In a new announcement, FDA states that it is “considering” a new master file pilot program for certain approved devices that would potentially allow manufacturers to change their sterilization approaches more easily. Currently, this pilot is limited to manufacturing changes that limit the use of ethylene oxide (EtO).
Medical device sterilization and the CDRH’s Master File Pilot Program
- Ethylene Oxide (EtO) is commonly used to sterilize medical devices. According to research cited by the FDA, about half of all sterile medical devices in the U.S. are sterilized with EtO, ranging “from devices used in general health care practices (for example, wound dressings) to more specialized devices used to treat specific areas of the body (for example, stents).”
- However, there are some concerns with the widespread use of EtO for device sterilization. First, the Environmental Protection Agency (EPA) classifies EtO as a hazardous air pollutant, and is “taking steps to address emissions of ethylene oxide from some types of industrial facilities around the country.” These include a final rule requiring additional controls on equipment and processes that emit EtO, and additional reviews of standing regulations. In 2020, the U.S. Department of Health and Human Services (HHS) put out a report on EtO toxicology that identified sterilization companies and companies “associated with medical devices” as top users of EtO.
- The device industry is highly reliant on EtO for sterilization, which means that any shortages or disruptions in the supply chain of this single compound can have catastrophic implications for the industry at large, making it a key vulnerability in the overall device supply chain. As standards for allowable EtO emissions are reduced, device manufacturers and sterilization plants can face challenges ensuring that they both meet the emission standards and that their products are available for patients.
- The agency is looking for ways to reduce EtO reliance to help shore up the supply chain’s resiliency. While the FDA acknowledges that “sterilization with ethylene oxide may be the only method that effectively sterilizes and does not damage the device during the sterilization process,” it is also actively looking for alternative methods – or those that reduce reliance on EtO. The EPA’s concerns about emissions have led to uncertainty for sterilization facilities, which in some cases have even closed. In 2019, the FDA put out a statement indicating that the agency was aware of these issues and outlining steps to mitigate supply concerns if sterilization processes were disrupted. The agency held an advisory committee meeting on the subject in 2019, and launched two associated innovation challenges – one to identify new modalities for sterilization, and another that focused on reducing emissions when using EtO sterilization.
- One option: Make it easier for manufacturers to voluntarily move away from EtO and reduce emissions. At the 2019 advisory committee meeting, panelists urged the FDA to consider streamlining regulatory processes for device manufacturers who voluntarily seek to reduce their EtO emissions. The panel noted that this could facilitate and incentivize adoption of new methods that could mitigate EtO emission levels, even while there were no viable alternatives to shift away from EtO completely. The panel specifically recommended allowing for fewer pieces of paper (e.g., instructions for use manuals) to be included within the sterile package, as it is likely not necessary for the paper to be sterile and increases the amount of EtO needed. Further, it also recommended that the agency expedite and streamline processes for regulatory sign off on manufacturing changes related to EtO processes and facilities.
- The FDA’s EtO Sterilization Master File Pilot Program was launched in late 2019. The pilot, available to a limited number of Pre-Market Approval (PMA) holders, allows a streamlined process for implementing manufacturing changes. Under this program, participants that conduct sterilization of single-use devices using fixed chamber EtO could submit a Master File when making certain changes that would reduce the total amount of EtO or when changing the location of their sterilization facility – a manufacturing process change that typically requires a PMA supplement. This effectively reduces the regulatory burden for manufacturers looking to reduce their EtO use, with participating manufacturers able to reference the Master File from their sterilization provider in a post-approval report rather than submitting a PMA supplement for the change. As of 2022, there are five participants (Boston Scientific, BD, Steris, Oscor and Medtronic) in the PMA version of the pilot.
- The agency is now “considering a radiation sterilization change master file pilot program.” According to a bulletin sent out by CDRH, the agency is considering expanding the master file pilot program to PMA holders “whose devices are sterilized using radiation, including gamma radiation.”
- While details on the pilot are scarce, the agency states that the program would be intended to “help medical device manufacturers advance alternative ways to sterilize their approved medical devices, including changing radiation sources, in a least burdensome regulatory approach.” That said, it’s likely that the types of changes that a pilot participating PMA holder could make without a supplement would align with those under the EtO sterilization pilot. However, it’s not yet clear when – or if – the agency may move forward with this proposal.
- What’s next? The announcement comes as the FDA is focusing heavily on medical device supply chain resiliency – in fact, the announcement that they are “considering” such a pilot came just hours in advance of the kickoff of a three-day meeting on the subject. If adopted, the pilot could provide some cushion for manufacturers who are facing challenges with their current sterilization practices and reduce regulatory barriers to finding alternative solutions. The EtO version of the master file pilot program is considered a success, with the agency looking to build out a version for 510(k) cleared products. AgencyIQ will keep an eye out for any further information, including calls for participation in this potential pilot.
To contact the author of this item, please email Laura DiAngelo.
To contact the editor of this item, please email Alexander Gaffney