As medtech advances, device makers need to consider sterilization methods that won’t compromise electronics, drugs or biologics.

Matt Conlon, Revox Sterilization Solutions

The medical device industry has undergone an impressive transformation over the last several years, resulting in new and innovative devices and solutions. As companies continue to innovate, they are finding that commonly used sterilization methods impose limitations in terms of efficacy, quality or production processes of many of the newer device components (electronics), coatings (drug), or contents (drugs or biologics). New approaches have the potential to overcome the constraints of legacy sterilization methods.

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The challenges of ethylene oxide

Proper and thorough sterilization of medical devices is critical. One of the most commonly used sterilization methods is exposure to ethylene oxide (EO) to kill microorganisms. Though other methods come with their own challenges, EO presents the greatest risk in terms of patient and worker safety – and costs associated with risk mitigation requirements.

The following three areas are where EO presents its most serious challenges to medical device manufacturers:

1. Materials compatibility

New materials for medical device manufacturing, such as biosensors, bioabsorbables and electronics, are not able to withstand heat- and humidity-inducing sterilization methods such as EO. Also, any chemical reactions that might occur at higher temperatures and with humidity could create adverse chemical reactions that speed up degradation and corrosion of the device. In situations where a drug or biologic is present during sterilization, such as with prefilled syringes or drug-coated stents, the drug is also at risk. Heat can affect the active pharmaceutical ingredient (API) or biologic and impact the stability or pH, which threatens its overall functionality.

2. Patient and employee safety

The limitations outlined in the ISO 10993-07 standard set guidelines on how much EO can be left on medical devices. This amount varies depending on the intended use of the device. There has been particular attention to this issue in France, where 85% of single-use sterile devices in neonatal wards are sterilized using EO. Because of this, stricter regulations are in the ISO proposal process to further discourage the use of EO by requiring that manufacturers provide documentation of the rationale for choosing EO for sterilization (as opposed to an alternate method) and quantifying and limiting aggregate (multiple products) potential exposure to special patient populations, such as neonates. Due to the difficulty of making these calculations (with potentially multiple products by the manufacturer being used on a single patient), most would prefer a “risk versus benefit” approach. This enables the continued use of EO sterilization processes on critical life-saving devices for which there is no other commercially feasible sterilization method.

The other side of this issue is the danger of EO to the health and safety of the employees in the manufacturing facility using it for sterilization. OSHA has strict regulations around exposure to EO, which medical device manufacturers have to adhere to when using it in their facilities. For example, EO chambers must use blast-proof containment facilities and employees are required to take extensive health and safety precautions. While protective measures are standard operating procedures whenever a process/material presents danger to employees, these precautions can become costly. Few manufacturers that do not already have experience with the risk and cost of on-site EO processing are willing to take on the regulatory and safety hurdles it brings.

3. Manufacturing efficiency

While the sterilization process time itself varies greatly in accordance with the product being sterilized, every EO process requires pre-sterilization conditioning and post-processing aeration periods. This can add significant time to the overall process, ranging from several days to weeks. Because of the risks and costs associated with on-site EO sterilization, roughly 75% of medical devices are sent out to contract sterilization service companies. Depending on the location of the sterilization facility and the distribution logistics of the product itself, this can also add significant transportation time and inventory requirements that will impact the cost of goods sold. On-site EO operations bring the associated costs of required risk mitigation.

VPA as an alternative

Novel methods of sterilization can include high-intensity light/pulse light, microwave radiation, sound waves, ultraviolet light and vaporized peracetic acid (VPA).

If a manufacturer wants to switch to one of these novel methods, the change requires the product and sterilization process to be resubmitted for 510(k) clearance. However, it makes the most sense to consider these alternative methods if a company is designing a new product, is going through changes that will need to be submitted for FDA 510(k) clearance anyway or is planning new manufacturing processes/sites.

VPA can improve material compatibility and enable integration of less costly designs and materials by eliminating the use of heat for sterilization, which can damage newer, heat-sensitive materials such as sensors and biologics. Instead of using heat, a proprietary peracetic acid (PAA) biocide is injected into a vacuum chamber at room temperature (18°C to 30°C) in vapor form, gently sterilizing the product with a total processing time of two to four hours. The VPA process is noncarcinogenic, nonexplosive/flammable, requires no external ventilation and breaks down to H₂0, CO₂, and O₂ within hours.

Additionally, although newer sterilization methods, such as gas plasma and vaporized hydrogen peroxide (VHP), have proven efficacy and utility for various applications, they do not offer commercial feasibility in the industrial sterilization space in terms of their throughput capabilities. With chamber capacities of up to eight pallets and short processing times, VPA is now a commercially feasible alternative that may help manufacturers further reduce the risk in the risk versus benefit decision tree. VPA can also be used as a valuable tool for bioburden reduction for preterminal sterilization, eliminating pre-sterilization bioburden fluctuation and enabling lower terminal sterilization exposure to whichever method is being used.

Matt Conlon is VP and general manager of Revox Sterilization Solutions (Minneapolis).