PT  - JOURNAL ARTICLE
AU  - Houston, Christopher T.
AU  - Rodrigues, Andrea Desantis
AU  - Smith, Brenda Birkestrand
AU  - Wang, Tao
AU  - Richardson, Mary
TI  - Principles for Management of Extractables and Leachables in Ophthalmic Drug Products
AID  - 10.5731/pdajpst.2022.012744
DP  - 2022 May 01
TA  - PDA Journal of Pharmaceutical Science and Technology
PG  - 278--294
VI  - 76
IP  - 3
4099  - http://journal.pda.org/content/76/3/278.short
4100  - http://journal.pda.org/content/76/3/278.full
SO  - PDA J Pharm Sci Technol2022 May 01; 76
AB  - 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.