FDA Issues Final Guidance on Evaluating Substantial Equivalence

By Allyson B. Mullen —

On July 28, 2014, FDA issued the final guidance document “The 510(k) Program:  Evaluating Substantial Equivalence in Premarket Notifications [510(k)].”  The draft of this guidance was issued on December 27, 2011 (see our earlier blog post here).  Very little has changed since the draft guidance.  

As you may recall, many felt that the draft guidance represented a significant change in policy with respect to the 510(k) program.  See Minnesota Medical Device Manufacturer Alliance Citizen Petition (Jan. 22, 2013), which was supported, via the issuance of comments, by the Washington Legal Foundation, on October 31, 2013. Most notably, the draft guidance:   prohibited use of split predicates, use of one predicate for intended use and another predicate for technological characteristics (which had been previously disfavored by FDA, but not prohibited); introduced the concept of a reference device; and allowed FDA to consider information outside of the proposed device labeling and 510(k) when making a determination of substantial equivalence – all of these concepts still remain in the final guidance. 

Unsurprisingly, FDA received 26 sets of comments, totaling over 400 individual comments in response to the draft guidance.  70 Fed. Reg. 43753, 43754 (July 28, 2014).  What is perhaps surprising is that after all of those comments and two and a half years, the final guidance looks nearly identical to the draft, with a few notable exceptions, discussed below.  This guidance and FDA’s unapologetic dismissal of the Minnesota Medical Device Alliance’s Citizen Petition late last week suggest that FDA is holding firm to heightened standards for the 510(k) program, and industry should not expect FDA to ease up in the foreseeable future.

The final guidance does have two changes from the draft guidance that are blog-worthy.  First, the final guidance only includes Traditional 510(k)s.  The discussion of Special and Abbreviated 510(k)s in the draft guidance has been removed and apparently will be finalized separately.  70 Fed. Reg. at 43754.  The Special and Abbreviated 510(k) sections from the final guidance were removed because, according to FDA, they were the sections that received the most comments.  Id.  Thus, until a new guidance is issued, FDA advises industry to continue following FDA Guidance Document, The New 510(k) Paradigm – Alternate Approaches to Demonstrating Substantial Equivalence in Premarket Notifications (Mar. 20, 1998).

Second, the final guidance features a new appendix with a sample 510(k) summary.  For those who have not written a 510(k) summary for a while, the new appendix may come as a bit of a shock.  In the olden days of the 510(k) program (circa early 2000’s and earlier), 510(k) summaries provided very little information.  The requirements of 21 C.F.R. § 807.92 were very narrowly (and literally) construed such that conclusory and generalized statements were often contained in the 510(k) summaries.  This approach resulted in 510(k) summaries that when read by someone who knew nothing about the subject device, were basically useless – one could typically find out more information about the device from the manufacturer’s marketing materials on its website.  If a company really wanted to find out what was in a predicate device’s 510(k), a Freedom of Information Act (FOIA) request was necessary.  Even then, what the company received back usually more closely resembled a zebra (covered with black lines) than a 510(k) submission because so much of the document was redacted. 

More recently, we have seen FDA requesting additional detail in 510(k) summaries.  For example, we have seen 510(k)s rejected under the Refuse to Accept policy for failure to include a comparison table showing the similarities and differences between the proposed and predicate devices (see our earlier blog post here).  Thus, the detailed, five plus page (single spaced) model 510(k) summary in Appendix C of the final guidance did not come as much of a surprise. 

Since approximately 2004, the Office of In Vitro Diagnostics and Radiological Health has been issuing decision summaries when a new IVD 510(k) is cleared (similarly to the summaries that are issued when a De Novo petition is cleared).  From what we understand, industry has found these summaries to be quite helpful in predicate device research. 

While the Office of Device Evaluation has not followed suit (see our earlier blog post on this topic), we have hope that the additional detail required in new 510(k) summaries may start to close the gap and provide more useful information for predicate device research.  It will depend, in part, upon whether FDA applies this guidance fairly and uniformly. 

From a competitive standpoint, we think additional detail in the 510(k) summaries will be helpful for companies struggling to understand the data requirements that a potential predicate device was required to meet in order to apply that knowledge to their own submission.  On the other hand, companies will want to be vigilant about not disclosing proprietary or confidential information in their 510(k) summaries.  We also wonder if this increased level of public information will result in FDA receiving more push back when it asks a company to do new or additional testing that was not required for a currently marketed predicate device.

In addition to these two main changes, the guidance includes a number of clarifying revisions that do not materially affect the overall messaging of the guidance.  These minor changes include small clarifications of the language in the Substantial Equivalence Decision Making Flowchart in Appendix A.  

The guidance document does provide a number of additional examples and scenarios to try to clarify and explain the “new” requirements.  Some might say that these helpful examples are too little too late, and they would have been more useful a few years ago before FDA implemented these “new” rules.

Since the final guidance is essentially the same as the draft, we do not expect to see significant changes in the 510(k) program as a result of finalizing this guidance – except for perhaps more 510(k)s refused under the RTA Policy for failure to contain a sufficiently detailed 510(k) summary.