In 2005, the U.S. Environmental Protection Agency considered banning ethylene oxide in new sterilizing facilities because of the cancer risk it posed to residents who lived around the plants.
“We also considered prohibiting the use of ethylene oxide for new facilities, which would necessitate the use of an alternative sterilization process,” reads the proposed rule, published in the federal register on Oct. 24, 2005.
Ultimately, under pressure from industry, and with the EPA’s acceptance of companies’ claims they were doing everything feasible to cut their emissions, the agency failed to act — worried about disrupting a key part of the process of sterilizing medical equipment in the U.S.
Fast-forward to 2019, and what’s past looks a lot like prologue.
Once again, the EPA is considering new restrictions on ethylene oxide sterilization because of the cancer risks it poses. Once again, the sterilizing and medical device industries are pushing back, warning of harm to patients if ethylene oxide is restricted. Federal lobbying disclosures show medical device makers and sterilizers have spent more than $1 million over the past 12 months lobbying Congress and the EPA on ethylene oxide issues.
There’s a big difference this time around, though: public awareness.
“Nobody in the last 40 years has been pressuring from the outside that there are community exposures from this,” said Peter Orris, MD, a professor and chief of occupational and environmental medicine at the University of Illinois at Chicago.
Greater appreciation of the environmental health threat has — for the first time — raised an outcry from residents in Georgia, Illinois, and elsewhere who’ve been exposed to ethylene oxide pollution — sometimes for decades — without any real warning that it was near them or could be dangerous.
In 2018, the EPA published a report that flagged 109 census tracts across the U.S. as having higher cancer risks, mostly due to ethylene oxide. Three of those census tracts are in the metro Atlanta area — two are in Fulton County, just south of Smyrna, and the third is in Newton County in Covington.
Orris first encountered ethylene oxide when he was a regional medical officer for the National Institute for Occupational Safety and Health. In the 1980s, he investigated cases of hospital staff getting lightheaded and dizzy and having other neurologic symptoms working around tabletop sterilizing devices that used ethylene oxide gas. The sterilizing devices — which look a bit like big microwaves — were leaking, making people who worked near them ill.
In learning about the gas, he recalls, “I finally concluded that you just couldn’t do this because every amount of exposure contributes to cancer risk.”
The outrage from exposed communities has federal regulators and device makers seriously rethinking a question that’s been hanging over the sterilization industry for decades: Can ethylene oxide be replaced?
A resolution pending before the American Medical Association’s Board of Trustees urges the nation’s doctors to push for substitutes to ethylene oxide sterilization “that are currently available” and do not cause cancer. It also urges hospitals and other health care facilities, when considering buying medical devices, to choose those that are the most effective for patients and safest for the environment.
The FDA also recently issued a pair of innovation challenges to researchers and industry in an effort to reduce dependence on the toxic gas.
The challenges come several months after Illinois Democrats — including U.S. Sens. Tammy Duckworth and Dick Durbin — urged the agency to find alternatives to ethylene oxide, or EtO, after a public outcry over the cancer-causing gas erupted in Willowbrook, IL, the site of a Sterigenics medical sterilization facility.
“It is critical that FDA begin investigating alternatives to the EtO sterilization process and prioritize swift adoption of safer methods and substances. Americans should not be forced to choose between sterile medical equipment and increased cancer risks,” the letter states.
Why Ethylene Oxide Has Persisted
When cardiologists need to repair the heart, they often use a cardiac catheter — a long, flexible tube threaded up to the heart through an incision in the leg. These catheters use a guide wire that has to slip easily along the walls of the plastic tubing. The guide wires are sometimes coated with Teflon to reduce friction.
Teflon can’t withstand gamma radiation, the second most common kind of sterilization for medical products. When Teflon is treated with gamma radiation, the radiation turns it to powder. Other kinds of materials can bond more tightly after exposure to radiation, which can make them brittle. In public statements, Phil Macnabb, president of Sterigenics, likes to point to vascular catheters as an example of a medical device that can’t be sterilized with anything but ethylene oxide.
But that’s an overgeneralization, says Jeff Sauter, director of business development for a company called Steri-Tek, which is based in Fremont, CA. Steri-Tek sterilizes products with electron beam and X-ray radiation, which represent smaller segments of the market.
Sauter says not all catheters use radiation-sensitive materials.
“We sterilize catheters every day. We sterilize millions of catheters,” including heart catheters that use guide wires, he says.
Sterilization is a concern for hospitals and other health care facilities. Healthcare-associated nfections cause thousands of deaths every year, and hospitals can be penalized financially and publicly if their patients catch preventable infections while in their care.
From a strictly technical standpoint, most materials used in medical devices don’t have to be sterilized with ethylene oxide, says Karl Hemmerich, a medical device consultant based in Salt Lake City.
In 2017, Hemmerich was chairman of a 40-member working group for the Association for the Advancement of Medical Instrumentation that created a guide to help medical device engineers understand which sterilization methods could be used with different kinds of materials. Their guide shows there are alternatives to ethylene oxide for most materials.
“In some limited number of cases, it’s going to be difficult to switch,” Hemmerich says. He estimates that only 20% of medical supplies need to be sterilized with ethylene oxide.
For example, the only method now used to sterilize electronic medical devices is ethylene oxide. The bigger hurdle, Sauter says, is that companies have to certify to the FDA that the method they choose will kill germs well enough.
“Once companies have their product validated with ethylene oxide, it’s very, very expensive to switch,” he says.
Sauter says proving that a different method will meet the FDA’s sterility standard requires rounds of studies.
“It can take a couple of years, and it could cost a million dollars,” he says.
Greg Crist, chief advocacy officer for the Advanced Medical Technology Association, or AdvaMed, says device manufacturers have been exploring other sterilization methods, but so far, none have been a perfect fit. “It would take 7 to 10 years to bring an alternative.’’
“We’re studying packaging alternatives. Using less cardboard, less plastic, would use less ethylene oxide,” Crist says.
He says there is a “very active search” for alternatives.
“No one is arguing that ethylene oxide is not toxic,’’ Crist says. “Ethylene oxide is not the first best choice to sterilize medical devices.”
Still, Crist says his pitch to lawmakers is simple: “As you consider regulating this, please bear in mind the public health impact of potential device shortages.’’
Currently, ethylene oxide gas is used to sterilize 50% of all medical supplies that require that high level of disinfection — everything from plastic surgical gowns to syringes, catheters, bandages, gauze, and pacemakers.
It doesn’t require high heat to kill germs, so it works on supplies that are sensitive to high temperatures. It is also readily absorbed through most types of packaging and seeps deeply through layers of materials — it even passes through plastic — which means device makers can sterilize whole pallets of hospital supplies at the same time, without ever having to unwrap them.
Gamma radiation handles about 40% of sterilized supplies. Like ethylene oxide, products don’t have to be removed from their final packaging, which helps to cut down on handling and the chance that something could be contaminated again.
Other kinds of radiation — like electron beams and X-rays — can also kill germs, but they’re not as commonly used. Not all materials can withstand radiation. Besides finding sterilization methods and materials that work well together, another potential problem is that sterilization facilities would be expensive for companies to overhaul.
The EPA acknowledged that in its 2005 proposed rule.
“Ethylene oxide and radiation technologies (both gamma and e-beam) share no common equipment. Any conversion would involve scrapping the ethylene oxide chambers and related specialized equipment and systems and likely displacing the existing workforce,” the proposed rule reads.
Still, a manufacturer can switch the sterilization method they want to use for a given device as long as they clear it with the FDA. In a 2005 email exchange between the FDA and EPA about device sterilization, FDA chemist Elaine Mayhall explained that all medical device manufacturers are required to choose a sterilization method that will meet the FDA’s specifications.
A number of different methods can get to that same point, she said. The limitations are the cost, how devices are packaged, and whether a sterilizer can penetrate the device packaging so that the device doesn’t need to be handled after all the germs are killed.
Besides ethylene oxide, there are other gases that can sterilize products at lower temperatures.
Besides ethylene oxide, there are other kinds of gases, such as hydrogen peroxide and nitrogen dioxide, that can be used to sterilize medical devices. Steam, the original method for killing germs, still handles much of the sterilization in doctor’s offices and hospitals. Hydrogen peroxide gas is mostly used in small machines in hospitals to sterilize reusable medical devices. It breaks down into hydrogen and water at the end of its cycle, leaving no toxic residues.
Like ethylene oxide, the process works for equipment that’s sensitive to moisture and heat. One disadvantage of this method, though, is that it doesn’t penetrate materials the same way ethylene oxide does. The nitrogen dioxide sterilization method is sold by a company called Noxilizer, which is headquartered in Hanover, MD.
Like ethylene oxide, it can sterilize devices at lower temperatures, which is good for things that are sensitive to heat, but it doesn’t penetrate material the same way ethylene oxide does. It works on surfaces.
“There are strengths and weaknesses to every sterilization process,” says Maura Kahn, vice president of business development for Noxilizer.
Nitrogen dioxide gas isn’t completely harmless. As a component of air pollution, it can cause lung problems, and it’s associated with lung cancer. Noxilizer says its equipment lowers the amount that’s released from the small chambers it uses to .1 part per million, far lower than the law requires.
Hemmerich says that most things that kill harmful germs aren’t very good for people, either. Gamma radiation can be deadly if workers are accidentally exposed, he points out. Despite its downsides, Hemmerich doesn’t want to see ethylene oxide taken off the market. He says it is an effective product that has to be handled carefully.
“You have to have systems in place to keep the end user, the factory workers, the management all safe. One facility wasn’t very good at it, and now we’re all running around, trying to find alternates. It’s going to be a tough road,” he says.
Fear of Shortages Slows Change
Both device makers and the FDA have warned there could be shortages if ethylene oxide is taken offline too quickly. In February, after state regulators abruptly closed a Sterigenics facility in Willowbrook, IL, for elevated levels of ethylene oxide in outdoor air, the FDA published a list of 594 different types of medical devices that could have been in short supply because of the closure.2
Sterigenics is one of the largest commercial sterilizing companies. It operates 19 facilities around the world that use ethylene oxide for sterilization; another 28 use gamma radiation for the same purpose. Ultimately, the shutdown only affected one device — a tracheostomy tube — and it was available again about 10 days later, after the FDA cut its own red tape. Regulators expedited a process the FDA requires manufacturers to follow to change what facility they use to sterilize a device.
“Normally, that would go through a 180-day, 6-month review,” said Suzanne Schwartz, MD, associate director for science and strategic partnerships at the FDA’s Center for Devices and Radiological Health. Schwartz says the agency has agreed to cut the time to review changes to sterilization sites to just 30 days.
There are other regulatory hurdles to overcome. When device makers seek approval from the FDA to sell their products, they have to specify not just how they will be sterilized, but where. The FDA keeps records on where devices are sterilized in case it needs to investigate an infection outbreak. Manufacturers have to get permission from the FDA to switch a sterilization site or method.
With regulation for ethylene oxide on the horizon, some device manufacturers have been telling legislators that their hands are tied when it comes to sterilization.
Medtronic, for example, when asked about its use of ethylene oxide, sent this statement:
“The FDA currently requires ethylene oxide sterilization for certain medical devices due to the sensitive nature of their materials or complexity of design,” the statement reads.
“While Medtronic continues to explore and advocate for safe sterilization alternatives that preserve the performance and integrity of our devices, we will continue our responsible use of EtO to sterilize certain medical equipment used in surgeries and other medical procedures, in compliance with FDA requirements,” it reads.
That’s an argument that’s been made for decades by device makers, but it isn’t quite accurate, the FDA says.
“The FDA does not require a specific modality of sterilization for medical devices,” an agency spokesperson said in response to Medtronic’s statement. The agency does acknowledge that ethylene oxide may be the only way to sterilize a sensitive device without damaging it, but the manufacturer determines that, not the FDA.
Hemmerich says ethylene oxide has become a default choice.
“A lot of that comes predetermined at a lot of companies,” he says, and medical device engineers turn to ethylene oxide because, “That’s what we always do.”
For its innovation challenges, the FDA is asking participants to come up with sterilization alternatives to ethylene oxide that are compatible with a wide variety of materials and can sterilize supplies in bulk. The second challenge asks for new ways to reduce ethylene oxide emissions from facilities that use the gas.
Applications for the challenges are being accepted through mid-October. Chosen submissions will be announced in December.
The FDA has also asked outside advisers to meet to discuss how to reduce ethylene oxide emissions to the environment without compromising the sterility of medical devices. That 2-day meeting will be held in November in Gaithersburg, MD, and webcast to the public. The advisory committee will consider public comments submitted through Oct. 21.
Orris says the FDA is moving in the right direction.
“The process we have to begin to move on is what the FDA is currently moving on,” he says. “If I was one of these companies,” instead of spending money to lobby to save ethylene oxide, “I’d be spending money on finding alternatives.”