Vaporized Hydrogen Peroxide Sterilization Gets FDA Established Category A Status

Ethylene oxide for medical device sterilization remains a controversial topic between regulatory bodies, the environmental protection agency (EPA), and the medtech industry, even more so in 2023 with new rules pertaining to the chemical becoming more likely. But, after a quiet second half of 2023 since the close of the comment period on EPA’s proposed rule updates, FDA has relit the fire with an announcement reporting it now considers vaporized hydrogen peroxide (VHP) as an established method of medical device sterilization and updating it to be an Established Category A method of sterilization.

The agency said that the update “will facilitate broader adoption of VHP as a sterilization method for the medical device industry, [and it] is part of the agency’s multi-pronged approach to reducing the use of [EtO] where possible and further supports the agency’s efforts to advance medical device supply chain resiliency.”

Background on the EtO controversy

EtO sterilization for medical devices has been controversial for years because of its ecological effects like pollution and its potential of causing cancer and other ailments in humans. However, the conversation did see a new spike in 2018 when it was reported that Sterigenics Willowbrook facility would be closed after EPA detected high concentrations of EtO in the air near the building. The discovery eventually resulted in the state issuing a seal order that closed the plant in 2019 and a wave of lawsuits by people who developed cancer after living near the site, one of what is colloquially known as a “cancer alley”.

While the chemical is dangerous, it is also seen industry wide as integral to medical device sterilization. Roughly 50 million devices a day in the United States are sterilized using EtO because its properties make it especially good at killing viruses, bacteria, and human cells by reacting with proteins, DNA, and other essential cellular components. In fact, FDA and EPA report it as necessary to protect public health as “the chemical is the only sterilization method available for many medical devices because other options can cause damage to product components,” according to a pervious article by MD+DI.

Since the Sterigenics shutdown, EPA has cracked down on EtO exposure from sterilization. Just last year, the agency proposed tougher standards on pollution from EtO and other toxic chemicals used for sterilizing medical equipment. The rules took shape in two proposals that were open for comment until June 12, 2023: The National Emission Standards for Hazardous Air Pollutants (NESHAP, EPA-HQ-OAR-2019-0178-0154) and Pesticide Registration Review: Proposed Interim Decision and Draft Risk Assessment Addendum for Ethylene Oxide (FIFRA, EPA-HQ-OPP-2013-0244-0044).

The controversy of proposing such far-reaching standards, according to multiple industry experts, poses the threat of potential negative impacts on patient care, supply, and suitability of sterilization.

Industry reactions to EPA’s proposed rules included statements from Advanced Medical Technology Association (AdvaMed), the American Association of Orthopaedic Surgeons (AAOS), and the Medical Device Manufacturers Association (MDMA).

Submitting comments to the two proposals, AdvaMed urged continued cooperation between industry and the agency as regulations move forward but highlighted the potential for massive interruption in patient care and access due to the changes in sterilization practices resulting in a reduction of capacity for life-saving devices.

“The medtech industry and EPA must continue working together to improve these two proposals because as written, we could see significant shortfalls and a risk to patient access resulting from a device sterilization capacity reduction of 30% to 50% nationwide,” said Scott Whitaker, AdvaMed president and CEO, at the time.

AAOS echoed these concerns, noting that while it supports the notion that no single sterilization method is optimal for all applications, proposed processes to reduce EtO could “lead to delays in the completion of sterilization and turnover of surgical devices,” said Kevin J. Bozic, MD, MBA, FAAOS, AAOS president.

In an effort to uncover alternatives for medical device sterilization, FDA also opened multiple master file programs to help remove regulatory hurdles when changing sterilization methods, including its Radiation Sterilization Master File Pilot Program, 510(k) EtO Sterility Change Master File Program, and PMA EtO Sterilization Master File Program.

Read More: Andersen Sterilizers Awarded First 510(k) Master File for EtO Sterility Change

What is VHP and how does it work?

One of those potential alternatives is VHP. The recent news updating the sterilization method to its new status underscores the agency’s goal of moving away from EtO sterilization where possible, as an Established Category A sterilization method has a long history of safe and effective use on medical devices, putting VHP on the same level as EtO and radiation.

VHP is a deep vacuum, low-temperature vapor process traditionally used to sterilize reusable medical devices in patient care facilities, according to Steris. The sterilization method is compatible with a wide range of polymeric materials, making it also effective for single-use products like implants and devices with electronics, pharmaceutical containers, parenteral drug delivery systems such as pre-filled syringes, combination delivery devices, single-packaged assembled complex devices, complete assemblies or devices with loose components, and temperature sensitive devices.

Of note, cellulose-based materials and highly absorbent materials are not compatible with VHP. Additionally, the method is for surface sterilization and has limited penetration capabilities, according to Steris. Unlike EtO, hydrogen peroxide breaks down to water and oxygen, and aeration time is greatly reduced. This means that any concern for toxicity is very low risk, according to a study in Implantable Sensor Systems for Medical Applications.

The VHP sterilization process happens in three phases: the conditioning, sterilant exposure, and post-conditioning, all performed within a single chamber. “The process is carried out under deep vacuum conditions of typically 1-10 millibar (0.03-0.3 inches Hg), with a temperature range of typically 28-40°C (82-104°F),” according to Steris. “Total cycle time (from door closed to door open) is typically eight hours or less. However, cycle time may vary depending on product composition, packaging materials, temperature, and load size and configuration.”