Ethylene Oxide (ETO) sterilization is a widely used method for sterilizing medical devices, especially those sensitive to heat and moisture. ISO 11135 provides guidelines for the validation of ethylene oxide sterilization processes. Here are key considerations for ETO sterilization validation of medical devices in accordance with ISO 11135:

Biological Indicator (BI) Placement:

Place biological indicators (BIs) at critical locations on the medical device. BIs contain a known number of highly resistant microorganisms and serve as a challenge to the sterilization process. Monitor the BIs to confirm the effectiveness of the ETO sterilization.

Process Challenge Device (PCD) Placement:

Use process challenge devices (PCDs) that simulate the characteristics of the actual medical device. PCDs help ensure that the ETO penetration is sufficient to reach all areas of the load during the sterilization process.

Load Configuration:

Configure the medical device load for the validation studies to represent worst-case scenarios, ensuring that the sterilization process is effective under challenging conditions.

Sterilization Cycle Development:

Develop and optimize the ETO sterilization cycle parameters, including gas concentration, temperature, humidity, and exposure time. The cycle should be validated to consistently achieve sterilization while preventing damage to the medical devices.

Gas Distribution Studies:

Conduct gas distribution studies to ensure uniform distribution of ETO throughout the sterilization chamber. This is particularly important for large loads or loads with complex geometries to ensure that all areas receive adequate gas exposure.

Bioburden Assessment:

Determine the bioburden of the medical device, which is the population of viable microorganisms on the device before sterilization. This information helps establish the initial microbial load that the sterilization process must effectively eliminate.

Bioburden Reduction Studies:

Conduct bioburden reduction studies to determine the effectiveness of the ETO sterilization process in reducing the bioburden to an acceptable level. This may involve conducting validation runs with actual production units.

Routine Monitoring:

Implement routine monitoring of the ETO sterilization process through ongoing bioburden assessments, BIs, and other relevant measures. Regularly review and record critical parameters during routine sterilization cycles.

Validation Runs:

Perform validation runs using production-size batches of medical devices. Monitor and record critical parameters during these runs, and collect samples for bioburden testing and BI testing.

Drying Verification:

Verify the effectiveness of the aeration or degassing phase in the ETO sterilization cycle. Adequate aeration is crucial to remove residual ETO and ensure the overall effectiveness of the sterilization process.

Documentation:

Maintain comprehensive documentation of the ETO sterilization validation process, including protocols, results, and any deviations observed during the studies.

Requalification:

Requalify the ETO sterilization process when there are changes to the device design, manufacturing process, or sterilization conditions. Periodic requalification may also be necessary to ensure continued process effectiveness.

Residual ETO Testing:

Perform residual ETO testing on representative devices to ensure that the residual levels are within acceptable limits after the aeration phase.

Regulatory Compliance:

Ensure that the ETO sterilization validation process complies with relevant regulatory requirements, such as those outlined in FDA guidance documents and international standards.

ISO 11135 provides a comprehensive framework for the validation of ETO sterilization processes. Manufacturers must carefully follow these guidelines, conduct thorough validation studies, and maintain ongoing monitoring to consistently achieve the required level of sterility assurance.