Container Closure Integrity (CCI) refers to the ability of a packaging system to prevent product loss, microbial ingress, and entry of gases (oxygen, air, water vapor, etc.) or other substances, thereby ensuring that the drug product remains safe and meets quality standards throughout its shelf life.
For injectable packaging systems, CCI requirements fall into three categories:
1. maintain sterility and product composition without the need to preserve headspace gas;
2. maintain sterility, product composition, and headspace gas;
3. for multi-dose containers that must maintain sterility after opening – prevent microbial ingress and product leakage during use. CCI studies for injectable products should be tailored to product characteristics.
A packaging system is generally considered to have acceptable CCI when it has passed or is capable of passing a microbial challenge test. In a broader sense, CCI means the absence of any leakage that could compromise drug quality. Based on scientific research and risk assessment, the Maximum Allowable Leakage Limit (MALL) should be determined considering packaging composition and assembly, product contents, and the environment to which the product may be exposed over its lifecycle. If a package’s leakage does not exceed its MALL, the closure system is considered integral.
