FDA Experts Delve into Sterilization Topics
A behind-the-scenes discussion covered bioburden, endotoxins, and the unexpected challenges of ensuring packaging integrity for life-saving medical devices.
On August 7, 2024, a panel of sterilization experts at the Food and Drug Administration (FDA) discussed bioburden, bacterial endotoxin, and packaging integrity testing for sterile medical devices during a virtual town hall meeting. The meeting is part of an ongoing series to support FDA’s multi-pronged approach to reducing reliance on ethylene oxide sterilization while ensuring supply chain integrity so that patients and providers have continued access to the sterile devices they need.
Jennifer Berg, senior staff fellow, Office of Product Evaluation and Quality (OPEQ), surgical and infection control devices, addressed some of the general requirements and definitions related to package integrity testing. This included information from ISO 11607, the standard for packaging for terminally sterilized medical devices.
Regarding the difference between ISO 11607 and testing standards, Berg explained that ISO 11607 offers a high-level description of packaging and testing. It mentions a number of testing standards but does not specify how to perform package integrity testing.
In addition to discussing package performance and package stability testing, Berg addressed sample size considerations, stating the importance of selecting sample sizes commensurate with the level of risk to the patient if failure were to occur.
“We recommend a sample size is chosen that demonstrates the primary sterile barrier remains intact with 95% confidence and 95% reliability,” she said.
Dave Craft, microbiologist, OPEQ, renal, gastrointestinal, obesity, and transplant devices, provided an overview of packaging integrity tests and explained how these tests can be used to establish shelf life. These include:
• ASTM D4332: Environmental Conditioning Testing
• ASTM D4169: Performance Testing of Shipping Containers
• ASTM F1886: Seal Integrity Testing
• ASTM F2096: Bubble Leak Testing
• ASTM F88: Seal Strength Testing
This list is not exhaustive, and companies are not required to use these particular tests.
According to Craft, testing should be performed on the final, finished sterilized packaging. Key takeaways include:
• The sponsor should age the devices in real time up to the desired shelf life.
• For most devices, accelerated aging is permitted at time of marketing.
• Document real-time aging results as an internal letter to file (510(K)) or an annual reportable change (premarket approval).
Craft clarified that shelf-life determination is driven by the data; therefore, FDA does not have any expectations or recommendations for shelf life.
Continuing the conversation.
Following the presentation, FDA opened the meeting to participant’s comments and questions, some of which related to packaging:
Q: Does all device packaging need to be tested?
FDA: The agency wants to see testing done on primary packaging, which has direct contact with the device, to ensure that the barrier is maintained throughout the established shelf life of the device.
Q: Should we conduct packaging integrity and performance testing at the maximum radiation dose range?
FDA: Typically, FDA does want to see the worst case scenario for radiation dosage. You may have a particular dose that you use for your sterilization validation, but there might be a maximum threshold for that dose. So you may want to test it at that maximum threshold just to ensure that the package integrity is maintained, even at the maximum sterilization dose.
Q: ASTM 11607 does not include any testing that can be validated for paper packaging due to porosity. Does FDA have any recommendations for testing on these package types to confirm the sterile barrier system?
FDA: If you feel you have a packaging system that does not meet the criteria to use the packaging validation tests outlined in the standard, you can work with the review division via pre-submission to determine if there’s a test you can perform — either one sourced from a different standard that may not be FDA-recognized or a method that’s developed in-house.
FDA’s next town hall will take place on Wednesday, September 11, from 1:00 to 2:00 p.m. ET. Topics include sterility master files and effective use in pre-market submissions. Questions or comments can be directed to [email protected].
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