Recent 510(k) Study Outlines Challenges and Opportunities

According to a recent survey conducted by researchers at Northwestern University about industry’s reaction to the U.S. Food and Drug Administration’s 510(k) approval process, two-thirds of small medical device and diagnostic companies are obtaining clearance for new products in Europe first, suggesting delayed market entry in the United States. The survey was sponsored by the non-profit Washington, D.C.-based Institute for Health Technology Studies, also known as InHealth. Survey findings were presented May 24 at an event at the National Press Club in Washington.

Survey respondents—356 industry professionals—reported that unclear guidelines, inconsistent implementation, and lead reviewer turnover within the FDA’s Center for Devices and Radiological Health (CDRH) are contributing to increasing unpredictability of the process. Only 8 percent of survey respondents believe FDA’s 510(k) product review process is the most predictable regulatory system, compared with roughly two-thirds of respondents who indicated that the European Union’s (EU) CE marking process is the most predictable.

For 98 percent of those surveyed, the predictability of regulatory requirements is a crucial factor in deciding whether to invest in developing a new product. According to lead researcher John Linehan, Ph.D., professor of biomedical engineering at Northwestern University, the U.S. regulatory system has been widely credited with ensuring high standards of patient safety and device effectiveness, while also facilitating innovation. But increasing uncertainty about the implementation of the 510(k) process—partly attributable to increases in device complexity—is posing challenges for FDA and industry that may lead the United States to experience a “brain drain” in the medtech sector.

“As FDA considers regulatory revisions, what’s at stake is the ability of companies to attract investors in order to continue developing innovative, life-saving products and sustaining American competitiveness in the global marketplace,” Linehan said.

Researchers sought to determine what works well in the 510(k) process and how its implementation can be further strengthened. In turn, they were looking for insight into how U.S. companies are navigating the changing regulatory environment at home.

Among key findings of the survey:

• Respondents find the consistency and efficiency of FDA’s review process a concern.
• Three-quarters of respondents (76 percent) found preparation requirements for a 510(k) submission to be uncertain or unclear; 72 percent felt that information requests from FDA reviewers went beyond the requirements established in guidance documents, and 59 percent reported no guidance documents existed for their devices.
• During the past three years, respondents experienced changes in the lead FDA reviewer for approximately 14 percent of their submissions; of those, 60 percent felt the change negatively affected the product review.
• More than two-thirds of all respondents reported that FDA requests had a significant impact on their financial resources.
• Small companies are more likely to incur expensive and time-consuming difficulties in navigating the process.
• The development process for small companies—which are involved with new products twice as often as large companies—is significantly longer than for large companies (26.6 months vs. 17.7 months).
• Small company respondents report an average total review time of 330 days, while those in large companies report 177 days.
• Seeking regulatory clearance and market launch outside the United States is becoming increasingly common.
• Only 4 percent of respondents reported approaching FDA as the first regulator to discuss and plan their submission for a new device, while 80 percent initially approached EU regulatory bodies.
• In the device-specific portion of the survey, respondents said that 65 percent of devices were CE-marked before receiving FDA clearance.
• Data suggest that current U.S. review time is more than twice as long as in the EU (part of it attributable to differences in regulatory requirements between the United States and the EU).

Co-investigator Jan B. Pietzsch, Ph.D., president and CEO of the technology consultancy Wing Tech Inc., and a consulting associate professor in Stanford University’s biodesign program and department of management science and engineering, emphasized that the survey offers both industry and FDA opportunities to improve the 510(k) pathway, and that collaboration is needed to secure the future of medical innovation in the United States and patient access to the safest and most-effective medical devices in the world.

Among opportunities identified in the survey:

• Respondents stated that their companies could have improved the initial submission for 39 percent of applications submitted in the past three years.
• On average, respondents felt that 26 percent of FDA’s follow-up questions should have been anticipated.

“The responses indicate that there may be opportunities for industry to better anticipate FDA’s evidentiary needs during the regulatory process, as long as they are clearly stated and communicated,” said Pietzsch. “Similarly, the process would benefit from FDA better training inexperienced reviewers on how to treat submissions consistently.”

He added that 92 percent of respondents perceived a correlation between inexperienced reviewers and more FDA questions.

Interviews with more than 80 medical device experts from FDA and industry informed the survey’s content. For the survey, investigators queried product designers and developers, entrepreneurs, academic physician inventors and regulatory affairs professionals––all of whom have been involved with the submission of 510(k) products in the past three years, researchers noted. The survey is part of a larger study, “A Comprehensive Analysis of the FDA 510(k) Process: Industry Practice and the Implications for Reform.” Over the next several months, investigators said they would expand on the survey findings by compiling case studies and performing a more in-depth examination of the U.S. and EU regulatory processes.

The CDRH has undertaken an internal review of the 510(k) program and has instituted new processes and procedures based on those findings. Additionally, a study commissioned by the FDA conducted by the Institute of Medicine (IOM) is expected to be released this summer, though some industry insiders have argues that the IOM doesn’t have the internal expertise to appropriately evaluate the 510(k) program.

Jeffrey Shuren, director of the CDRH as on hand during the presentation of the study’s findings. Researchers invited Shuren to respond to the survey results.

Shuren thanked the researchers for their work, but was quick to note that survey was based on a small percentage of industry representatives and that many questions lead to “purely subjective” responses.

“While this survey is informative about the experiences and perception of this group of respondents, we should be cautious about the actual percentages,” he said. “With those limits in mind, the survey does highlight some informative findings and opportunities for FDA and industry to make improvements.”

Shuren said the evolution and increasing complexity of medical devices is a challenge for his agency.

“We are seeing more sophisticated devices coming onto the market,” he said. “We sometimes ask for more data than we might have previously, but good data is critical for understanding problems, when they exist, and developing solutions.”

Susan Alpert, a panel member present during the survey presentation, who recently retired as Medtronic’s vice president of global regulatory affairs, countered Shuren’s comments by saying that while she understood that evolving technology could present a problem for the industry, the agency has been slow to respond or has asked for more date for devices “that already have been on the market for 10-15 years.”

Shuren also acknowledged that the turnover at CDRH is a problem, and that keeping staff onboard is essential to the predictability that the agency and industry seek.

“It’s critical that we reduce the unacceptably high staff turnover at CDRH,” he said, adding that plans a already are underway to help retain key staff. The industry also is looking for increased guidance from the FDA, and Shuren noted that while the agency has plans to issue more guidance documents, it also comes down to questions or resources and manpower. He said the increase would not happen until CDRH is able to create a stable of technical writers to churn out information to industry, which frees reviewers to focus on their main objective—evaluating device submissions.

But it’s not all about the agency, Shuren said. Industry has a responsibility, too. He said less that a quarter of companies that meet with CDRH follow the center’s advice when submitting their applications. In addition, more than half of the 510(k) submissions the agency received had quality problems.

“Poor-quality submissions divert time and resources from the review of other devices,” he said.