Orthopedic and medical device manufacturers are constantly looking for means to make all aspects of design, development, and production faster, safer, and less expensive. This includes packaging and sterilization, which can unfortunately be overlooked or underestimated as vital parts of the production process. There are both very strict regulatory requirements for packaging and sterilization, as well as increased challenges as newer, innovative products with complex designs enter the market. Many of these can be combination products or tissues/biologics that aren’t compatible with traditional packaging and sterilization methods.
Packaging and sterilization are both quickly expanding markets within the orthopedic and medical device industry. Both are integral to ensure devices are free of contaminants, safe to use, and can withstand a variety of shipping and storage conditions. And although medical packaging materials still rely on legacy products like Tyvek and nylon, OEMs are finding it more difficult to remain with these options because of evolving regulations. The trend toward product complexity also makes it more difficult to totally sterilize these products with standard methods.
Over the last few weeks, ODT spoke with several industry experts to gain further insight on the packaging and sterilization industries:
John Abraham, president of Atlas Vac Machine LLC, a Cincinnati, Ohio-based manufacturer of medical device tray sealers and sealing tool nests.
Seán Egan, director of global marketing and VoC development at Nelipak Healthcare Packaging, a Cranston, R.I.-based provider of custom thermoformed packaging solutions for the healthcare industry.
Mark Hagerty, business development associate at Summit Medical, an Innovia Medical Company. Based in Eagan, Minn., Summit Medical specializes in the manufacturing of various ENT products, InstruSafe Instrument Protection Trays and Care + Maintenance Products for sterile processing, and Minne Ties Agile MMF for jaw fixation.
Britt Jones, manager—chemistry and package testing at WuXi AppTec’s Laboratory Testing Division. WuXi AppTec is a global medical device and biopharmaceutical outsourcing firm with operations in China and the United States. The company’s Laboratory Testing division, a comprehensive integrated testing platform supporting customers across the full spectrum of their development efforts, is based in Mendota Heights, Minn.
Maura O. Kahn, vice president, business development & marketing for Noxilizer, a Baltimore, Md.-based seller of NO2 sterilization equipment, lab services, and consulting to the medical device, biotechnology, and pharmaceutical industries.
Pal Khangaldy, consulting manager at Nelson Laboratories, a Sotera Health company based in Salt Lake City, Utah, that provides full lifecycle microbiology testing services for the medical device, pharmaceutical, tissue, and natural products industries.
John Neville, Ph.D., technical specialist at WuXi AppTec’s Laboratory Testing Division.
Brian Nissen, principal project engineer at QTS Medical Device Outsourcing, a Cretex Medical company. Based in Bloomington, Minn., QTS offers extensive medical device packaging and outsourcing expertise including precision assembly, kitting, and packaging.
Jeff Sauter, director of business development, Steri-Tek, a Fremont, Calif.-based provider of E-beam sterilization and X-Ray irradiation for complex medical devices and sensitive materials.
Sopheak Srun, principal sterilization specialist at QTS Medical Device Outsourcing.
Don Tumminelli, senior technical manager—client services, at HIGHPOWER Validation Testing and Lab Services, a Rochester, N.Y.-based provider of reusable medical device cleaning, packaging, and sterilization validation services.
Brian Whalen, director of sales and marketing for CleanCut Technologies, an Anaheim, Calif-based FDA QSR-compliant and ISO 13485-certified, one-stop source medical device packaging company.
Sam Brusco: What are the most exciting recent advances in packaging and/or sterilization technology? How is the technology advancing to meet the needs of medical device manufacturers?
John Abraham: Regulations and the realities of daily production are driving medical device manufacturers to find infallible approaches to verification of each step of the packaging process. Previous approaches involving checklists, lot ID and process documentation, and operator sign-offs have left gaps in the “chain of evidence” that may be required to provide traceability. For almost 20 years, our medical device packaging equipment has been able to match tooling and process recipe to assure no mix-ups using RFID tagging of the tooling. Now, technology exists to capture data to document who and when someone edited a validated recipe, who and when someone calibrated the equipment, what alarms occurred during the production run, and even when and on what package. This provides a verified match of the tooling, recipe, and production lot information. Even UDI information (parsed or complete nomenclature) can be captured to provide evidence of the parameter conditions at the moment of packaging.
Seán Egan: Development of simulation testing for package integrity of thermoformed rigid plastic trays is an exciting advancement. We have developed NeliSim, a simulation process giving OEMs upfront data on how well a package design will perform during physical testing before entering the prototype stage. The advantages of understanding design and material impact on the pack early in the process is a game changer, especially when it comes to speed to market—it enables confidence in the solution before entering validation.
Mark Hagerty: The most exciting recent advance in packaging and sterilization is the introduction of instrument trays with vented silicone organizational components. Silicone holders keep delicate instruments in place during sterilization, preventing damage. The vented silicone holders allow sterilant to access the entire instrument, reducing the risk of contaminants entering the OR.
Maura O. Kahn: There are a couple new sterilization methods with faster cycles that are easily brought into a company’s manufacturing facility—providing a just-in-time option. Nitrogen dioxide (NO2) gas sterilization is one of the new methods. The benefits of NO2 include an ultra-low temperature sterilization process, the total process time is typically 2-4 hours (including aeration), and it is safe and simple to operate and bring in house.
Brian Nissen: I am excited about advancements in X-Ray sterilization, and the potential of processors coming online in the U.S. soon. X-Ray has better penetration than E-beam radiation, which offers some better options to packaging engineers when creating load configurations for terminally sterilized packages. Also, X-Ray and E-beam are both potentially more environmentally friendly radiation sources than gamma sources.
Jeff Sauter: With the advancement and increased use of specialized polymers, hydrogels, and biomaterials in products such as implantable devices, bioresorbables, and combination devices, terminal sterilization is becoming more complex. E-beam has emerged as preferred terminal sterilization modality for these types of sensitive materials, as E-beam is not as harsh to product as gamma. Plus, E-beam offers flexibility to optimize sterilization including continuous temperature control, split dose processing, and other advance methods to minimize the deleterious effects of irradiation.
Don Tumminelli: In the world of reusable devices, many wrap manufacturers and container manufacturers are adapting to CS (Central Service) departments’ needs. For instance, to minimize holes in wraps, the wrap manufacturers are designing systems to help reduce the number of holes and tears that could compromise sterility. Some of these systems are unique shelving and tray transport systems. In the world of containers, there is a rise in larger size multi-tray containers that deploy directly into the sterilizers.
Brian Whalen: One area of advancement we see is centered on automated systems and robotics. Our customers are looking for ways to improve efficiency in their plants and are turning to automated systems for that. In response, our packaging products and materials must be designed to work with and take advantage of these automated systems. We work closely with their engineering teams to ensure our products help maximize their efficiency. This collaboration will help the medical device packaging industry overall by increasing productivity, optimizing workflows, and cutting costs and lead times for medical device manufacturers.
Brusco: How can orthopedic/medical device manufacturers benefit from considering packaging and/or sterilization early in the design process? What are the caveats of waiting too long to consider packaging design and/or design for sterilization?
Abraham: Packaging failure is just as critical as a device failure when looking at the timeline for a new product launch. Even early in the process, based on general dimensions, the packaging engineer can confirm any existing equipment capacity vs. the need to expand with the purchase of new equipment.
Will there be a special packaging feature or material unfamiliar to the team needed, increasing risk without up-front homework? Has production been having issues with existing packaging, on parallel products, where a root cause should be identified and not repeated on the upcoming project? Can the packaging engineer be allowed a day to visit the manufacturer for focused, hands-on immersion training before the packaging equipment is shipped? Any one of these questions can lead to avoidance of a catastrophic project delay.
Egan: The FDA is focusing on ensuring clear partnerships between OEMs and suppliers and transparency in working together toward the common goal of patient safety. The FDA is doing this in part by working very diligently with OEMs to ensure suppliers are being integrated as a vital part of the OEM’s processes and not just treating them as a customer/supplier relationship.
Hagerty: Medical device manufacturers could benefit from determining a packaging partner with the necessary sterilization validations for their device early in the design process. A strong partnership could help accommodate real-world applications such as the instrument size with consideration to the size of the container and sterilizer. Waiting too long to consider design for sterilization could lead to a number of issues for the manufacturer, including instruments that are improperly sized for protection during reprocessing or product delays due to regulatory constraints.
Britt Jones & John Neville: During product development, packaging design and sterilization go hand-in-hand. Planning and executing the package validation early ensures the product will maintain its sterile barrier and the package assembly is suitable for distribution. Once the packaging is finalized, the sterilization load configuration and validation of this process is determined. All of the validation evidence is essential to meet ISO standards and regulatory expectations within a product submission.
Moreover, prioritizing packaging early in the design process can help avoid product launch delays. This enables OEMs to detect potential flaws of packaging and sterilization processes, as well as make decisions to enhance or reduce the amount of packaging. It’s helpful to engage end-users early in the design process to ensure the packaging is easy to open in a sterile environment while wearing gloves.
It’s also important to note establishing expiration dates depends on package integrity testing after real-time and accelerated aging of a sterilized product in its final packaging. Real-time and accelerated aging coupled with package integrity testing provides essential data to support shelf life stability. With package integrity testing performed at various times through aging and real-time studies, a medical device manufacturer will have data to verify the sterile barrier is maintained.
Kahn: The earlier in the design process the product development team considers sterilization and packaging, the better. It reduces “surprises” after the product design is finalized. By evaluating sterilization options early in the process, the team expands the range of device materials (existing and new) and designs that can be used in the device.
Pal Khangaldy: It is critical to consider packaging (both design and validation) as well as sterilization validation early in the process. Oftentimes packaging is left as the last step and companies scramble to get packaging and packaging validation conducted. Packaging design and validation studies can take months to complete, so it is essential to plan for the timing early in the design phase. The following are tests that must be considered for a full packaging validation:
Shelf-life validation: Real-time aging is required by ISO 11607. A company can go to market using accelerated aging data, but real-time aging has to be started concurrently and validate the results of accelerated aging studies. The most common temperature to use for accelerated aging is 55ºC, which simulates one year of real time in 46 days.
Transportation/distribution testing: This test consists of subjecting the packaging to a series of inputs including drop/shock, vibration, compression, altitude, temperature, and humidity. Essentially, potential hazards that a package system can be subjected to in a real-life shipping/distribution environment are brought into a lab setting to validate the performance of the packaging and its ability to protect the product.
Baseline testing: The samples must be subjected to strength, integrity, and microbial barrier testing to determine if there are breaches in the sterile barrier. The strength tests include seal peel and/or burst. The integrity tests include visual inspection, bubble emission, or dye migration. The microbial barrier tests include either whole package aerosol challenge, ASTM F1608, ASTM F2638, or the Gurley permeability test.
These are conducted post-transportation (baseline) and after each aging time point. Other items to consider are a justification for sample size and minimum seal strength.
Sopheak Srun: Failing to consider packaging design and compatibility with a sterilization process early on in product design is actually a fairly common mistake that many device manufacturers will make. For example, gas-based sterilization processes require a gas pathway to reach and sterilize all surfaces, so it’s important to ensure a device is designed with holes and other features to allow for the sterilant to reach those surfaces. It will typically require a longer (and costlier) sterilization cycle if those gas pathways are restricted. Some materials will also degrade or change during certain sterilization processes. This is an especially important consideration for polymers that will be sterilized by irradiation (gamma, e-beam, or X-Ray). It is common to use additives to ensure the stability of polymers following irradiation. Certain polymers can also be more compatible with e-beam compared to gamma radiation. E-beam typically does not penetrate as well as gamma, so the use of e-beam will typically require special considerations in product and packaging design to ensure adequate sterilization dose penetration.
Sauter: Sterilization, packaging, and material compatibility are often considerations determined at the end of the product development cycle. Yet these considerations, if not made properly, can often lead to costly product delays and redesigns. The more complex a device is, the more important the sterilization method choice. Improving the design of the device to minimize complexity, limit handling, and incorporate biomedical materials and safe microbial agents can make sterilization easier and more efficient. It is absolutely vital to determine suitability of sterilization modality for given product, then optimize the sterilization process, incorporating advanced techniques to preserve product performance/functionality—not to mention optimal throughput—early in the product development cycle.
Whalen: Setting the stage for long-term success means clearly defining the requirements of a packaging system early in the product development phase. Prequalifying those requirements prior to full package system validation will save time and money in the long run. Preliminary evaluation of product-package compatibility allows for early detection of design or manufacturing problems and time for revisions prior to full validation. Identifying possible packaging failures and addressing them proactively during early design phases greatly increases the chance of successful validation and patient safety. When this step is skipped or left to the last minute, shortcuts often utilized to save time and money can increase the risk of noncompliance with regulations. Instead, during this process, different sterile barrier systems can be evaluated and manufacturing methods evaluated to best meet the needs and characteristics of a particular device.
Test failures are not uncommon and must be considered during the development process. By starting this process early in product development, these contingencies can be addressed early and unwanted delays and added costs can be avoided.
Brusco: Can you offer insight on the impact of recent regulatory activities on orthopedic/medical device packaging and sterilization?
Abraham: The tracking and traceability of the device in its package with an easily produced infallible audit trail has been a subject for many of our customers. Additionally, maintenance schedules and proper execution thereof for the equipment (e.g., service per OEM recommendation, no “home-made” software edits, safety system bypasses) and tooling (e.g., gasket replacements) has been subject for examination by auditors. Incorrect calibration “adjustments” by third party contractors not trained on the equipment and/or not following OEM instructions have resulted in equipment operating, unknowingly, at parameters outside the validated recipe.
Jones & Neville: The EU Medical Device Regulation (MDR) has significant implications on device packaging and sterilization. OEMs should be aware of changes in device classifications, as well as new classifications of devices, such as Class 1r, reusable. Device manufacturers will need to submit a technical file for review by a Notified Body to show data that proves safety and efficacy of the cleaning, disinfection, and sterilization processes outlined in their instructions for use (IFUs). Technical files must be compliant with all relevant standards, including ISO 17664 for reprocessing validations. To provide robust technical file data and have the best chances of regulatory approval, device manufacturers should develop studies and test plans that challenge devices in “worst-case scenarios.” Devices must be certified to Class 1r under MDR by a Notified Body by May 25, 2020. Extensions won’t be granted, and there will not be grandfathering for this class.
Nissen: There is a pending update to ISO 11607-1 and 11607-2, which adds usability studies as a requirement for medical device packaging. To satisfy these new requirements, manufacturers must conduct a study demonstrating the device packaging allows the device to be effectively transferred into the sterile field without being contaminated by the users. Additionally, with the more restrictive requirements in the EU MDR (Medical Device Regulation), I would expect to see more manufacturers digging into and possibly repeating older package validation studies as part of their recertification under the new rules.
Sauter: Within the sphere of terminal sterilization, there are concerns with Ethylene Oxide(EtO) residuals, which are known carcinogens. The EU mandates all medical device companies exhaust all terminal sterilization methods before resorting to EtO. EPA has proposed lowering maximum allowable limits of EtO residuals. There are also significant concerns over the environmental effects in communities with EtO sterilization facilities. While legislation has not been enacted, there are big concerns. For gamma sterilization, there are environmental and security concerns. There is also a shortage of Cobalt 60, which is likely to be a long-term issue unless imported from Russia—which is another concern.
Tumminelli: Most FDA cleared packaging systems for reusable medical devices subject to the FDA 510(k) system are requiring testing of the full range of the product line. For instance, for a packaging system which comes in multiple models or sizes, testing should be considered for the entire range of models and sizes, not just one worst case model. We have seen increasing deficiency letters when only one worst case model is chosen to represent the entire line.
Whalen: We are seeing increased regulatory activity related to individually sterilized implants. There is growing concern over the integrity, sterility, and traceability of orthopedic implants and screws packaged in large format trays or sterilization caddies. Hospitals are growing concerned that this current system of implant transportation and sterilization may contribute to increased infection rates. As a result, orthopedic/medical device implant manufacturers are looking for ways to individually package and sterilize these implants and screws without adding significant packaging and processing costs.
Brusco: What changes to orthopedic/medical device packaging and/or sterilization do you see happening in the years to come?
Abraham: Data will become paramount. Evidence, traceability, infallibility, and long service life due to validation requirements will see the commercial providers fall behind the more technically proficient.
Hagerty: We anticipate a shift from single-use disposable products used during reprocessing to reusable sterilization containers. With this change, we predict a consumer expectation that device manufacturers supply packaging with the necessary validations, allowing customers to use their desired sterile barrier and method of sterilization. We aim to design our products to fit popular instruments and be compatible with the 510(k) clearances of various sterile barriers.
Kahn: We are working with more and more orthopedic companies with custom implant product lines. This provides new opportunities and challenges for companies. Companies want to ship the custom implant as soon as possible, and the patient is waiting. Nitrogen dioxide sterilization provides unique benefits for these types of devices: total process time is typically 2-4 hours (including aeration) and they are safe and simple to operate and bring in house, providing control of the supply chain. NO2 may reduce sterilization to 2 days versus 5-30 for contract sterilization.
Khangaldy: ISO 11607 is currently being revised and a new version will be published early in 2019. In addition, the new Medical Device Regulations (MDR) is being released in Europe. Stay tuned for updates.
Nissen: I expect to see continued proliferation of additively manufactured devices, both in standard sizes and prescription, custom devices. Due to this growth, I also expect to see considerable price and lead-time pressure on manufacturers of those devices. It is possible the manufacturing of prescription, custom devices could begin to move from manufacturers to hospitals and surgical centers, much like how dental offices are starting to offer on-site manufacturing of crowns. I also see an industry shift away from gamma sterilization toward X-Ray and e-beam sterilization.
Tumminelli: We see a growing demand by healthcare facilities to have faster turnaround times for orthopedic/medical device reprocessing. Packaging products will need to accommodate devices that can be validated with shorter cycle times, i.e. exposure time if the device requires an extended cycle and/or a much shorter dry time.
Sauter: We see X-Ray emerging as sterilization technology that will eventually displace gamma. X-Ray, like E-beam, is an environmentally friendly technology and is not as harsh to produce as gamma. Companies are looking to move away from gamma already because of the Cobalt 60 shortage, now and in the future. Within the sphere of gas sterilization, we see the emergence of Vaporized Peracetic Acid (VPA) and NO2 displacing EtO with the likes of Revox and Noxilizer as interesting companies to follow in this space.
Whalen: Eventually, I believe all orthopedic/medical device implants, screws, drivers, bits, etc., will be individually packaged for improved integrity, sterility, and traceability. We are seeing the start of this trend now and I am confident it will be industry-wide within the next three to five years.
Brusco: Is there anything else you’d like to say regarding orthopedic/medical device packaging and sterilization, any particularly important topics within the sectors that you feel ODT readers should know?
Abraham:The greatest resource for the medical device manufacturer is their people. Searching for the best and keeping them is a formula for long-term success. I see so many young people in the field of medical device packaging frequently moving about to improve their careers. The question for employers is why. Staff and knowledge turnover are a detriment to long-term excellence. Why seek out the best candidate only to hook them to the plow without further regard? Giving them experience, responsibility, and a dose of mentoring will groom a future team leader. It is also incumbent on the young engineer to be inquisitive and learn as much as possible about the processes upstream and downstream of their assigned post as a means to become something more than just another box on the org chart.
Egan: We cannot have a disconnect between the medical device product, its packaging, and the sterilization process. This must be perceived as “the complete process” to ensure efficiency and efficacy. Speed to market is also critical to launch the latest and greatest medical devices that will ultimately improve or save lives. That is why not working these three processes (the product, packaging, and sterilization process) in parallel (through partnership) could delay the launch of a new device and the competition may take advantage to get the “next” best product out there—absorbing a large part of the market. This leaves little room for mistakes for our customers. Not involving the packaging SME at the early stages could represent a significant monetary impact by losing market share/opportunities, delaying FDA approval, or losing credibility if the new device does not fulfill the patient and/or market expectations, which at the end is a very high price paid by OEMs.
Hagerty: Do your research when vetting a packaging partner; make sure the tray you choose has validations for your instrument’s sterilization cycle. Ask about lead times for design and testing so you’ll be able to get your device to market on time. Lastly, choose a partner with experience.
Kahn: There has been a lot of change in the sterilization industry over the last 10 years, especially around consolidation and market presence. Some orthopedic companies rely on sterilization methods and equipment no longer supported by the original sterilizer company. As challenging as it is to make any changes to a device (including sterilization), there are many options for companies that will allow them to strengthen their supply chain and reduce risk, whether that be contract or in-house sterilization.
Srun: After being exempt from bacterial endotoxins testing (BET) requirements for a number of decades, sterile implantable orthopedic products are now required to be evaluated for bacterial endotoxins per the FDA’s latest guidance for 510(k) submissions. However, there are still some ongoing discussions and debate about what bacterial endotoxins testing requirements should be for implants. Look for a new version of ANSI/AAMI ST72 in the near future, which will provide some guidance on this topic.
Tumminelli: The growing demand by healthcare facilities to have faster turnaround times is and will continue to be a critical topic for healthcare facilities reprocessing orthopedic/medical devices. The entire reprocessing cycle, starting with point of use, transport, decontamination, inspection, packaging, sterilization, and transport, will be scrutinized by healthcare facilities who have a desire and demand to do more with less.