Aerosol challenge for Container Closure Integrity studies

By Michele Cavalleri, Eurofins BioPharma Product Testing Italy, MicheleCavalleri@eurofins.com

Container Closure Integrity (CCIT) studies are designed to show whether a bacterial aerosol challenge is capable of breaching the integrity of the Sponsor's sterile packaging in a worst case scenario condition.

These studies may be required to determine the closure integrity of containers for sterile pharmaceutical products or medical devices terminally sterilised in their final configuration, and when the verification of barrier properties of single components and/or bacterial immersion challenge testing are not either sufficient or relevant. CCIT studies are performed following a sterility breach risk analysis, for instance when:

• A defect in packaging assembly might lead to aerosolised microbial contamination in class C or D environments (e.g. raised vial stoppers).
• Leaks in piping for aseptic bulk production may lead to a risk of cross contamination from aerosolised microbes.
• Sterile containers for medical devices are exposed to physical-chemical stress, which might lead to a loss of sterile barrier properties for the filters and potentially lead to cross contamination from aerosolised microbes.

The experimentation requires a robust validation of the test system. Particularly, the bacterial challenge has to be qualified in terms of challenging particle size (a high level inoculum dry spores of Bacillus atrophaeus nebulised at 60°C from a Collison NSF nebulizer), homogeneous distribution in the test chamber, density of aerosolised inoculum, flow rate, and environmental conditions.

A robust system validation requires therefore:

• The validation of reliable positivecontrols in order to verify the viability of the inoculated spores, the inoculum density and distribution, and the recovery process from the media fill.
• The validation of reliable negative controls in order to verify that the recovery process from the media fill is actually performed under aseptic conditions.

The described studies are performed by Eurofins under standard environmental conditions or at specific customised conditions of pressure, temperature, etc., in this case, a specific setup phase is strictly necessary.

For more information on conducting a CCIT study, contact: GMP_EU@eurofins.com