FDA has created a new pilot program for industry to expedite approvals of certain changes to ethylene oxide (EtO) sterilization processes and facilities. In an effort to expedite approvals of certain changes to EtO sterilization processes and facilities, FDA is asking for participation in it Ethylene Oxide Sterilization Master File Pilot Program (EtO Pilot Program) . This voluntary program has two components — one pertaining to sterilization facilities and one for device manufacturers.

First, under the pilot program sterilization facilities that sterilize single-use medical devices using fixed chamber EtO sterilization processes (in which the device is placed in a chamber and the EtO is injected) would submit a Master File to the FDA when making certain changes to the location of the sterilization facility (i.e. changes between sterilization sites), or when making certain changes to sterilization processes that utilize reduced EtO concentrations.

The Master File is a submission to the FDA that may be used in support of premarket submissions to provide confidential detailed information about establishments, processes, or articles used in the manufacturing, processing, packaging and storing of medical devices. A Master File is a reference document that helps facilitate the sound scientific evaluation of devices and may be used when several applications are submitted for different products that may use a common material or process, such as the same sterilization method.

Second, under this voluntary program, manufacturers and sponsors of Class III devices (generally devices that are high risk and/or life-supporting or life-sustaining) affected by changes made by a sterilization facility participating in the EtO Pilot Program (and within the scope of the program) can, upon FDA’s permission, reference the Master File submitted by their sterilization provider in a post approval report, rather than a PMA supplement. The pilot program is intended to provide expeditious review and feedback to sterilization facilities and PMA holders on Master File submissions used to support changes made to sterilization site and/or processes in a postapproval report.

By facilitating more efficient review and feedback, this pilot program should also result in sterilization facilities using a reduced amount of EtO several months sooner than they otherwise would while still providing robust patient safeguards. 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 EtO needed to sterilize PMA-approved medical devices. This could reduce the impact of EtO on the environment and on the public health while at the same time continuing to ensure patient access to safe medical devices.

The agency also identified the results of its two new Innovation Challenges designed to accelerate the development and review of sterilization technology innovations as part of its next steps in improving medical device sterilization with EtO.

The two new Innovation Challenges were intended to encourage ideas from academics, industry, and others about novel solutions for improving sterilization processes. Challenge one was to identify new sterilization methods and technologies that are alternatives to those that use EtO. Challenge two was to identify strategies or technologies that can significantly reduce the amount of EtO used to sterilize devices. Today we are announcing the results of both of these challenges.

"We received 46 applications, from companies large and small, and after careful review have selected 12 applications," saidJeffrey E. Shuren, MD, JD, director of CDRH, in a statement. "These applications run the gamut of innovative ideas and novel methods, including nitrogen dioxide sterilization, vaporized hydrogen peroxide sterilization, reduced sterilant concentration and use of EtO-flexible chamber technology to name a few examples. As a next step, we’ll work directly with these selected applicants to accelerate the development and review of innovative technologies for sterilization processes."

Shuren said the agency is also moving forward on recommendations received from the public advisory committee meeting held earlier in November 2019.

"It was a robust meeting where we discussed how best to encourage innovation in medical device sterilization with speakers from the FDA, the U.S. Environmental Protection Agency (EPA), the Centers for Disease Control and Prevention’s Agency for Toxic Substances and Disease Registry, the Medicines and Healthcare Products Regulatory Agency of the United Kingdom and several other stakeholders and members of the public," he said.

The EPA spoke about its role to regulate the emission of EtO from industrial facilities, which could include manufacturing facilities as well as sterilization facilities. The FDA gave presentations on the agency’s role in ensuring the safety and effectiveness of all medical devices, including oversight of the sterility of medical devices, and our role in monitoring and addressing medical device shortages due to reduced supply of certain EtO sterilized medical devices. The FDA and EPA continue to engage on EtO concerns and facility closures.

Invited speakers presented information to the advisory committee panel on the impact of contract sterilization on medical device supply chains, reducing EtO emissions for medical device sterilization, and alternative modalities for industrial sterilization with existing industrial infrastructure. Members of the public spoke about the adverse impact of the environmental release of EtO on communities surrounding EtO industrial facilities and the adverse impact of the loss of EtO sterilization on the supply of medical devices for patient care. The advisory panel agreed that all available avenues should be pursued to reduce EtO use.

One recommendation FDA received at the advisory committee meeting is for device manufacturers to begin, as soon as possible, to reduce the amount of paper (such as the labeling and instructions for use manuals) that is included in a sterile device package. An EtO-sterilized medical device must be sealed in a carefully designed gas-permeable package that enables the EtO gas to enter. When the sterilization load (i.e., all of the materials inserted into the sterilizer chamber with the device) includes a large amount of paper with the device, it hinders the EtO getting to the device and generally means that more EtO is required for effective sterilization. Therefore, the FDA is encouraging device manufacturers to move to electronic materials where feasible and safe for device users. We are currently engaging with medical device industry members to make this change.

A second recommendation received at the advisory committee meeting is that the FDA could help mitigate medical device shortages and advance medical device sterilization by expediting approvals of certain changes that medical device manufacturers make to EtO sterilization methods, processes, and facilities. Before most sterile medical devices are on the market, the FDA reviews premarket submissions to determine whether the sterility information is adequate (i.e., in accordance with internationally agreed upon voluntary consensus standards that the FDA recognizes).

If a medical device manufacturer changes the method, process, or the facility identified in its original premarket approval (PMA) submission for sterilizing its devices, the manufacturer generally needs to submit a PMA supplement to the FDA for review and approval before they can make those changes. However, considering the recent sterilization facility closures and concerns about their impact on medical device availability, FDA recognizes the need to facilitate timely process and site changes that may reduce the amount of EtO used and minimize the impact of supply interruptions.

"We look forward to seeing what the selected applicants of the innovation challenge do next as well as the outcome of our EtO Pilot Program," said Shuren. "The FDA will continue in our steadfast commitment to develop solutions to avoid potential device shortages and encourage new, innovative ways to sterilize medical devices while reducing adverse impacts on the environment and on the public health."