By Kimberlee Dickman, Study Director III, Pharmaceuticals, BS, RM(NRCM), ASQ(CQPA)
Container Closure Integrity Testing is performed to evaluate the adequacy of a closure in maintaining a sterile barrier. Of primary concern is whether the container can provide an effective barrier against ingress of microorganisms and other substances that may compromise or contaminate the product.
In the past, sterility testing was performed to demonstrate container integrity; however, due to the insensitivity and other complications associated with sterility tests, a variety of container and closure integrity tests were developed. While no strict standard exists for all integrity test methods, the Parenteral Drug Association (PDA) Technical Report (TR) 27 and FDA guidance on the subject does have recommendations for integrity test performance. It is recommended that container closure integrity testing during initial packaging validations incorporate both physical and microbial challenge tests. Nelson Labs offers a variety of methods to evaluate container closure integrity.
The microbial challenge test is performed as a direct evaluation of the container and closures ability to prevent microbial ingress. All sterile pharmaceutical containers must not allow organisms into the container which would contaminate the product. A commonly accepted microbial challenge method is integrity testing via microbial immersion. The PDA TR 27 encourages that the challenge should simulate worst-case production and shipment conditions. At Nelson Labs we have a unique challenge apparatus, which allows testing to be performed under a variety of both negative (vacuum) and positive pressures. This allows simulation of all types of production and shipment methods, including air freight.
Many manufacturers are not sure when or how often they should conduct Container Closure Integrity, but the testing is extremely important to ensure the product will remain sterile in the package configuration for the shelf life of the product. Container Closure Integrity Testing should be conducted during the initial packaging validation. Additionally, as detailed in the FDA Guidance document on the subject, testing should be performed as part of the stability protocol in lieu of Sterility Testing. Testing should be conducted annually on production lots to monitor for any changes in the process and/or materials.