Linking extractables and leachables in container/closure applications.

Establishing a link between extractables and leachables may be necessary to understand, interpret, assess, quantify, or control the interaction between a drug product and its container/closure system. This paper considers the various factors that affect the rigor with which such a linkage is established and justified. Such an assessment considers the origin and/or genesis of the leachable or extractable, enumerates situations in which extractables/leachables linkages are useful, ties such situations to the drug product's lifecycle, defines a hierarchy of linkages based on the rigor with which the linkages are established and justified, and establishes guidelines for how to determine what kind of linkage is appropriate for certain circumstances and situations. Additionally, this paper gives several examples of linkages relevant to flexible plastic drug product containers.