Testing services for medical devices have never been in higher demand. Key drivers include more discretionary medical treatments and procedures, as well as at-home diagnostic and monitoring self-care devices. This reflects the trend toward a higher level of innovation in medical devices, such as greater functionality, advanced software, microelectronics, and tight tolerances required for minimally invasive equipment.

“With COVID-19 well behind us and budgets back on track, 2023 was a bustling year and 2024 looks like it is off to a good start,” said Donald Tumminelli, technical manager for client services for HIGHPOWER Validation Testing & Lab Services, a Rochester, N.Y.-based validation and testing laboratory. “Last year was full of challenges for medical device manufacturers, with more on-site FDA audits leading to more non-compliance findings, which then required additional testing to fill those gaps.”

Testing firms and equipment manufacturers are investing more money in R&D and innovation to keep up with medical device manufacturers’ (MDMs) demands. For example, there has been significant growth in the development of combined devices that include a drug product within the device itself. There is also considerable interest in temperature-sensitive combined devices that must be maintained within a specific temperature range while remaining sterile. “These growth areas provide a fun challenge for us to help our partners ensure that their products are delivered to their customers with the sterile barrier intact and within the specified temperature range,” said Greg Schwinghammer, general manager for WESTPAK, a San Jose, Calif.-based accredited testing laboratory specializing in mechanical and environmental testing for life sciences.

Testing instrumentation continues to advance in terms of functionality and precision (including being embedded in the manufacturing equipment itself), which improves quality, saves time, and makes production more efficient—especially when integrated with Internet of Things (IoT) technologies.

“Customers are increasingly interested in having product testing integrated into their manufacturing equipment, with artificial intelligence making inroads into this space,” said Dave McMorrow, technical director at MMT Automation, the Ireland-based automation division of MMT that specializes in designing and building custom automated equipment for the manufacture and testing of minimally invasive medical devices. “The ability to integrate software capabilities to monitor trends in the data improves quality and makes manufacturing faster and more cost-efficient.”

One of the biggest drivers for testing labs is helping MDMs achieve compliance with new or changing regulations. The most impactful change in the testing field is the replacement of the EU Medical Device Directive (MDD) with the EU Medical Device Regulation (MDR), which now covers more devices and promotes a lifecycle approach to regulation. MDMs continue to focus on preparing for MDR, even as regulations in the EU face further delays. “Companies are either completing their remediation efforts or opting to postpone testing until there is more clarity on timelines,” said Thor Rollins, vice president and global market segment leader for Nelson Labs, a Salt Lake City, Utah-based provider of laboratory testing and expert advisory services. “Another notable shift is observed in the redirection of R&D efforts and investments towards connected devices and artificial intelligence.”

Even as the pandemic continues to fade, supply chain disruptions as well as material and personnel shortages can still be problematic, which makes forecasting, deliveries, lead times, and production schedules difficult to predict.

“Supply chain issues continue to challenge the device industry, necessitating material changes that impact chemical characterization/biocompatibility or delay testing,” said Geoffrey Moodie, director of biocompatibility for Eurofins Medical Device Testing, a global provider of testing for Class I, II, and III medical devices and validation for product designs. “Upcoming changes to REACH [Registration, Evaluation, Authorization, and Restriction of Chemicals] regarding polyfluoroalkyl substances [PFAS] are also a key area of concern for impacted device manufacturers.”

For those companies that are still wary, the slow recovery of supply chains, shifting regulatory environment, and stubborn global inflation have made them more cautious about outsourcing their testing. “Many large OEMs have pulled back to restructure their debt, spin off low-profit product divisions, insource testing, or place R&D projects on hold,” said Matt Pasma, program manager for DDL, a Minneapolis. Minn.-based third-party testing laboratory that provides packaging and device and materials testing.

Latest Trends

Industry consensus standards such as ASTM and ISTA are being updated to more accurately reflect the actual distribution environment in lab testing. “For prolonged and permanent exposure devices,” said Chris Parker, head of in vivo biocompatibility for Labcorp, a preclinical medical device testing and development contract research organization with dedicated locations in the San Francisco and Boston areas, “there is also strong emphasis on analytical evaluation threshold [AET] considerations in design of chemical characterization and toxicological risk assessment.”

Biocompatibility remains a top concern for medical devices that make contact with human tissue, either on the skin or inside the body. There is growing emphasis on in-vitro alternatives to animal testing, accompanied by industry-wide initiatives to assess outdated scientific practices and explore new options. The demand for an in-vitro model for irritation testing, especially by countries outside the U.S., is growing. “As the FDA currently does not recognize this model, we continue to work with other laboratories and manufacturers to provide data in support of this in-vitro test method, with hopes that the FDA will add this to its list of acceptable methods for irritation testing,” said Sheri Krajewski, senior global product manager, biological safety, for NAMSA, a Toledo, Ohio-based medical device contract research organization with multiple worldwide locations.

Some labs have seen an uptick in biocompatibility risk assessments and chemical characterization for gas pathway devices, including inhalational drug delivery systems. This includes additional scrutiny on aldehydes, carbon monoxide, carbon dioxide, and ozone. “There is also increased activity in CCIT [container/closure integrity testing] as manufacturers prepare for USP 1207 updates and the new 382 chapter,” stated Moodie.

Regarding sterilization methods, there is still large demand for low-temperature sterilization using vaporized H₂0₂. “Last year, one manufacturer dropped out of the market, discontinuing its low-temperature sterilizer,” said Rollins. “This small void in the market will likely be filled by larger H₂0₂ manufacturers.”

Ultimately, regulatory bodies are pushing hard for a risk-based approach in testing and for justifications for submissions. Some of the major device standards have been updated to emphasize this approach. “Using a risk-based approach ensures devices and the potential issues that can arise during use are fully vetted out and a device is tested to the correct standards and sample sizes based on the risk of a failure of a device,” said Pasma. “The more severe an outcome of a device failure is, the more the device is tested to ensure the device is fully functional.”

What OEMs Want

Compliance with the EU MDR and other regulations continues to drive most of the trends in the testing industry. However, for many testing labs, there were fewer MDR testing requests in 2023 compared to the previous few years, which may signal MDMs are catching up to the MDR, or they feel like they have more time, considering the MDR extension announced in December 2022.

For the single-parcel environment, the most popular tests are ASTM D4169, DC13, and ISTA 3A. For the palletized or skidded environment, ASTM D4169, DC12, and ISTA 3B or 3E tend to be the most requested. In extractables and leachables (E&L), the industry continues to face challenges regarding test designs, “such as aggressive solvents or unrealistic extraction parameters,” said Rollins.

“There is also momentum in the standard committee this year to refine and simplify these extraction parameters, aiming to reduce frustrations without compromising patient safety and enable consistent methodologies across laboratories.”

Top concerns by MDMs for their additively manufactured (AM) devices are biocompatibility, extractables, and cleanliness (removal of residual waste materials). In addition, as AM evolves and matures, so must the associated testing standards, including the presence of potential harmful residuals and/or particulates. “Determining the optimal methods for cleaning or preparing these samples remains a key challenge,” said Rollins.

Cleaning validations are still near the top of the list of studies that most manufacturers request “Many MDMs are still in the process of assessing compliance to AAMI ST98, which was published in August 2022,” said Tumminelli. “There is still a large learning curve for understanding what is needed. Many companies have performed assessments to verify if previous studies conducted under AAMI TIR12 could be leveraged; however, the majority of the time, the TIR30 studies lack in the sample size and controls needed to comply with the ST98 standard.”

Advancements and Improvements

The FDA ASCA (Accreditation Scheme for Conformity Assessment) program is a resource that more manufacturers are starting to embrace as they learn more about the efficiency and speed of using an ASCA laboratory. As the first ASCA laboratory for biocompatibility, NAMSA has seen interest increase over the past year and—with support from the FDA—“this is a key way manufacturers can speed up the review process by essentially submitting reports that have been pre-approved by the FDA,” said Krajewski. “As more data comes out from the FDA on the success of the program, companies will come to trust the value of this program.”

Rapid sterility methods gaining momentum in the industry include:

• ATP bioluminescence detection (Celsis Advance II, Milliflex Rapid System 2.0)
• Growth-based methods for gas detection, typically CO2 (BacT/Alert 3D)
• Non-growth base method with labeling and laser scanning for fluorescent signal (ScanRDI)

“At Nelson Labs, we are working to validate and implement these new methods for our clients that are looking to reduce the total time for sterility testing,” said Rollins. “These methods look to reduce the current required incubation time for sterility tests from a required 14 days to four to seven days with qualification.”

On the materials front, MDMs that want to reduce the use of plastics are finding more sustainable ways of packaging medical devices and durable goods. “We have done a lot of testing recently with new and innovative cushion systems that replace the classic, expanded polystyrene, polyethylene, and polyurethane cushions with more environmentally friendly solutions,” said Schwinghammer. “Starch-based, paper, and corrugated fiberboard can be effective substitutes for some of these petroleum-based materials.”

Also impacting materials is ASTM 1980, which was revised in 2021. One of its new requirements is for MDMs to examine the impact of moisture on their products and package materials and factor that in when determining the accelerated aging temperature and humidity inputs. MDMs that were able to avoid the humidity requirements in the past are now scrambling to purchase new chambers with controlled humidity. “This has resulted in a delay in compliance with the standard as the manufacturers of the chambers and the MDMs need additional time to purchase, install, and qualify the new chambers,” said Tumminelli.

The CT scanning of medical device components continues to grow in popularity, especially for miniaturized devices. These images allow “manufacturers to have dimensional analysis/first article inspection completed on internal features as well as other key features of parts and devices,” said Pasma. “It also allows manufacturing defects such as porosity and shrinkage to be evaluated in a faster and more reliable manner, as a part no longer has to be sectioned to observe internal features.”

Using this technology, manufacturers can make changes to non-conforming parts more quickly than ever before. Since many parts and devices are created with plastics and other lower-density materials, these can be scanned and point clouds created, which can then be compared to either a drawing or a CAD model. CT scanning also allows operators to evaluate individual manufacturing processes—for example, ensuring a part did not over-shrink in a mold, or the porosity of the material is adequate and the process is running smoothly.

Internet of Things

One of the most popular applications of IoT technologies has been the testing of wireless devices—MDMs and their contract manufacturers (CMs) must ensure these devices work over WiFi during the procedure and are transmitting secure patient data that cannot be tampered with. “The Association for the Advancement of Medical Instrumentation [AAMI] has spent quite a bit of time ensuring that standards are created and available for tackling the current standards that govern cybersecurity in the healthcare setting,” said Tumminelli. “Along with the standards, AAMI has also held symposiums and training on cybersecurity. This will be a dynamic, ever-changing challenge for all involved to keep pace with cybersecurity advances.”

With the rapid advancement of technology, regulatory bodies are pushing for more traceability and data integrity. “Ensuring these electronic records remain unbiased and correct is a very important part of a third-party testing lab’s quality management system,” said Pasma. “Validation of these systems to ensure outputs of testing are recorded correctly is critical to ensure confidence of data and results.”

Artificial intelligence (AI) presents a significant opportunity to create a much wider range of testing services. For example, AI is increasingly being used in automated vision inspection systems. “AI applications in vision are becoming increasingly mainstream with machine learning being leveraged for defect detection,” said McMorrow. “An example of this is in braided shaft production where MMT has applied machine learning to automate vision inspection for attribute defects in the outer jacket, due to lamination defects or braid inconsistencies.”

Although current utilization of AI may be limited, the future holds vast possibilities. AI will soon be instrumental for advancing automated image analysis, predictive maintenance for testing equipment, data analytics for performance monitoring, as well as AI-driven analytics processing of extensive testing data to identify patterns, trends, and potential issues. “Additionally,” said Rollins, “there are prospects for simulation and modeling, robotics in testing, quality control and traceability, adaptive testing protocols, and integration with internet-connected testing devices.”

Regulatory Considerations

With the recent changes in the MDR and other regulatory bodies, MDMs need to focus on data integrity and the validation of methods and systems. A risk-based approach ensures the test methods are validated and the results are repeatable and reproducible. The FDA, especially over the last year, has started enforcing a risk-based approach for conducting testing and validation of devices. “This approach ensures a device has been fully reviewed and proven prior to submissions,” said Pasma. “It creates a road map for what is needed in a submission of a device to the FDA/regulatory bodies when a manufacturer is submitting a device for review.”

The FDA has also shown increased scrutiny of chemical characterization processes. Examples include FDA requests for additional chemical standards for liquid chromatography/mass spectrometry and gas chromatography/mass spectrometry. The FDA is also expanding some requirements for packaging systems, specifically flexible packaging systems such as pouches and wraps.

For the biological safety of medical devices, the FDA has published an updated guidance, as well as a significant addition to the 2023 ISO 10993-17 standard, for its consensus standards. Both documents give some direction in biocompatibility and toxicological risk assessment. “One key update within the biocompatibility guidance is located in ‘Annex G: Biocompatibility of Certain Devices in Contact with Intact Skin’ made from certain synthetic polymers and natural fibers,” said Krajewski. “This allows manufacturers of these devices to utilize a least-burdensome approach, and should certainly give manufacturers of lower-risk devices a clear path to market clearance with very limited testing, if any.”

“The update of ISO 10993-17 and recognition by the FDA significantly changes the way that toxicological risk assessments are performed for medical devices,” added Moodie. “For most devices, these changes are welcome as they represent a more considered approach to risk from chemicals associated with medical devices.”

The new AAMI ST98 has also created significant challenges. The standard has increased the amount of work and cost that goes into FDA-compliant cleaning validations. This has resulted in an unexpected financial burden on MDMs.

“The HIGHPOWER team spent countless hours finding ways that the analysis can be completed at the least cost to the customer, but still yield an FDA-compliant analysis,” said Tumminelli. “One way the team was able to minimize costs was that, in the event that acceptance criteria were not being met and a retest was needed, we were able to work with the negative control and include this in up-front simulated use soiling. This resulted in both less cost and time to initiate a retest, without compromising the analysis.”

Meeting Customer Expectations

One of the top challenges for testing firms is meeting the tight timelines and turnaround times their MDMs want. Not all MDMs understand that some tests simply cannot be rushed. “Testing labs are often asked to complete testing on tight timelines, and thus, we are often asked to turn around projects in an unrealistic period,” said Pasma. “With any testing project, the earlier you get started, the better.”

Sometimes, MDMs think they can do their own testing in-house to save money or time. This is not an inexpensive venture—before trying their own testing, MDMs should keep in mind the initial cost of the equipment, the cost to maintain and calibrate the equipment, and the cost to retain skilled 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. For most MDMs, it is still less hassle and more cost-efficient in the long run to outsource their testing. Having a third-party lab perform testing also provides a more independent and less-biased view of the data.

The size of medical devices and their components continue to get smaller, yet with increased product functionality and complexity in a reduced product footprint. This creates new challenges and opportunities in product testing, which can be realized with innovative and ever-advancing technologies such as AI, automation, sensors, and nanoelectronics.

It is absolutely essential to have the testing team be part of an MDM’s design for manufacturability (DFM) sessions. DFM should cover all the steps of the entire design/production/shipping process.

Engineers are often too focused on the design of a product and the technologies and materials involved, and give testing and shipping just a passing thought. For example, one of the biggest challenges in smaller and more complex devices is that “the product designers often do not consider the product must be shipped and they create beautiful designs that are so fragile, they are impossible to get to the end customer safely,” said Schwinghammer. “The packaging group in any company should be brought in at the beginning of the development process to help designers create a product that reduces the amount of required packaging and increases the use of environmentally friendly materials while making a more robust product.”

Within the context of smaller and more complex devices, regulatory scrutiny, challenging testing requirements, and innovative new testing methods and equipment, Krajewski believes the last two to three years have been the most exciting time in biological safety/biocompatibility since the inception of the ISO 10993 series in 1995.

“We have had a number of very important standards updated, as well as new challenges with the advances in chemical analysis of medical device extractables and the toxicological risk assessment and of course the introduction and subsequent extension of the MDR,” said Krajewski. “As we work through daily experiences with both regulators and sponsors, we are seeing struggles with getting new devices cleared, as well as addressing changes to already-marketed devices, potentially delaying innovative solutions. Being closely involved with not only a laboratory but also a toxicologist experienced with medical devices is more critical than ever. Experienced labs and experts are key to minimizing delays with market approval globally.” 

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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 more than 15 years and is the author of five books.