Sample sizing approaches for container closure integrity (CCI) testing

Sample size approaches for container closure integrity testing (CCIT) for routine commercial biopharmaceutical production vary across the industry. Currently, there is no official standard or published procedure to follow for sampling approaches or defining appropriate sample sizes.

Unpublished industry surveys highlight that the majority of leading biopharmaceutical companies do not routinely perform CCIT for each batch of a commercial product but rather rely on a holistic approach guaranteeing consistent quality of the finished parenteral product with respect to CCI (container closure integrity).

The BioPhorum  CCIT workstream considers that a holistic approach is preferable to sampling and testing for assuring CCI. However, it is accepted and appropriate that, when sampling is required, scientifically valid sampling plans should be based on risk assessment, including information such as supplier approval, packaging component specifications and process knowledge.

This paper provides some considerations and guidance on defining a justifiable sample size for CCIT when required for parenteral biopharmaceutical finished products. This is a particularly important consideration when using destructive test methods. It is also summarizes a practical and risk-based strategy, both representing scientifically justified approaches. These approaches prevent unnecessary sampling and testing while retaining high product quality. Where the integrity of each individual container is assured by a suitably qualified process, additional CCI sampling and testing would not normally be required.