By Jeff Peterson, B.S. Study Director, Packaging
Container Closure Integrity testing can be performed using physical tests for stability programs rather than sterility testing according to the draft FDA document “Guidance for Industry- Container and Closure System Integrity Testing In Lieu of Sterility as a component of the Stability Protocol for Sterile Products”. Due to the limitations of sterility tests (which only detect a viable organism if promoted in the correct media) alternative test methods are being considered as more appropriate. One of the most popular and simple packaging tests to help accomplish this is the Dye Immersion or Container Closure Integrity test.
Up until recently the test has been providing only attribute data (pass/fail). Outside of the draft document instructions for compliance has been limited, with no direction from the USP or other committee’s concurrently. However, recently there have been important new signs from the FDA indicating they are requiring more information than just pass/fail for companies that choose to follow the guidance document. There is also a growing feeling that standards will be developed and put in place down the road.
The premise behind the guidance document is that a sterility breach is event related; therefore by challenging sample containers through a stability program and then exposing them to a dye immersion test method proves a product has remained sterile. Nelson Labs is seeing a growing trend among FDA reviewers that are looking for manufacturers to not only show their containers pass the dye immersion test, but are also requiring the limit of detection (LOD) be determined in their product.
To better help manufacturers prepare for their FDA submissions and provide requested information, Nelson Labs recommends using the UV/VIS with any dye immersion tests in order to fully determine the LOD for their product. Nelson Labs is currently implementing new best practices to facilitate the new approach to the test:
- Nelson Labs is using the International Conference on Harmonization of Technical Requirements of Pharmaceuticals for Human Use (ICH) guidelines for determining product specific LOD.
- Nelson Labs is also streamlining the method to conduct the test.
- As a standard part of the dye immersion test, Nelson Labs is providing limit of detection data, which creates a confidence level that meets manufacturers’ product matrices for which they are testing.
Nelson Labs feels the new trends from the FDA are actually making the dye immersion test better for the industry in complying with safety and efficacy regulations. By obtaining the limit of detection, manufacturers are going to have the information they need when the FDA asks for it. It's a preemptive strike that puts the company ahead of the game in regards to new FDA trends and requirements.