By Leonard Harris, Manager of Chemistry and Container Testing
Published in: Pharmaceutical ONLINE Eurofins Biopharma Product Testing
Published on: April 15, 2025
Container Closure Integrity Testing (CCIT) is a critical component that must be considered in the manufacturing of a drug product or combination device, such as a prefilled syringe. The landscape of CCIT has been changing over the past 15+ years due to changes in the regulatory mindset regarding sterility testing and detection limits around CCIT. In 2008, the FDA published a guidance document “Container Closure System Integrity Testing In lieu of Sterility Testing as a Component of the Stability Protocol for Sterile Products.” This document gave clear indication that CCIT was the preferred avenue for confirming product sterility during stability studies and thus through the lifecycle of the product. While sterility testing is necessary at the release of a product to ensure that the product is sterile upon completion of manufacturing, there are limitations to using this test to indicate the product will remain sterile until the end of the lifecycle. This document did not provide testing specifics for CCIT but stated that during stability testing, sterility testing should be replaced by “properly validated physical or chemical container closure system integrity test (e.g., bubble tests, vacuum/pressure decay, trace gas permeation/leak tests, dye penetration tests, seal force of electrical conductivity and capacitance tests, etc.), or microbial container closure system integrity.
