This Report has been authored by:Fran L. DeGrazio at West PharmaceuticalServices Inc. #with# Jim Castner at Lantheus Medical Imaging #with# Wai Keung Wong at ExxonMobil Chemical Europe #with# Dennis Jenke at Baxter Healthcare Corp. #with# Daniel L. Norwood at Boehringer Ingelheim Pharmaceuticals Inc. #with# Michael Ruberto at Material Needs Consulting L.L.C.

Rubber materials are widely used in systems used to manufacture, package and deliver pharmaceutical products. While the rubber material's nature and composition gives it its necessary and desirable performance characteristics, these material properties can have important and potentially detrimental consequences for the pharmaceutical products. Interactions between these materials and the pharmaceutical products they contact are well known and documented and can result in a change in the product's composition, which may adversely affect product safety (e.g., the product produces an unanticipated and adverse user response) and/or efficacy (e.g., the product performs in a manner inconsistent with its labeling and indication). Therefore, rubber materials used in pharmaceutical products must be evaluated to determine what material components can, and do, migrate from the materials and accumulate in the pharmaceutical product, as it is through the presence and actions of such substances that product safety and/or efficacy may be compromised.

The characterization of materials for their extractables (substances that can migrate) and of products for their leachables (substances that do accumulate) is a necessary and complex part of the development, registration and manufacturing and distribution and therapeutic products.

This manuscript provides a general overview of the extractables and leachables issues associated with materials used with/in therapeutic products.