Recent Pressure to Reform the 510(k) Regulatory Pathway Points to Possible Shift in FDA’s Acceptance of Combination Predicate Arguments

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May 2008 Regulatory Affairs Monthly Topic

Recent congressional pressure exerted on FDA in the form of demands for legislative reform of the 510(k) premarket notification program may be leading to a narrower view of how companies can establish substantial equivalence of their devices. Critics of the 510(k) program have taken the position that the pathway is being overly utilized by companies to get complex devices to market that should be subject to premarket approval (“PMA”). Although there is currently no pending legislation to change the 510(k) process, and FDA has not announced any formal policy shift in terms of how the agency will handle 510(k) notifications in the future, recent experience indicates that this pressure may already be resulting in a narrower reading of substantial equivalence, in addition to an overall increase in the scrutiny of 510(k) notifications.

While the 510(k) premarket notification pathway was originally established as part of the 1976 Medical Device Amendments, FDA issued a Blue Book Memorandum, Premarket Notification Review Program (1.) in 1986, commonly referred to as the “Mohan Memorandum,” that set forth the specific requirements for demonstrating substantial equivalence in light of various practices that had been developed within the agency over many years of operation of the 510(k) program. Per the Mohan Memorandum, a device can be found substantially equivalent to an identified predicate device if the new device has the same intended use and the same technological characteristics as a predicate device, or the same intended use and different technological characteristics that do not raise new questions of safety or effectiveness. In addition to clearly setting forth these requirements, the Mohan Memorandum explicitly allows for the use of multiple predicate devices to demonstrate substantial equivalence. Thus, it is possible to argue substantial equivalence using one predicate with the same intended use/indications for use as the new device, while relying on another predicate in support of the technological features.

Since the Mohan Memorandum was released, FDA has routinely cleared devices as substantially equivalent based on combination predicate arguments. However, recent experience suggests that the agency is becoming increasingly restrictive with the use of such combination predicate arguments and that its willingness to accept such combination predicate arguments may be on the decline. One reason for this apparent shift may be the increased pressure recently placed on the agency with respect to the 510(k) program generally. Specifically, congressional pressure is being exerted on the agency in the form of threatened legislative reforms. Although there is currently no pending legislation to change the process, critics of the 510(k) program have called for additional testing requirements for devices seeking 510(k) clearance, including a requirement that each new device be tested directly against a predicate device in a randomized trial. (2.) In addition, the Government Accountability Office (“GAO”) is in the process of evaluating the 510(k) program under a mandate found in the FDA Amendments Act of 2007 (“FDAAA”).

At this time, FDA has not announced a formal policy shift in terms of how the agency will handle 510(k) premarket notifications and, specifically, combination predicate arguments. However, over the past several months, industry has experienced pushback from the agency on substantial equivalence arguments that are based on a combination of predicates—pushback that has not been seen for similar types of devices and substantial equivalence arguments in the recent past. In many cases, the agency is clear that it does not intend to require premarket approval for these devices; however, the agency seems to be increasingly focused on the specifics of the substantial equivalence rationale. This recent experience suggests that the current pressures facing the agency may have already led to informal changes within the Office of Device Evaluation.

In defending the current 510(k) program and its flexibility to appropriately address the more complex devices that often require combination predicates, Center for Devices and Radiological Health (“CDRH”) Director, Daniel Shultz, M.D., seemed to confirm this potential trend. In acknowledging that many of the devices currently entering the market via the 510(k) pathway are “really very close to the edge in terms of whether they are 510(k) or PMA,” (3.) Dr. Schultz cautioned device manufacturers that in order to address such combination devices, the agency may request data beyond what was required for clearance of the predicates. It seems apparent that the potential for increased data requirements may very well be accompanied by increased scrutiny of combination predicates.

1. Blue Book Memorandum #K86‑3, Premarket Notification Review Program (June 30, 1986).
2. Anxiety Over Prospects for Legislative 510(k) Reform Appears to be Growing, The Gray Sheet, March 31, 2008.
3. FDA Device Chief Issues Caution on 510(k)s: Data Requests Could Get Steeper, The Gray Sheet, March 24, 2008.