In light of recent shutdowns of two contract sterilization facilities over environmental concerns, FDA said it is exploring ways to ensure sterilization processes are safe and effective and evolving with the current science.MD+DI/Amanda Pedersen
Shutdowns of two facilities that use ethylene oxide to sterilize medical devices have raised concern about potential shortages in the medtech industry because this is such a popular sterilization method for medical devices.
Ethylene oxide (EtO) is a flammable, colorless gas used to make a range of products. EtO also is used to sterilize equipment and plastic devices that cannot be sterilized by steam, such as medical equipment. In fact, about half of all sterilized medical devices undergo sterilization using this gas.
According to the EPA, long-term exposure to EtO can irritate the eyes, skin, nose, throat, and lungs, and harm the brain and nervous system (causing headaches, memory loss, and numbness). Studies show that breathing air containing elevated EtO levels over many years increases the risk of some types of cancers, including cancers of the white blood cells (such as non-Hodgkin's lymphoma, myeloma, and lymphomatic leukemia). It also has been found to cause breast cancer in women.
Sterilization of medical devices is critical to the healthcare system, and ethylene oxide sterilization helps ensure the safety of medical devices and helps deliver quality patient care, according to outgoing FDA Commissioner Scott Gottlieb. Devices sterilized with EtO range from wound dressings to stents, as well as kits used in routine hospital procedures or surgeries that include multiple components made of different materials, the commissioner noted.
"However, the FDA recognizes the environmental considerations that are currently impacting manufacturers' ability to use this process," Gottlieb said.
Here is a breakdown of what prompted these shutdowns, the history of using EtO sterilization in medical devices, and alternative sterilization methods that have emerged in recent years.
EPA Shuts Down EtO Sterilization at IL Facility
Last month the Illinois Environmental Protection Agency (EPA) issued a seal order to the Sterigenics facility in Willowbrook, IL to prevent the plant from beginning any new sterilization cycles using EtO after the agency found dangerously high levels of the gas in air around the facility. Sterigenics is a large contract sterilization facility.
"The Illinois EPA and Illinois Attorney General's Office have been in numerous discussions with Sterigenics to discuss how to further reduce ethylene oxide emissions. Recent elevated sampling results, along with Sterigenics' refusal to voluntarily suspend operations, have resulted in the issuance of the seal order," the Illinois EPA said.
According to the FDA’s Establishment Registration & Device Listing database, Sterigenics listed a total of 594 types of devices that undergo an EtO sterilization process at the Willowbrook facility and therefore could be affected by the closure. These include products such as sutures, clamps, knives, stents, and needles.
FDA said it is not aware of any device shortages attributable to the facility closure at this time, but the agency said existing supply that has already been distributed may be diminished or even depleted as healthcare facilities use their inventory before alternative arrangements can be made to accommodate the sterilization of new products coming off the manufacturing lines.
A grassroots organization called Stop Sterigenics began lobbying for action against Sterigenics and its use of EtO for at least six months. The issue has also been a hot topic among Illinois lawmakers. Rep. Sean Casten shared the image below on his Twitter account March 12 after meeting with the mayor of Willowbrook to discuss the ongoing concerns regarding the facility.
"After our meeting, I walked across the street to the Sterigenics facility to read the seal order issued by [Governor Jay Robert Pritzker] and the [Illinois EPA]. I am thankful for their leadership even as I was dismayed by the inaction from our federal EPA," Casten tweeted.
In light of the state EPA order, FDA said it has been working to "quickly and proactively" secure alternative locations and methods for the sterilization of devices that were previously processed at the Willowbrook facility in order to mitigate potential product supply issues.
"We’re taking steps to prevent patient harm from potential device shortages that could delay or disrupt critical care," Gottlieb said. "At the same time, we’re undertaking new efforts to encourage innovative and improved sterilization options."
Viant Plans to Close EtO Sterilization Facility in Michigan
Earlier this month Viant Medical, another contract sterilizer, reported plans to close its EtO sterilization facility in Grand Rapids, MI after receiving attention from the Michigan Department of Environmental Quality (MDEQ) for air quality issues.
According to the FDA’s Establishment Registration & Device Listing database, Viant listed a total of 46 types of devices that undergo an ethylene oxide process at the Grand Rapids facility which, in the future, could be affected by the closure of the facility. These include devices such as catheters and surgical mesh.
In July 2017, Viant informed the MDEQ about an emissions issue resulting from a faulty rubber seal on a part of the sterilization system. The company said it immediately stopped operations and repaired the seal. Later, Viant received a notice of violation from the MDEQ as a result of that self-reported incident. The company said it has since worked closely with the agency to test and monitor air quality at the plant.
Emissions tests performed in December 2018 by an independent air quality assessment firm determined that Viant is in compliance with its MDEQ permit limits and limits set by the Subpart O of the National Emission Standards for Hazardous Air Pollutants. Nonetheless, Viant told Grand Rapids residents in a recent letter that the company has decided to shut down the sterilization facility because "that work is not part of our core business."
Because of the shutdown of the Sterigenics Willowbrook facility and the planned closing of the Viant Grand Rapids facility, FDA is urging medical device manufacturers that use these facilities to begin assessing any potential downstream impacts of the closures on device distribution through their supply chain to end users (such as healthcare facilities), and ultimately on patient care. The agency said it also encourages manufacturers to consider alternative contract sterilizers that can process their devices.
"We’ve already started exploring ways we can continue to ensure sterilization processes are safe and effective and evolving with the current science. This includes considering validation of methods that would support using lower levels of currently-used agents like ethylene oxide gas, thereby reducing environmental exposure risks, while still ensuring effective device sterilization," Gottlieb said. "There may also be ways to employ—and eventually, validate—new sterilization agents or processes that don’t come with the same environmental risks but still enable the safe and effective sterilization of devices."
FDA said it plans to discuss this issue with the infection control community at the May meeting of the Healthcare Infection Control Practices Advisory Committee. The agency also said it will host a public advisory committee meeting later this year dedicated to discussing how best to encourage innovation in medical device sterilization. Finally, later this year, FDA plans to announce a public innovation challenge to encourage the development of new sterilization methods, which could include new devices or new modalities that are safe and effective for sterilizing medical devices.
On Tuesday, FDA launched a new web page to act as a resource on this sterilization method as well as any future actions the agency takes regarding shortages or other activities associated with this issue.
Is Ozone Sterilization the Answer?
Environmental impact is just one motivator for medical device manufacturers to consider alternative sterilization methods. The complexity of today's medical devices is another driving factor.
As MD+DI reported last year, a new process for ozone sterilization could resolve earlier limitations with the gas and position it as a solution for complex and fragile products.
“Modern medical and life science products are increasingly sophisticated devices in terms of materials such as advanced polymers and novel surface coatings. Furthermore, the incorporation of electronic or optic components in an active device adds further complexity and sophistication to the device,” said Dick Barton, a senior product engineer at Anacail. “Traditional sterilization techniques are mature technologies, which when developed were never intended to sterilize such complex or fragile devices. Such techniques are now causing significant damage to new and emerging devices."
Autoclaving can damage surfaces and bulk materials through thermal degradation, dimensional change, or moisture-induced corrosion, Barton said. Radiation can cause irreparable damage to integrated circuits and cause significant degradation of polymeric materials through cross-linking or chain scission, which can render the device unusable, he added. EtO sterilization, on the other hand, has comparatively good material compatibility, but as we've seen, the chemical is a known carcinogen and even residual amounts must be carefully monitored and controlled.
That's where ozone sterilization comes in.
“Ozone has a unique blend of properties that make it an ideal candidate for decontamination and sterilization across a range of application areas. The ability to decontaminate and sterilize without leaving residue and to decay back to native oxygen makes this technology environmentally ideal,” Barton said. “Ozone is generated on demand and in situ, so has the further advantage of no transport, storage, or disposal of hazardous or toxic chemicals. These fundamental advantages transcend market segments and application areas.”
Anacail claims it has overcome historical disadvantages of ozone and developed a process that integrates sterilization into the packaging stage.
“Historically, ozone has been used as a disinfectant and biocide for many years, and a device has been marketed that was intended to sterilize reusable devices in healthcare settings. This device used a chamber, into which ozone was injected and thereby sterilized the chamber contents," Barton said.
While this earlier technology was effective, Barton said throughput was low, with a cycle time of several hours coupled with a relatively small chamber volume.
Because cycle time is “determined by the so-called D value of the sterilant, the time required for a log reduction in population of a most-resistant organism, it cannot easily be manipulated,” he explained. The alternative would be to increase the chamber size, but that could present fire and explosion risks, as traditional ozone sterilizers use oxygen as a feedstock gas, and the risk increases with additional chamber volume. “Extra hazard is presented by the means of generating ozone in the oxygen, which is usually though corona or similar gas discharge, which use kV voltages to break down the oxygen molecules,” he said.
Anacail’s solution is to develop a gas composition capable of providing the high ozone yields required for sterilization, but with only 21% oxygen content, Barton told MD+DI. This removes the flammability issues of previous ozone-based sterilization devices and could conceivably be used to make large chamber based systems. The throughput could be increased, and the lack of residuals would require no aeration time, giving advantages over EtO processing times, he said.
By exploiting the natural decay of ozone back to native oxygen, Anacail is able to inject pre-ozonated gas into a primary pack and seal the gas inside.
“The ozone sterilizes the pack contents in a few hours and then decays back to safe levels," Barton said. "The key advantage of integrating sterilization into a packing stage is that sterilization becomes a continuous rather than batch process and that the process is highly scalable without the large infrastructure requirements associated with traditional technologies.”
What About VPA Sterilization?
Vaporized peracetic acid (VPA) sterilization, in which room-temperature VPA is injected into a pressurized chamber to eliminate surface contaminants, has also emerged in recent years as an alternative to EtO sterilization in some cases. The method allows for quick turnaround time and can be performed on an OEM's production floor.
Safety and environmental risks with VPA are lower because the process breaks down into carbon dioxide, oxygen, and water. Since it doesn't result in carcinogenic fumes, VPA also doesn't require a lengthy aeration period. As a result, the product does not have to leave the facility until it's ready for delivery to the customer.
According to Revox Sterilization Systems, VPA sterilization is also compatible with a broader range of materials used in medical device development than EtO sterilization. Thanks to its gentler, room-temperature process, VPA enables medical manufacturers to sterilize chemical and heat-sensitive materials that are off-limits with EtO.
In-House vs. Contract Sterilization
A couple of decades ago there was a movement away from in-house sterilization to contract sterilization in the medical device industry. At the same time, some companies attempted to convert some of their products to irradiation sterilization.
"Today, those trends are reversed," said Clark Houghtling, vice president of development and technical affairs for Cosmed, a supplier of both turnkey sterilization systems and contract sterilization services.
At one time, Cosmed was among the largest contract EtO sterilization suppliers in the United States, until the company divested its healthcare facilities roughly 14 years ago. But after acquiring an EtO sterilization facility in Erie, PA in December 2016, Cosmed returned to the medical device industry. Houghtling told MD+DI at the time that changing demand is what drove Cosmed to reinvest in the space.
"Companies are optimizing their sterilization processes by integrating logistics, distribution, materials, and other factors into decision making. As a result, the move towards [EtO] from other modalities, and the ongoing investment in in-house sterilization are evident," Houghtling said.
Of the top-three industrial sterilization methods (EtO, gamma, and electron beam), Houghtling said the easiest to move in-house, and the most widely accepted is EtO.
How to Choose a Contract Sterilization Vendor
In the world of contract sterilization, selecting the most appropriate service provider can be a daunting task.
Location, turnaround time, cost, chamber equivalency, process controls, and the supplier's regulatory compliance history are all factors that should come into play when choosing a contract sterilization vendor.
For more insight regarding these considerations, see this article written exclusively for MD+DI by experts at Nelson Laboratories.