Stretched thin due to extenuating circumstances, medical device companies are working to save time and reduce costs in all stages of project development. But what is the true price of taking potential shortcuts?

As devices near the final stages of development, testing for efficacy, safety, and biocompatibility are the fail-safes before submitting a device for approval. Streamlining testing is vital to keeping project development on track. Still, improper study design jeopardizes overall study objectives, leads to delayed timelines, and increases costs—three things medical device manufacturers can’t afford under current conditions.

Medical device testing can yield a range of results. With the capabilities of modern testing, it is tempting to try to gather more findings from a study than initially intended. When approaching the process with the hopes to investigate beyond what is necessary, overextending the study design could result in the reverse effect by interfering with testing goals.

Manufacturers need to evaluate their approach to preclinical testing. Avoiding contradictory study design is the most effective path forward for study sponsors, and that starts with going back to basics. Companies that focus on testing goals and objectives by defining relevant primary endpoints can improve the results of medical device testing and analysis.

What’s the Rush?
Earlier this year, regulators pushed back the deadline of the EU Medical Device Regulation (MDR) in order to keep critical products on the market during an unprecedented pandemic. The delay may have caused misled relief for manufacturers who were already struggling to meet the initial timeline. Even with the delayed EU MDR implementation, however, manufacturers are still racing to ensure their devices will remain on the EU market—especially those who took a less aggressive approach in adjusting to the significant regulatory changes.

Furthermore, the supply chain disruptions due to COVID-19 make keeping projects on track even more difficult. Companies are under enormous pressure to maintain progress and are seeking any opportunity to gain efficiency. While identifying areas for process efficiency is important, compromising steps along the way could lead to delays, and in the case of preclinical testing, force sponsors to perform additional testing.

Why Are We Here?
The only way to get the right results is by asking the right questions. Communicating the intention and purpose behind the proposed testing builds a solid foundation for each study design. If that’s not clear, it could lead to uninterpretable results, such as running a study under Good Laboratory Practices (GLP) when it’s not necessary, which would drive up costs and extend timelines.

Manufacturers need to come to the table ready to discuss what specific information they need from the study and define the intention for these findings, whether that be to fulfill regulatory requirements, expand their research and development base, or work toward publication. This background determines which direction the testing lab should take with the study design. No matter the intention, trying to squeeze too many objectives into a single study design can compromise the overall study results.

Identifying a Starting Point
Once the objective is clear, the next step is understanding what data is already available. Sharing information specific to the novelty of the device and its unique characteristics with the testing lab can help guide this discussion. A clear starting point can expedite the conversation and support a focused path forward.

When identifying a starting point, keep in mind regulators prefer familiar and established study designs. Testing partners can use a detailed background of the device to research similar products and identify previous study design examples. Even if the objective behind a study isn’t to submit to a regulatory agency, referencing proven methodologies saves time and helps ensure accuracy. Labs can quickly identify appropriate methods and determine similar endpoints from testing like-devices when provided with as much information as possible.

Efficacy and Safety Studies
Preclinical testing can investigate three very different aspects of devices: efficacy, safety, and biocompatibility. Efficacy studies focus on the device’s functionality or performance of its intended use. Safety studies are focused on worst-case scenarios during use of a device and ultimately is a primary focus of the regulatory review. Biocompatibility testing evaluates the safety of chemical materials in a device’s makeup, including chemicals from packaging and sterilization procedures. The endpoints can vary dramatically for each approach. Understanding the foundational differences of each and why simultaneously assessing multiple factors exposes results to uncertainty can prevent putting the investment in testing at risk.

Efficacy Studies—The purpose is to understand the functionality and performance of devices as the intentions claim. These tests typically take place in a process where the endpoints may not require specific regulatory standards, such as GLP.

Eliminate extra design steps by sharing background about the device’s intended use and the purpose behind the testing to help expedite the process. Facilitate conversations with the lab to share the thinking behind the device design and any unique factors compared to competitors to help define endpoints to support the claims companies hope to make.

Safety Studies—These push a device’s exposure limits and are used to observe tissue interactions or other potential adverse effects. Compared to efficacy studies, the specific endpoints are subject to fewer errors, but prioritizing clinically-relevant endpoints is still essential.

Companies should come to the conversation with the foresight on how safety studies work into their broader testing strategy and support the transition to their project’s next step. The main challenge with safety testing is its typical requirement to comply with GLP practices, which increases steps to the process. Additionally, with safety studies, even more so than efficacy studies, it is more critical for labs to evaluate the intention behind product design and unique device characteristics for potential adverse effects.

Biocompatibility Studies—Biocompatibility studies evaluate the safety risks a patient and medical provider are exposed to under device use. These studies focus on the chemical materials a device is made from or was exposed to during packaging and sterilization. These study designs are very well defined by each regulatory agency, although there are some differences between testing labs. Manufacturers that share their regulatory goals in advance have the advantage of aligning with preferred endpoints.

Finding Balance in Study Design
As sponsors work through the study design process, it’s critical to find a balance between customization for device-specific risks and proven methodology. Keeping in mind regulator preferences for consistent approaches, testing labs can alter their approach to specific company cultural priorities, such as preferred test systems, while still considering what options will yield an appropriate physiological response. Labs can also accommodate studies to introduce an intended clinical phenotype that would better predict the device use scenario by using models that mimic the clinical use target.

Manufacturers running either efficacy, safety, or biocompatibility studies can also take advantage of prestudy meetings with the FDA when testing a device for stateside submissions. Requesting FDA feedback on study design is a proactive approach to ensuring a smooth path to compliance.

While preclinical testing may seem straightforward, there are distinct roles each approach can fulfill. Knowing these ahead of time can drastically impact the timeframe, study design, and cost. Sponsors that come prepared to these conversations can ensure reliable study design and define their primary endpoints more accurately. Should conversations with lab testing partners reveal that desired endpoints explore multiple objectives, there may be a need to perform multiple studies.

Facing the Results
Testing labs and manufacturers can start each study with the same end goal in mind, but miscommunication can occur and lead to issues. The stakes are high, so when studies deliver unsuccessful test results, a sponsor’s visceral reaction may be to become defensive. But fear not—while jumping to conclusions may be unavoidable, acting on assumptions is never productive. Instead, it’s critical to remain calm and further investigate the data and the lab’s process.

The company and lab must begin with the learning stage to understand the results. Reviewing the data and process can reveal whether or not the study followed the original plan or adjustments caused interference with resulting data. In either case, sponsors need to ask themselves not only what are the new, unexpected learnings from this study, but also why this is new information and what it means before moving forward with the next steps.

Ultimately, if a study doesn’t yield a manufacturer’s expected results, it may need to repeat the study with minor adjustments to see if reproducing those results is possible. If sponsors pursue further testing, they must re-evaluate their primary study goal and align endpoints accordingly. Otherwise, the results may remain unsatisfactory following repeat testing. Performing this testing can add unexpected costs for the manufacturer, but the only thing more disheartening than repeating testing is having to go back and do it a third time.

By defining study objectives and primary endpoints before starting any study, companies can ensure the study design provides the answers they need. While this action may seem inherent, it’s the simple mistakes that can slip past one’s radar. Between aggressive efforts to make the new 2021 EU MDR compliance deadline and keep pace amidst a global pandemic, no manufacturer wants the small details to be their undoing. Fortunately, they don’t have to face these challenges alone.

This process requires a collaborative approach that brings together the device expertise and background knowledge from the sponsor with the far-reaching experience and critical thinking of a testing lab. While testing partners are bound to agreements of confidentiality, they can bring their broad expertise to create a more focused, precise study design. Granting these partners trust allows them to identify opportunities to reduce the risk of over- or under-testing and preserves testing materials and time.

To avoid unintentionally compromising a study, there are critical steps manufacturers need to take to mitigate the chance of creating a contradictory study design. Getting back to basics and evaluating their approach to preclinical testing can support accurate assessments. Without the proper attention at the initiation of this process, the cost of shortcuts could prove significant down the road, either with regulators who can cause delays in getting to market, or worse, result in patient safety issues.

There’s plenty of uncertainty in the world today from changing regulatory requirements to the unforeseen industry disruptions caused by the pandemic, so it is crucial to identify opportunities to stay on—or get ahead of—schedule. 

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Mark R. Cunningham, Ph.D., senior director of science and technology of technical services, has more than 25 years of experience in the biotechnology and medical device preclinical research industry. He works for WuXi AppTec, which provides a broad portfolio of R&D and manufacturing services that enable companies in the pharmaceutical, biotech, and medical device industries worldwide to advance discoveries and deliver groundbreaking treatments to patients. Dr. Cunningham draws from first-hand experience of molding what the future of safety and efficacy assessment will be for medical device testing. For more information, visit: http://medicaldevice.wuxiapptec.com