Orthopedic products have more to examine than ever before. Regulatory bodies expect polymeric materials to be screened for low molecular weight impurities and additives like residual monomers and solvents, light stabilizers, and antioxidants. For 510(k) submissions, the U.S. Food and Drug Administration (FDA) demands more detailed material compatibility and device cleaning studies. Testing isn’t limited to the device themselves either—packaging is subject to increased scrutiny, including usability and environmental impact.
The regulatory landscape will prove particularly challenging for medical and orthopedic device manufacturers looking to have products tested and analyzed, as both the EU and FDA will be modifying their standards in the near future. The May 2020 EU MDR deadline looms ever closer, and will promote a lifecycle approach to medical device regulation, as opposed to the previous MDD’s more significant focus on the pre-approval stage of medical device manufacturing. The FDA has also made several recent announcements declaring a planned review of its 510(k) submission process, which may call for more detailed testing and analysis.
In order to gain more insight on testing and analysis services for the orthopedic and medical device industries, ODT spoke to the following experts:
Maciej Jakucki, medical device manager at Element Materials Technology, a Fairfield, Ohio-based global provider of testing, inspection, and certification services for a diverse range of materials and products.
Matthew Jorgensen, senior extractables and leachables expert at Nelson Laboratories, a Sotera Health company based in Salt Lake City that provides full lifecycle microbiology testing services for the medical device, pharmaceutical, tissue, and natural products industries.
Dawn Lissy, president of Empirical Testing Corporation, a Colorado Springs, Colo.-based provider of mechanical testing for medical devices.
Christopher Parker, associate department head, in-vivo biocompatibility at Toxikon Corporation, a Bedford, Mass.-based preclinical contract research organization providing in vivo, in-vitro, and analytical testing services for the pharmaceutical, biotechnology, and medical device industries.
Rudy Pina, president of Dynatec Scientific Labs, an El Paso, Texas-based medical device testing laboratory.
Thor Rollins, director of toxicology and extractables and leachables consulting for Nelson Laboratories.
Christopher Scott, vice president of Eurofins Medical Device Testing, a Lancaster, Pa.-based international laboratory services company that provides a broad range of testing capabilities to the medical device industry.
Don Tumminelli, senior technical manager, client services, at HIGHPOWER Validation Testing & Lab Services, a Rochester, N.Y.-based provider of reusable medical device cleaning, packaging, and sterilization validation services.
Sam Brusco: Has your business been experiencing a rise in any particular testing methodologies? If so, why?
Maciej Jakucki: With the positive growth experienced in the extremities market, companies are exploring multi-axis methodologies where several different loads can be applied to a test setup instead of just axial or torsional loads. Shoulder, ankles, elbows, and wrists are complex joints that require thinking outside of the box, particularly if a unique design component is featured. Many of these tests borrow from methodologies of more well-established joints like hip and knee, but need to be modified and aligned to physiological loading. This has been an area of significant growth and our ability to partner with the customer and design custom methods continually adds to our expertise. Another growing area is evaluating wear debris, which can range from intentionally introducing media into the test chambers in order to accelerate wear (3rd body wear testing) or simply quantifying the morphology of particulate generated during a fatigue or corrosion test.
Matthew Jorgensen: There has been a sharp increase in evaluations of biological endpoints leveraging analytical data instead of traditional biological testing. For example, gas path device testing per ISO 18562 has started to become mainstream and is rising sharply as manufacturers of devices within this class prepare for the MDR.
Dawn Lissy: We are seeing a rise in new and updated versions of older technologies—for example, trauma plates, screws, IM nails, etc.
Christopher Parker: When ISO 10993-1 was published in 2018, which was predicated by FDA’s Use of ISO 10993-1 document in 2016, there was an increased requirement for chemical and physical characterization, and we’ve seen a big rise in the needs for analytical chemical characterization with associated toxicological risk assessments. In general, the need for risk based evaluations, both biological and toxicological, has increased as ISO 14971 and ISO 10993-1 have moved in that direction.
Rudy Pina: An increase has been noted in cleanroom services such as design, certification, and implementation due to the movement of U.S. companies to other countries. The reason for this movement is unknown to Dynatec.
Thor Rollins: Yes, extractable and leachable (E&L) testing. There are two main reasons behind the rise in demand, MDR and the new ISO 10993-1. In the new version of ISO 10993-1, we added a requirement to gather material or chemical information for every medical device. This doesn’t necessarily mean every device needs full E&L, but should be based on risk of the device and previous knowledge from the materials and process. For high risk devices, this tends to mean that E&L testing is needed to fully address the risk of the device. The other reason is the new MDR in May 2020—all devices need to be reevaluated to the current standard, so a lot of devices currently in the EU market don’t have the chemistry data and there is a scramble for labs to try to get this information before they have to submit to a Notified Body.
Christopher Scott: We have seen an increased demand for chemical characterizations, as our clients are responding to the changes in ISO 10993 standard, which mandate this testing as a precursor to in vitro and in vivo elements of biocompatibility testing.
Don Tumminelli: Yes, cleaning validations for reusable devices have been increasing due to the increased scrutiny of FDA and regulatory agencies around the globe enforcing that cleaning instructions for use (IFUs) are validated. This increased scrutiny comes after multiple superbug outbreaks resulting from inadequately cleaned devices.
Brusco: Which technological advancements/new equipment offerings have most impacted your testing services business?
Jakucki: The continued and growing use of additive manufacturing is driving a significant amount of testing for the medical device industry. Companies are concerned about build plate variation, consistent performance, and validation during both the R&D and production phases. The necessary testing includes powder characterization, material evaluation of the printed material through tensile, chemistry and metallography, and product level testing that simulates physiological conditions. With unique geometries like expandable spine cages or other trabecular type structures, trying to predict failure can be a challenge. Overall, manufacturers are asking more questions about material performance and really trying to understand the mechanical behavior—much more so than in the past.
Jorgensen: The key advancements have been related to analytical chemistry. Highly specialized methods that have been more traditionally found in academic research laboratories are now being applied routinely in medical device chemistry studies. A good example of this is liquid chromatography with high-resolution accurate mass detection, which can measure the mass of an unknown compound to several decimal places. Measuring compound mass with this precision allows determination of an unknown compound’s empirical formula, which is a great aid in identification.
Lissy: Mechanical test frames are pretty constant; there are relatively little or new equipment or advancements in this regard.
Pina: Robotics seems to have made a significant impact on the specialized side of manufacturing.
Scott: Advancements in alternative in vitro biocompatibility methods represent an exciting area for our industry, as there is a widely embraced motivation to reduce our dependency on in vivo testing. Although there will be some time before this data will be accepted in lieu of animal testing, we see clients opting to pursue these methods for early stage feasibility work.
Tumminelli: The increased use of low-temperature sterilization, due to more complicated devices that cannot be processed through steam sterilizers.
Brusco: How have recent regulatory activities impacted your testing services business?
Jakucki: The dominant trend right now is MDR and the upcoming May 2020 deadlines for compliance. It has definitely resulted in an increase in testing as companies align with MDR and bring their current product lifecycles in line. This has also resulted in additional pressure to support their efforts in areas like protocol development and general supply chain management. One of the interesting areas that has had a positive impact is the increased pressure on post market surveillance. Customers are asking more questions about safety, implementing failure analysis on failed parts and instruments to tie back to trends, and performing functional testing to replicate clinical failure modes. We have seen an increase in requests for autoclave and durability testing on instrumentation as well as component insertion/removal test programs.
Jorgensen: The FDA is in a period of transition with respect to what they will and will not accept regarding some of the details of chemistry testing. This transition has resulted in a currently moving target with regards to testing expectations.
Lissy: It seems the EU MDR activities are impacting R&D and product development efforts, in that engineers are being pulled off these projects and working on what is needed to meet the May 2020 implementation deadline.
Parker: With the MDR regulations having various time points coming due over the next few years, there has been an increased need for biocompatibility, chemical characterization, risk assessments, gap assessments, and biological evaluations as manufacturers rush to complete their evaluation—or re-evaluation—programs in time.
Pina: There was a slight drop in services, specifically those services related to import/export via Mexico. The drop was short-lived, since the negotiations for the NAFTA agreement appear to have been resolved by all parties involved.
Rollins: As mentioned previously, the MDR is a big impact. Since a lot of older devices have not been kept up to the current standards, each device has to go through a gap analysis to the current requirements and then brought up to standard before getting a new CE mark.
Scott: The new MDR in Europe has created a surge in demand for testing services, as manufacturers seek to complete their technical dossiers prior to the spring 2020 transition deadline.
Tumminelli: The revamped MDR and FDA guidance document for reprocessing have both increased the responsibility of the device manufacturer to validate their IFUs and provide objective evidence of such. In the EU, internal disinfection is being enforced using the A0 method of thermal disinfection to demonstrate the device is safe for reprocessing personnel. In the U.S., cleaning is being enforced to include simulated use testing and increased sample size.
Brusco: What changes in testing protocol do you foresee based on FDA’s planned update of the 510(k) program?
Scott: The FDA has made their expectations fairly clear that the cybersecurity of electronic devices must be addressed. This is one of the most dynamic aspects of our business, as digital technologies permeate the medical device industry, and manufacturers face a new element of risk in their design control process.
Tumminelli: This is yet to be seen. We do not predict increases in volume of testing, but rather decreases in FDA response in regards to test protocols.
Brusco: If applicable to your business, how is continued rise of the use of additive manufacturing impacting your testing protocols?
Jakucki: Testing protocols are becoming more complex with additional requirements for inspection and post-test analysis. Identifying a fracture in a complex geometry may be next to impossible, as they may not be visible to the naked eye or under a 10x magnification. One of the telltale signs is debris generation, but that also may not always be clear for a complex structure. Technologies such as CT scanning can help evaluate the post-test devices, but there is a cost/benefit analysis that must be considered. As mentioned previously, size and shape analysis of debris is common, coupled alongside ion or metal content analysis in the fluid. In some parts of our medical testing business—cardiovascular for example—we are performing nickel ion leaching tests to evaluate whether there are elevated ion levels during testing. On the materials side, build directions need to be considered. A tensile test on a cast or forged device used to be sufficient. With additive, multiple orientations at different locations are routinely taken to confirm performance in the build plate. A level of complexity has been introduced in terms of keeping track of not just performance, but performance related to where the device is printed. Another area critical for additive is the chemical composition. As the materials are exposed to heat during the builds, re-use powder, or go through post processing, it can be a challenge to ensure the chemical compositions meet the target acceptance criteria, particularly around oxygen content. This has impacted our processes and specimen preparation, making sure testing process variability is minimized. Essentially, what used to be routine testing is no longer as routine due to the potential variability of the printing process.
Jorgensen: Additive manufacturing often involves novel materials that have limited existing toxicological information, and the hallmark of these devices is they are infinitely able to be personalized. Handling these devices requires great care in designing a representative test article, and extra rigor in testing due to regulatory skepticism of novel materials. We often partner with additive device manufacturers very early in the product development process to try and avoid heartburn down the road when it comes to testing for actual FDA submission.
Lissy: Additive manufactured devices are changing the landscape of the orthopedic industry. From a mechanical testing standpoint, some changes have to be made for the testing to accommodate these types of devices, but to date, the acceptance criteria and overall methodology has not changed. Patient-specific devices, through AM devices, will impact how we determine and test worst-case implants for a family of devices.
Parker: In the world of biocompatibility, we work with a fixed set of methods and testing programs are built with the specific devices in mind. Additive manufactured devices are assessed like any other device with the same contact type and duration. One of the unique advantages of these devices is that once a base material and manufacturing process has been evaluated for biocompatibility, a cranial plate is no different than a plate used for a leg fracture as long as surface characteristics and other physical properties have been risk assessed appropriately.
Rollins: The main impact comes from new and novel types of chemicals to the medical device industry. For years, most devices were made from the same materials using the same processing, but with additive manufacturing, we see new materials, new process residuals, or both. This creates a challenge to predict safety from chemicals that don’t contain sufficient toxicological information.
Scott: 3D printing has allowed us to fabricate custom test fixtures more quickly than traditional manufacturing techniques, thus improving turnaround time for our testing services.
Brusco: How do you see orthopedic/medical device testing services and equipment progressing in the coming years?
Jakucki: Uniaxial testing will continue to serve its purposes, but there has been a trend toward multi-axis testing to try to evaluate more relevant failure mechanisms. Traditional equipment will continue to evolve as standardization catches up, but there is definitely more interest in multi-axis evaluation. As technology continues to improve, FEA simulation and validation will really start transforming design and the overall testing process. From a materials perspective, the industry still primarily relies on titanium, cobalt chrome, and stainless steel. While there has been progress in the use of combined nonmetallic and traditional materials, it is a matter of time before new materials start transforming the medical space.
Parker: In biocompatibility, there will be a continued effort to create validated in-vitro alternatives to various animal tests. Currently underway in various biocompatibility documents are alternatives to irritation, sensitization, and pyrogenicity tests, although their acceptance by various regulatory bodies may vary.
Rollins: We see more and more pressure away from animal testing and more to alternative methods. This change is impacting both the standards and the regulatory authorities.
Brusco: Is there anything else you’d like to say regarding orthopedic/medical device testing trends and challenges?
Jakucki: Another trend we have observed is an increase in feasibility testing—testing multiple configurations prior to a final design or submission. With additive specifically, companies can create unique geometries at relatively low cost, but may not be sure which direction to take or which device iterations align with their acceptance criteria. Changes in printing parameters or process changes can also have a major impact on the performance of these devices. As such, feasibility testing allows quick evaluations to help decide the best direction. While additive has provided many benefits, challenges around patient-specific solutions and personalized medicine have increased. Trying to identify worst-case or regulatory risk on unique implants, minimal material conditions, and software integration have led to additional validation requirements.
Lissy: If patient-specific devices take off in applications beyond maxial-facial applications, more testing and scrutiny will occur.
Scott: We see increased scrutiny by regulators on data integrity and Part 11 compliance. As the testing industry generates more digital data and manages that data with electronic laboratory notebooks and LIMS systems, ensuring data integrity compliance has become a critical operational requirement. As a result, we are hiring more IT specialists who work alongside our chemists, microbiologists, and engineers to review electronic data audit trails and maintain data security.
Tumminelli: There will be a larger demand for low-temperature processes. As devices become more complex, a need for new sterilization technologies will be needed. Additionally, for industrial sterilization, ethylene oxide is being questioned regarding residuals and emissions, which is spurring the industry to look for ways to minimize the use of ETO and bring residuals and emissions to near-zero levels. It is inevitable to look for alternative processes as part of the solution.