Abstract

The issue of extractables and leachables in drugs and packaging is one of the most complex, challenging, and often (from a regulatory perspective) perplexing in all of pharmaceutical development. Unlike drug substancerelated impurities and degradation products, organic leachables present in a drug product (and organic extractables potentially present) can represent a wide variety of chemical structures and types, and exist at widely varying concentrations in a particular formulation. The extent of regulatory concern is related to the identity and potential patient exposure level of a particular organic leachable, as well as to the type of drug product, dosage form, and route of patient administration. Organic extractables and leachables therefore pose not only a significant qualitative/quantitative analysis problem for analytical chemists, but also a packaging component selection problem, safety qualification problem, strategic regulatory problem, and qualitycontrol problem for the entire pharmaceutical development/manufacturing team. At the time of this writing, detailed regulatory and scientific best practice guidances are available for inhalation drug products and dosage forms, but not for other drug product types.