Glowienke, Susanne (2016) Assessing safety of extractables from materials and leachables in pharmaceuticals and biologics – current challenges and approaches. Regul Tox Pharm, 81 (?). pp. 201-211. ISSN not available

Abstract

Leachables from pharmaceutical container closure and delivery systems are known to present potential safety risks to patients. Extractables studies may be performed as a risk mitigation activity to identify potential leachables for dosage forms that have a high degree of concern associated with the route of administration. To address specific safety concerns, approaches to toxicological safety evaluation of extractables and leachables have been developed and applied by pharmaceutical and biologics manufacturers. Details of these approaches may differ depending on the nature of the final drug product. These may include, but not be limited to, application, the formulation, route of administration and length of use. Current regulatory guidelines and industry standards provide general guidance on compound specific safety assessments but do not provide a comprehensive approach to safety evaluations of leachables and/or extractables. This paper provides a perspective on approaches to conducting such evaluations by reviewing and applying general concepts and integrating key steps in the toxicological safety evaluation of individual extractables or leachables. These include application of structure activity relationship studies, development of permitted daily exposure (PDE) values, and use of safety threshold concepts. Case studies are provided. The concepts presented in this paper are provided to facilitate and encourage further discussion among the industry, regulatory and scientific communities, and are not intended to represent a final opinion of the Extractables and Leachables Safety Information Exchange (ELSIE) consortium or “guidelines.”

Item Type:	Article
Date Deposited:	09 Nov 2016 00:45
Last Modified:	09 Nov 2016 00:45
URI:	https://oak.novartis.com/id/eprint/29480