Container closure integrity (CCI) is the ability of a container closure system to maintain the sterility and product quality of sterile final pharmaceutical, biological, and vaccine products throughout their shelf-life. It is a regulatory requirement that the design of a container closure system be qualified.
There are multiple methods available to qualify the effectiveness of a selected container closure system as detailed in industry guidance and literature. Selection of an appropriate method is based on the container closure system to be qualified and its contents. The normal variation within the manufacturing process should be taken into consideration when qualifying the integrity of the closure system. While the regulatory expectations and industry standard practices for initial CCI qualification are well defined, the regulatory requirements with respect to in-process or routine manufacturing remain unclear with the exception of fused containers. This paper addresses the benefits and challenges of CCI testing (CCIT), the importance of process control and in-process testing to ensure product quality, as well as circumstances under which 100% integrity testing during routine manufacturing should be considered.
The scope of this paper includes drug product manufacturing of sterile injectable products, including vials, syringes, bags for intravenous application, and inhalation products, but not products compounded in pharmacies.