What is CCI Testing?

Container Closure Integrity Testing (CCIT) is an analytical method used to test the adequacy of a container closure system in order to maintain a sterile barrier against potential contaminants. Contaminants that are assumed to potentially cross the container closure barrier are microorganisms, reactive gases, and other substances. The primary purpose of a container closure system is to maintain sterility and product quality of sterile pharmaceutical, biologic, and vaccine products throughout their shelf life.

The container closure system has primary and secondary packaging components. Primary packaging components are those components that come in direct contact with the product. Secondary packaging components are those that maintain the integrity of the package and ensure proper packaging. Secondary packaging components include aluminum caps on stoppers, etc.

In order to establish the integrity of the container seal during the product packaging life cycle, a special test method was developed to check for defects throughout the product packaging life cycle. This test method must be sufficient to determine leakage given a specific product and its service life.

The development and importance of CCI testing in the medical field

Initially, only sterility testing was performed on pharmaceutical packaging. Soon after, it was realized that sterility testing alone was not sufficient to maintain the integrity of medical products. In 1994, the U.S. FDA published the Guidance for Industry for Submissions for Validation of Sterilization Processes in Human and Veterinary Drug Product Applications. This promoted and emphasized the importance of validating the microbial barrier properties of parenteral product packaging (such as CCI). Later, improvements to the guidance were published again to explain the importance of CCI testing relative to sterility testing and to cite the limitations of sterility testing, such as the possibility of false positive readings due to adventitious microbial contamination introduced during testing. After this, in another publication, more emphasis was placed on the CCI method, especially promoting the use of deterministic methods and emphasizing the importance of maximum allowable leakage limits (MALL) for drug products in pharmaceutical companies.

Container closure integrity test method:

Container closure integrity testing can be performed in a variety of ways. Each of these test methods has advantages and disadvantages. Updates in the USP <1207> series divide testing into two main categories: deterministic and probabilistic. Deterministic methods are less prone to error and provide quantitative results. Probabilistic methods have greater uncertainty in the determination results and include more traditional test methods.

There are few deterministic methods and techniques, which are:

High Voltage Leak Detection (HVLD)

Vacuum decay

Pressure decay