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Navigating the 510(k) EO Sterility Change Master File Program

In 2019, the U.S. Food and Drug Administration (FDA) became aware of sterilization facilities shutting down due to Ethylene Oxide (EO) emission concerns, resulting in some medical device shortages. In order to keep medical devices on the market and to improve sterilization rates, the FDA took a number of actions regarding this situation.

  • The first action was to investigate how EO emissions could be reduced and/or identify new sterilization methods and technologies (see FDA Innovation Challenges*) that could be utilized by the medical device industry. The FDA then held a General Hospital and Personal Use Devices Panel meeting to discuss the best way to advance innovations in sterilization.
  • The second action was to institute the Master File Pilot Program for devices subject to Premarket Approval (PMA). For PMA devices, sterilization change(s) to reduce EO emissions were previously subject to a 180-day review period. By referencing an EO Sterilization Master File, a 30-day change notice could be submitted instead, therefore reducing the timeline for approval.

*FDA Innovation Challenges
The FDA Innovation Challenges made clear to MedTech manufacturers two areas to reduce the impact or need for EO sterilization in the medical device industry:

1. Identify new sterilization methods and technologies

Most manufacturers that use EO sterilization do so because it is either the most cost-effective method of sterilization, or because alternative methods of sterilization are not viable or compatible with the device’s materials/components. Therefore, the FDA has suggested that new, viable sterilization alternatives should be developed.

2. Identify ways to reduce EO emissions

As an example, the FDA recommends that manufacturers reduce materials within medical device packaging, such as paper inserts and Instructions for Use (IFUs), and switch to electronic information formats for eligible devices. This reduction in load density would ultimately result in a lower concentration of EO to deliver sterile doses. Additionally, sterilization facilities should continue to identify new technologies that can further reduce EO residual emissions and bring emissions down to as close to zero (0) as possible.

Through reductions in EO concentrations during sterilization cycles and development of innovative technologies, the hope is that the medical device industry will decrease EO residual emissions and environmental impacts.

FDA Master Files
In its most recent action (May 20, 2022), the FDA announced the 510(k) Sterility Change Master File Pilot Program [510(k) Sterility Pilot Program] in the Federal Register.

The FDA has a number of Master File programs for various FDA divisions (Biologics, Drug, Food and Veterinary Master Files) with the Master Access File (MAF) being used for Center for Devices and Radiological Health (CDRH) devices. Sometimes a party (Party A) submitting an IDE, PMA, 510(k)—or other device submission type—may use another party’s (Party B) proprietary component. This includes information regarding Party B’s device, materials, methods, study data, etc. and may also include data on manufacturing processes and may be used for a portion of the device submission data.

Most commonly, an MAF contains trade secret and/or confidential information. Due to these circumstances, Party B provides a letter of authorization to Party A to reference the MAF in their own FDA submission, which  allows the FDA to review the MAF when reviewing Party A’s submission in confidentiality (as Party A doesn’t have access to this information).

However, the Master File for the 510(k) Sterility Pilot Program works differently than the above outlined process. In this case, a sterilization provider changes their sterilization method from an EO method to 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). For a 510(k) holder using this sterilization provider, the change would likely mean submitting a new 510(k). Under the Pilot Program, the sterilization provider compiles and submits a Master File to the FDA and, in the event the MAF is accepted and the 510(k) holder is granted a right of reference to the MAF, submission of a new 510(k) for the sterilization change may not be required.

The 510(k) holder has full access to the Master File so they may reference it to complete device-specific analysis to ensure there is no effect to safety or effectiveness. If there is no effect, the 510(k) holder can reference the Master File internally (e.g. in a Letter to File) addressing why the decision was made that a new 510(k) does not need to be submitted.

Similarly, the FDA announced on June 7, 2022 that a similar Master File program for PMA Holders using Radiation Sterilization for their device(s) is being considered for launch. This would allow for changes to alternative sterilization methods (including changing radiation sources) by referencing a Master File creating a least burdensome approach.  More information on this announcement can be found on the FDA’s website for Sterilization of Medical Devices.

How can NAMSA Help?
Navigating FDA regulatory requirements for sterilization can be overwhelming for any medical device manufacturer—not to mention very cost-intensive. That’s why having the right partner, at the right time, can be invaluable in achieving regulatory requirements, market success and accelerated timelines.

NAMSA is here to help. We are the industry leader in driving successful regulatory strategies for medical device manufacturers.  NAMSA’s regulatory team can assist in developing or reviewing EO Sterilization Master Files. Our regulatory team can also assist in determining if this Master File strategy is appropriate for your team. NAMSA has a strong relationship with the FDA and can provide communication and logistic resources.

Changes to sterilization will require manufacturers to assess design changes, update risk management, and identify regulatory impact.  NAMSA has the services to assist in the assessment and documentation of these updates and changes.

Drawing from its 55+ year history of offering reliable biocompatibility, microbiological, and analytical chemistry solutions to clients, NAMSA provides an extensive range of testing services to support the technical requirements within the EO Sterilization Master Files. Our team can help with technical development strategies as well as the execution of testing needs.

If you are interested in speaking with us about FDA-related activities or other global regulatory strategies, please Contact Us here, or learn more about our  Regulatory Experts.

Marcella Martin

Marcella Martin, MBA, RAC is a Senior Regulatory Consultant at NAMSA with over ten years’ experience working in regulatory affairs in the medical device and pharmaceutical industries. She has authored and managed a variety of submissions to FDA, Health Canada and notified bodies. These have included pre-submission, IDE, IND, technical file, master file, device license application, ANDA, Annual Report and vigilance reporting. She has completed regulatory assessments and regulatory strategies for products in development and for proposed changes to products already on the market. Marcella holds a Masters of Business Administration (MBA) degree from Colorado State University, Fort Collins and Regulatory Affairs Certification (RAC) from the Regulatory Affairs Professionals Society (RAPS).

Rich Granquist

Richard M. Granquist

In 2014, Rich joined NAMSA as a Quality Systems Consultant and has now been with the company for eight years. Over his 16 years in the industry, he has participated in numerous AAMI ISO standards committees and currently sits on the committees for ISO 14971, ISO 13485 and ISO 15223. Rich’s medical device industry experience also includes extensive time working with both start-up manufacturers and larger, global device manufacturers. He specializes in quality system development and risk management. Rich started in the medical device industry as a Microbiologist focusing on aseptic technique and terminal sterilization at Cook Medical. During his 8-year career at Cook, he expanded his responsibilities to include coordination of preclinical testing, packaging validation, biocompatibility testing and reprocessing instruction validation for urology and women’s health devices.