Over the past decade, the FDA has published a number of guidance documents on benefit-risk determinations for a variety of medical device application types. This fall the agency supplemented that guidance package by releasing two additional guidance documents. The first is a draft guidance on how to consider uncertainty when making benefit-risk decisions for PMAs, De Novo requests, and humanitarian device exemptions (HDE) applications. This draft guidance is intended to work with the other benefit-risk guidance documents to help sponsors understand how the agency intends to to incorporate uncertainty in the “type, magnitude, duration, frequency, and other aspects of a device’s benefits and risks” in the review process. The draft gives a list of the nine factors the agency will consider (at minimum), discusses generally how the factors may apply, and then covers 2 examples where greater uncertainty may be appropriate in an application. These 2 examples are are breakthrough devices subject to a PMA and devices for small patient populations subject to PMA. This guidance is broad enough that I expect the comments will be an interesting read in themselves (see here for the notice in the Federal Register, open for comments until 05DEC2018).

The second document is the final guidance “Benefit-Risk Factors to Consider When Determining Substantial Equivalence in Premarket Notifications (510(k)) with Different Technological Characteristics” [the SE guidance] was also issued this fall. This guidance covers those 510(k) submissions where there is a legally marketed predicate device with the same intended use but different technological characteristics than the proposed device. Different technological characteristics are defined in the FD&C Act [in section 513(i)(1)(B)] as “…the term ‘different technological characteristics’ means, with respect to a device being compared to a predicate device, that there is a significant change in the materials, design, energy source, or other features of the device from those of the predicate device.” The final SE guidance uses an adaptation of the flow chart from the 510(k) Program Guidance and a benefit vs. risk table to clarify under which situations a benefit-risk assessment is recommended. Briefly, an assessment is only recommended when 

1. there is an increase in risk accompanied by an increased or equivalent benefit, or 
2. there is decreased/equivalent risk accompanied by a decrease in benefit. 

The guidance also provides case examples for each of the different benefit vs. risk table quadrants.

There was a webinar for the SE guidance held on 01NOV2018 (see this page for the slides and transcript). This webinar reviewed the main changes between the draft and final versions of this guidance, noting:

• The final guidance does not change the 510(k) review process,
• Benefit-risk assessment does not automatically mean clinical assessments are required, and
• The guidance is intended to clarify when a benefit-risk assessment is required.

I felt the webinar offered a few additional details about the thought process that went into the final SE guidance, but did not add a tremendous amount of clarity to the already clear tables and examples in the actual document. Benefit-risk assessments are a key part of product and process lifecycle management concepts, and I expect to see more integrated guidance on this topic.

Text Copyright © 2018 Katrina Rogers