Medical device sterilization has been a complicated opportunity for everyone within industry, including regulators, to navigate. Ongoing material, technology, and ecological factors have continued to add layers of responsibility and complexities to the critical role of sterilization in global human healthcare—especially concerning Ethylene Oxide (EO).
Overall, there are three sterilization methods in commercial use today: thermal, gas/chemical, and irradiation. Due to broad compatibility and without excessive heat required by some other sterilization methods, EO has been the go-to for half of all medical devices and pharma products worldwide. One of the reasons EO has been such a go-to is that rather than extreme heat, it uses a chemical reaction to destroy cell membranes and kill all microorganisms present. This is the basic mechanism by which EO sterilizes. Because of this, EO is often the optimal choice to sterilize without degradation of the medical device, medicine, or packaging. As effective and appealing as it is, EO has constraints.
CONCERNS
Formal research into cancer-causing substances came to the forefront of U.S. health policy with the enactment by Congress of Public Law 95-622 in 1978. In response, the Department of Health and Human Services (DHHS) went on to submit the First Annual Report on Carcinogens (RoC) in 1980. The report identified “likely” and “known” agents, based on scientific research that was also directed by PL 95-622. Ethylene Oxide first appeared in the 1985 RoC, when it was listed under agents “reasonably anticipated to be human carcinogens.” The gas was moved to the “known human carcinogen” category in 1993.
Ethylene Oxide health risks (like many substances named in the reports) occur due to over-exposure through either working in an environment where EO is present or through emissions into the atmosphere through EO processes. As such, finding a means of reducing or eliminating and monitoring human exposure becomes the focus for substances whose benefits outweigh risks, such as EO sterilization.
CONSEQUENCES
Throughout the ensuing decades, governmental safeguards, and OSHA standards for EO management were implemented and updated as research informed through the annual-then-biennial Reports on Carcinogens. In response to the concerns around EO, the FDA launched a pair of “public innovation challenges.” FDA Innovation Challenge 1 invited companies to participate with the agency to identify and develop novel, safe and effective sterilization technologies other than EO. Additionally, working with the FDA to develop strategic directives on regulatory processes and scalable implementation to mitigate (or eliminate) EO health risks.
Innovation Challenge 2 invited applicants to also work closely with the FDA on methodologies that will reduce, or ideally eliminate, emissions from EO sterilization processes. Specifically, Challenge 2 sought ways to:
- Use less EO while achieving the same results
- Capture and/or render EO emissions into “harmless byproducts”
- Monitor and alert systems to track and measure, prevent, or minimize emissions at EO facilities
- Remove or reduce employee and community exposure through the findings
WHAT’S TO COME
A 2022 FDA bulletin offered an update on the challenges and work with the EPA that has taken place since 2019. A premarket approval pilot program (EtO Sterilization Master File Pilot Program) was implemented for high-risk devices, while selected participants for the two challenges are conducting ongoing initiatives to disrupt constraints and optimize advantages for as-yet elusive “replacement” options.
In 2023, the FDA Center for Devices and Radiological Health launched the Radiation Sterilization Master File Pilot Program. The pilot aims to be a catalyst for novel sterilization methods for medical devices. The program seeks alternative radiation sources and methods (other than gamma, or changing from gas/chemical to a radiation modality), considering their potential impact on already significant regulatory demands. This initiative can potentially help medical device manufacturers move away from EO to a radiation modality. For those who want to transition to something other than gamma, it might make that path easier.
A virtual FDA Town Hall took place in spring 2024 to bring together regulators and industry professionals to discuss key impacts and strategies surrounding medical sterilization and safety. The shared goal was to assess and collaborate on current and potential novel sterilization science to address challenges and maximize opportunities. As has been the case since the spotlight turned to EO exposure risks, FDA and industry seeks to reduce exposure to carcinogens related to sterilization, promote practical and effective development of new sterilization means, while maintaining and enhancing patient safety and effectiveness of medical devices.
The potential for breakthrough technologies across all sterilization avenues for the medical device and pharmaceutical sectors brings new energy to the scientific and tech experts as we set forth our global commitment to transforming the status quo into a safer and healthier setting for sterile medical manufacturing in the months and years ahead.
