On July 28, 2014, FDA issued an important final guidance relating to the Agency’s substantive review of 510(k) notifications, entitled “The 510(k) Program: Evaluating Substantial Equivalence in Premarket Notifications [510(k)].”  This guidance applies to the 510(k) review process for both diagnostic and therapeutic devices and is applicable to 510(k) reviews undertaken by the Center for Biologics Evaluation and Research (CBER) as well as the Center for Devices and Radiological Health (CDRH).  Although FDA notes that this guidance is “not intended to implement significant policy changes,” the guidance clarifies and addresses many key issues in the 510(k) program.  FDA describes in detail the Agency’s critical decision points in the 510(k) review process and updates the 510(k) review flowchart that was first introduced in 1986.  This guidance also discusses key concepts in the 510(k) program, such as the difference between “indications for use” and “intended use,” the use of multiple predicates, and requests for clinical data.

Main Distinctions Between Draft and Final Guidance

The final guidance includes more examples than the 2011 draft guidance to better illustrate the Agency’s decision-making process during a 510(k) review.  In addition, the final guidance includes two new appendices, a sample 510(k) Summary and a glossary of significant terminology used in the guidance.  The 510(k) Summary is a high-level summary of a 510(k), which is created by the submitter of the 510(k).  The guidance states that the Agency may request updates to the 510(k) Summary to accurately reflect the decision-making process during 510(k) review.  The sample 510(k) Summary, which is included to demonstrate the level of detail FDA expects for the elements specified in the regulation, appears to be more detailed than most 510(k) Summary documents currently found on the FDA website.

The final guidance does not include sections on Special or Abbreviated 510(k)s.  In the Federal Register notice for the final guidance, FDA notes that it removed these sections in response to industry concerns relating to the connection between the Special 510(k) Program and the issue of when a new 510(k) should be submitted for a modification to a marketed device.  We described the contentious topic of when a new 510(k) is required for modifications to a marketed device in earlier posts, see here and here.  Until a new guidance is issued by FDA on these alternative programs, manufacturers interested in submitting a Special 510(k) or an Abbreviated 510(k), should follow the 1998 guidance, “The New 510(k) Paradigm – Alternative Approaches to Demonstrating Substantial Equivalence in Premarket Notifications.”

Summary of Key Provisions

The 510(k) Decision-Making Flowchart included in the guidance identifies the five key decision points during the review process.  The text of the guidance provides detail on each step of the review process. 

FDA’s guidance addresses the appropriate use of multiple predicates, where two or more devices are used as predicates to support a substantial equivalence determination.  Manufacturers may use multiple predicates “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.”  Although multiple predicates may be used in certain circumstances to help demonstrate substantial equivalence, FDA encourages the use of a single predicate.  FDA also discusses the use of “reference devices” in a 510(k) submission.  A reference device is not a predicate device, but rather a “legally marketed device that is intended to provide scientific and/or technical information (e.g., test methodology) to help address the safety and effectiveness of a new technological characteristic.”  Finally, FDA makes clear that the use of “split predicates” – “using one legally marketed device for intended use and a different legally marketed device for technological characteristics to demonstrate substantial equivalence” – is “inconsistent with the 510(k) regulatory standard” and will not be accepted.

FDA explains the difference between “intended use” and “indications for use,” and describes when FDA may determine that a change in an indication for use may result in a finding by FDA of a new intended use.  How FDA compares technological characteristics between the new device and the predicate device is also discussed in the guidance, and FDA provides examples to illustrate a decision that a new device raises different questions of safety and effectiveness.  Finally, FDA discusses performance data requests in a 510(k) review and provides examples of when clinical data may be required (e.g., in changing from prescription use to over-the-counter use, from a rigid design to a more flexible design, or from an open procedure to a minimally invasive procedure).