Closed Container Integrity Testing
There are many pharmaceutical products that are supplied sterile:
- Pre-filled syringes
- And many more.
Container Closure Integrity testing (CCI testing) is an integral part of the design and process validations for these products if contamination is to be avoided.
The FDA have issued guidance on CCI testing in lieu of other sterility testing methods, which can be viewed on their website. Additionally, there is more information available at: 21CFR211.94, EudraLex volume 4 part II, ICH - QC5, and USP <1207>.
How does CCI Testing work?
The CCI test is a method of demonstrating that there is no leak (or fluid path) between the contents of the container and the outside environment. It is set up to identify whether a communication can be established between the contents of the vial and outside the vial. We consider here only non-destructive methods. There are also destructive methods of testing such as dye ingress and microbial ingress.
Types of Non Destructive Testing
Non-destructive methods include trace gas analysis and vacuum decay (electromagnetic absorption and electrostatic discharge can be applied in some cases).
Vacuum Decay Test
In the vacuum decay method, vials are placed inside a close fitting tool, which is then closed and a vacuum applied. If the container has a leak it will reduce the expected vacuum inside the tool (around the vial). Alternatively, this test is carried out underwater and bubbling from the container is inspected visually.
In an electronic test, the rate of pressure change can be used to calculate the size of a leak. For flexible containers, a compressive pressure (squeezing) can be applied, with leaks again being searched for visually.
Trace Gas Analysis
To avoid the use of product-specific tooling or water, a trace gas method may be applied, MET has an ISO/IEC 17025 accredited method using hydrogen as a trace gas. In this case, the test parts are placed inside a chamber within an atmosphere of the trace gas at slightly elevated pressure.
After a short soaking period, the containers are removed and analysed for gas leakage with sensitive electronic equipment. If there is a leak path, the trace gas will have entered the product. Its subsequent release can be quantified, and the location of a leak identified. It is also possible to conduct this test using a helium mass spectroscopy method.