PURPOSE

This general chapter presents a framework for the design, justification, and implementation of assessments for drug product leachables derived from pharmaceutical packaging and delivery systems. A scientifically sound leachables assessment is important to manufacturers and their various suppliers primarily as a means of establishing the suitability for use of pharmaceutical packaging/delivery systems, as leachables can potentially affect drug product efficacy, safety, and quality. Additionally, such a leachables assessment could provide an understanding of the sources of leachables and how to evaluate and manage leachables during the drug development and manufacturing processes. The chapter establishes critical dimensions of a leachables assessment and discusses practical and technical aspects of each dimension. The chapter does not establish specific analytical methods or leachables specifications and acceptance criteria for any particular dosage form or packaging system or drug product combination; nor does it delineate every situation in which a leachables assessment is required. It is not possible for a general discussion of drug product leachables to anticipate and cover all situations which can occur in the pharmaceutical industry where a leachables assessment might be required. Designing an individual leachables assessment is a process that strikes a balance between sound science, prudent resource allocation, and effective risk management with an emphasis on patient safety and product quality. Achieving this balance is the responsibility and obligation of the drug product manufacturer, and assumes due consideration of applicable legal and regulatory requirements. The principles and best demonstrated practices outlined in this general chapter represent a consensus interpretation of sound science and can therefore be extrapolated and applied to any situation in which a leachables assessment is required for pharmaceutical application.