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FDA has escalated the conversation about medical device ethylene oxide (EtO) sterilization over the past month, holding a public meeting, launching a pilot program and announcing companies that were chosen to participate in FDA’s innovation challenge.
FDA’s focus on EtO sterilization comes after facility shutdowns earlier this year were prompted by the presence of higher-than-acceptable levels of EtO in the air around the facilities. These closures led FDA to monitor medical device supply chain shortages. Currently, approximately 50% of medical devices (more than 20 billion in number) are sterilized using EtO, with no readily available, viable alternative processes or facilities.
The agency’s recent actions provide an indication for orthopedic device manufacturers that FDA is serious about its commitment to decrease the use of EtO, and highlight what could be a primary focus for regulators and industry in 2020.
We’ve recapped three announcements from November to keep you updated on the sterilization subject.
FDA Announces Sterilization Changes after Committee Meeting
During the November 6-7, 2019 Public Advisory Committee Meeting, the group heard from representatives from FDA, the U.S. Environmental Protection Agency, the Centers for Disease Control and Prevention’s Agency for Toxic Substance and Disease Registry, the Medicines and Healthcare Products Regulatory Agency of the United Kingdom, industry and hospitals.
The meeting hosted talks on EtO emission regulations; the safety, sterility and effectiveness of all medical devices; and ways to address medical device shortages due to reduced supply of certain EtO sterilized medical devices.
The advisory panel agreed that reduction of EtO use is a priority, and that all methods to do so should be explored. One recommendation that arose from the meeting was to reduce the amount of labeling, instructions and manual paper that are included on sterile device packages. Paper in the sterilization load hinders EtO from getting to a device, requiring more of the gas to be used for effective sterilization. FDA is now working with and encouraging device manufacturers to use electronic materials instead of paper, when possible and safe for device users.
A second recommendation from the advisory committee meeting is for FDA to expedite approval of changes that medical device manufacturers make to EtO sterilization methods, processes and facilities. FDA noted that it will focus on devices with premarket approval (PMA) submissions through a pilot program to implement this recommendation.
FDA Launches Pilot Program For Expedited Approvals
To kickstart the effort to expedite approvals of certain changes to EtO sterilization processes and facilities, FDA announced the Ethylene Oxide Sterilization Master File Pilot Program (EtO Pilot Program). The agency seeks participation in this voluntary program, which has two components: one in connection with sterilization facilities, and the other for device manufacturers.
The pilot program allows manufacturers of Class III devices to reference a Master File submitted by up to nine sterilization providers instead of submitting a PMA supplement application when manufacturers change their sterilization site or process. The program intends to streamline review and feedback to support device companies’ decisions to change their sterilization sites and processes. FDA believes that the program should result in a reduction by sterilization facilities in use of EtO months sooner than they otherwise would.
FDA’s Innovation Challenges Pinpoint New Sterilization Methods
FDA announced that out of 46 submissions, it selected 12 applicants, including orthopedic device manufacturers and well-known sterilization companies, to move forward in its innovation challenge. FDA initiated the innovation challenges earlier this year to encourage novel ideas for sterilization processes that would reduce reliance on EtO.
According to FDA, the goal of Challenge 1 was to identify safe and effective sterilization methods or technologies for medical devices that do not rely on EtO and that meet these criteria:
- Compatibility: The method or technology should be compatible with a large cross-section of materials used to manufacture or fabricate medical devices, as well as packaging materials or sterile barriers. The materials, devices and barriers of particular interest are those that are compatible with EtO sterilization.
- Scalability and High Throughput: The method or technology should have the potential to be scalable and allow for the effective sterilization of large volumes of devices.
The following submissions were selected, and provide industry with thoughts on future sterilization method adoption.
- NovaSterilis: Supercritical Carbon Dioxide Sterilization
This method employs carbon dioxide in a fluid state when both its temperature and pressure are equal to or greater than the critical point, with properties of both gas and liquid. It’s nontoxic, has a low environmental impact, and is a powerful solvent with sterilization efficacy indicating one contaminated item in one million. - Noxilizer, Inc.: Nitrogen Dioxide Sterilization (NO₂)
(NO₂ is a surface sterilant. Noxilizer uses sterilant concentrations that are well below the vapor pressure of NO₂, so the gas won’t condense on medical devices. Therefore, NO₂ gas can sterilize medical devices with complex geometries. - STERIS: Accelerator-Based Radiation Sterilization
The use of accelerator technology in radiation sterilization of medical devices shows increased performance over other radiation sterilization methods, such as x-ray. - STERIS: Vaporized Hydrogen Peroxide Sterilization
Hydrogen peroxide (H₂O₂) sterilization is a low-temperature sterilization process that involves H₂O₂ vapor that typically takes less time than alternative forms of sterilization, including EtO sterilization. - TSO3 (acquired by Stryker): Vaporized Hydrogen Peroxide-Ozone Sterilization
Vaporized hydrogen peroxide-ozone sterilization is a low-temperature sterilization method that utilizes the dual-sterilants of vaporized hydrogen peroxide (H₂O₂) and ozone (O₃) to achieve terminal sterilization of heat- and moisture-sensitive medical devices.
According to FDA, the goal of Challenge 2 was to develop strategies or technologies to reduce emissions to as close to zero as possible from the EtO sterilization process. Strategies could entail adjustments to current sterilization processes or workflow, such as changes in the supply chain, transportation of medical devices, or procedures in the sterilization site. Strategies may also include alterations to EtO process waste to reduce emissions. FDA announced that it will work with the following companies to develop new strategies and technologies: Abbott, Anderson Scientific, Becton Dickinson and Company, DMB Apparatebau, Medtronic, Sterigenics U.S., STERIS and Taiwan Advanced Sterilization Technologies.
FDA will work directly with the companies selected from the innovation challenges during the development and review process of the technologies for sterilization. The goals of the FDA/industry collaboration include:
- Create a mutual understanding of the target technology profile, including the important risks and benefits.
- Discuss development of the technology or potential regulatory pathways going forward.
More announcements are expected as FDA rolls out these programs and further follow up is decided based on the November public meeting. Until then, these recent announcements give orthopedic device manufacturers an understanding of FDA’s focus on EtO in the coming months and provide background on how and why manufacturers should consider adopting new sterilization processes.
