What is a major difference between an HDE and a PMA application?

The correct choice highlights a key distinction between Humanitarian Device Exemptions (HDE) and Premarket Approval (PMA) applications in terms of effectiveness requirements.

HDEs are designed for devices intended to treat or diagnose conditions affecting fewer than 8,000 individuals per year in the United States. Because these devices are aimed at rare conditions or diseases, the FDA allows for a different approach regarding efficacy. Specifically, HDE does not require the applicant to demonstrate the same level of effectiveness that a PMA would necessitate. For PMA applications, the manufacturer must provide substantial evidence of safety and effectiveness for the device to receive FDA approval, which involves rigorous preclinical and clinical testing.

In contrast, an HDE application only needs to demonstrate that the device is safe and that there is a reasonable assurance of its safety, along with showing that it provides a significant benefit, implying that it could help treat a condition that otherwise might not have sufficient treatment options. This relaxed standard reflects the unique nature of devices intended for rare diseases and supports innovation in areas where conventional approval trials might not be feasible.

The other choices focus on technical aspects of the applications, such as content, labeling requirements, and supplemental applications, but the notable difference lies in how