The US Food and Drug Administration (FDA) has announced the release of a new guidance document intended for both its staff and the medical device industry pertaining to the issuance of humanitarian use device (HUD) designations for devices intended to treat rare diseases or conditions.

Much like orphan drugs, which are intended to treat conditions that affect fewer than 200,000 people in the US, HUD designations are given to medical devices that are intended to cure, treat or diagnose a condition that is found in fewer than 4,000 individuals in the US per year. As with its pharmaceutical counterpart, the HUD designation affords sponsors faster review time and additional support from FDA reviewers.

The designation is separate from the approval or non-approval of the application itself, known as a Humanitarian Device Exemption (HDE) application, which is similar in nature to a Premarket Approval (PMA) application in that it must prove that it is safe for use in humans. It does not, however, need to meet standards of efficacy, which a PMA application must prove.

The Guidance

In December 2011, FDA released a draft guidance on the topic, inviting comment from industry and those seeking the HUD designation.

Those designations need to contain certain information not ordinarily found in other types of applications, including a statement indicating the sponsor is seeking a HUD designation, a description of the rare disease, demonstration of the medical plausibility of the disease as a medically important subset, and proof that the disease affects fewer than 4,000 individuals in the US.

The population estimate is particularly important, as a population of more than 4,000 will automatically disqualify the device from being able to obtain a HUD designation and thus the ability to obtain approval using an HDE application.

There are two distinctions that FDA said it wanted manufacturers to understand clearly: prevalence and incidence. The former refers to the total number of patients with a given disease at a given point in time, and is sometimes referred to as point prevalence. The latter term refers to the number of new patients, and is sometimes referred to as annual incidence. FDA's HUD designation is based upon incidence, not prevalence.

Certain devices, such as diagnostic devices, can also run into some tricky interpretations of the HUD designation's legislative wording. A diagnostic device that is intended to screen all newborn children to look for a disease that affects fewer than 4,000 individuals would not be eligible for a HUD designation, while one only intended for use in those 4,000 individuals would be, FDA said.

Medical Plausibility

The "medically plausible" subset is also important. A manufacturer would, for example, be hard-pressed to take an annual incidence of 8,000 affected individuals-for the sake of argument, equally divided into men and women-and claim that its product only treated the men in order to obtain a HUD designation.

"Medically plausible subset" or "orphan subset" is a regulatory term used to describe a situation where the incidence of a disease or condition is 4,000 or more patients per year in the US, but because a product can only be used in a smaller subset of people with the common disease or condition, it qualifies for HUD designation," FDA explained. "A medically plausible subset must be based on some feature of the device (i.e., mode of action, adverse event profile, etc.) that actually precludes its use in the treatment of patients outside the smaller subset of individuals."

"There should be justification as to why the device could not be used to treat or diagnose all remaining persons with the disease or condition," FDA added.

FDA said its final guidance reflects some "minor revisions to improve clarity," but is otherwise the same as the December 2011 draft guidance, Humanitarian use Device Designations: Guidance for Industry and Staff.