Charting the Universe of Organic Extractables and Leachables: Compounds with Confirmed Identities

Abstract

Drug product leachables are substances that are leached from the drug product’s manufacturing system components during manufacturing operations, drug product packaging systems during storage over shelf-life, and delivery systems during administration. Medical device leachables are substances that are released from medical devices during their clinical use. Thus, packaged drug products and medical devices are profiled for leachables (and/or extractables as probable leachables) to establish that the levels of leachables are sufficiently small that they present a negligible risk of adversely affecting patient health. This profiling is accomplished by screening the drug product or extracts of the medical device for released organic substances via non-targeted analysis (NTA) employing chromatographic methods coupled with mass spectrometric detection. The topics of how many possible organic extractables and leachables (E&Ls) there are and what are the most commonly reported organic E&Ls has been widely dscussed in the E&L community of practice. One means of charting this universe of organic E&Ls is to review and collate those substances that have been encountered over the course of performing E&L studies. To this end, Nelson Labs Europe, a major contract research organization performing E&L testing for decades, has collated the results of several thousand E&L studies performed over the past several years, representing modern best practices in E&L assessment. These collated results, considering only those compounds reported with confirmed identities, are summarized and discussed herein. Although the use of compounds with only confirmed identities limits the number of considered compounds somewhat, so doing ensures that potentially false identifications are not published and do not result in a biased analysis of the collected information.