FDA Releases Draft Guidance Document on Benefit-Risk Analysis for 510(k) Notification

On March 28, 2012, the Food and Drug Administration (FDA) published its first-ever guidance document on the risk-benefit analysis that forms the cornerstone of medical device approval.1 The 2012 guidance addressed considerations governing pre-market approval (PMA) and de novo submissions, but notably absent from the final version of the 2012 guidance was an explanation of the risk-benefit analysis for premarket notifications [510(k)]. On July 15th of this year, more than two years later, and amid a flurry of FDA guidance documents,2 the FDA released a draft guidance document specifically focused on the risk-benefit analysis for devices undergoing the 510(k) process. Although remarkably similar to the 2012 guidance, the 2014 guidance includes a handful of subtle differences that may be important for device manufacturers to keep in mind when making any type of submission.

Under the 510(k) process, medical device manufacturers must demonstrate that their device is substantially equivalent to a legally marketed “predicate” device. A new device is substantially equivalent to a predicate device when it has the same intended use and the same technological characteristics (materials, design, energy source, etc.). However, a new device can be found to be substantially equivalent to a predicate device, even though it has different technological characteristics, so long as the FDA determines that those characteristics do not raise different questions of safety and effectiveness, and so long as the new device is as safe and effective as the predicate device. The FDA analyzes safety and effectiveness, at least in part, by “weighing any probable benefit to health from the use of the device against any probable risk of injury or illness from such use.” Thus, the 2014 guidance regarding risk-benefit analysis only applies to new devices that are found to have different technological characteristics than their predicate device.

Much of the 2014 guidance is copied verbatim from the 2012 guidance. Both documents emphasize that the FDA will consider only scientific data in assessing risks and benefits, not “theoretical risks and benefits,” and that it will consider both clinical and non-clinical data. Both guidance documents indicate that the FDA will consider the magnitude, probability, and duration of benefits and harmful events, in addition to a list of “additional factors” such as uncertainty in trial design and patient tolerance for risks. Finally, both documents conclude with a list of practical examples of applying the risk-benefit factors to hypothetical medical devices.

Perhaps the most noteworthy similarity between the 2012 and 2014 guidance documents is their shared emphasis on the comparison between a new device and devices already on the market. The comparison is obviously the focus of the 510(k) process, which requires that the new device be “as safe and effective” as the predicate device. Surprisingly, however, this comparison also features prominently in the 2012 guidelines. The “availability of alternative treatments or diagnostics,” which includes a comparison of their relative benefits and risks, is listed as a factor in the 2012 guidance and plays an important role in the practical examples.3 Thus, from the FDA’s perspective, there appears to be little practical difference between the risk-benefit analysis for medical devices undergoing PMA, de novo, and 510(k) pathways.

Although there are a handful of differences between the 2012 and 2014 guidance documents, several do not appear to relate to differences between 510(k) notification and PMA or de novo submissions. For instance, the 2014 guidance introduces “benefit for the healthcare provider or caregiver” and “probability of the patient experiencing one or more harmful events”—as opposed to the “probability of a harmful event,” which is listed as a factor in both documents—as additional considerations.4 In addition, when discussing the use of postmarket data, the 2014 guidance includes new language about the FDA’s authority to require postmarket surveillance when a new device is “expected to have significant use in pediatric populations.” Given that it is not immediately obvious how these changes relate to differences between 510(k) notification and PMA or de novo submissions, they may simply reflect updates in the FDA’s thinking on certain issues and may apply to any risk-benefit analysis. Accordingly, device manufacturers dealing with any regulatory pathway should consider factors discussed in both the 2012 and 2014 guidance documents in their submissions.

1 For more information on the 2012 guidance, see FDA Publishes Guidance Document on Benefit-Risk Analysis for Medical Device Approvals (available at

2 To list a few examples: on July 28, 2014, the FDA released the final version of the guidance on determining substantial equivalence in premarket notifications [510(k)], on August 5, 2014, the FDA released the final version of the guidance on design considerations for devices intended for home use, and on August 14, 2014, the FDA released a draft guidance on the de novo classification process.

3 For instance, in the second example of the 2012 guidance, “[t]he fact that there are no alternative treatments for this condition is another important consideration.”

4 Although the considerations comprising the “probability of the patient experiencing one or more harmful events” factor merely appear to replace language spread throughout the 2012 guidance relating to consideration of subgroups, its inclusion in the 2014 guidance may reflect the FDA’s judgment that the consideration of subgroups was an important enough factor to merit its own bullet point.

This update was prepared by Nutter's Intellectual Property practice. For more information, please contact your Nutter attorney at 617.439.2000.

This update is for information purposes only and should not be construed as legal advice on any specific facts or circumstances. Under the rules of the Supreme Judicial Court of Massachusetts, this material may be considered as advertising.

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