On July 15, 2014, FDA issued draft guidance Benefit-Risk Factors to Consider When Determining Substantial Equivalence in Premarket Notifications [510(k)] with Different Technological Characteristics. We think of it as a sequel to the guidance over a year ago, Factors to Consider When Making Benefit-Risk Determinations in Medical Device Premarket Approval and De Novo Classifications.
Like last year's guidance, the 510(k) guidance describes how FDA assesses benefits and risks. It discusses a number of factors the agency might consider in making a benefit-risk determination, and offers a respectable number of examples.
You might be asking, "But wait, aren't 510(k)ed devices substantially equivalent to a predicate device? And doesn't substantially equivalent mean the new1 device has the same intended use and the same technological characteristics as the predicate device?2 What's safety and effectiveness, or benefit-risk got to do with substantial equivalence?"
The guidance document does a nice job of explaining the situation.
In a nutshell, a new device is substantially equivalent to a predicate device when it has the same intended use, and the same technological characteristics as the predicate device. If these two factors are the same, there's no need for FDA to conduct a benefit-risk analysis when determining that the new device is substantially equivalent to the predicate. If the intended use and technological characteristics are the same, then it's easy to conclude that the new device is substantially equivalent to the predicate device. That risk-benefit determination has already been made and confirmed by real world use of the product.
But what if the new device has different technological characteristics?3 In that case, the new device can still be found substantially equivalent to the predicate device if:
The new device does not raise different questions of safety and effectiveness than the predicate device, and
The new device is as safe and effective as the predicate device.4
FDA makes safety and effectiveness determinations through an assessment of the probable risks and benefits of the product, hence the value of this guidance providing information on how the agency approaches benefit-risk assessments.
The Act also states that the FDA can require "appropriate clinical or scientific data if deemed necessary" to support an assertion that the new device is as safe and effective as the predicate device.5 Whether clinical data will be required to support a 510(k) with new technological characteristics is frequently unclear to the medical device industry. FDA addressed this issue in the 2011 draft guidance The 510(k) Program: Evaluation Substantial Equivalence in Premarket Notifications [510K)]. According to this guidance, FDA currently requests clinical data for fewer than 10 percent of all 510(k) submissions. When technological differences between the new device and predicate device are significant, but not significant enough to support an immediate "not substantially equivalent" determination, FDA is likely to request clinical data. Although this guidance gives a few examples, it may still be difficult to determine whether clinical data will be required for actual devices. Perhaps FDA will continue to illuminate this issue.
In the meantime, if your new device has different technological characteristics from the identified predicate device, you should be prepared to demonstrate that the new device is as safe and effective as the predicate device. FDA's new guidance should be very helpful in presenting that information in the most effective way.
1 For purposes of this client alert, "new device" means the device for which pre-market clearance is being sought under a 510(k). The guidance document adopts a similar approach.
2 Section 513(i)(1)(A) of the Act, 21 U.S.C. § 360c(i)(1)(A). See also 21 CFR 807.100(b).
3 And what does it mean to have "different technological characteristics?" Under the Act, "different technological characteristics" means a significant change in materials, design, energy source or other features of the new device relative to the predicate device. Section 513(i)(1)(B) of the Act, 21 U.S.C. § 360c(i)(1)(B). See also 21 CFR 807.100(b)(2)(ii)(A).
4 Section 513(i) of the Federal Food, Drug, and Cosmetic Act (the Act); 21 U.S.C. § 360(c)(i)).
5 Section 513(i)(1)(A)(ii), 21 U.S.C. 360c(i)(1)(A)(ii). See also 21 CFR 807.100(b)(2)(ii)(B).