Preventing Medical Device Shortages Through Improving the United States Sterilization Supply Chain

Both Ethylene Oxide (EtO) and gamma radiation are highly effective sterilizers for medical devices, but they face significant supply chain vulnerabilities that have already led to shortages within the United States. To mitigate these risks and bolster the sterilization supply chain, the FDA recently approved a new “Established Category A” sterilization method and implemented three key programs designed to encourage medical device manufacturers to adopt alternative methods, all within the last five years (FDA, 2024). 

Many medical device manufacturers rely on third-party providers for their sterilization needs, creating potential bottlenecks in the manufacturing supply chain. Moreover, the use of EtO and radiation methods not only comes with liability concerns but also creates property exposures due to the flammability of EtO and radiation contamination from gamma rays. The FDA’s recent initiatives offer manufacturers and sterilization service providers more options for alternative sterilization methods, effectively creating a more resilient and flexible supply chain that can adapt to regulatory and logistical disruptions while also reducing risk to people and property.

Sterilization Supply Chain Constraints

EtO remains the most commonly used sterilization method for medical devices in the U.S., with over 20 billion devices sterilized using EtO annually (FDA, 2024). However, between 2019 and 2020, several U.S.-based EtO sterilizers were forced to temporarily close their facilities to install emission-reduction equipment, resulting in critical medical device shortages across the country (FDA, 2021). As of April 2024, EtO sterilizers face increased emissions regulations from the Environmental Protection Agency (EPA) due to public health concerns (Federal Register, 2024). While sterilizers have been diligent in responding to these new regulations, there is a risk that similar facility closures could occur once again to meet these new regulations.

According to the FDA, there are three approved sources of radiation sterilization: gamma radiation, x-rays, and electron beams (FDA, 2023). Gamma radiation is the second most frequently used method behind EtO, accounting for 40-45 percent of sterile medical devices. Gamma radiation for device sterilization is generated using radioactive cobalt (Cobalt-60 or CO-60), which is produced from a small number of nuclear reactors located in Argentina, Canada, China, India, and Russia (World Nuclear News, 2023). With production taking place exclusively outside the U.S., the United States is at heightened risk of a potential CO-60 supply shortage.

In 2024, the FDA approved using Vaporized Hydrogen Peroxide (VHP) as an Established Category A sterilization method for medical devices. VHP is a process where a solution of water and a high concentration of hydrogen peroxide is converted into a gas and then circulated at specific concentrations throughout the sterilization chamber. Once the process is complete, the vapor is vacuumed out of the chamber and converted back into water and oxygen. While there are still risks of inhalation or skin contact, which could cause irritation to the eyes, nose, and throat (Boiano & Steege, 2015), the process leaves behind by-products that are much less hazardous than EtO. The International Agency for Research on Cancer (IARC) has determined that HP is not classifiable as a carcinogen to humans (CDC, 2024). Overall, VHP significantly reduces liability concerns for sterilizers. However, this new method must be as effective as EtO and Co-60 to show promise for widespread future use.

According to Estahbanati (2023), VHP has become a more reliable option than EtO for non-industrial applications that involve temperature-sensitive medical instruments. The technology for VHP continues to advance, making it more effective on a broader range of devices. Additional research and development efforts around its sterilization process will only help address challenges, such as HP penetration in diffusion-restricted environments. Although VHP will certainly not be the answer to the effective sterilization of all medical devices, the addition of it as a Category A sterilization method shows the FDA’s response to finding alternatives for EtO and gamma radiation methods to prevent a medical device shortage in the future.

FDA's Master File Pilot Programs

Prior to announcing VHP as an approved Category A sterilization method in 2024, the FDA developed and implemented three programs between 2019 and 2023 to enable medical device manufacturers and sterilizers to explore alternative sterilization methods (FDA, 2024). Collectively called the Master File Pilot Programs, the FDA has launched the following initiatives:

• Radiation Sterilization Master File Program for PMA Holders (April 2023)
• 510(k) EtO Sterility Change Master File Pilot Program (May 2022)
• EtO Sterilization Master File Pilot Program for PMA Holders (July 2019)

These voluntary programs help contract sterilizers and medical device manufacturers identify alternate or less concentrated sterilization methods may be subject to fewer regulatory constraints while maintaining the same sterilization outcomes. Each program is looking for up to nine participants. The EtO Sterilization Master File Pilot Program for PMA Holders has the most participants at a total of five as of the date of this article.

Conclusion

While EtO and gamma radiation remain the predominant methods for sterilizing medical devices in the U.S., both are increasingly scrutinized for their supply chain vulnerabilities, health risks, and liability concerns. In anticipation of future supply chain challenges, heightened regulation of EtO, and increases in internationally supplied CO-60, the FDA has introduced VHP as an alternative sterilizer and has implemented several programs to encourage device manufacturers and sterilizers to identify techniques that would be just as effective as EtO and gamma radiation. VHP technology still has a long way to go before it proves itself an effective and reliable sterilization alternative to EtO and gamma radiation for particular devices. However, new techniques and processes will continue to emerge in years to come. While the pilot programs have not had the participation the FDA initially hoped for, it is likely that more device manufacturers will turn to the sterilizers already participating in these programs as regulations and sterilization constraints become more commonplace. There is room for growth and innovation within this space to help the U.S. better plan for tomorrow and assist device manufacturers in reducing their risk of supply chain exposure by sourcing other validated sterilization methods.

Authored by Medora West, Berkley Life Sciences, Sr. Life Sciences Risk Management Specialist