FDA Launches Pilot Program To Streamline EtO Facility, Process Changes

As concerns continue to mount over a potential shortage of medical devices due to the closure of ethylene oxide (EtO) facilities, the US agency is looking for nine sterilizers in a pilot project that could allow them to get facility and process changes approved faster.

Some medtech manufacturers could get their products approved sooner for sterilization using different ethylene oxide (EtO) plants and/or less ethylene oxide if the sterilizing company they use participates in a new pilot project.

On 25 November, the US Food and Drug Administration announced it is looking for volunteers to participate in its Master File Pilot Program, which is also called the EtO pilot program. Regulators are hoping to recruit up to nine EtO medical device sterilizers that sterilize single-use medical devices using fixed chamber EtO to submit a master file when making changes, such as where they sterilize products and/or how much of the gas they use.

Under the program, sterilizers would be able to submit a master file reference document to the FDA, which would streamline the information required to greenlight changes by the agency to the sterilization facility or process.

Currently, if a device maker changes the method, process or the facility listed in its original PMA submission for sterilizing its devices, they need to submit a PMA supplement to the FDA for review and approval before they can make those changes. The pilot program allows high-risk class III device makers that are affected by those changes to simply reference the master file submitted by their sterilizer to the agency instead of submitting a new premarket authorization supplement, which tends to be much more time-consuming.

FDA spokesperson Brittney Manchester said considering the recent sterilization facility closures and concerns about their impact on medical device availability, the agency realized it needed to speed up its process to approve site changes and when sterilizers reduce the amount of EtO used.

“PMA holders of devices sterilized using processes that are acceptable for inclusion in this program will be expected to notify FDA of their sterilization process change in a post-approval report,” she told Medtech Insight. “This is not a PMA supplement, and support of the process change is expected to be addressed with the content of the master file.”

Jeff Shuren, director of the FDA’s Center for Devices and Radiological Health (CDRH), issued a statement in conjunction with the announcement noting that the program is part of the agency’s ongoing efforts to prevent a public-health crisis from potential medical device shortages.

“By facilitating more efficient review and feedback, this pilot program should also result in sterilization facilities using a reduced amount of ethylene oxide several months sooner than they otherwise would while still providing robust patient safeguards,” Shuren said in a statement. “Consequently, we believe this pilot program will allow more nimble response to sterilization site closures by more quickly approving sterilization site relocations and speeding up the implementation of sterilization methods that reduce the amount of ethylene oxide needed to sterilize PMA-approved medical devices.”

Ultimately, the FDA says that if the program is successful, it will reduce the environmental and public-health impact of EtO while preventing any potential device shortages.

Over the past year, several EtO sterilization facilities have either been permanently or temporarily shut down due to concerns about increased levels of the toxic chemical detected around those plants. The issue has also alarmed the FDA, industry and other stakeholders that are worried it could lead to severe device shortages, leaving patients without lifesaving products. That’s because roughly half of all devices are sterilized with EtO, and many products can’t be cleaned with other technologies. (Also see "Risk Of Sterilization Plant Shutdowns Across US Sends Shockwave Through Industry" - Medtech Insight, 31 Oct, 2019.) and (Also see "Teleflex Says It Will Lose $9m – And Maybe More – Due To EtO Plant Shutdown" - Medtech Insight, 6 Nov, 2019.)

Most recently, the FDA held a two-day advisory committee meeting to tackle the potential device shortage concerns from EtO plant closures, and the agency’s experts discussed topics including other sterilization methods, allowing use of less EtO to clean devices and dropping the required sterility assurance level. The new pilot program is a direct result of the FDA’s advisors asking the agency to come up with a more streamlined process for sterilizers and manufacturers to make changes to their EtO facilities and processes. (Also see "US FDA Experts Caution Against Banning EtO, Encourage More Duodenoscope Training" - Medtech Insight, 8 Nov, 2019.)

The agency is taking a very narrow approach in terms of which sterilizers and what types of devices would be eligible for the pilot. For example, reusable devices or those that have undergone a design or packaging change would not be eligible. Also, sterilizers that do not already have an approved fixed chamber EtO sterilization or use cycle parameters outside the validated tolerances recognized by the FDA are left out of the pilot.

The pilot also isn’t for PMAs that are reviewed by the FDA’s Center for Biologics Evaluation and Research (CBER) or those that are considered a part of a combination product.

During the recent advisory committee meeting, experts proposed that the FDA may want to explore allowing a lower sterility assurance level, which is based on internationally agreed upon voluntary consensus standards when cleaning medical devices. However, in the pilot the agency is maintaining the same level of sterility assurance it currently uses as a gold standard. (Also see "Listen: Medtronic Exec Highlights Ethylene Oxide Standards At First Day Of FDA EtO Meeting" - Medtech Insight, 7 Nov, 2019.)

The FDA says it will evaluate pilot participants over the next six months and provide any updates when appropriate. Further, the pilot doesn’t absolve manufacturers from submitting annual reports identifying any changes to their PMA.