E&L System Suitability – Finding the Right Mix

To ensure USP prioritization of the industry’s most urgent challenges related to extractable and leachable (E&L) impurities screening and testing, we are seeking stakeholder feedback on the Stimuli article, “Proposals for the Development, Composition and Routine Use of System Suitability Standard Mixtures in Support of Chromatographic Screening for Organic Extractables & Leachables.”

From the time of manufacture—beginning from starting materials to the point of administration to the patient—a drug product will have contact with manufacturing components, packaging systems, and administration devices and is likely to chemically interact with them.

Leachables are substances that have transferred from manufacturing components, packaging, and devices into the drug product under typical conditions of manufacturing, storage, and use. Substances that are leached (extracted) by, and accumulate in, solutions other than the drug product are extractables. This leaching occurs under laboratory conditions of contact that differ from and are generally more aggressive than clinical conditions of contact between the item and drug product.

Leachables can impact a drug product’s purity and/or exert effects on other key quality attributes such as drug potency and stability, and unsafe leachables can adversely affect users’ health and safety.

Growing regulatory scrutiny of E&L impurities in packaged drug products and increasingly complex formulations are making it more important than ever for manufacturers to produce accurate results when screening for and assessing the risk of these impurities. Screening for a wide range of possible organic E&L analytes in packaged drug products is challenging, and appropriate reference compound mixtures are necessary to ensure that the systems used are suitable.

By proposing the development of reference system suitability mixtures highlighted in this article, USP hopes to facilitate consistent analytical performance across laboratories conducting organic E&L screening.

To capture stakeholder input and better understand current practices for E&L impurities testing, we invite stakeholders to take a brief survey (5-7 minutes). We hope that you and your colleagues will take a moment to share your insights and experiences with us so that we may continue to develop the kind of science-based solutions you have come to rely on and trust from USP.