Container Closure Integrity Testing (CCIT) By Dye Ingress and Microbial Challenge

Rigid containers are often tested as part of a stability study to ensure that the closure of the container can maintain a sterile barrier. The FDA recommends performing a container closure integrity test in lieu of a sterility test as a component of a stability testing protocol.

At PBL, we routinely run the dye ingress and microbial ingress container closure tests. For routine testing, the dye ingress method uses ten test samples and three positive controls. The samples are placed in a vacuum chamber with dye and either pressure or vacuum is applied to the samples. The positive controls are punctured with a microtube to allow dye into the vials. Test samples that show dye inside the vials fail the integrity test and samples that do not contain dye pass the test. Typically this assessment is done by spectrophotometer. A qualification of the method is performed by determining the minimum breach size detectable, the LOD/LOQ and a standard curve with known amounts of dye added to the vials.

The microbial ingress method is similar to the dye ingress method however the test vials will need to be filled with media rather than drug product so that any microbial ingress into the vials can be detected by observing turbidity of the media. Because of its small size, Breundimonas diminuta is used for these studies.

The materials of these containers may need USP Class Plastics certification, and may need in vitro cytotoxicity testing to ensure any leachable materials from the containers are not harmful to cells.

Container Closure Testing Services

  • Dye Ingress Container Closure Integrity Test for Rigid Containers
  • Microbial Ingress Container Closure Test
  • Helium Leak CCIT*
  • Vacuum Decay CCIT*
  • Cytotoxicity (in vitro)
  • USP Class Plastics (in vivo)
  • Extractable Leachable <661> Testing

* denotes a subcontracted test

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