Choice of Secondary Predicate versus Reference Devices in a 510(k) Submission

It’s been almost 11 years since FDA first clarified use of multiple predicate devices and introduced the concept of Reference Devices in the draft guidance titled The 510(k) Program:  Evaluating Substantial Equivalence in Premarket Notifications [510(k)], which we blogged about here.  The final guidance with the same title (Guidance), which we blogged about here at the time of release in 2014, provided additional clarity, but we find that, even with years of experience, it is still a challenge in many cases to decide how best to bring a second device into a substantial equivalence discussion.  One frequent issue that arises is whether to designate that second device as a secondary predicate device or so‑called reference device.

A little history may be helpful.  Prior to the Guidance, FDA had sometimes allowed so‑called split predicates in 510(k)s.  A split predicate was one “using one legally marketed device for intended use and a different legally marketed device for technological characteristics to demonstrate substantial equivalence.”  Guidance at 39.  In the Guidance, FDA took the position that “the use of a ‘split predicate’ is inconsistent with the 510(k) regulatory standard.” Id.  Since that time, this practice has essentially been taken off the table for 510(k) submissions.

Even as the Guidance ruled out the use of split predicates, it acknowledged that the practice of relying on multiple predicates in a submission can be valid.  However, the Guidance recommended designating a single device as the “primary predicate device” while citing additional devices as either “secondary predicate devices” or “reference devices.”  The Guidance defined a secondary predicate as one used when “combining features from two or more predicate devices with the same intended use into a single new device, when seeking to market a device with more than one intended use, or when seeking more than one indication for use under the same intended use.” Id. At 11.

Things are a bit clearer with reference devices.  The Guidance defines a reference device as a device that is used to “support scientific methodology or standard reference values.” Id. at 13.  This device explicitly does not need to satisfy each step in the SE flow chart.  Rather, it aids with respect to step 5a related to acceptability of methods for performance testing.

When combining features from two or more devices with the same intended use, the determination of whether to consider the second device a secondary predicate or reference device is not always obvious.  Based on the guidance, the second device would be identified as a secondary predicate device.  However, as the primary predicate is sufficient to reach a determination of substantial equivalence, one may also consider an argument that the second device is merely referenced for support of test methods or standard reference values for specifications related to the features not present in the primary predicate device.

Given FDA concerns over split predicates, it seems that most applicants lean towards use of a reference device, even when identifying the device as a secondary predicate may be more appropriate.  As long as the primary predicate device is appropriate, we have not seen FDA raising concerns during review over whether a second device is a secondary predicate or a reference device.  However, given the drift towards considering any second device a reference device, it is important to review the definitions and descriptions of both secondary predicates and reference devices so that the most appropriate choice can be made in the preparation of 510(k) submissions.