Probabilistic methods

Dye ingress (tracer liquid test) is one of most widely used CCIT method across the biopharmaceutical industry. It is based on holistic approach to CCI, where a container closure system is immersed in a dye solution and then exposed to dye ingress challenge conditions (over specified time to predefined vacuum and/or pressure challenge). The integrity of the container is evaluated  by analyzing its content in order to assess the dye penetration from a possible leak. The test could be performed either visually inspection or by spectroscopic measurement at absorbance maximum of the dye.

Advantages:

• Simple experimental design
• Versatile method: no limitations on product conductivity, product composition

Disadvantages:

• Destructive method
• Probabilistic method
• Lyophilized product could be challenging to test

The immersion exposure microbial challenge is a destructive, qualitative measurement approach for confirming leaks in nonporous, rigid or flexible packages. A standard approach consists in a preliminary filling of the container with a nutrient medium and then they are soaked in a bacterial suspension. After the exposure, the containers are examined for bacterial growth within the containers.

Advantages:

• No particular limitations regarding the type and volume of container closure system
• Application in project and development of container closure system: efficiency of container closure system as microbial barrier can be evaluated

Disadvantages:

• Destructive method
• Probabilistic method
• It is not technique of choice to test the combination of drug product and container closure system