May 19, 2022 Update: 510(k) Sterility Change Master File Pilot Program
As a part of the FDA’s ongoing effort to streamline certain changes to ethylene oxide (EtO) sterilization processes and facilities, the FDA is announcing a 510(k) Sterility Change Master File Pilot Program. This new pilot program is for sterilization changes to 510(k) cleared medical devices. The 510(k) Sterility Change Master File Pilot Program encourages new, innovative ways to sterilize medical devices that reduce the potential impact of EtO on the environment and on public health.
On this page:
- Why Is Ethylene Oxide Used to Sterilize Medical Devices?
- What Devices Are Sterilized with Ethylene Oxide?
- How Does the FDA Help Ensure that Medical Devices Sterilized with Ethylene Oxide Are Safe?
- EPA's Role in Ethylene Oxide Sterilization
- FDA's Actions to Advance Medical Device Sterilization
- Report Sterilization Site Changes to the FDA
- Report a Medical Device Supply Issue or Shortage
- Contact Us
- Ethylene Oxide Sterilization Facility Updates
- FDA Innovation Challenge 1: Identify New Sterilization Methods and Technologies
- FDA Innovation Challenge 2: Reduce Ethylene Oxide Emissions
Medical devices are sterilized in a variety of ways including using moist heat (steam), dry heat, radiation, ethylene oxide gas, vaporized hydrogen peroxide, and other sterilization methods (for example, chlorine dioxide gas, vaporized peracetic acid, and nitrogen dioxide). Ethylene oxide sterilization is an important sterilization method that manufacturers widely use to keep medical devices safe. Learn more about sterilization methods in the Submission and Review of Sterility Information in Premarket Notification (510(k)) Submissions for Devices Labeled as Sterile Guidance (PDF - 386kb).
For many medical devices, sterilization with ethylene oxide may be the only method that effectively sterilizes and does not damage the device during the sterilization process. Medical devices made from certain polymers (plastic or resin), metals, or glass, or that have multiple layers of packaging or hard-to-reach places (for example, catheters) are likely to be sterilized with ethylene oxide.
- Read more: Statement on concerns with medical device availability due to certain sterilization facility closures (October 25, 2019)
- Read more: Preventing Medical Device Shortages by Ensuring Safe and Effective Sterilization in Manufacturing (July 15, 2019)
Literature shows that about fifty percent1,2,3 of all sterile medical devices in the U.S. are sterilized with ethylene oxide. The types of devices that are sterilized with ethylene oxide range 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).
Before most sterile medical devices are on the market, the FDA reviews premarket submissions to determine if the sterility information (for example, the method the manufacturer is choosing to sterilize their device and validation activities used to show that the device can be effectively sterilized) is in accordance with internationally agreed upon voluntary consensus standards that the FDA recognizes. An important element of our regulatory framework is a robust standards program. The FDA encourages medical device sponsors to use FDA-recognized voluntary consensus standards in their submissions, as conformity to relevant standards streamlines regulatory review and fosters quality. Learn more about the FDA's Recognized Standards Program.
For ethylene oxide sterilization, two voluntary consensus standards (ANSI AAMI ISO 11135:2014 and ANSI AAMI ISO 10993-7:2008(R)2012) describe how to develop, validate, and control ethylene oxide sterilization processes for medical devices and the acceptable levels of residual ethylene oxide and ethylene chlorohydrin left on a device after it has undergone ethylene oxide sterilization. These standards help ensure levels of ethylene oxide on medical devices are within safe limits since long-term and occupational exposure to ethylene oxide has been linked to cancer. Learn more about the risks of ethylene oxide on the National Institutes of Health web page on ethylene oxide.
If a medical device manufacturer changes the method, process, or the facility identified in its original PMA submission for sterilizing its devices, the manufacturer generally needs to submit a PMA supplement so that the agency can review these changes and determine if they also meet internationally agreed-upon voluntary standards that the FDA recognizes. For manufacturers that are 510(k) holders, sterilization method, process or site modifications can be assessed with the FDA guidance document: "Deciding When to Submit a 510(k) for a Change to an Existing Device" for determination on whether the sterilization modifications would trigger the need for resubmission.
The FDA also inspects industrial facilities that sterilize medical devices and medical device manufacturing facilities to make sure that they have validated sterilization processes that meet FDA-recognized standards.
State health departments inspect health care facilities that use ethylene oxide to sterilize medical devices. Learn more about guidelines for sterilization in health care facilities on the Centers for Disease Control and Prevention web page.
The US Environmental Protection Agency (EPA) reviews and enforces the Clean Air Act regulations for sterilization facilities that emit ethylene oxide to ensure that they protect the public from significant risk. Learn more about the EPA's Regulations for Ethylene Oxide on EPA's website.
The FDA is actively working with sterilization experts, medical device manufacturers, and other government agencies to advance innovative ways to sterilize medical devices with lower levels of currently used agents, and employ new agents or alternatives, while maintaining device safety and effectiveness.
- Read more: Statement from FDA Commissioner Scott Gottlieb, M.D., on steps the Agency is taking to prevent potential medical device shortages and ensure safe and effective sterilization amid shutdown of a large contract sterilization facility (March 26, 2019)
Healthcare Infection Control Practices Advisory Committee (HICPAC) Meetings
In May and November 2019, the FDA engaged the infection control community at the Healthcare Infection Control Practices Advisory Committee (HICPAC) meeting to update the public on the FDA's work and engagement with industry on sterilization modalities with devices that are normally sterilized using ethylene oxide.
FDA Innovation Challenges
On July 15, 2019, the FDA announced two public innovation challenges to encourage development of novel sterilization methods, which could include new devices or new modalities that are safe and effective for sterilizing medical devices:
- Challenge 1: Identify New Sterilization Methods and Technologies: The goal of this challenge is to encourage the development of new approaches to device sterilization methods or technologies for medical devices that do not rely on ethylene oxide.
- Challenge 2: Reduce Ethylene Oxide Emissions: The goal of this challenge is to develop strategies or technologies to reduce emissions to as close to zero as possible from the ethylene oxide sterilization process.
On November 25, 2019, the FDA announced that 46 applications were received and 12 participants selected for the challenges. Refer to each challenge page for details on the selected participants and next steps.
General Hospital and Personal Use Devices Panel of the Medical Devices Advisory Committee
On November 6-7, 2019, the FDA held a meeting of the General Hospital and Personal Use Devices Panel of the Medical Devices Advisory Committee meeting to discuss how best to advance innovations in medical device sterilization. Meeting materials are available on the Advisory Committee Meeting Announcement page.
One recommendation from the advisory committee meeting is for device manufacturers to begin, as soon as possible, reducing the amount of paper (such as the labeling and instructions for use manuals) that is included in the sterile device package. An ethylene oxide sterilized medical device must be sealed in a carefully designed gas-permeable package that enables the ethylene oxide gas to enter. When the sterilization load (encompassing all the materials inserted into the sterilizer chamber with the device) includes a large amount of paper with the device, it hinders the ethylene oxide getting to the device and generally means that more ethylene oxide is required. Because of this, the FDA is encouraging device manufacturers to move to electronic materials where feasible and safe for device users. We are committed to working with industry to make this change.
The FDA developed the Sterilization Master File Pilot Programs to help ensure patients have access to safe medical devices and encourage new, innovative ways to sterilize medical devices that reduce the potential impact of EtO on the environment and on public health.
510(k) Holders and Contract Sterilizers
The FDA announced, in May 2022, a Sterility Change Master File Pilot Program for sterilization changes to 510(k) cleared medical devices for sterilization providers with an Established Category B or Novel Sterilization Method, as described in the FDA guidance Submission and Review of Sterility Information in Premarket Notification (510(k)) Submissions for Devices Labeled as Sterile.
The 510(k) Sterility Change Master File Pilot Program is open to all current 510(k) holders and is intended to help with changes to a cleared medical device’s sterilization method from a fixed chamber EtO sterilization cycle to the sterilization method described in the Master File. Under certain conditions, medical device manufacturers can reference the Master File rather than submitting a new 510(k) for the sterilization change.
The pilot program is not limited to the sterilization Innovation Challenge participants (Identify New Sterilization Methods and Technologies or Reduce Ethylene Oxide Emissions). However, the FDA encourages Innovation Challenge participants to consider participation in the pilot program, because they may benefit from it as a part of their Innovation Challenge interactions. The pilot program may be an impactful endpoint for Innovation Challenge participants with Established Category B or Novel Sterilization Methods.
If you have questions about the new 510(k) Sterility Change Master File Pilot Program, email firstname.lastname@example.org.
Premarket Approval (PMA) Holders
On November 25, 2019, the FDA announced its EtO Sterilization Master File Pilot Program for PMA holders. This voluntary program is intended to allow companies that sterilize single-use medical devices using fixed chamber EtO to submit a Master File when making certain changes between sterilization processes and facilities that reduces the amount of EtO concentrations on medical devices.
Under this voluntary program, PMA holders of Class III medical devices may reference the Master File submitted by their sterilization provider in a post approval report rather than submitting a PMA supplement.
The EtO Sterilization Master File Pilot Program for PMA holders includes the following participants:
|Boston Scientific||March 18, 2020|
|Becton, Dickinson & Company (BD)||September 11, 2020|
|Steris Corporation||October 25, 2021|
|Oscor, Inc.||December 17, 2021|
|Medtronic, Inc.||February 17, 2022|
If your products are affected by the stop of operations at a sterilization facility and you are planning to use an alternative facility to sterilize your products:
- Premarket Approval (PMA) Holders: You should submit a 180-day site change supplement. However, the FDA intends to review such PMA supplements within 30 days. The FDA recently issued the final guidance, Manufacturing Site Change Supplements: Content and Submission (PDF), that PMA holders can refer to for more information about site change supplements. If you have questions about your PMA device or need help with submitting a site change supplement, contact CDRHPremarketProgramOperations@fda.hhs.gov.
- 510(k) Holders: Submitting a new 510(k) is typically not required for this type of change. You should document qualification activities supporting this change in your internal files. However, the FDA recommends that affected 510(k) holders refer to the FDA's guidance, Deciding When to Submit a 510(k) for a Change to an Existing Device: Guidance for Industry and Food and Drug Administration Staff (PDF - 1.04MB) when determining if a new 510(k) is required.
Supply issues can lead to shortages of medical devices—and can pose a threat to public health by delaying or disrupting critical care for patients. Mitigating product supply issues and working to prevent patient harm from device shortages are important to the FDA.
Planning for and preventing device supply shortages is an important responsibility. The FDA can help anticipate, prevent, or mitigate future shortages by working with device manufacturers that voluntarily provide us with information on potential product supply issues. Learn more about how to report a medical product shortage or supply issue.
To report a medical device shortage or supply issue, email Deviceshortages@fda.hhs.gov or phone 1-800-638-2041 or 301-796-7100.
1 (2017, August 31). A Comparison of Gamma, E-beam, X-ray and Ethylene Oxide Technologies for the Industrial Sterilization of Medical Devices and Healthcare Products. Retrieved March 13, 2019, from http://iiaglobal.com/wp-content/uploads/2018/01/White-Paper-Comparison-Gamma-Eb-Xray-and-EO-for-Sterilisation.pdf
2 Blass, C. (2001). The Role of Poly(vinyl Chloride) in Healthcare. Shawbury, UK: Rapra Technology Limited. Retrieve from https://books.google.com/books?id=vNp3bFNOU_AC&pg=PA47&lpg=PA47&dq=Ethylene oxide sterilization,medical devices, market share&source=bl&ots=oQzply-FBq&sig=ACfU3U0bKGYVubW_3UEj0Kq7G3CpF6SbuQ&hl=en&sa=X&ved=
2ahUKEwiKso3BnuzgAhWFk1kKHeiIC8Q4KBDoATAHegQIARAB#v=onepage&q=Ethylene oxide sterilization,
medical devices, market share&f=false
3 Regulatory Review of the Occupational Safety and Health Administration's Ethylene Oxide Standard, 29 C.F.R § (2005) 1910.1047 https://www.osha.gov/dea/lookback/ethylene_oxide_lookback.pdf.