FDA Finalizes 510(k) Substantial Equivalence Guidance

By Nick Otto

The FDA recently released final guidance addressing key issues in the agency’s 510(k) clearance program, describing in detail the critical decision points in the 510(k) review process.

The final guidance also includes an updated 510(k) decision-making flowchart that was first introduced in 1986. The flowchart identifies the five key decision points of the review process. The flowchart, however, is not a “stand-alone” reference, according to the document, and it should be used in conjunction with the rest of the guidance. 

The guidance also addresses the appropriate use of multiple predicates, where two or more devices are used as predicates to support a substantial equivalence determination. 

According to the document, 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, the FDA encourages device-makers to use a single predicate. 

The agency also details the use of “reference devices” in 510(k) submissions. 

The guidance makes sure to note that 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.”  Additionally, the agency says the applicability of a reference device will need to be reviewed for its appropriateness.

Lastly, the FDA clarifies that the use of “split predicates,” which entails splitting the decision making process by comparing a new device to “one legally marketed device for intended use and a different legally marketed device for technological characteristics to demonstrate substantial equivalence.” According to the document, this practice is inconsistent with the current 510(k) regulatory standards and wouldn’t be accepted.

Earlier this month, the FDA issued a draft guidance focusing on the benefit-risk factors the FDA uses to determine whether a new 510(k) device with different technological characteristics that does not raise different questions of safety and effectiveness is as safe and effective as a predicate device.