Although some companies still rely on traditional sterilization methods and legacy packaging materials, these are becoming less common for increasingly complex devices, sensitive materials, electronic components, and combination products. It is also harder for traditional methods and materials to meet tougher regulatory standards. Orthopedic OEMs are moving toward terminally sterilized packaging, where the product is sterilized within its final container. An increasing number of hospitals are moving away from in-house sterilization and outsourcing to sterilization providers.
Medical devices and products are increasingly “smart,” with embedded electrical or optical components that can be damaged easily by traditional sterilization methods. Smart products often require gas sterilization and customized package designs to protect their sensitive components. Ethylene oxide (EO) sterilization, however, has fallen out of favor due to toxicity issues and the recent closure of several EO facilities, creating capacity issues. In addition, serialization of parts can be more complex, requiring more attention to labeling and ensuring traceability is maintained at a higher level than standard batch-based processing.
In packaging, FDA and ISO standards are—and will always be—an evolving challenge for OEMs. Interpretation of these regulations can be complex. In general, over the last few years, U.S. and European regulatory bodies have increased focus on compliance, package validation, in-process testing, and process verification. In May 2020, EU MDR regulations will go into effect—for example, non-sterile product lines must be converted to sterile lines. Some companies are still scrambling to meet that compliance date.
When all these challenges are combined—regulatory impacts, smaller and more complex devices, sensitive materials and electronics, moving away from legacy materials and approaches, and more challenging designs from OEMs—sterilization and packaging providers must keep up with the pace of innovation.
“Orthopedic/medical device packaging points in the production process are becoming busy intersections of the traditional, reliable, validated sealing process, as well as enterprise bi-directional data, component tracking, productivity measures, device confirmation/communication, UDI tracking, and other critical operations normally not associated with ‘just packaging,’” said John A. Abraham, president of Atlas Vac Machine, a Cincinnati, Ohio-based manufacturer of medical device tray sealers and tooling.
Jeff Barrett, CEO of J-Pac Medical, a Somersworth, N.H.-based one-touch packaging and sterilization company, agreed. “OEMs are increasingly looking for one-touch contract manufacturing solutions,” he said. “Treating packaging and sterilization as a unique production capability, rather than a service, is growing.”
PETG [polyethylene terephthalate with a glycol modification] thermoformed trays paired with Tyvek lidding remain the workhorse in packaging for orthopedic devices, noted Melissa Green, global senior director of marketing and strategy for Tekni-Films, a Wayne, Pa.-based provider of packaging materials for a variety of industries. “Gamma, e-beam, and EO are the most common sterilization methods used, with EO being used most—more than 50 percent of all sterile medical devices purchased in the United States are sterilized with EO.”
Medical device manufacturers (MDMs) are also increasing the number of non-traditional packaging configurations for the sterile barrier system. Whereas a few years ago, the only sterile barrier systems were pouches and trays, today many companies are electing to use novel packaging. For example, a tubing set that was traditionally packaged in a pouch might alternatively be fitted with caps and validated as its own sterile barrier system.
“Although this reduces the amount of packaging materials used for the device, it also poses a challenge when it comes to the validation since packaging validation test methods were developed for traditional packaging types,” said Jennifer Gygi, technical consulting manager for Nelson Laboratories, a Salt Lake City-based provider of laboratory testing and advisory services. “These novel packaging approaches require more creative thinking to find appropriate test methods to prove the barrier has adequate strength, integrity, and microbial barrier properties, when the traditional test methods are not suitable.”
Another novel approach is using simulation analysis to design packaging solutions. Simulation analysis, long used by the injection molding sector, is being adapted to meet the challenges of thermoformed healthcare plastics, “presenting stakeholders with intellectual data to clearly verify, communicate, and understand the complex information required to select valuable solutions efficiently,” said Seán Egan, director of global marketing and voice-of-customer development for Nelipak Healthcare Packaging, a Cranston, R.I.-based developer and manufacturer of packaging solutions for medical and healthcare products. “Simulation not only has the power to efficiently solve real-world problems such as plastic thinning, cracked flanges, seal creep, and product migration, but also reduces design churn, through models developed for thermoform packaging.”
Although PETG is the default standard material for trays, more customers are seeking alternatives that allow for improved recyclability versus PETG for non-hazardous waste and are trying to minimize overall packaging when they can. “PETG is now being labeled a 7, so the search is on to find materials that are better suited for the recycling stream,” said Green. “High-density polyethylene and Tekni-Plex’s Tekni MD PX, a proprietary co-polyester material, are two such materials that are under evaluation by packaging engineers.”
The most pressing issue in sterilization is the closure of EO facilities.
“There is definitely a reduction in EO usage and redefinition of the sterilization process to ensure EO is controlled,” stated Dania G. Cortes, senior manager of science for Nelson Laboratories. “With the recent environmental developments, agencies are requesting more information and controls around EO sterilization.”
Although some worry that EO could be phased out, it is well known that a replacement for EO that can be scaled to the current demand, and has the same sterilizing efficiency, does not exist. In the meantime, non-traditional EO cycle validation methods that help with the reduction of residuals are being more widely accepted, including by the FDA, which was reluctant in the past. “For instance,” said Cortes, “in the past, a BI/bioburden approach would be scrutinized and at times rejected by the FDA, given its unfamiliarity. Now, the FDA itself is requesting innovative ways to sterilize, including cycle calculation and the fraction negative approach.”
An alternative approach to EO is gamma sterilization, but “many companies are moving away from gamma sterilization to e-beam due to the shortage of supply of cobalt 60,” said Larry Nichols, CEO of Steri-Tek, a Fremont, Calif.-based provider of high-volume, e-beam/x-ray sterilization for the medical device, biotech, and pharmaceutical industries. E-beam is less harsh than gamma, has quicker turnaround, and can be a good approach for small-volume, niche, or high-value products. However, complex and/or sensitive devices typically require specialized packaging and lower-temperature, less-harsh sterilization methods, such as nitrogen or ozone.
What OEMs Want
OEMs want short, simple, and clean processes that take as little time as possible. More OEMs are also seeking packaging performance data and equipment life extension, without having to go through total re-validation of existing equipment.
“Purchasing new equipment, and validating and placing it into production can be a rather long and expensive process,” said Abraham. “There are many validated units that are still operating reliably and correctly after 20 years. If we can replace the operator interface with a new system and not change the programmable logic controller operating program, many users can track sign-ins, cycle by cycle data, audit log date, and even integrate enterprise resource planning [ERP] bi-directional communication easily. By simply enhancing the operator screen, we can add functionality and shorten any re-validation efforts.”
Oxygen barriers provide extra protection for medical device components when they are being sterilized, especially resin-based components that can become brittle during sterilization. Since the oxygen barrier protects their integrity post-sterilization, more MDMs want the addition of an oxygen and/or moisture barrier into their primary package. “With the desire to minimize overall packaging, packaging engineers want to design the barrier properties directly into the primary package versus adding barrier with an unnecessary foil overwrap,” said Green. “This approach minimizes hospital waste and has the potential to lower overall packaging costs for the OEM.”
For sterilization, the medical device industry is looking to build capacity using different methods in the wake of EO restrictions by the EPA. “The number-one question that contract sterilizers are being asked is, ‘Do you have capacity to run our product?’” said Nichols.
Manufacturers are also looking to reduce their footprint to minimize waste in the overall package—not just to save operational costs, but to also improve brand image. “OEMs want better, more efficient and effective packaging designs that eliminate the use of inessential materials and components but are still optimized for the manufacturing process and can be shipped and stored conveniently while maintaining product efficacy,” said Egan.
Simulation analysis helps save valuable time, money, and other resources and mitigates risk by exploring “what if” scenarios—for example, engineers can design in safety factors, remove uncertainty from package designs, and improve the speed to market. Simulation also aids in product investigation and root cause analysis to understand field failures of existing products in the market that have met customary testing standards.
“In addition to significantly reducing or even eliminating the need for physical testing, simulation can help identify critical quality attributes and create optimal packaging from the start, resulting in improved sustainability,” said Egan. “The transformative product development enabled through simulation may lead to reduced product components and raw materials usage, as well as prevent unnecessary manufacturing and shipping of defective product.”
Companies often conduct their own internal studies to improve performance and customize their own technology and processes in-house. For example, Millstone Medical Outsourcing—a Fall River, Mass.-based provider of post-manufacturing services, including cleanroom packaging, medical-device-specific warehousing, and finished goods distribution—wanted to explore variations in peel strength it was seeing in its operations.
“We determined that a large percentage of variation in peel strength data was caused by sample preparation, rather than the sealing process itself—a result of how the samples were cut for testing,” said Tom Williams, general manager for Millstone Medical Outsourcing. “For example, test samples cut by hand can exhibit greater variability than those cut by machines. We remedied this by using a CO2 laser cutter with custom software that allows the equipment to interface directly with our manufacturing documentation. Each tray SKU has its own definition, is automatically selected, and is error-proofed, which has created considerably less variation.”
Millstone Medical is also developing several vision systems driven by custom software to error-proof kitting processes for finished goods comprised of numerous components. “Doing so boosts quality and efficiency by inspecting the orientation and verifying the components of each kit before sealing,” added Williams. “As a result, patient risk is minimized, along with potential rework—saving both time and cost.”
Atlas Vac Machine can integrate its equipment with a customer’s enterprise resource planning software. “No longer do our sealers run in the cleanroom as stand-alone processors, just sealing trays,” said Abraham. “They are expected to be able to provide bi-directional exchange of data, if needed.” This capability is driven by FDA requirements to provide evidence the process of each tray seal cycle is in control and complying with the validated process.
With instructions coming from systems such as SAP and Netsuite, Atlas machines can be downloaded with “recipes” for each lot of trays to be processed. Once each tray is sealed, exacting data records relative to each seal cycle are sent back to the ERP system. “Recipe settings for platen temperature, seal time, and pressure are compared to actual platen temps, seal time, and pressure so that comprehensive analytics can be uploaded and studied to prove that processes in place are meeting or exceeding requirements,” said Abraham. “Other data can include dates, times, odometer readings, alarms, sign-ins, and more. The value of the data that is received and transmitted back to the ERP systems upon sealing has become as important as the quality of our sealers and tooling nests. The Internet of Things has truly allowed us to become interactive partners in the production processes.”
For medical procedures that require bone grafting to replace a missing bone, or repair bone fractures that are extremely complex, it is essential for the sterile integrity of the bone/tissue grafts to be maintained. Therefore, it is imperative packaging used to transport and store the materials necessary for these procedures do not negatively impact its contents. “Protective packaging used to store bone and tissue can only perform as well as it vents,” said Jack Chan, global marketing director for medical for Porex, a Fairburn, Ga.-based provider of porous polymer solutions for product design and packaging. “POREX Virtek Medical PTFE [polytetrafluoroethylene] lyophilization vents can be incorporated into protective packaging as a cap liner for bone graft and other tissue containers to provide a sterile barrier with high efficiency venting that help maintain the sterile integrity.” The vents are hydrophobic and able to repel water, with high airflow and high bacterial filtration efficiency. Unlike common expanded polytetrafluoroethylene (ePTFE) materials, Virtek is strong, durable, and designed for easy handling in automated assembly processes and protecting delicate implant contents.
Additionally, when performing orthopedic and surgical procedures, potential harmful fumes can result from the bone cement mixing process and affect both patients and medical personnel alike. To reduce the impact of the fumes, “our activated carbon filters allow high airflow rate from the bone cement mixing chamber and efficiently absorbs and traps monomer fumes to optimize removal of offensive gases prior to discharge in the operating room,” said Chan. “This reduces the toxic side effects of inhaling fumes that are generated using a pre-packed vacuum system for cement mixing.”
EO is the sterilization method for about of 50 percent of all medical devices that require sterilization. Sterigenic’s large EO sterilization facility in Willowbrook, Ill., was forced to close by the Illinois Environmental Protection Agency due to elevated levels of EO in the air around the facility. Other closures are being considered.
“The closure of EO facilities has had a cascading impact throughout the supply chain,” Barrett told Orthopedic Design & Technology. “Shortage of capacity is not only impacting supply, but also resulting in sterilization errors as well. Everyone is looking at this as a capacity problem, but we are seeing quality problems as well, as sterilization facilities are under significant pressure to increase throughput.”
“I feel the FDA overreacted when the EPA closed the Sterigenics Willowbrook facility,” said Nichols. “EtO is a good technology. For now, the FDA is encouraging companies to consider sterilizing with another method other than EtO if they can, before settling on that method.”
The closure of EO facilities is creating delays in the delivery of medical devices. Some OEMs have made the move to gamma radiation sterilization, but there is finite capacity because the radioactive isotope is a finite resource. Others are considering x-ray sterilization methods.
“E-beam has been an alternative to gamma for decades,” said Nichols. “It does have some limitations on penetration, but it is much better than most people think. X-ray can sterilize any product that gamma can sterilize. There is currently only one facility in the world, and that is in Switzerland; however, there will be four new x-ray facilities in operation in the U.S. in about two years.”
As OEMs evaluate different methods, new concerns on device integrity post-sterilization may be introduced. “Depending on the sensitivity of the device and its components, certain sterilization methods could compromise the devices if they are not protected properly during sterilization,” Green explained. “This is where different packaging materials could help, providing the barrier properties still protect the devices during sterilization.”
Another approach is reducing EO gas requirements. There is currently serious discussion about ways to reduce residual EO on medical products, shorten processing time, and reduce EO concentrations—thereby minimizing potential EO exposure to the environment.
“Some countries around the world are exploring the ideas of requiring lower residue limits for all product types, and some are wanting to consider different limits based on the patient on which the device will be used,” said Martell Winters, director of scientific competency for Nelson Laboratories.
Reducing processing time is driven primarily by a desire to improve utilization of EO chambers. This means that to increase utilization of a chamber, the sterilization facility needs to reduce processing time. “For most orthopedic products, which are 510(k)-regulated devices, a process optimization does not result in a need to change a filing with the FDA or other regulatory bodies,” said Winters. “As long as the sterility assurance level originally selected is still met, the process can be substantially optimized and still provide equivalent safety to the patient and, at the same time, increase utilization of the sterilizer chamber.”
Finally, a reduction in EO gas concentration during the exposure can potentially result in fewer residuals after sterilization. “In some cases, when gas concentrations are reduced, the corresponding increase in sterilization time to achieve sterilization is minimal or negligible,” Winters noted.
Even though package design and sterilization are critical parts in the medical device manufacturing process, too many MDMs deal with them as afterthoughts, late in the development process. Packaging design and validation studies can take months to complete, so it is beneficial and cost-effective to include them early in the design phase.
“We always encourage OEMs to consider product and packaging design as two halves of a whole, to decrease the risk of design or validation delays in getting products to market,” said Williams, who also noted that the rush to market sometimes overshadows these key areas late in the game.
Working with packaging and sterilization partners during design for manufacturability saves MDMs time and money. For example, Millstone Medical streamlines processing operations for customers by utilizing pre-validated packaging options. “We offer these in both tray and pouch options in a range of sizes, and they can fit up to 80 percent of spinal and extremity implants,” said Williams. “Use of pre-validated packaging can cut risk, decrease costs, and speed time to market significantly, sometimes by as much as 50 percent.”
In another example, companies considering alternative sterilization methods or reduction studies may not fully understand how these changes will affect the packaging validations that are already in place. “If anything established as part of the original validation will be changed, then a risk evaluation needs to occur to determine if additional testing is needed,” said Wendy Mach, an expert technical assistant with Nelson Laboratories.
“Medical packaging manufacturers can be more than just product suppliers,” added Egan. “They deliver the most value when they become true partners with the OEM and work collaboratively to design optimized products that are fit-for-purpose, reduce waste, and even improve the experience for the end-user.”
Mark Crawford is a full-time freelance business and marketing/communications writer based in Madison, Wis. His clients range from startups to global manufacturing leaders. He also writes a variety of feature articles for regional and national publications and is the author of five books.