21 CFR 211.94 - Drug Product Containers and Closures

What it says

Drug product containers and closures must not be reactive, additive or absorptive so as to alter the safety, identity, strength, quality or purity of the drug product, must provide adequate protection against external factors, and container-closure systems must be tested to demonstrate they meet appropriate standards or specifications.

Paraphrased for plain-language clarity. Always verify against the current published regulation text.

What it means in practice

• This provision covers the container-closure system as it interacts with the finished product over the product's full shelf life, not just at the moment of packaging.
• Container-closure integrity testing is expected to be part of the product's overall control strategy, particularly relevant for sterile products where a compromised closure creates a direct sterility risk.
• Compatibility between the specific formulation and the specific container-closure system must be demonstrated - a closure system validated for one formulation cannot be assumed compatible with another without its own assessment.

What FDA inspectors look for

• Whether container-closure integrity testing data exists and supports the product's actual shelf life claim, not just its initial release.
• Whether extractable and leachable studies, where applicable, reflect the actual formulation and container-closure system combination in commercial use.
• Whether any change to container-closure system components was assessed for its effect on product protection and stability before implementation.

Related regulations