Impact of Changing Medical Device Sterilization Methods

Modifying sterilization modalities for medical devices is a complex endeavor, requiring careful evaluation of material compatibility, technological accessibility, and long-term availability. To help medical device manufacturers (MDMs) prepare for these changes, Sterigenics, a Sotera Health Company, recently hosted a webinar, Navigating the Decision Flow: Changing Sterilization Modalities for Medical Devices. It featured three sterilization experts: Aaron DeMent, VP, sterilization technologies at Sterigenics; Thor Rollins, VP global market leader at Nelson Labs; and Jordan Elder, director, regulatory affairs at Regulatory Compliance Associates (RCA).

To kick off the webinar, Elder outlined the two categories of sterilization methods recognized by the Food and Drug Administration (FDA): established and novel. Established modalities are broken into two categories, the first of which includes methods that have longstanding histories of safe and effective use (dry heat, moist heat, ethylene oxide, gamma or electron beam, and vaporized hydrogen peroxide). The second category includes established methods that have no FDA-recognized consensus standards, but published information on the development, validation, and routine control is available (nitrogen dioxide and chlorine dioxide).

Novel methods — newly developed methods for which there is little or no published information, and no history of FDA evaluation — use chemicals that have not been previously cleared or approved by the agency (microwave radiation, sound waves, UV light).

If you can, keep it simple From a business perspective, DeMent recommends considering the simplest modality first, such as dry or moist heat, before moving to more complex options. Most of today’s devices are complex, which means they may not accept heat sterilization. In these cases, radiation may be a good methodology.

For products that cannot withstand radiation, manufacturers may want to consider some of the newer chemical modalities gaining strength in the industry, such as chlorine dioxide and hydrogen peroxide. Finally, EO is a “bullet-proof” sterilization method, although it comes with concerns about residuals.

When choosing the right technology for medical devices, manufacturers need to consider the following questions:

Is the technology readily available for use?

Is it in the right geography?

Is there a contingency if the technology doesn’t work?

What are the product limitations?

Trust the process Manufacturers should consider whether their sterilization process is going to impact their medical device technology in terms of mechanical or electrical function. They will also need to ensure their technology of choice isn’t detrimental to the product during shelf life.

According to DeMent, process time is important — from the time of manufacture to distribution. Given the cost of sterilization equipment, contract providers will want to use it as much as possible, ideally on a 24/7 basis. This can lead to production queues, and processes that conceivably can be delivered in hours may take days. Therefore, DeMent advises MDMs to take agreed-upon turn times into account when planning for product deliveries from the contract sterilizer.

Ultimately, responsible parties will need to present their business case to management. DeMent encourages them to come up with a plan and be honest and accurate regarding its critical points. “There’s a lot of money, and your personal credibility is at stake as you make these decisions, so think through that,” he advises.

Screening test plans Once MDMs decide to potentially pursue other sterilization modalities, they will need to evaluate whether the device and packaging are compatible with the parameters of that modality. They may wish to evaluate multiple modalities to determine the best option. Rollins walks through three common modalities and details some of the potential impacts on materials from a biocompatibility and packaging standpoint. These include physical impacts (strength, wear), chemical impacts (leachable profile), and surface residuals.

Fourier Transform Infrared Spectroscopy (FTIR) is a simple chemical test that compares polymer bonds and could be useful when changing modalities from EO to gamma or vice versa. Rollins clarifies that FTIR provides a chemical footprint; however, it does not provide a leachable evaluation.

Depending on the material makeup of the device, manufacturers may be able to conduct a paper risk assessment with limited testing. Rollins points out that some materials actually get better with radiation, which is why paper risk assessments are important initially. “Don’t think radiation is going to cause your materials to be less biocompatible,” he says. “It is potentially the opposite of that.”

Rollins relates that cytotoxicity is the most sensitive biocompatibility test available — and one of the cheapest and quickest. It’s a good screening test when changing modality to see if there are any potential leachables that weren’t there before.

For an extractable profile, compounds that come off a device under worst-case conditions are typically extracted using three common solvents: polar (water), mid-polar (ethanol), and non-polar (hexane). Once compounds are extracted, they’re evaluated for safety using a toxicity assessment. According to Rollins, this is the only way to evaluate your leachable profile and its impact on your device of changing modality.

Process definition DeMent explains that process definition is different for radiation and gas technologies. Gas sterilization is not typically bioburden-based. The process definition exercise allows for the identification of the appropriate process challenge device(s) (PCD) of a defined resistance equivalent to or greater than the actual product bioburden. A bioburden-based approach is possible but requires tight controls over bioburden levels.DeMent advises using a PCD that is just the right resistance for the product and not overly resistant, which will result in an appropriate cycle design and avoid a longer cycle time than required. Longer cycle times can drive residual levels up in gas processes.

On the other hand, radiation sterilization is a bioburden-based method. With this process, the focus is on establishing the sterilization dose, which is based on bioburden count and resistance to that bioburden. When defining a process, manufacturers need to be cognizant of the transfer impacts when converting from one radiation type to another.

Regarding radiation, the most-used validation processes are the VDmax method and Method 1 validations. These methods count the number of organisms and measure resistance to them against the standard distribution of resistance. VDmax will establish a specific minimum sterilization dose without necessarily identifying the exact minimum sterilization dose. Method 1, which tests 10 times the number of product samples, will allow for the establishment of a more precise minimum dose.

Packaging validations When changing sterilization methods, manufacturers will need to consider the impacts of those changes on the medical device’s packaging. Rollins refers to packaging validations as a three-legged stool. MDMs will need to demonstrate that the change has not altered the packaging’s integrity, microbial barrier, and strength.

Rollins highlights the need to understand worst-case scenarios and test those. Other considerations related to sterilization changes include how the package performs during transit and how it performs over time (shelf life).Elder concluded the webinar with an overview of regulatory requirements once the change has been documented and validated. In most cases, manufacturers moving from Category A to an alternate Category A, or from Category B to A, will not need to submit a new 510(k). But just because you don’t need a 510(k) doesn’t mean you don’t need internal documentation evaluating the totality of the change.

If the change impacts critical parameters or introduces substantial new risks, Elder recommends looking at FDA’s guidance Deciding When to Submit a 510(k) for a Change to an Existing Device.

If manufacturers are moving from Category A to B or to novel methods, FDA typically requires a new 510(k) submission. For manufacturers who are looking to change sterilization modalities but aren’t sure if the change meets the threshold for a new 510(k) submission, the FDA offers a pre-submission process whereby MDMs can ask questions and receive feedback to help ensure compliance.

It should be noted that while the above examples given relate to the FDA approval pathway, many products are produced for global distribution. When implementing a new modality, it is critical to develop a regulatory strategy as early as possible. As part of this strategy, it is important to identify the requirements for each of the jurisdictions where a product will be marketed.