FDA Town Hall Series on Ethylene Oxide Sterilization and Alternative Sterilization Modalities

Sterilization is a critical step in manufacturing certain medical devices and Ethylene Oxide (EO or EtO) is the most commonly used method in the United States. However, the FDA and EPA are committed to reducing reliance on EO while ensuring a stable supply of sterile medical devices. This multipronged approach includes regulatory flexibilities, supply chain analysis, collaboration, innovation, and communication with the public, medical device manufacturers and other interested parties.

EPA Final Rule Announcement

The U.S. Environmental Protection Agency (EPA) recently announced (March 14, 2024) their final amendments to the air toxics standards for EO commercial sterilization facilities. Through the installation of proven and achievable air pollution controls, commercial sterilizers will reduce emissions by more than 90%, the strongest measure in US history to reduce emissions of EO. EPA Administrator, M S. Regan recently commented, “We have followed the science and listened to communities to fulfill our responsibility to safeguard public health from this pollution – including the health of children, who are particularly vulnerable to carcinogens early in life. We’ve arrived at a historically strong rule that will protect the most exposed communities from toxic air pollution while also ensuring that there will be a process that safeguards our nation’s critical supply of sterilized medical equipment.”

FDA Town Hall Series

The United States Food and Drug Administration (FDA) has recently hosted a series of town hall meetings focused on the current status of EO sterilization for medical devices in the US. The FDA recognized the need to disseminate current information and to provide a forum to stakeholders. In these town hall meetings, the following discussion points are of note:

1. The FDA aimed to describe its early actions to ensure sterilization capacity in the US and recent efforts to reduce reliance on EO while maintaining a resilient supply of sterilized medical devices.
2. Challenges and Opportunities: The FDA’s understanding of opportunities and challenges related to using alternative sterilization methods.
3. EtO Tiger Team: The FDA has established a dedicated EtO Tiger Team to advance innovations in medical device sterilization.

Note: What is a tiger team? A tiger team is a specialized, cross-functional team brought together to solve or investigate a specific problem or critical issue.

Alternative Modalities 

One recent area of advancement was the inclusion of Vaporized Hydrogen Peroxide (VHP) as an established sterilization method in the FDA’s guideline for sterilized medical devices titled “Submission and Review of Sterility Information in Premarket Notification (510(k)) Submissions for Devices Labeled as Sterile” Guidance for Industry and Food and Drug Administration Staff, issued in January 2024. The inclusion of VHP sterilization along with the other longstanding “established” sterilization modalities (e.g., dry heat, EO, steam, radiation) allows for reduced submission information for VHP sterilization. This is because there are now voluntary consensus standards for development, validation and routine control of VHP sterilization that are recognized by the FDA, similar to the other sterilization methods.

The use of VHP as an alternative to EO sterilization is intriguing since it is a low-temperature sterilization process like EO, which is a key factor when evaluating material compatibility for an existing device and may allow for easy transition away from EO for certain devices. The other established sterilization methods use higher temperatures (dry heat or saturated steam) or ionizing radiation (gamma, electron beam or x-ray) which may prohibit their use due to device material compatibility issues. AAMI TIR17 Compatibility of Materials Subject to Sterilization provides users a detailed review of all established sterilization methods and guidance on the compatibility of a wide range of materials used in the construct of medical devices intended to be sterilized.

VHP sterilization has been used for decades by medical device manufacturers either in-house at a manufacturing facility for terminal sterilization or at hospitals for reusable device sterilization. However, the full commercial use of VHP on a contract sterilization base is currently very limited and is not likely to supplant EO sterilization any time soon. The acceptance of VHP as an established sterilization modality provides an opportunity for medical device manufacturers to explore the potential use of VHP along with other sterilization modalities (other than EO).

Why Is This Important?

The product development life cycle begins with outlining the device construction requirements and acquainting design engineers with the tools and endpoints for choosing materials. These materials must be compatible with a sterilization method from both a strategic and operational standpoint. The sterilization choice for a new device should be paramount in the design feasibility stage with management approval in terms of:

• Product sterilization volume
• Materials of construction costs
• Material availability and supply chain
• Sterilization contractor supply chain restrictions/capacity

Establishing these design inputs as early as possible in the design process allows the entire product development design team (engineering, sterilization, marketing, regulatory and operations) the opportunity to create the most feasible and manufacturable design. This also ensures the device succeeds in all facets of the development process in a sustainable and patient-centric way.

Despite the other sterilization modalities and the increased acceptance of VHP as a low-temperature sterilization process, EO will continue to be a process that is used for the sterilization of medical devices. EO sterilization facilities have an ever-increasing focus on process improvement with respect to environmental concerns. The final rule for commercial sterilizers issued by EPA is one in a series of coordinated actions that the body is taking to reduce exposure. Facilities have been actively reducing EO sterilization concentrations in their sustainable EO cycles and revalidating these cycles with a focus on cycle optimization during this validation process to allow for an overall net reduction of EO consumption/ usage.

How Can NAMSA Help?

NAMSA has a dedicated team of EO sterilization validation experts available to work with medical device companies. Our experts can review, design and validate (or re-validate) current EO sterilization processes, and help optimize EO sterilization cycles that may currently use a higher concentration of EO gas. Additionally, we can conduct radiation sterilization (gamma or ebeam) validations for Sponsors interested in those sterilization methods. Our sterilization experts are ready to discuss VHP sterilization options and address any related inquiries. Contact us today to begin your sterilization validation project.