West Technical Operations
Accepting Sterile Container Closure Components
Manufacturers of sterile drug products have a long history of receiving elastomeric plungers for use in a prefilled syringe in a sterilized, ready-to-use (RU) condition. This trend has more recently evolved to include other container closure components including, glass or plastic vials, aluminum over seals and elastomeric stoppers. When accepting RU components into a new or existing manufacturing process, it is important to consider how sterility assurance of the components will be determined.
Although sterility testing of the components upon incoming receipt may be an option, it has practical limitations. The limitations of sterility testing are well documented including by the FDA in the Guidance for Industry, Container and Closure System Integrity Testing in Lieu of Sterility Testing as a component of the Stability Protocol for Sterile Products
. The FDA comments include:
- Sterility tests will only detect viable microorganisms present at the time of the test
- Viable organisms present at the time of the test can only be detected if they are capable of growth in the specified culture media
- Sterility tests may be subject to potential interference due to adventitious microbial contamination introduced at the time of testing, resulting in false positive readings
- Sterility tests are always destructive of the samples tested and do not offer the opportunity to reexamine the same samples in the event of either positive or negative findings
Sterility assurance can only be established by process design, validation and process controls. Applying the use of an incoming sterility test is only one indicator that may provide limited information. It is important to assess the entire process from your supplier to point of use on the filling line and determine through risk assessment the potential for sterility assurance loss. If deemed necessary, avoid potential issues by enacting the proper controls as identified by the risk assessment.