Potential limits on a key chemical used to sterilize more than half of all medical devices in the U.S. has industry scrambling to lobby for a more measured approach to avoid disruptions to the supply chain.
The closure of a Willowbrook, Illinois facility due to elevated levels of the sterilizing gas ethylene oxide has already hit major medical device manufacturers such as Medtronic, Boston Scientific and Smiths Medical with millions of dollars in lost revenue. Shortly after the Illinois EPA shut down Sterigenics' plant, the FDA issued a warning that corresponding potential device shortages could delay or disrupt patient care.
In 2016, the Environmental Protection Agency found the gas, known as EtO, to be carcinogenic and linked to breast cancer, lymphoma and leukemia. Next month, the agency is set to propose a plan to address emissions from commercial EtO sterilizers such as Sterigenics' plant, and a risk and technology review of the maximum achievable control technology for emissions from the manufacturing of the gas.
But the industry points to potential unintended consequences that could come from an effective ban.
"If you're looking at regulations that would essentially remove EtO as a major sterilant in our manufacturing process, there could be serious threats in the supply chain, it's just that stark," Greg Crist, AdvaMed executive vice president of public affairs, told MedTech Dive.
During the first quarter of 2019, AdvaMed spent a portion of its $710,000 lobbying spend on "issues related to medical device sterilization and the use of ethylene oxide to sterilize medical devices." And, since the third quarter of 2018, Sterigenics spent $245,000 on issues including ethylene oxide, more than tripling its overall spending during the first quarter of 2019 to $125,000 compared to previous year.
EPA's spring agenda states the agency will "propose a course of action for dealing with emissions from commercial EtO sterilizers," but it's unclear how drastic the proposed rule will be.
"We are in the process of reviewing the rules regarding emissions from commercial EtO sterilizers, and considering how best to address emissions from this source within the guidelines of the Clean Air Act," an EPA spokesperson told MedTech Dive in an email.
Penny Fenner-Crisp, a former senior science advisor to the director of EPA's Office of Pesticide Programs, told MedTech Dive it is likely EPA will stop short of a ban, but it's possible the agency will propose companies reduce ethylene oxide emissions to a specified level.
"That would be done through technology, if technologies are available," Fenner-Crisp said. "Or the facility could make a business decision and say we can neither afford to nor do we have the appropriate technology to achieve that standard. And they could choose to slow down or find a substitute for disinfection."
Industry argues it can ensure public safety from emissions in the areas surrounding commercial sterilizers and is willing to work with EPA to reach a solution.
"We feel we have strong ability to abate and remove ethylene oxide emissions control for them and very environmentally safe way," Crist said. "If there are technology updates that are necessary, we're happy to work with EPA to arrive at them. What our concern is, is that this threshold is set at a level that simply is unattainable."
Alternative sterilant options limited
The medical device industry maintains ethylene oxide is irreplaceable, at least in the short term, due to its unique properties.
Currently, the gas constitutes approximately 50% of medical devices sterilization due to its ability to be used on products that cannot withstand radiation or moist heat, according to the International Irradiation Association. The group found 40.5% of industry uses gamma sterilization, 4.5% uses e-beam sterilization and the remainder such as steam and x-ray sterilization represent 5%.
"The broad application to a range of medical devices is attributed to the fact that EtO is compatible with many materials that cannot tolerate or are degraded by radiation and moist heat sterilization," a white paper written by the Gamma Industry Processing Alliance, which advocates for industrial use of gamma irradiation, said.
Crist said there simply is not a short-to-medium-term method to replace ethylene oxide without threatening the supply of medical devices containing plastic or electronics. Steam and radiation sterilization aren't feasible alternatives, he said.
"Any changes to the mode of sterilization for many products would require major changes to product design, material selection, manufacture and distribution – all regulated by FDA," AdvaMed said in a fact sheet.
"The redesign process could take several years and require lengthy regulatory approval. The direct impact of any elimination or severe restriction would potentially threaten the entire health care system, as low product inventories and severe backorders of sterile single-use devices could result, putting patients at risk," the group said.
Systems to capture and control ethylene oxide emissions released during the sterilization process such as wet acid scrubbers, catalytic or thermal oxidizers, absorbent materials, and incinerators or regenerative thermal oxidizers are often employed to meet EPA mandates, the GIPA white paper said.
"Typical systems require significant investment and ongoing maintenance and monitoring and can consume large amounts of energy," the white paper, subsequently reviewed by the International Irradiation Association, said.
Sterigenics has 47 facilities across 13 countries, including nine sites in the U.S. In total, there are about 155 contract sterilizers in the U.S., but one, Viant, is set to close by the end of 2019, according to FDA.
"FDA in their correspondence has said that short term capacity challenges have been addressed," Crist said. "Our concern is trying to help policymakers in the statehouses or here in Washington understand just how big of a role ethylene oxide plays in medical devices." strong quote
Despite the industry's concern, one expert at a nonprofit science advocacy organization said it is the responsibility of the FDA and EPA to balance potential health risks from EtO and potential disruptions to the medical device supply chain.
"That is a concern for the FDA and EPA to sort out. Of course it is important that medical devices are safely sterilized – but we shouldn't have to choose between safety at the hospital and safety in the air we breathe, the government has a responsibility to do both those things," Geena Reed, lead science and policy analyst at the Union of Concerned Scientists, told MedTech Dive.
FDA and Congress are acting to find alternative methods to sterilize medical devices. After the Willowbrook Sterigenics facility's closure, the Illinois House and Senate delegations sent separate letters to FDA asking the agency whether it was evaluating alternatives to ethylene oxide.
At a May 16 Healthcare Infection Control Practices Advisory Committee meeting held by the Centers for Disease Control and Prevention, an FDA representative said the agency is exploring whether a reduction in the amount of ethylene oxide used to sterilize medical devices can ensure sterility.
FDA plans to launch an innovation challenge during the summer to encourage ethylene oxide reduction and alternative sterilization methods. And it plans to hold a fall advisory committee meeting to gather stakeholder input.
"In view of the concerns about the environmental impact of this method, we recognize the importance of identifying new and improved ways of sterilizing medical devices," former FDA Commissioner Scott Gottlieb said in a March statement.
On May 30, Illinois Rep. Dan Lipinski introduced a bill that would create a $20 million prize competition to develop novel sterilization methods. The Democrat, who represents a district near Willowbrook, has been vocal in pressing EPA to update its regulations governing ethylene oxide sterilization facilities. His office told MedTech Dive the FDA offered feedback during the development of the bill.
"It's critical for the health of our communities that we use less-toxic sterilization methods," Lipinski said. "As an engineer, I don't want there to be shortages in our medical device supply chain, but we should not put the health of families in surrounding communities at risk."
Impact on medtech's bottom line
Boston Scientific CEO Michael Mahoney told investors on the company's first quarter earnings call the Sterigenics closure forced the company to move certain men's health product line sterilization in-house. In a Securities and Exchange Commission disclosure, the company said its urology and pelvic health business units could experience a material impact from the Willowbrook plant closure.
"We do expect softness in global supply during the second quarter and we will return to full supply by the end of the second quarter," Mahoney said.
Boston Scientific has also received approval from Australia's Therapeutic Good Administration and the British Standards Institution Notified Body to relocate sterilization to existing facilities.
"We do not anticipate significant shortages. These approvals encompass 99% of the business impacted by the Sterigenics shutdown," Boston Scientific spokesperson Katie Schur told MedTech Dive.
Medtronic's surgical innovations business, which produces certain surgical devices and instruments, was also impacted by the Sterigenics closure. The company told MedTech Dive it's working to sterilize products through other facilities and plans to reach full sterilization capacity during the first quarter of its fiscal 2020, or the middle of the 2019 calendar year.
"We did use our inventory on hand to help mitigate that in the fourth quarter and now we have less on hand as we move into Q1," CFO Karen Parkhill said during Medtronic's fourth quarter earnings call. "We expect the sterilization issue to be behind us as we said at the end of the quarter but will face some slowdown in revenue given that probably to the tune of about $20 million to $30 million."
And some industry players questioned the basis for EPA's IRIS Assessment on ethylene oxide, saying it could have been based on faulty assumptions.
"There are significant issues with the unusual approach that EPA applied in the EO IRIS Assessment to derive one of the highest cancer UREs in IRIS history," the American Chemistry Council wrote in a comment to EPA on an recent regulatory filing on hydrochloric acid.
"If the risk estimates for EO are not reliable, they should not drive the Agency's decision making in determining whether and to what extent further reductions of EO emissions from the source category under review are necessary to appropriately manage risk," the group said.
Sterigenics appears to agree.
According to a March handout Sterigenics circulated on Capitol Hill, the company said the "IRIS level for EO is set below levels detected in ambient air monitoring and even below EO levels produced by the human body."
But data collected after Willowbrook was forced to close bolsters the IRIS review, Reed said. In comments to the EPA, she noted that ethlyene oxide emissions dropped 90% after the plant closed and pointed to a March report from the Illinois Department of Health that found cases of Hodgkin's lymphoma among women in Willowbrook were almost 90% higher than the number of cases diagnosed in women in a nearby county.
"The question is whether EPA's current control technologies that are required are keeping us safe, and, if they aren't, EPA has a responsibility to update those," Reed said.
Crist said while the Sterigenics closure represented a short-term shock to the medical device supply chain, device manufacturers should be able to work with EPA, FDA and Congress to maintain access to ethylene oxide as a sterilant, arguing commercial sterilizers have the ability to contain their emissions.
"No one is questioning the toxicity of ethylene oxide," Crist said. "It is a toxic chemical."