By Sean Fenske, Editor-in-Chief

Changes in the regulatory landscape, innovation of medical devices and materials, and the need for advanced supply chain resiliency have led to a demand for a wider selection of sterilization modalities. Traditional methods have been unchanged for many years, but with the modernization of medical devices, materials, and novelty designs, the industry must now look outside those traditional methods to meet the needs of the industry.

Vaporized Hydrogen Peroxide (VH2O2) is a sterilization method that has been utilized for decades; however, the publication of ISO 22441:2022 and the FDA’s recent reclassification of vaporized H2O2 sterilization as an Established Category A method in 2024 have reignited interest in this method. One of the most appealing aspects of the use of this method is the wide range of material compatibility with vaporized H2O2, including the ability to sterilize electronics and other low-temperature-dependent devices and accessories.

With VH202 gaining prominence again as a viable sterilization option, a trio of experts from Nelson Labs, A Sotera Health company, have responded to a series of questions around this modality and what it could mean for medical device manufacturers. Helin Räägel, Ph.D., Principal Biocompatibility Expert; Bryce Telford, Senior Expert Consultant; and Lee Wence, Ph.D., Toxicologist, recently took time to speak with me on hydrogen peroxide’s use as a sterilization option.

Sean Fenske: From your perspective, why has there been so much discussion on medical device sterilization?

Dr. Helin Räägel: Alternative sterilization methods are a topic of high interest as the industry moves to making important health care options available globally. Resources for sterilization vary widely, while the need for medical care remains constant.

Bryce Telford: Exactly, Helin. Medical device sterilization is critical and necessary to ensure patient safety. The need for sterile products is only increasing. Additional and alternative sterilization methods are necessary to meet demands for safe and sterile products for patients.

Fenske: H202 sterilization is gaining more attention lately. How does this method sterilize?

Telford: H2O2 is a chemical sterilant. Vaporized H2O2 sterilizes through oxidation. It provides a sterilization solution for devices that are non-compatible via other means, such as heat or radiation-based sterilization.

Fenske: What has the FDA said about vaporized H202?

Dr. Räägel: VH2O2 has been around for some time; however, it was traditionally considered a less established method for sterilization. As a result, many manufacturers shied away from using it, thinking the regulatory pathway may be more scrutinized.

That changed earlier this year (January 2024) when the FDA came out with an update focused on a broader adoption of VH2O2 for medical device sterilization that highlighted and recognized the long history of safety and effectiveness of this modality. Most importantly, with their announcement came the revision of the FDA guidance on information required for submission of sterility for medical devices, which now listed vaporized H2O2 as an example of an Established Category A method of sterilization (alongside dry and moist heat, EO, and radiation).

The biggest impact of this reclassification (and I would say a strongly positive one) is for manufacturers who are considering switching to VH202. When switching from one Established Category A sterilization method to another, if it can be demonstrated that the change does not significantly affect the performance or biocompatibility of the device, a new 510(k) is not necessary, and documentation can cover the change assessment (per FDA guidance: Deciding When to Submit a 510(k) for a Change to an Existing Device).

For assessing the potential impact of switching to vaporized H2O2 for a specific device, the FDA is currently in the process of developing a tool that would highlight what type of data should be provided within that documentation to demonstrate the impact is not concerning. This tool is being developed in collaboration with industry experts (mainly from the great folks at Medtronic) and is based on scientific data generated on various materials when in contact with H202. The objective is to demonstrate that when a given material is being treated with vaporized H2O2, it does not change its chemical structure, molecular bonding, surface characteristics, etc. The shift to vaporized H2O2 becoming a Category A sterilant and the collaboration of the FDA with industry partners to make the transition as least burdensome as possible is an excellent positive example of the agency applying a genuine risk- and science-based approach to policies that affect us all.

Telford: In addition to the FDA’s recent reclassification of VH202 to an Established Category A sterilization process, as Helin explained, ISO 22441 (published in 2022) has been recognized by the FDA as a consensus standard (FR Recognition Number 14-586). This document is “Sterilization of health care products—Low temperature vaporized hydrogen peroxide—Requirements for the development, validation and routine control of a sterilization process for medical devices.”

Fenske: What are the considerations/concerns regarding packaging and vaporized H202?

Dr. Räägel: As with any medical device, the main concern with packaging is whether it has any potential to impact the finished product while stored. This pertains not just to sterility but also to the potential for particulate generation, any extractables that might settle on the device itself, etc. The same goes for assessing the concerns for VH202. Understanding how the packaging materials may potentially be impacted by exposure to VH202 treatment is key in defining whether there is any additional risk from the packaging to the device in the end.

Fenske: Are there biocompatibility issues or challenges when using vaporized H202?

Dr. Lee Wence: Compatibility of the device materials, as well as packaging materials, with VH202 should be considered so the performance or biocompatibility of the device is not affected by the sterilization method. For example, cellulose materials should be avoided.

Specific limits for residual VH202 on medical devices are not stated in ISO 22441:2022 (the standard Bryce mentioned). This standard states that the limits shall be based on a health-based risk assessment in accordance with ISO 10993-17, which outlines the toxicological risk assessment of medical device constituents.

What this means is manufacturers need to determine acceptable limits for vaporized H202 residuals for their devices based on the intended device use and patient populations. For example, a device that may be used in the breathing pathway for a neonate may have a much lower allowed limit for VH202 residuals than a device used on the skin of an adult. These limits should be determined through a toxicological risk assessment process, with specific considerations for the device use. Companies with many device types and different use cases may have a variety of limits for VH202 residuals for their products. If a device is used with sensitive populations, such as preterm neonates, it may be beneficial to ensure the sensitivity of the test method is appropriate for the safety limits set for the device.

Dr. Räägel: Just to expand on what Lee said, materials can behave differently when exposed to sterilizing gases, including VH202. While the process can use reasonable temperature ranges, which may protect them from potential degradation, the impact of the chemical itself on the material should be characterized. The VH202 acts as an oxidizer and can potentially react to certain chemical groups within the materials used, create radicals, induce cleavage of certain sites, impact the strength of polymers, etc. Therefore, understanding these aspects for the specific materials used in a given device is integral to defining whether there could be an impact on the biocompatibility profile of the finished device.

As mentioned previously, a useful tool that could help define the characteristics of materials that should be assessed is being developed by FDA in collaboration with Medtronic primarily. The goal of this collaboration is to guide these assessments as well as to collect data on how some widely used materials interact with VH202 to assist in the evaluation of the biocompatibility of the final finished device.

Fenske: What must device manufacturers keep in mind with regard to vaporized H202 that you don’t see brought up or mentioned very often?

Dr. Räägel: There is a long-standing perception in industry that VH202 does not or cannot penetrate packaging and device materials. It might be wise to step back and question some of these assumptions and possibly generate new data to challenge this idea. It might be useful to reimagine VH202 cycles and reveal how this option behaves in conditions similar to what we currently use for EO (e.g., use of vacuum, longer cycles, etc.) to see if it actually could produce equally effective penetration.

Telford: In addition, what jumps out to us is VH202 is not a like-for-like substitution. Itis not a direct replacement for other sterilization modalities and requires its own set of considerations. Currently, there are limited options for contract sterilization.

Fenske: Do you have any additional comments you’d like to share based on any of the topics we discussed or something you’d like to tell medical device manufacturers?

Telford: The industry doesn’t take residues as seriously as perhaps it should. Just ask Helin or our colleague Audrey Turley sometime about biocomp or residuals. Then again, that’s probably a whole other discussion or the subject of a different Q&A. Of course, folks are welcome to reach out to us directly about that issue or anything about vaporized H202.

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