In a new final guidance issued today, the FDA announced that it will frown upon the use of multiple predicate devices in 510(k) submissions, unlike when it cleared metal-on-metal hip implants, which the agency later said can damage surrounding bones and contaminate the body by releasing ions into the bloodstream.
The document cites a statute saying that "for a new device to be considered substantially equivalent to a predicate device, the new device must have the same intended use as the predicate device and the same technological characteristics or different technological characteristics that do not raise different questions of safety and effectiveness than the predicate device."
The use of more than one "substantially equivalent" predecessor device was known as a "split predicate" and involved cases in which a company used one device to show equivalence regarding intended use and another device to prove substantially equivalent technology. This occurred in the case of the now-recalled DePuy ASR XL Modular Acetabular Cup System, which was cleared on the basis of 6 substantially equivalent devices, the New England Journal of Medicine explained.
In cases not involving a split predicate, multiple predicate devices are acceptable, the document says, such as "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." Even those devices should designate a primary predicate device to assist the application reviewers.
For example, an application may use different devices to prove equivalence for a catheter combining an extension similar to one already on the market with a tip similar to another tip on the market, as long as both predicates have the same intended use as the new device, the guidance explains. Either the similar tip or extension could serve as the primary predicate.
"Reference devices" may also be used to prove substantial equivalence with specific aspects of a new device's technology. Suppose there is a knee implant with an antimicrobial coating up for review that is similar to another knee implant in every way except for the coating. The knee implant could still be cleared if there is a hip implant on the market (the reference device) that uses the same coating, the document explains.
The rest of the final guidance is essentially an overview of the 510(k) pathway and contains only minor changes. To the delight of industry, planned changes to the regulation of modifications of already cleared devices and reforms to the "abbreviated" 510(k) pathway were left out of the document, the Regulatory Affairs Professional Society points out.
The 510(k) clearance pathway is meant for low to moderate risk Class II devices that have a "substantially equivalent" predecessor. But regulatory gaffes, like the clearance of metal-on-metal hips, shows that the definition and appropriate application of that infamous regulatory term of art can be tricky.