Container Closure Integrity Testing: Risks And Methods

By Dennis Seibert

The quality and effectiveness of drugs significantly depends on their proper packaging: Sterile products and moisture/oxygen sensitive drugs require excellent barrier during the shelf life of the product (up to a couple of years) to protect them from biological contamination, water and oxygen ingress. Otherwise, serious consequences might occur. This was proven by a grave incident in the 1970's: During this period, contaminated intravenous fluids packaged in glass bottles – which were typical at the time for packaging such dosage forms – caused an estimated 2,000 to 8,000 episodes of bloodstream infection, resulting in the deaths of about 10 % of the patients. This severe package-integrity failure incident has triggered a heightened awareness of package integrity in the life science industry.

The key risks for contamination are by humidity, oxygen or microbiological ingress, which can impact the drug stability throughout the product life cycle. To prevent the risks of stability failure of highly moisture sensitive drugs (e.g. dry powder for inhalation) or the risk of biological ingress of sterile parenteral drugs, integrity tests with a high sensitivity are required.