Recent 510(k) Study Outlines Challenges & Opportunities

According to a recent survey conducted by researchers at Northwestern University about the U.S. Food & Drug administration (FDA) 510(k) review 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 respondents—356 industry professionals—reported that unclear guidelines, inconsistent implementation, and 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 widely has been 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.

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

Three-quarters of study 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. In addition, 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, researchers noted. 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. Respondents said that 65 percent of devices were CE-marked before receiving FDA clearance.

“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 Jan Pietzsch, study co-investigator, as well as president and CEO of the technology consultancy Wing Tech Inc., and a consultingassociate professor in Stanford University’s biodesign program and department of management science and engineering.
“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.

The survey is part of a larger study, and over the next several months investigators will expand on the survey findings by compiling case studies and performing a more in-depth examination of the U.S. and EU regulatory processes.

Jeffrey Shuren, director of the CDRH was on hand during the presentation of the study’s findings. He thanked the researchers for their work, but was quick to note that the survey was based on a small percentage of industry representatives and that many questions led 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.

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

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 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 of resources and manpower.

But it’s not all about the agency, Shuren said. Industry has aresponsibility, too. He said less than 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 receives have quality problems.