Medical Device Testers Are Caught Up in a Whirlwind

In its prime, COVID-19 had a massive impact on testing services for medical devices. Even though the pandemic continues to fade, supply chain disruptions and material and personnel shortages still remain, all of which make forecasting, deliveries, lead times, and production schedules difficult to predict. Although they are generally optimistic, testing labs cannot help but feel somewhat uncertain about 2023.

“It’s almost a feeling of, okay, what else?” said Thor Rollins, director of toxicology and extractables and leachables for Nelson Labs, a Salt Lake City, Utah-based provider of laboratory testing and expert advisory services. “The uncertainty in the economy, and not being sure if we can get our needed materials in time, make it feel like we are walking into an uncertain area, without any real light to guide us.”

Matt Pasma, program manager for DDL, a Minneapolis. Minn.-based third-party testing laboratory that provides packaging, device, and materials testing, agreed.

“While much of the world returned to normal in 2022, many challenges remain from the impact of the pandemic, with remote work continuing to be a norm for many, logistical challenges of getting samples delivered, supply issues, staffing issues, and manufacturers putting projects on hold,” said Pasma. “Going into 2023, the hope is that we will continue to see these things return more to normal, particularly regarding supply and staffing.”

One of the biggest drivers for current testing work is medical device manufacturers (MDMs) that need support in being compliant with new or changing regulations. For example, validations for reusable medical devices are on the rise as more regulatory agencies recognize the importance of validating the specific instructions for reprocessing devices for multiple uses.

The most impactful change for the testing field is the replacement of the EU Medical Device Directive (MDD) with the EU Medical Device Regulation (MDR). “The EU MDR has expanded to cover more devices and promote a lifecycle approach to regulation,” said Donald Tumminelli, technical manager for client services for HIGHPOWER Validation Testing & Lab Services, a Rochester, N.Y.-based validation and testing laboratory. “The EU MDR now requires the usage of a unique device identifier [UDI] for medical devices used in the EU. UDIs must be accessible and readable throughout the duration of the product’s intended lifespan.”

In the interest of patient safety, regulators around the world are calling for more thorough testing and greater evaluation of device data. Practically, this means testing programs are moving from three test panels to five or six test panels, with significant analytical chemistry added as well.

“Device manufacturers are conducting more portfolio rationalization than ever before,” said Lisa Olson, senior vice president of global laboratory services for NAMSA, a Toledo, Ohio-based medical device contract research organization with multiple worldwide locations. “The EU MDR is causing manufacturers to look at their data for each device—in some cases, the data are coming up short compared to today’s standards. However, the cost and risk of re-doing tests versus pushing new devices to market is causing MDMs to really think about their portfolios.”

In the U.S., AAMI ST98, the first comprehensive standard for cleaning validations, has been published. This standard clarifies requirements for sample size, soils, and analytes, depending on device complexity and intended use. AAMI ST98 will replace AAMI TIR 30. “The new requirements ultimately will add more cost and time to execute a cleaning validation for a reusable device,” said Tumminelli. “However, the importance of standardizing these tests cannot be overstated; it now puts the medical device community on a level playing field in that all testing must be done to a set standard, whereas before there were many variations and similarities for cleaning validations that could be followed.”

The overall dynamics of an aging population, coupled with an ever-increasing prevalence of chronic diseases, treatment options, and the complexity and diversity of devices (including home care and monitoring), have brought an increased need for specified equipment to test each component and function of the devices.

“Constantly changing regulations that are more complex and stringent are also driving the need to validate equipment and processes,” said Pasma. “Accreditations have also brought reliability in processes, equipment, and data produced from test labs to ensure the devices are meeting the regulations.”

What OEMs Want

MDMs are in a hurry. They want faster turnaround times. Extended slowdowns and cost constraints in device R&D due to COVID-19 have delayed new device development. Product development plans were often shelved, with discretionary funding used instead to support the making and delivery of approved products. Now, even as operations slowly improve, “supply chain problems from hold-ups in raw materials and extended sterilization queues continue to occur,” said Olson. “Because these factors still delay product submissions and market releases of new devices, MDMs are evaluating every step to determine where they can make up some time to get products to market faster.”

Complying with EU MDR and other testing changes by regulatory bodies continues to drive many of the current trends in package testing. For example, many MDMs will need to redo packaging validations for many of their legacy devices, especially transportation distribution testing, to generate the documentation that is now required by EU MDR (and not previously required by EU MDD).

MDMs are lining up with their testing partners for ST98-compliant cleaning validations and testing to fill in the gaps created by EU MDR. “If the requirement is fairly new—for example, extractables and leachables for toxicology—then most devices will need this testing before they can be submitted to their notified body for MDR,” said Rollins. “As a result, there is a run on these types of tests.”

The ASTM F1980-22 update is also impacting MDMs. For example, MDMs must conduct validation studies if their products are affected by high or low relative humidity levels. “In response, WESTPAK has grown its fleet of chambers to accommodate customer needs by increasing our capacity for a wide range of temperature and humidity combinations,” said John Baumwoll, production manager at WESTPAK, a San Diego, Calif.-based accredited testing laboratory specializing in mechanical and environmental testing for life sciences.

Canyon Labs, a Bluffdale, Utah-based microbiology and chemistry laboratory that provides laboratory testing and clinical research services, is seeing more requests for chemical characterization, biocompatibility testing, sterility testing, and testing to support 510(k) submissions.

“These requests are tied back to the changing healthcare landscape,” said David Locke, chief clinical research officer and regulatory affairs specialist for Canyon Labs. “Nationally, healthcare spending accounts for nearly 20% of the U.S. economy. Many state and national governments are incentivizing life sciences companies to develop preventive solutions to reduce the burden of healthcare costs on the economy. This support has led to the introduction of innovative medical devices and implantables that restore mobility and address cardiovascular and brain health. This of course requires assessment of the safety and efficacy of these devices, for which many companies develop a biological evaluation plan.”

DDL indicates there is significant demand for testing of syringes, auto-injectors, and packaging validations. Requests are also coming in for medical connector testing under the ISO 80369 standard. “The bulk of this work is testing physical and mechanical performance to measure attributes such as leakage, break loose, extrusion force, and deliverable volume as outlined in the ISO 11040 and ISO 11608 series of standards,” said Pasma.

MDMs are also doing more testing for packaging made from sustainable materials as part of their sustainable development goals (SDG). For example, MDMs are seeking thermal maps of insulated shipping containers that are made with sustainable, reusable materials. Many of these tests typically involve dry ice and require multiple pack-outs. “A problem, however,” said Andrew Thomas, lab manager for WESTPAK, “is that these packs are not as robust as traditional materials and often fail during dynamic testing. Medical device manufacturers of large units also require dynamic test data from vibration and shock inputs on crates and sizeable shipping containers. Accelerometers generate this data and it takes technical expertise to evaluate the responses.”

Now that COVID-19 is winding down, and projects that were put on hold and newer projects are all piling up for release in the 2023 fiscal year, “we are seeing a sort of whiplash effect and everything is coming to a head with increased demand on services,” said Tumminelli. A big problem, however, is that testing houses do not have enough qualified analysts and technicians to get testing finished as quickly as their MDMs would like. In addition, there are still significant interruptions in China with COVID-19 shutdowns. “This has forced many companies to rethink their long-term supply chain strategies and bring more manufacturing back to the Western regions,” said Pasma.

From Biocompatibility to Industry 4.0

As the ethylene oxide (EO) shortage continues, MDMs have prioritized finding effective alternative solutions to ETO sterilization. Many of these technologies (for example, vaporized hydrogen peroxide, nitrogen dioxide, chlorine dioxide, and peracetic acid) could be significant potential replacements for ETO; however, the safety and effectiveness of each technology must be fully assured, as well as scale/capacity.
“It is important to understand that these newer technologies may take an MDM many years to transition away from ETO, so patience is required as this process happens,” said Tumminelli. “The premature shutting down of ETO before new technologies were accepted is a big problem for the industry and could lead to shortages of some single-use devices.”

Biocompatibility remains the top concern for medical devices that make contact with human tissue, either on the skin or inside the body. If a device does not have any direct or indirect tissue contact, biocompatibility testing is not required for submission. However, for devices such as wearables and implants, the FDA assesses the biocompatibility of the entire device and not just the component materials. The frequency and duration of contact and type of material must also be considered.

As a result, testing labs are seeing increased demand for chemical characterization studies that more thoroughly assess the biocompatibility risks of these devices. Growing in popularity is the skin irritation test (SIT) that uses reconstructed human epidermis (RhE) tissue. This in-vitro test measures cell viability in RhE tissues that are made from human epithelial cells, which are cultured and differentiate to form a fully differentiated epidermis. With RhE tissues, test materials can be applied topically, at full formulation strength, without dilution. “Perhaps the greatest benefit from the RhE irritation test,” said Rollins, “is that it will greatly reduce or eliminate animal testing.”

The Internet of Things

Machine learning has been rapidly evolving in the fields of chemistry and microbiology. However, in the testing services field, there are still labor-intensive manual processes that require the skills of a microbiologist or chemist to analyze and provide data to customers and consultants. “By being able to see patterns and understand how things interact and impact each other, testing service providers can help their customers gain insights on their devices and potential redesigns,” said Locke. “FDA-regulated products require a robust risk management process and machine learning has the potential to find a more efficient way to create safe and effective devices.”

Internet of Things technologies such as automation, sensor networks, big data analytics, real-time data transmission, predictive maintenance, and artificial intelligence all contribute to improved efficiency and productivity and are especially valuable for documenting performance.

“We are seeing a push to have more traceability and audit trails in processes to ensure data integrity is maintained throughout the entire testing process,” said Pasma. “Laboratory information management systems [LIMS] and other specific add-ons are making this possible, especially since this is something the FDA and other regulatory bodies would like to see.”

For example, new and enhanced software does a better job of capturing, analyzing, and reporting data, which increases the accuracy of testing. Web cameras are often used to record testing, which can be played back to review particular points of interest frame by frame. “Videos can be stored and sent electronically for use in reporting,” said Pasma. “There is also more need for mapping a device to ensure that it will show up on X-rays and other medical scans to ensure its location is correct in the body.”

Additive Manufacturing

To date, additive manufacturing/3D printing (AM/3DP) has not had a significant role in safety testing, but labs need to understand the process and the potential for by-products that can be generated during manufacturing, or through later wear and tear. There are still unknowns regarding the comparative long-term safety and efficacy of AM-made devices—each and every process that uses AM must go through the same regulatory requirements that “regular” devices do, but with greater scrutiny on material performance over time and the longevity of the device.

“Finding the correct material to use in additive manufacturing is more important than ever,” said Pasma. “When devices are exposed to extreme temperature and humidity they react differently. Just because it is durable at room temperature does not mean it will last after an accelerated aging cycle or an environmental conditioning cycle where it is seeing temperatures of 55°-80°C. Even extreme cold can cause devices and materials to act differently, so all these factors need to be considered when selecting a material.”

Another top regulatory concern for additive-manufactured devices, specifically orthopedics, is cleanability, noted Rollins. “These devices are still unique in structure, materials, complexity, and possible manufacturing residuals, so proving that they can be adequately cleaned is a challenge,” he said.

Regulatory Challenges

Regulatory agencies are increasingly focused on the validation of test methods as they seek higher-quality data, especially for repeatability and reproducibility. There is also a shift toward more deterministic methods for testing. This allows MDMs to receive more statically sound data that can be analyzed to ensure their devices are conforming to standards (there have been recent updates to various regulatory standards, such as increasing the number of controls that labs must use with validations and qualifications).

“The FDA started taking a closer look at the paper trail and audit history of software and processes,” said Pasma. “With more people working remotely, this can cause issues with the traceability of a process. LIMS systems and software add-ons have aided in ensuring that we are compliant with the requirements from the regulatory bodies.”

The FDA has determined the pilot program for the Accreditation Scheme for Conformity Assessment (ASCA) demonstrated enough benefit to continue the program. The FDA is also considering modifications to widen its utility for biological safety testing. “This is important for both the FDA and manufacturers because it can really lessen the burden during the submission and review processes,” said Olson.

MDMs also need to be aware of the new cleaning standard ST98. The FDA has recognized it and may require it without any grace period. “It is possible the FDA will enforce ST98 during current submissions, even if the submission predates ST98 being published,” said Tumminelli. “MDMs need to be aware that even if a TIR 30 validation was submitted prior to ST98 being published, the agency may still ask for ST98 compliance, which could lead to a revalidation.”

Moving Forward

As the industry adapts to the current environment, regulatory and industry groups are meeting again to discuss the improvement of testing paradigms. “Discussions of evaluation of new methods, inter-laboratory development protocols, and standards development are taking off again,” said Olson. “Alternative testing is at the forefront of every scientist’s mind as COVID-19 demonstrated to us how things can be done differently with creative thinking.”

This includes developing new advances in testing equipment and software to make testing more accurate and efficient. Organizations such as ISO and ASTM continue to work to update and refine the standards to improve testing methodologies. “For instance, as changes with the way products are shipped or delivered, testing standards must also be adjusted to meet these changes,” said Pasma. “And, as innovation in product development continues, new test methods must be developed to match these updates.”

Changes to regulatory and testing requirements will continue to evolve in the coming years. As medical devices get smaller and more complex, and incorporate new and innovative materials, testing will become more specific and precise.

“Medical device science is trying to make huge bounds forward, but most of us feel the drag of ‘this is how we have always done it’ pulling us back,” said Rollins. “But things are moving forward—ranging from in-vitro alternatives to animal testing to risk-base approaches to testing, it feels like 2023 will be a transitional year from decades-old ways of thinking to the advances that will be commonplace in the future.” 

What MDMs Need to Know “There can be more than one path for demonstrating safety and efficacy to a regulatory body. Every standard provides guidance on approaches, but manufacturers do not often realize that with a thorough explanation addressing the actual question, alternate pathway can be accepted.” —Lisa Olson “Turnaround times are misunderstood by many MDMs, who often come to us and expect a study to be completed in a couple of weeks. The reality is these are very complex studies that can take 5-10 weeks to complete. Do not wait until the end of the design process to address the reprocessing validations.” — Donald Tumminelli “OEMs often consider doing testing in-house to save money and time. Before doing this, they should keep in mind the initial cost of the equipment, the cost to maintain and calibrate the equipment, and the cost to retain people with the technical expertise to run the equipment and perform the testing. Time is also a critical aspect to consider if a test needs to be completed quickly in order to meet a deadline.” —Matt Pasma “Test procedures can get challenging, especially when an OEM creates its own with sections copied and customized from standard industry protocols. As a result, we see mistakes, over-specification, and conflicting information, often with custom protocols.” —John Baumwoll “MDMs must be aware of the strong focus that FDA has on cybersecurity when it comes to medical devices that contain software. FDA has issued guidance documents around cybersecurity and developers need to be aware of the agency’s current thinking and recommendations when seeking to market these devices.” —David Locke

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Mark Crawford is a full-time freelance business and marketing/communications writer based in Corrales, N.M. His clients range from startups to global manufacturing leaders. He has written for MPO and ODT magazines for over 15 years and is the author of five books.