pdajpst.2022.012744}, publisher = {Parenteral Drug Association (PDA)}, 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.}, issn = {1079-7440}, URL = {https://journal.pda.org/content/76/3/278}, eprint = {https://journal.pda.org/content/76/3/278.full.pdf}, journal = {PDA Journal of Pharmaceutical Science and Technology} }