Small victories.

Gradually, ever so slightly, fortunes are beginning to turn for residents of a gritty South Memphis neighborhood.

The triumphs are sporadic, unpredictable, and often masked in the ordinary—legal assistance, government data, a shuttered industrial plant, clean(er) air, good (for now) health.
Small victories.

The latter two wins have long been elusive for residents in Mallory Heights, a dense residential neighborhood that sits in the shadow of a sterilization plant and oil refinery in Grind City’s southwest corner. Cancer is rampant in the area, as are air and land pollutants. Residents blame their poor physical and environmental health on the sterilization facility (Sterilization Services of Tennessee, or SST), which silently pumped toxic chemicals into the atmosphere for decades. The 45,000-square-foot plant used ethylene oxide (EtO), an odorless, colorless gas to disinfect medical equipment and materials.

EtO sterilization has fueled a firestorm of controversy in recent years as conflicting reports surfaced about its health dangers. Although it had long been considered a hazardous air pollutant (earning that label in 1994), the organic compound was only deemed a human carcinogenic in 2016, courtesy of U.S. Environmental Protection Agency (EPA)-cited evidence: lab animal carcinogenicity, cancer rates in EtO-exposed workers, and genotoxicity data, among others.

Mallory Heights residents were unaware of the silent peril in their backyard until the EPA outed SST and EtO as the likely sources of their ailments. In the two years since that revelation, South Memphis community activists fought to reduce or altogether cut emissions from the sterilization plant.

Their efforts were unsuccessful at first. But a series of small victories over the last 10 months is improving Mallory Heights residents’ chances of achieving environmental justice for their neighborhood.

Small victory number one: Four attorneys file a lawsuit in August 2023 on behalf of seven South Memphis residents accusing SST of gross negligence. The suit contends SST engaged in “reckless, willful, or wanton conduct” by placing “its own economic interests above the health and well-being of those in the Memphis community” and subjecting residents to an elevated cancer risk.

Small victory number two: Around the same time the lawsuit is filed, SST informs local lawmakers it will close its facility and move from Memphis. The company did not provide a reason for its decision, but in a letter to U.S. Congress, executives said the plant had “never been out of compliance with reference to federal, state, and local mandates.” Mallory Heights residents are made unaware of this development.

Small victory number three: The EPA in March (2024) releases a new rule to cut sterilization plant EtO emissions by 90%. Facilities also must implement new pollution control measures (better ventilation), continually monitor and report EtO emissions, and comply with more stringent requirements for emissions that previously were not regulated (i.e., room air emissions).

Small victory number four: True to its word, SST closes up shop on April 30.

“We are happy that Sterilization Services of Tennessee is leaving, and what we hope for is that this place is [used] differently,” Memphis Community Against Pollution President KeShaun Pearson told media outlets. “The fight for environmental justice is going to continue. This fight was never Sterilization Services of Tennessee. This fight was for clean air, clean water, and clean soil for everybody who lives here.”

While admirable, the fight for environmental justice is prompting the medical device industry to scramble to find alternative sterilization options. Industry trade group AdvaMed has repeatedly noted there are no viable substitutes for many medtech products and has warned of supply chain shortages for critical medical products.

Finding other cleaning methods won’t be easy or quick, and the validation process necessary for new methods could be particularly troublesome. The change is just one of the many challenges packaging and sterilization providers face as they struggle to ensure the products they handle are safely cleaned and prepared for shipping.

To discover the other issues impacting the packaging and sterilization sector, Medical Product Outsourcing spoke to more than a half-dozen experts over the last few weeks. They included:

• Seán Egan, director of global marketing and VoC Development at Nelipak Healthcare Packaging, a Cranston, R.I.-based designer, developer, and manufacturer of custom designed packaging for the medical device and pharmaceutical industries.
• Brant Gard, managing member of Blue Line Sterilization Services LLC, an ISO certified, independent contract sterilization company in Novato, Calif.
• Abhi Gautam, executive engineer at DDL, a package, product, and materials testing provider for the medical device, pharmaceutical, and consumer goods industries.
• Brandon Hoser, sales engineer at Packworld, a Nazareth, Pa.-based manufacturer and distributor of validatable medical impulse heat sealing equipment.
• Roy Morgan, president and CEO of Eagle Medical, a Paso Robles, Calif.-based medical device packaging and sterilization service provider specializing in blister tray and pouch packaging.
• John Nino, CEO of Brea, Calif., contract manufacturer Life Science Outsourcing.
• Tom Williams, general manager at Millstone Medical Outsourcing, a Fall River, Mass.-based customized outsourcing solutions provider.

Michael Barbella: How have the services your company provides to customers changed in the last decade (if at all)? What are the predominant reasons for the change(s)?

Seán Egan: In the last decade, Nelipak has adapted its services to align with evolving customer demands and regulatory requirements. One significant change has been the emphasis on sustainability in packaging design and sterilization services. Customers increasingly prioritize environmentally friendly solutions, driving us to develop packaging options that minimize waste and are compatible with various sterilization methods. Additionally, there’s been a focus on regulatory compliance, particularly with the introduction of new regulations like Europe’s Medical Device Regulations (MDR), which have expanded the scope of products requiring protective packaging to reduce contamination risks.

Brant Gard: Our services have stayed pretty much the same. We started with the intent to sterilize small loads for start-ups with fast turnaround and quality service with expedite options. The primary change is the addition of an expedite service level that is even faster than the ones we started with. Our ability to focus over time on a limited number of services has allowed Blue Line to refine our processes, quality system, and documentation to better support our reliability and regulatory compliance.

Other than the additional expedite option, we have had a couple of interruptions in our supply of EtO. We have responded by modifying our validation program to allow the use of multiple EtO concentrations for any validated cycle. This gives us the flexibility to continue processing customer product without interruption when we can’t use our standard concentration.

Brandon Hoser: Over the last decade, our customers have requested more traceability associated with validated heat sealing processes. Data logging events such as what happens in a seal cycle, user logins, and alarm occurrences are all areas of interest. Machine user-restricted login access is desirable to prevent unwanted changes to machine settings. All of this helps equipment comply with 21 CFR Part 11.

Roy Morgan: It’s changed pretty dramatically in the last decade. The background behind this is that a lot of the forces at work in our industry are putting efficiency pressure on the CMs in our space. Naturally, we’ve gravitated to automation, and some might think of that as just robotics or mechanization, but that’s only part of the answer. We’re also using AI-enabled tools for streamlining certain aspects of information transfer from stage to stage in the manufacturing process. On a broader level, it’s more about how to take in district customer information and attempting to reformat it to a system that is compatible with something our systems can use, from station to station. I don’t see that slowing down; in fact, I see that becoming a mandate for all companies in our space.

John Nino: Customers come to us seeking alternatives to unacceptable lead times offered by traditional EtO service providers. In response to this, we have continued to expand our in-house EtO and steam sterilization capabilities to provide true quick-turn sterilization processing. Our added sterilization capabilities and capacity have resonated well in the market, resulting in significant year-over-year growth. We have also implemented specialized steam sterilizers specifically designed to service drug delivery combination devices for our growing medical device and pharma customers.

Tom Williams: Over the past decade, we’ve seen a significant shift from non-sterile packaged products to terminally sterilized products. This transition reflects broader industry trends toward higher patient safety standards and regulatory compliance. Key drivers include increasing regulatory requirements in Europe demanding terminally sterilized implants and a growing focus on reducing hospital infection rates. Additionally, there’s been a strategic shift towards more complex assembly services to deliver sterile-packaged instrument kits directly to surgery suites, enhancing efficiency and traceability in hospital inventory management.

Barbella: What evolving customer demands are driving innovation in the packaging/sterilization sector?

Egan: Evolving customer demands are driving innovation in several key areas. Firstly, there’s a growing demand for packaging solutions that not only protect medical devices but also align with sustainability goals. Customers are seeking packaging materials and designs that are recyclable and minimize waste. Secondly, there’s a need for compatibility with different sterilization methods, prompting exploration of alternative sterilization technologies. Thirdly, customers require packaging that meets stringent regulatory requirements, such as those outlined in the MDR.

Gard: We are seeing more demand for adoption of previously validated cycles migrating from other contract EtO sterilizers. The main reason is lack of capacity at other facilities, partly due to the closure of some of the larger pallet sized sterilizers and maxing out of capacity at the small load sterilizers like Blue Line Sterilization. We are also seeing larger volumes from existing customers as they commercialize their devices than we have in the past. We believe some of this is driven by capacity constraints at the pallet facilities.

Abhi Gautam: More sustainable materials, higher recyclable content, recyclable materials; low-gas EtO for more environmentally sustainable sterilization; reusable devices; and resealable packaging design.

Hoser: Sustainability is one of the leading topics driven from customer demand. The demand starts at the consumer level where sustainability claims may influence a purchasing decision. This drives back through the supply chain and Packworld USA can see projects with sustainability goals. One such example could be using an altered film composition for heat sealing which is biodegradable. Packworld machines are an advanced form of impulse sealing which means the machine is heated only when a heat seal is performed. This can help achieve some additional level of sustainability through lower electrical consumption when compared to a constant heat sealing machine, especially if the application calls for making heat seals occasionally throughout the day, such as once every few minutes. Sustainability goes hand in hand with scrap rates from a heat sealer. A properly sorted application and process should have no or very little scrap rate. A high scrap rate should trigger investigation into the equipment and process as well as discussions with material and equipment suppliers.

Morgan: In the packaging sector, what is driving innovation is the sensitivity of many devices and their fragility. As treatments become more personalized and solutions incorporate combination devices and there is software integrated in those devices, the challenge is that you have a product that is a miniature. It’s not nano product but it is miniature—it’s a discreet device that can be used in public or at home, like a “wearable.” It’s not meant to stand out but has to be robust.

How do you protect devices like that and their delivery from both the sterile and non-sterile side? The difficulty here is to ensure that typical things like shock, drop, environmental hazards, rain, humidity, etc., are kept out of the package. It’s difficult enough when it’s hand carried.

There is innovation taking place in the way products can be suspended. Think of something like a trampoline or a protective barrier. The challenge is designing them to be applied in a somewhat universal manner. Other elements coming out of universities is that some sterilants are being included in medical device packaging and these sterilants are stimulated by lights or sound. Now, this brings about challenges but it also brings about innovation. The regulatory validation challenges with this still need to be overcome.

Nino: Pricing, time-to-market, and continuity of supply are driving packaging innovation. Our guidance is centered on helping customers to develop robust, cost-effective designs that meet design, transportation and Sterilization requirements. Many customers come to us with a frozen design and ask “Now what? What are the next steps?” Our team of technical design, development, and testing experts then help to specify the best packaging configuration for their device by leveraging proprietary offerings such as “pre-validated” packaging configurations that take much of the risky trial and error out of packaging development.

Williams: OEMs demand cost-effective and safe packaging and sterilization solutions, driving the innovative approaches of outsourcing partners. Introducing advanced vision systems for error-proofing the kitting process within sterile packaging represents one example of how Millstone has committed to these demands. These technologies ensure compliance with stringent safety standards and align with the industry’s push toward more cost-effective solutions without compromising quality.

Barbella: How will the EPA’s new EtO regulations affect your business (if at all), and the industry at large? How do you plan to deal with the new regulations? Are customers interested in/requesting alternative sterilization methods?

Egan: The EPA’s new EtO regulations may impact our business and the industry by requiring adjustments to processes to comply with new regulatory requirements. We plan to address these regulations by investing in new technologies or modifying existing processes to meet regulatory standards. Additionally, there may be increased interest in alternative sterilization methods as customers seek options with less environmental impact.

Gard: Blue Line is in compliance with the EPA standard thanks to the design of our 3M sterilizers and abators (scrubbers). The emission reduction equipment we use shows that we reduce emissions by 99.99%. Our requirement under the new rule is 99.9%, so we are already a factor of 10 under the requirement. In addition, the entire process, including aeration occurs in one chamber so there is no need to remove devices before they are aerated to move them to an aeration chamber. This keeps the EtO levels in the production areas very low, so staff exposure is limited to well below that in the larger services. We are currently working with a consulting firm to evaluate the need for additional production area monitoring and fence-line monitoring for EtO emissions.

Gautam: With the EPA’s new regulations, customers are resorting to low-dose and cold EtO cycles. Customers are re-considering metals vs. polymers to change product design for resorting to irradiation.

Morgan: Customers are clearly beginning to think about it front and center. There are two things with EtO that people need to consider in the device space. One, it’s probably never going to go away because it’s an effective sterilant. For the immediate term—three to five years—the industry is going to dump a whole lot of money and resources into retooling EtO facilities. The challenges that come with that is localities of these facilities are all very different and can add to the recent updated EPA regulations. The time it’s going to take to go through the permit process, etc., is another concern. So, I think the EtO challenges in the market are going to stick around for a while. But that creates a window of opportunity for new and alternative methods of sterilization to come in and flourish. We offer hydrogen peroxide gas plasma, for example. We are going to see more of that kind of innovation going on in the industry. We see a good deal of buzz around some of the alternative methods being tested.

Here’s the challenge: the FDA has an edict from the U.S. government to ensure whatever sterilization process we use is safe and effective. That means there will be a strong need for data, publication of that data, submission of the data, and meetings to get any new form of sterilization sanctioned by the FDA as a Category A sterilant. It has to climb the ladder and that takes a lot of time. It took H2O2 50 years to get all the way to the top of the ladder as a Category A sterilization modality. We’re going to need to speed that sanctioning time up. The pandemic taught us that the ability to sterilize medical devices is a matter of national security.

Nino: As a small-batch EtO sterilization house, LSO has until April 2027 to comply with the revised EPA regulations. By 2027, LSO will be documenting daily EtO usage for each site and continuously monitoring EtO emissions. With state-of-the-art catalytic abatement technologies, LSO’s in-house EtO operations already comply with EPA’s revised emission reduction controls. LSO is also committed to abiding by local air quality rules, which can be more stringent than federal regulations.

For large-batch EtO sterilization, LSO partners with contract sterilizers that are poised to meet all EPA deadlines. These partners were heavily involved in air quality legislation at the federal, state, and local levels.

There may be many ways to sterilize a medical product, but the choice of modality depends on the product and supply chain logistics. For new products, LSO assesses sterilization modalities using published industry guidance (e.g., McLaren, 2020; McLaren et al., 2021). Per McLaren’s decision tree flowchart, the sterilization specialist should assess heat first, radiation second, and gaseous chemicals third.

In January 2024, the U.S. FDA recognized vaporized hydrogen peroxide (VHP) as an established sterilizing agent. However, VHP and other gaseous methods are unlikely to usurp EtO in the foreseeable future. EtO has the longest history of use, largest logistical scale, unparalleled material compatibility, and numerous options for pre-validated packaging.

Williams: Evolving EPA regulations regarding EtO sterilization have prompted us to work closely with third-party providers to ensure compliance and, where necessary, revalidate processes. This regulatory landscape has not only accelerated the industry’s interest in alternative sterilization methods but has also underscored the importance of education in our sector. At Millstone, we are committed to educating our partners and clients about the benefits and feasibility of alternative methods, including X-ray sterilization. We actively discuss with our OEM partners and provide educational resources to help them make informed product validation and compliance decisions. This proactive approach ensures that we remain at the forefront of regulatory and environmental compliance while supporting the industry’s shift toward safer and more sustainable sterilization solutions.

Barbella: How does the medical device sterilization process affect packaging design/solutions and vice-versa?

Egan: The medical device sterilization process significantly influences packaging design and solutions. Packaging must ensure that the device remains sterile under specified storage and transport conditions until it is opened for use. Compatibility with the sterilization process is crucial to prevent damage to the packaging and ensure the integrity of the sterile barrier. Conversely, packaging design also affects the sterilization process, as certain materials and designs may be more compatible with specific sterilization methods.

Gard: EtO gas sterilization is compatible with most materials, so the choice of material for the packaging is essentially unlimited. The two requirements for the primary packaging are that there must be sufficient porosity for the EtO to pass through the package to get to the product and sterilize it. The gas must also be able to pass back through the package to be removed from the product. Tyvek and paper are commonly used for this. Second, the materials and the seal of the primary packaging must be robust to not be damaged during processing or transportation.

Gautam: EtO or any gas sterilization will require porous packaging and designs that will allow for ingress and outgas of gas. Irradiation will require packaging materials that will not cross-link and break down over time. Autoclaving, heat, or steam sterilization will require materials with a high melting point.

Morgan: I would say it’s a multi-layered answer. It’s best thought of early in the design phases of medical device development. If left to the very tail end of design can—and often does —surprise device developers, like how does the package interact with the device, or how does the package interact with the sterilant and the device together? For example, if one selects a labeling substrate that is susceptible to a silicone oil off-gassing and it has to go to the Middle East or Africa, the off-gassing can disintegrate the label and now you have an incorrectly labeled product. Although It sounds simple, it’s another potential ‘gotcha’, and it’s not a complicated idea to think of in advance. The design, the packaging, and sterilization modality is a triangle of design interactions. Thinking carefully through it will save you tons of time and headache if you do it In the early stages of product development.

Nino: The product, packaging, and sterilization process are all intertwined. A change to one could affect the others. To navigate the complexities, it is important to partner with a CMO that has end-to-end experience.

Williams: Sterilization processes heavily influence packaging design, as the materials and configuration must accommodate specific sterilization methods without compromising the integrity of the product. Conversely, packaging design can limit sterilization options, with particular materials and configurations more or less suitable for methods like gamma radiation or EtO. Our approach is to design versatile packaging compatible with multiple sterilization techniques, offering our clients flexibility and reliability.