Deterministic Container Closure Integrity Testing - Navigating the Essential Techniques

by Leonard Harris, Manager, Chemistry & Container Testing, Eurofins Medical Device Testing

According to USP <1207>, container closure integrity testing refers to any package leak test (either physicochemical or microbiological) that detects the presence of a package breach or gap that would allow a product to escape or contamination to ingress. There has recently been a move away from traditional dye ingress testing towards methods that are more robust and able to detect smaller defects more reliably. There are many techniques available to test for container integrity, each with its own set of advantages and disadvantages. Understanding the strengths and weaknesses of each test is critical to developing a suitable method to ensure package integrity.

Helium Mass Spectrometry – Strengths: extremely small defects, packaging development, isolation of specific area of container, test frozen samples. Weaknesses: large molecules, permeable containers.

High Voltage Leak Detection (HVLD) – Strengths: non-destructive, good for large molecules, glass containers. Weaknesses: difficulty with defects at crimp seals for vials and needles and stoppers for pre-filled syringes, lyophilised products, plastic containers.

Vacuum Decay – Strengths: non-destructive, test flexible and rigid containers, bag and blister packs. Weaknesses: large molecules block defects, product must be able to withstand vacuum pressures, pre-filled syringes (silicone oil can block defects).

Oxygen Headspace – Strengths: fast, non-destructive, not affected by large molecules, lyophilised products, rigid containers packaged in low oxygen environment, cryo-vials stored at ultracold temperatures. Weaknesses: must have headspace in container, container must be transparent to IR light, product packaged in ambient oxygen environment.

Carbon Dioxide Headspace – Strengths: fast, non-destructive, don’t need a modified packaging environment, carbon dioxide shipping studies, rigid containers, not affected by large molecules. Weaknesses: must have a headspace in container; transparent to IR light.

Choosing the correct technique for your product is paramount to successful CCIT. Using an experienced laboratory like Eurofins Medical Device Testing can help navigate the pitfalls that may arise during CCIT.