Mark Crawford, Contributing Writer06.02.21
Packaging and sterilization are dynamic markets these days in the medical device industry, thanks to the new EU Medical Device Regulation (MDR), the COVID-19 pandemic, wobbly supply chains, tougher regulations, and changing healthcare demands. Although there is still an abundance of change to contend with, medical device manufacturers (MDMs) are settling (cautiously) into a “new normal” for packaging and sterilization. However, “there is still some pressure on supply chains with raw material shortages, especially with recent market tightening for sourcing and lead times,” said Tom Williams, general manager for Millstone Medical Outsourcing, a Fall River, Mass.-based provider of packaging and distribution solutions for the medical device industry.
With the EU MDR newly launched, MDMs that are still behind are hustling to convert from non-sterile to sterile packaging. With MDR’s sharper focus on risk and safety, grandfathered devices with a CE mark will require recertification. “In some cases, this may also require re-validation of the packaging materials and design,” said Nora Crivello, president and CEO of Westpak, a San Jose, Calif.-based test laboratory specializing in product and package testing. “New rules requiring more technical documentation and labeling will have ripple effects on packaging and validation efforts. This includes adherence to and evidence of package testing to validated test methods.”
As MDM optimism grows, and delayed projects move forward with more orders coming in, time has never been more of an essence—yet there are still frustrating delays with packaging and sterilization, most notably the shortage of ethylene oxide (EO) facilities, which until very recently sterilized billions of devices in the U.S. every year. The EO sterilization industry has been hit hard by the FDA, with some facilities closed permanently and others temporarily, due to concerns over the toxicity of EO emissions.
“Making things worse, since COVID-19 hit, there has been additional demand for sterilization for personal protective equipment, which puts further strain on sterilization capacity,” said Peggy Fasano, COO for Boulder Sterilization and Boulder iQ, a Boulder, Colo.-based ethylene oxide contract sterilizer and provider of design and development services for medical device and in-vitro diagnostic companies. “The FDA is closely monitoring the supply chain effects of closures and potential closures of certain facilities that use EO to sterilize medical devices prior to their use.” Further, even though the medical device industry is working hard to adapt quickly to the changes and reduced capacity regarding EO, the U.S. Environmental Protection Agency is soon expected to propose even stricter emission requirements for contract sterilizers, which may further impact sterilization availability.
With such confusion and uncertainty, MDMs are turning to their supply chain partners for guidance and expertise regarding the best approach to sterilize and package their products, and even for ways to design medical devices that bypass these packaging and sterilization challenges.
“What OEMs prize most are partners with a solid understanding of the crucial intersections where device design and packaging can meet with adverse outcomes, and the know-how to avoid them,” said Roy E. Morgan, general manager of Eagle Medical Sterilization Packaging, a Paso Robles, Calif.-based provider of assembly, packaging, and in-house sterilization services for the medical device industry. “Clients look for a knowledgeable guiding partner through the packaging design process, especially with an understanding of the physics of distribution and the challenges to sterility barriers for terminally sterilized single-use devices.”
Latest Trends
Major packaging and sterilization trends in the medical device industry include the drive toward more sustainable forms and materials in packaging, greater interest in pre-validated solutions, and integrated solutions for packaging design with device design and regulatory submission planning. These trends reflect the increasing demand by regulatory agencies for complete validated submissions.
“Now, more than ever before, established OEMs and startups alike are being pushed to complete fully validated TSSUD [terminally sterilized single-use devices] development to a complete and documented level before submission,” said Morgan. “This increasing level of scrutiny catches some OEMs and suppliers off-balance, but those that can provide the guidance upfront to clients can help them circumvent delays in submission and prevent cycles of questions that simply speed up clearances.”
Gamma radiation and EO are the most popular methods of sterilization. Both methods have been used for decades but have come under increased regulatory and political pressures. For gamma sterilization, there are concerns about both the cobalt supply and the security of the radioactive isotope, Cobalt-60. And, with EO restrictions still in place, there is not enough supply from large-scale contract sterilizers, creating long lead times and delays.
MDMs are scrambling to evaluate potential alternatives to these methods and/or optimize their current processes if they cannot switch. Alternative methods include electron beam, X-ray, chlorine dioxide, nitrogen dioxide, vaporized hydrogen peroxide, vaporized hydrogen peroxide gas plasma, vaporized peracetic acid, vaporized hydrogen peroxide and ozone, and supercritical carbon dioxide.
Packaging materials are also being delayed. “Clients are telling us that, in addition to sterilization delays, many material vendors are four to six weeks out with various supplies such as pouches, trays, lids etc.,” said Scott Levy, packaging engineer for DDL, an Eden Prairie, Minn.-based package testing and medical device and combination products testing laboratory. “These types of delays are dramatically impacting complete package validations. For example, some clients are pushing package validations out four to five months, making overall cycles much longer.”
Designing the product, as well as the packaging, with the mode of sterilization in mind will become even more critical than it is today, considering the limitations of some of the alternate sterilization methods. For example, many gaseous methods do not penetrate nearly as well as EO. “Changes may need to be incorporated to the packaging to increase the breathable area to allow more efficient sterilant penetration,” said Dan B. Floyd, microbiologist and medical device and regulatory specialist for DuPont Tyvek Medical & Pharmaceutical Packaging, a Wilmington, Del.-based provider of innovative packaging materials and for the medical device and pharmaceutical industries under the Tyvek brand. “The product must be designed to ensure the sterilant can penetrate to all the hard-to-sterilize locations on the device. Modifications to the device configuration or even materials of construction may be needed.”
There is also a trend to reduce the amount of paper in an EO process. An FDA advisory committee meeting in November 2019 recommended device manufacturers reduce the amount of paper in their EO cycles. This can include paper packaging, instructions for use, and labels. In addition, paper is problematic for many of the alternative methods since cellulose absorbs the sterilant and can hinder the amount of sterilant available to the product.
Even though sustainability became less of a priority during the pandemic, MDMs are now focusing again on sustainable materials and processes that enable recyclability, smaller footprints, sustainable materials, and waste reduction—all of which improve operations and profitability, reduce environmental impacts, and improve brand image.
“Reducing waste can be achieved by optimizing packaging design, which can reduce material usage, as well as improve packaging functionality and allow for better product protection during sterilization, shipping, transport, and storage,” said Seán Egan, director of global marketing for Nelipak Healthcare Packaging, a Cranston, R.I.-based designer and manufacturer of custom packaging products for medical devices and pharmaceuticals.
Sustainability also involves reusing materials and containers, rather than simply throwing them away once they are opened. For example, “using reusable sterilization container filters for sterilization boxes will dramatically reduce the need for disposable blue-wrap type materials and add a higher level of safety to the surgical process,” said Gerry DiBattista, vice president of marketing for Porex Virtek PTFE, a Fairburn, Ga.-based provider of porous polymer materials and membranes made specifically for medical-surgical device applications.
Also, he noted, as the concept of reusable filters gains traction, so have the filter options. For example, Porex now offers three different versions of reusable sterilization box filters which “last hundreds of cycles with thinner products, but are also easily replaceable for users who prefer to have fresh gaskets and seals,” said DiBattista. “We have also developed the ability to print on the filter material, so branding logos or other useful information can be printed on the filter without harming the function of the product. This can be useful if you want to put a service date on the container that can then be replaced with a new filter and a new date.”
The reduction in EO capacity has MDMs and EO sterilization providers working together to reduce the amount of EO used in sterilization. This will, in turn, help them meet the expected strict changes to emission limits and potentially lower the product residual levels. Sterilization providers are asking for customers to adopt newer cycles utilizing much lower gas concentrations. “Since the gas concentration is a critical variable in EO sterilization, significant validation work is required to ensure the process is still meeting the required sterility assurance level,” said Floyd. “Providers are supporting customers in the change to parameters and are gathering significant data on the efficacy of these newer cycles which can be shared with other customers.”
What OEMs Want
The biggest question for many OEMs is how much the process parameters can change for EO while still achieving the necessary sterility assurance level. Significant validation work needs to be performed when reducing the gas concentration or changing the load configuration, but there is already growing experience regarding what the best combination of parameters should be. “Since much less EO is being used, OEMs are looking for packaging or product design changes that can help facilitate the ability of the sterilant to penetrate more efficiently into the product locations as well as be removed in the aeration phase of the cycle,” said Floyd. “Some examples of changes include providing more breathable packaging area, different case or loading configuration, or better product design with access ports to allow pathways for the sterilant to reach all the difficult to sterilize locations.”
With increased regulatory scrutiny, MDMs want to know if their suppliers’ test methods are validated, which reduces risk and makes the submittal process smoother and faster. More MDMs are reporting regulatory pressure to have full validations complete with respect to packaging and sterility assurance prior to submission. “RTAs [refuse to accept] from the FDA have been reported to us by several OEMs, due to rejections based on incomplete packaging validation of sterility barrier with a minimum of accelerated aging proof of capability,” said Morgan.
Some of these processes can be time-intensive. For example, test method validations (TMVs) require a substantial review of systems, processes, training, documentation, calibration, and adherence to test method standards, including statistical analysis where appropriate. Further, if any of these variables are altered, a re-validation—or justification not to re-validate—is required. “These changes caught many MDMs off guard and scrambling for TMV documentation from their testing providers,” said Crivello. “Because of the complexity and resources required to complete TMVs, many in-house labs have outsourced validated testing to independent laboratories who have completed this work.”
Also, to speed up validations and to keep costs down, OEMs seek contractors that can do both packaging and sterilization and cleanroom packages, on-site. This saves a great amount of time and reduces opportunities for errors, instead of sending the product to a sterilizer, a packager, and a testing lab. This vertical need has created a vibrant market for small independent “boutique” contract EO facilities, which focus on fast validations and customer service such as Boulder Sterilization, a segment of Boulder iQ.
“Companies want multiple services from one vendor,” said Fasano. “For example, Boulder Sterilization does the packaging, sterilization, biological testing, and all the validation testing in-house—we are in control of the entire process.”
New Technologies
Simulation testing is quickly advancing and can play a significant role in bringing optimal packaging products to market more effectively. Simulation analysis has long been used by the injection molding sector and is now being adapted to meet the challenges of thermoformed healthcare plastics.
“Simulation has the power to not only efficiently solve real-world problems such as plastic thinning, cracked flanges, seal creep, and product migration, but also to reduce design churn through models developed for thermoform packaging,” said Egan. “Simulation offers the opportunity to save valuable time, money, and other resources and mitigates risk by exploring ‘what if’ scenarios, allowing engineers to design engineering safety factors, removing uncertainty from package designs, and improving the speed to market.”
Simulation is also a powerful analytical tool for product investigation and root cause analysis to understand field failures of existing products. Transportation simulation is also a vitally important test and is commonly based on ASTM Standard D4169 (performance testing of shipping containers and systems). It involves a series of assessments designed to simulate various transportation stresses placed on shipper boxes during a worst-case transportation cycle to ensure products remain fit for use.
Accelerator-based methods (e-beam and X-ray) are gaining appreciation as an alternative to gamma and the use of radioactive isotopes. Although X-ray is an inefficient process, it does provide exceptional penetration that competes effectively with gamma and can process full pallets at one time. New X-ray facilities are currently being built around the world, providing a feasible option to gamma. However, many products currently sterilized with EO are unlikely to be able to switch to X-ray due to material compatibility issues with radiation.
“One configuration that we often get inquiries about is what we call ‘mixed-mode’ sterilization or hybrid sterilization,” said Morgan. “This is either a combination kit of sterile/non-sterile product or chemical/irradiated product. Eagle has mastered methods for processing and packaging design that facilitate the sequence and approach so that these solutions are possible. What they preserve is the surgical presentation of devices in a way that preserves sterility where it is warranted, but cuts costs where it is not. In the case of mixed-mode chemical/irradiation, it allows for things like programmable non-volatile memory or batteries to coexist in a sterile kit with irradiated metal components that cannot be steam sterilized. These can mean real advantages to OEMs working on new complex devices that require these internal features for improved novel surgical outcomes for better human health.”
2020 brought about another interesting packaging challenge: ultra-cool packaging for shipping vaccines (-78°C and colder). Patient safety is compromised when vaccines are not shipped or stored at their intended temperature. “This past year, Westpak saw an increase of active temperature shipping systems, including those that can maintain -150°C and colder,” said Crivello. “We anticipate these ultra-cool shipping conditions to continue into the future.”
An increasing number of devices are being designed with batteries, capacitors, circuit boards, and other microelectronic components. This presents a challenge to sterilization as the mode of operation must be understood to ensure the product is not damaged or there is not a safety risk. Radiation can damage semiconductors and the high heat and moisture in steam sterilization can be problematic to battery life. Pure EO is flammable and explosive and batteries or devices with stored energy can be an ignition source. Vaporized hydrogen peroxide without the use of plasma can be gentle on electronics but the vacuum can be an issue for embedded batteries. Hydrogen peroxide gas plasma generates radio frequency energy that can potentially be a problem for some electronics. Working with the sterilization providers or other industry experts can make the selection of the appropriate sterilization method less challenging.
Eagle is exploring the new areas of “reconfigurable” packaging solutions for familial products where a single protective element can be quickly reconfigured through mechanical or sealing means to become an alternate solution for a familial device. Additionally, its vertically integrated hydrogen peroxide gas plasma sterilization provides a more flexible method of sterilization that is accepted and recognized by FDA and other regulatory bodies as a crucial form of sterilization that can address the many challenges of self-powered, software-driven, electromedical devices. By-products are simple and safe—water hydrogen and oxygen.
Equally important is the recent push within the chemical sterilant community for new “minimum-dose” cycles that can reduce the amount of potentially hazardous sterilant used in the industrial settings of contract manufacturing/sterilization. STERIS recently published a white paper that demonstrated in a limited study that EO residuals on products could be significantly reduced when reducing the gas concentration from 600 mg/L to 300 mg/L.1 “In the case of a particular polyvinyl chloride product, they were able to reduce the product residuals by more than 50 percent,” said Floyd.
Working Together
Although it is rare, OEMs, sterilizers, and packaging vendors can work together early in the design process to develop systems that fully protect a product or a class of products. The efficacy of packaging for medical devices and pharmaceuticals, noted Egan, is shaped long before the manufacturing process—it starts with the design. “Choosing a provider that has experienced teams of designers and engineers with the ability to leverage modern software and technology, coupled with first-rate drawing skills during development, can result in solutions that best meet the OEM’s needs for pack performance, functionality, and product protection,” he said.
“Collaboration is a very exciting area of our industry where we are seeing some amazing partnerships and alliances develop,” said Morgan. “Perhaps driven by the sense of urgency and collective need in the human condition that the global pandemic has created, we find that working across our industry by sharing in development projects with previously sometime-competitors to create end-to-end solutions for OEMs and start-ups is really amazing.”
Eagle recently developed an alliance with several design firms to work in partnership with their device design outputs, toward novel packaging solutions, by parallelizing the timeline to deliver rapid total packaged product solutions that were submission-ready. “The collaboration was profitable for both the design firm, the OEM, and Eagle,” said Morgan. “The OEM was successful with fast development on robust multiple fronts, averting many of the potential pitfalls of complex kitted package designs.”
Porex prides itself on its unique collaborative innovation partnerships with both customers and supply chain partners. In the case of its reusable sterilization filter technology, the company has worked with many sterilization container makers to help them innovate and bring sustainability into their future product offerings—for example, “educating both the sterilization box vendors and the individuals responsible for infection prevention in hospitals,” said DiBattista.
Interestingly, a surprisingly high number of OEMs still do not consider product and packaging design together, resulting in inefficiencies and rework. However, integrating product and packaging design early in the design process reduces the risk of delays that can cost time, money, and opportunity. “This is especially important with the added complexities that robotic-assisted surgery products introduce to the market,” said Williams. “We continue to stress that package validation is an incredibly complex series of processes, and proven expertise can help OEMs navigate the challenges of package validation testing and kitting to get to market.”
Part of the value of collaboration is the combination of multi-disciplinary experiences and skill sets that will catalyze creativity, innovation, and problem-solving in a team.
“While every package design begins with some basic precepts in mind, such as protecting the payload or ensure no puncture, its equally important to remember sequence of surgical presentation, aseptic transfer, and environmental sustainability,” said Morgan. “All of these factors underscore the importance of having a multidisciplinary team capable of evaluating the susceptibility and sensitivity of device features from internal electronics to accessory placements, so that users have a convenient and intuitive experience of working with the packaging as much as the device itself.”
Reference
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.
With the EU MDR newly launched, MDMs that are still behind are hustling to convert from non-sterile to sterile packaging. With MDR’s sharper focus on risk and safety, grandfathered devices with a CE mark will require recertification. “In some cases, this may also require re-validation of the packaging materials and design,” said Nora Crivello, president and CEO of Westpak, a San Jose, Calif.-based test laboratory specializing in product and package testing. “New rules requiring more technical documentation and labeling will have ripple effects on packaging and validation efforts. This includes adherence to and evidence of package testing to validated test methods.”
As MDM optimism grows, and delayed projects move forward with more orders coming in, time has never been more of an essence—yet there are still frustrating delays with packaging and sterilization, most notably the shortage of ethylene oxide (EO) facilities, which until very recently sterilized billions of devices in the U.S. every year. The EO sterilization industry has been hit hard by the FDA, with some facilities closed permanently and others temporarily, due to concerns over the toxicity of EO emissions.
“Making things worse, since COVID-19 hit, there has been additional demand for sterilization for personal protective equipment, which puts further strain on sterilization capacity,” said Peggy Fasano, COO for Boulder Sterilization and Boulder iQ, a Boulder, Colo.-based ethylene oxide contract sterilizer and provider of design and development services for medical device and in-vitro diagnostic companies. “The FDA is closely monitoring the supply chain effects of closures and potential closures of certain facilities that use EO to sterilize medical devices prior to their use.” Further, even though the medical device industry is working hard to adapt quickly to the changes and reduced capacity regarding EO, the U.S. Environmental Protection Agency is soon expected to propose even stricter emission requirements for contract sterilizers, which may further impact sterilization availability.
With such confusion and uncertainty, MDMs are turning to their supply chain partners for guidance and expertise regarding the best approach to sterilize and package their products, and even for ways to design medical devices that bypass these packaging and sterilization challenges.
“What OEMs prize most are partners with a solid understanding of the crucial intersections where device design and packaging can meet with adverse outcomes, and the know-how to avoid them,” said Roy E. Morgan, general manager of Eagle Medical Sterilization Packaging, a Paso Robles, Calif.-based provider of assembly, packaging, and in-house sterilization services for the medical device industry. “Clients look for a knowledgeable guiding partner through the packaging design process, especially with an understanding of the physics of distribution and the challenges to sterility barriers for terminally sterilized single-use devices.”
Latest Trends
Major packaging and sterilization trends in the medical device industry include the drive toward more sustainable forms and materials in packaging, greater interest in pre-validated solutions, and integrated solutions for packaging design with device design and regulatory submission planning. These trends reflect the increasing demand by regulatory agencies for complete validated submissions.
“Now, more than ever before, established OEMs and startups alike are being pushed to complete fully validated TSSUD [terminally sterilized single-use devices] development to a complete and documented level before submission,” said Morgan. “This increasing level of scrutiny catches some OEMs and suppliers off-balance, but those that can provide the guidance upfront to clients can help them circumvent delays in submission and prevent cycles of questions that simply speed up clearances.”
Gamma radiation and EO are the most popular methods of sterilization. Both methods have been used for decades but have come under increased regulatory and political pressures. For gamma sterilization, there are concerns about both the cobalt supply and the security of the radioactive isotope, Cobalt-60. And, with EO restrictions still in place, there is not enough supply from large-scale contract sterilizers, creating long lead times and delays.
MDMs are scrambling to evaluate potential alternatives to these methods and/or optimize their current processes if they cannot switch. Alternative methods include electron beam, X-ray, chlorine dioxide, nitrogen dioxide, vaporized hydrogen peroxide, vaporized hydrogen peroxide gas plasma, vaporized peracetic acid, vaporized hydrogen peroxide and ozone, and supercritical carbon dioxide.
Packaging materials are also being delayed. “Clients are telling us that, in addition to sterilization delays, many material vendors are four to six weeks out with various supplies such as pouches, trays, lids etc.,” said Scott Levy, packaging engineer for DDL, an Eden Prairie, Minn.-based package testing and medical device and combination products testing laboratory. “These types of delays are dramatically impacting complete package validations. For example, some clients are pushing package validations out four to five months, making overall cycles much longer.”
Designing the product, as well as the packaging, with the mode of sterilization in mind will become even more critical than it is today, considering the limitations of some of the alternate sterilization methods. For example, many gaseous methods do not penetrate nearly as well as EO. “Changes may need to be incorporated to the packaging to increase the breathable area to allow more efficient sterilant penetration,” said Dan B. Floyd, microbiologist and medical device and regulatory specialist for DuPont Tyvek Medical & Pharmaceutical Packaging, a Wilmington, Del.-based provider of innovative packaging materials and for the medical device and pharmaceutical industries under the Tyvek brand. “The product must be designed to ensure the sterilant can penetrate to all the hard-to-sterilize locations on the device. Modifications to the device configuration or even materials of construction may be needed.”
There is also a trend to reduce the amount of paper in an EO process. An FDA advisory committee meeting in November 2019 recommended device manufacturers reduce the amount of paper in their EO cycles. This can include paper packaging, instructions for use, and labels. In addition, paper is problematic for many of the alternative methods since cellulose absorbs the sterilant and can hinder the amount of sterilant available to the product.
Even though sustainability became less of a priority during the pandemic, MDMs are now focusing again on sustainable materials and processes that enable recyclability, smaller footprints, sustainable materials, and waste reduction—all of which improve operations and profitability, reduce environmental impacts, and improve brand image.
“Reducing waste can be achieved by optimizing packaging design, which can reduce material usage, as well as improve packaging functionality and allow for better product protection during sterilization, shipping, transport, and storage,” said Seán Egan, director of global marketing for Nelipak Healthcare Packaging, a Cranston, R.I.-based designer and manufacturer of custom packaging products for medical devices and pharmaceuticals.
Sustainability also involves reusing materials and containers, rather than simply throwing them away once they are opened. For example, “using reusable sterilization container filters for sterilization boxes will dramatically reduce the need for disposable blue-wrap type materials and add a higher level of safety to the surgical process,” said Gerry DiBattista, vice president of marketing for Porex Virtek PTFE, a Fairburn, Ga.-based provider of porous polymer materials and membranes made specifically for medical-surgical device applications.
Also, he noted, as the concept of reusable filters gains traction, so have the filter options. For example, Porex now offers three different versions of reusable sterilization box filters which “last hundreds of cycles with thinner products, but are also easily replaceable for users who prefer to have fresh gaskets and seals,” said DiBattista. “We have also developed the ability to print on the filter material, so branding logos or other useful information can be printed on the filter without harming the function of the product. This can be useful if you want to put a service date on the container that can then be replaced with a new filter and a new date.”
The reduction in EO capacity has MDMs and EO sterilization providers working together to reduce the amount of EO used in sterilization. This will, in turn, help them meet the expected strict changes to emission limits and potentially lower the product residual levels. Sterilization providers are asking for customers to adopt newer cycles utilizing much lower gas concentrations. “Since the gas concentration is a critical variable in EO sterilization, significant validation work is required to ensure the process is still meeting the required sterility assurance level,” said Floyd. “Providers are supporting customers in the change to parameters and are gathering significant data on the efficacy of these newer cycles which can be shared with other customers.”
What OEMs Want
The biggest question for many OEMs is how much the process parameters can change for EO while still achieving the necessary sterility assurance level. Significant validation work needs to be performed when reducing the gas concentration or changing the load configuration, but there is already growing experience regarding what the best combination of parameters should be. “Since much less EO is being used, OEMs are looking for packaging or product design changes that can help facilitate the ability of the sterilant to penetrate more efficiently into the product locations as well as be removed in the aeration phase of the cycle,” said Floyd. “Some examples of changes include providing more breathable packaging area, different case or loading configuration, or better product design with access ports to allow pathways for the sterilant to reach all the difficult to sterilize locations.”
With increased regulatory scrutiny, MDMs want to know if their suppliers’ test methods are validated, which reduces risk and makes the submittal process smoother and faster. More MDMs are reporting regulatory pressure to have full validations complete with respect to packaging and sterility assurance prior to submission. “RTAs [refuse to accept] from the FDA have been reported to us by several OEMs, due to rejections based on incomplete packaging validation of sterility barrier with a minimum of accelerated aging proof of capability,” said Morgan.
Some of these processes can be time-intensive. For example, test method validations (TMVs) require a substantial review of systems, processes, training, documentation, calibration, and adherence to test method standards, including statistical analysis where appropriate. Further, if any of these variables are altered, a re-validation—or justification not to re-validate—is required. “These changes caught many MDMs off guard and scrambling for TMV documentation from their testing providers,” said Crivello. “Because of the complexity and resources required to complete TMVs, many in-house labs have outsourced validated testing to independent laboratories who have completed this work.”
Also, to speed up validations and to keep costs down, OEMs seek contractors that can do both packaging and sterilization and cleanroom packages, on-site. This saves a great amount of time and reduces opportunities for errors, instead of sending the product to a sterilizer, a packager, and a testing lab. This vertical need has created a vibrant market for small independent “boutique” contract EO facilities, which focus on fast validations and customer service such as Boulder Sterilization, a segment of Boulder iQ.
“Companies want multiple services from one vendor,” said Fasano. “For example, Boulder Sterilization does the packaging, sterilization, biological testing, and all the validation testing in-house—we are in control of the entire process.”
New Technologies
Simulation testing is quickly advancing and can play a significant role in bringing optimal packaging products to market more effectively. Simulation analysis has long been used by the injection molding sector and is now being adapted to meet the challenges of thermoformed healthcare plastics.
“Simulation has the power to not only efficiently solve real-world problems such as plastic thinning, cracked flanges, seal creep, and product migration, but also to reduce design churn through models developed for thermoform packaging,” said Egan. “Simulation offers the opportunity to save valuable time, money, and other resources and mitigates risk by exploring ‘what if’ scenarios, allowing engineers to design engineering safety factors, removing uncertainty from package designs, and improving the speed to market.”
Simulation is also a powerful analytical tool for product investigation and root cause analysis to understand field failures of existing products. Transportation simulation is also a vitally important test and is commonly based on ASTM Standard D4169 (performance testing of shipping containers and systems). It involves a series of assessments designed to simulate various transportation stresses placed on shipper boxes during a worst-case transportation cycle to ensure products remain fit for use.
Accelerator-based methods (e-beam and X-ray) are gaining appreciation as an alternative to gamma and the use of radioactive isotopes. Although X-ray is an inefficient process, it does provide exceptional penetration that competes effectively with gamma and can process full pallets at one time. New X-ray facilities are currently being built around the world, providing a feasible option to gamma. However, many products currently sterilized with EO are unlikely to be able to switch to X-ray due to material compatibility issues with radiation.
“One configuration that we often get inquiries about is what we call ‘mixed-mode’ sterilization or hybrid sterilization,” said Morgan. “This is either a combination kit of sterile/non-sterile product or chemical/irradiated product. Eagle has mastered methods for processing and packaging design that facilitate the sequence and approach so that these solutions are possible. What they preserve is the surgical presentation of devices in a way that preserves sterility where it is warranted, but cuts costs where it is not. In the case of mixed-mode chemical/irradiation, it allows for things like programmable non-volatile memory or batteries to coexist in a sterile kit with irradiated metal components that cannot be steam sterilized. These can mean real advantages to OEMs working on new complex devices that require these internal features for improved novel surgical outcomes for better human health.”
2020 brought about another interesting packaging challenge: ultra-cool packaging for shipping vaccines (-78°C and colder). Patient safety is compromised when vaccines are not shipped or stored at their intended temperature. “This past year, Westpak saw an increase of active temperature shipping systems, including those that can maintain -150°C and colder,” said Crivello. “We anticipate these ultra-cool shipping conditions to continue into the future.”
An increasing number of devices are being designed with batteries, capacitors, circuit boards, and other microelectronic components. This presents a challenge to sterilization as the mode of operation must be understood to ensure the product is not damaged or there is not a safety risk. Radiation can damage semiconductors and the high heat and moisture in steam sterilization can be problematic to battery life. Pure EO is flammable and explosive and batteries or devices with stored energy can be an ignition source. Vaporized hydrogen peroxide without the use of plasma can be gentle on electronics but the vacuum can be an issue for embedded batteries. Hydrogen peroxide gas plasma generates radio frequency energy that can potentially be a problem for some electronics. Working with the sterilization providers or other industry experts can make the selection of the appropriate sterilization method less challenging.
Eagle is exploring the new areas of “reconfigurable” packaging solutions for familial products where a single protective element can be quickly reconfigured through mechanical or sealing means to become an alternate solution for a familial device. Additionally, its vertically integrated hydrogen peroxide gas plasma sterilization provides a more flexible method of sterilization that is accepted and recognized by FDA and other regulatory bodies as a crucial form of sterilization that can address the many challenges of self-powered, software-driven, electromedical devices. By-products are simple and safe—water hydrogen and oxygen.
Equally important is the recent push within the chemical sterilant community for new “minimum-dose” cycles that can reduce the amount of potentially hazardous sterilant used in the industrial settings of contract manufacturing/sterilization. STERIS recently published a white paper that demonstrated in a limited study that EO residuals on products could be significantly reduced when reducing the gas concentration from 600 mg/L to 300 mg/L.1 “In the case of a particular polyvinyl chloride product, they were able to reduce the product residuals by more than 50 percent,” said Floyd.
Working Together
Although it is rare, OEMs, sterilizers, and packaging vendors can work together early in the design process to develop systems that fully protect a product or a class of products. The efficacy of packaging for medical devices and pharmaceuticals, noted Egan, is shaped long before the manufacturing process—it starts with the design. “Choosing a provider that has experienced teams of designers and engineers with the ability to leverage modern software and technology, coupled with first-rate drawing skills during development, can result in solutions that best meet the OEM’s needs for pack performance, functionality, and product protection,” he said.
“Collaboration is a very exciting area of our industry where we are seeing some amazing partnerships and alliances develop,” said Morgan. “Perhaps driven by the sense of urgency and collective need in the human condition that the global pandemic has created, we find that working across our industry by sharing in development projects with previously sometime-competitors to create end-to-end solutions for OEMs and start-ups is really amazing.”
Eagle recently developed an alliance with several design firms to work in partnership with their device design outputs, toward novel packaging solutions, by parallelizing the timeline to deliver rapid total packaged product solutions that were submission-ready. “The collaboration was profitable for both the design firm, the OEM, and Eagle,” said Morgan. “The OEM was successful with fast development on robust multiple fronts, averting many of the potential pitfalls of complex kitted package designs.”
Porex prides itself on its unique collaborative innovation partnerships with both customers and supply chain partners. In the case of its reusable sterilization filter technology, the company has worked with many sterilization container makers to help them innovate and bring sustainability into their future product offerings—for example, “educating both the sterilization box vendors and the individuals responsible for infection prevention in hospitals,” said DiBattista.
Interestingly, a surprisingly high number of OEMs still do not consider product and packaging design together, resulting in inefficiencies and rework. However, integrating product and packaging design early in the design process reduces the risk of delays that can cost time, money, and opportunity. “This is especially important with the added complexities that robotic-assisted surgery products introduce to the market,” said Williams. “We continue to stress that package validation is an incredibly complex series of processes, and proven expertise can help OEMs navigate the challenges of package validation testing and kitting to get to market.”
Part of the value of collaboration is the combination of multi-disciplinary experiences and skill sets that will catalyze creativity, innovation, and problem-solving in a team.
“While every package design begins with some basic precepts in mind, such as protecting the payload or ensure no puncture, its equally important to remember sequence of surgical presentation, aseptic transfer, and environmental sustainability,” said Morgan. “All of these factors underscore the importance of having a multidisciplinary team capable of evaluating the susceptibility and sensitivity of device features from internal electronics to accessory placements, so that users have a convenient and intuitive experience of working with the packaging as much as the device itself.”
Reference
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.
