Container Closure Integrity Test Method Development Using Headspace Gas Ingress

By Suzanne Kuiper

Recent regulatory guidance has made clear there is no ‘gold standard’ container closure integrity (CCI) test. An appropriate CCI test method should be applied depending on the specific product container closure system configuration, the stage in the product life cycle, and the testing throughput required. It is therefore considered best to create a toolbox of CCI testing methods.

The United States Pharmacopeia (USP) <1207> - Package Integrity Evaluation – Sterile products chapter describes the various available CCI testing techniques, and provides guidance on method development and validation in various stages of the product life cycles. Headspace analysis is described as one of the deterministic CCI tests, which are preferred over the use of probabilistic methods, such as blue dye ingress and microbial challenge testing.