A rare disease is defined in the Orphan Drug Act (ODA) of 1984 as a disease or condition that affects fewer than 200,000 people in the United. Because so few patients are affected, it can be difficult to gather enough clinical evidence for a drug or medical device to demonstrate safety and effectiveness under the normal FDA standards. To address this challenge, Congress created a new regulatory pathway for medical products that treat diseases or conditions that affect small populations (less than 8,000 individuals in the U.S.) in the Safe Medical Devices Act of 1990. This pathway is known as the Humanitarian Device Exemption (HDE) pathway, and devices approved under this pathway are called Humanitarian Use Devices (HUD).

The process for HDE approval has 2 steps. The applicant must first obtain an HUD designation from the Office of Orphan Products Development. The specifics of the designation request are detailed in the HUD designation guidance. A device is designated as an HUD for a specific application. Once the device has been designated an HUD the applicant submits an HDE application to the appropriate premarket Review Center (either CDRH or CBER). A key difference between an HDE and a PMA is HDE devices are exempt from the requirement of demonstrating a reasonable assurance of effectiveness. Instead, approval requires demonstration of probable benefit, along with a reasonable assurance that the product will not expose patients to a significant risk of illness or injury from the use of the device. There are legal restrictions on selling an HDE for profit and sponsors of devices that meet the for-profit eligibility criteria must include supporting documentation to request that status in their application.

Once approval is granted, the device may only be used in facilities that have an Institutional Review Board (IRB) which must approve each instance of the device use (except in emergency situations). Guidance is available on the HDE regulations for use of an approved HUD in clinical trials for safety and effectiveness and for other indications. If modifications are made that affect the safety and probable benefit of the device (for example, manufacturing, design, or labeling changes) an HDE supplement must be submitted for prior approval. Changes to the indications for use of an approved HUD require a separate HDE application.

A good example of an HUD with an HDE approval is the MESOMARK cancer monitoring test system. It’s original approval and supplements (such as a recent process change) may be found in the HDE database. Full details on the HDE pathway may be found at the HDE web page.

Text Copyright © 2019 Katrina Rogers