Background: The Increasing Regulation of Medical Devices Subject to 510(k) Clearance
The U.S. Food and Drug Administration's (FDA's) 510(k) premarket clearance pathway is the road to commercialization for thousands of medical devices in the United States. Under this program, non-exempt, mostly moderate risk—or Class II—medical devices are cleared for marketing by the FDA after successful review of a 510(k) premarket notification application.
In 2017, the FDA cleared 3,173 510(k) applications1 representing 82 percent of all device submissions that year. Yet, while clearing a record number of devices, the FDA acknowledges that it has "increased expectations for 510(k) submissions." This is an understatement.
For example, the FDA issued more than 50 new guidance documents (general and device specific) related to medical device clearance. The FDA also implemented a Refuse to Accept Policy2 (RAP), which evaluates any 510(k) submission for completeness before the agency will commence a substantive review. Under the RAP, if even one of 52 510(k) application elements is not accurately completed, the FDA notifies the applicant that the submission is not accepted for review. Thirty percent, or almost a third of 510(k) submissions are not accepted for review under the RAP. In addition, the average 510(k) submission has grown over 150 percent in length since 2009—to about 1,185 pages.3
Further, 510(k) application review times have increased by 32 percent since 2009;4 and the FDA has instituted a mandatory smart memo template (the template) for use by FDA reviewers.5 The template is frequently updated to incorporate newer review policies and practices, such as those published in final guidance documents. Put differently, if a 510(k) submitter missed or underemphasized "suggestions" from a final guidance, the template makes these omissions or actions more likely to be flagged by a reviewer.
Finally, the FDA has taken significant steps to shrink the pool of possible 510(k) predicate medical devices that can be cited by applicants. Since 2012, the FDA has "up-classified" 1,477 class I and II devices to class III, making those devices ineligible as predicates in the 510(k) program.
The Statement:
Against this backdrop, the FDA recently issued a joint statement (the statement) by Commissioner Scott Gottlieb and Center for Devices and Radiological Health (CDRH) Director Jeff Shuren. The statement described transformative new steps that the FDA has taken—and intends to take—to modernize the FDA's 510(k) program. We address several key aspects of the statement.
Continuing to Remove Older, and Risker, Predicate Devices
One of the statement's key points is that the FDA intends to pursue further actions that will "allow [the] FDA to retire outdated predicates, especially in cases where safer and more effective technology has emerged." The statement recites that the "most impactful way we can promote innovation and improved safety…is to drive innovators towards reliance on more modern predicate devices or objective performance criteria" when seeking to market new 510(k) devices.
One mechanism the FDA is considering to achieve this goal is to make the public aware, via the FDA's website, of recently cleared devices that demonstrate substantial equivalence to older predicate devices (e.g., device predicates that are more than 10 years old). The FDA is also developing proposals to "potentially sunset certain older predicates and promote the use of more modern predicates." The FDA has, and continues to remove higher-risk medical devices as predicates by up-classification. Up-classified devices must then undergo stricter premarket approval (PMA) to remain on the market.
De Novo Process
The statement recites that the FDA believes "more devices will use the de novo pathway." Accordingly, in the next few weeks, the FDA plans to "issue a proposed rule clarifying procedures and requirements for submissions of de novo requests."
NEST
FDA's statement also touches on the building of the National Evaluation System for health Technology (NEST). "The FDA regulates more than 190,000 different devices, which are manufactured by more than 18,000 firms in more than 21,000 medical device facilities worldwide." The FDA acknowledges that given this broad regulatory landscape, the FDA cannot always "know the full extent of the benefits and risks of a device before it reaches the market."
One of NEST's purposes is to gather real-world evidence that will be useful to the agency in pre- and post-marketing decisions. NEST should also speed the flow of information about a medical device, and provide another source of information for medical device makers to assess the safety and effectiveness of their devices. NEST may additionally aid device makers to develop innovative improvements. Finally, NEST may help patients and providers more accurately weight the risks and benefits of a particular medical device.
Outlook for Device Manufacturers
The FDA's current policy (as set forth in the statement) is to shift the current 510(k) program to a future-facing, updatable, "contemporary baseline" of predicate devices, rather than looking to the past. What this likely means for device manufacturers is a smaller pool of predicate devices, which are more complex (e.g., contain software, are interoperable, and present a security risk). Identifying a legally marketed predicate will now be more difficult, thereby increasing more de novo applications. Importantly, de novo applications in the past have been subject to a longer review cycle, because they were not covered by user fees—allowing the agency to prioritize reviews of other applications that were subject to user fees. User fees are now required for de novo applications, which should reduce the review times for these applications.
