On January 24, 2013, FDA finalized the Humanitarian Use Device (HUD) Designations guidance, issued in draft on December 13, 2011. The guidance addresses HUD requests, a first step in obtaining approval of a Humanitarian Device Exemption (HDE). A HUD is a “medical device intended to benefit patients in the treatment or diagnosis of a disease or condition that affects or is manifested in fewer than 4,000 individuals in the United States per year.” 21 C.F.R. § 814.3(n). An HDE application is similar to a PMA, but exempts the applicant from demonstrating a reasonable assurance of effectiveness. The guidance discusses only obtaining a HUD designation, and does not discuss submission of an HDE to either CDRH or CBER.
The guidance discusses several issues important to a successful HUD request, including the following:
Description of Disease or Condition. The Office of Orphan Products Development (OOPD) is responsible for initially reviewing a HUD request. Unlike a PMA approval or 510(k) clearance, a HUD designation is not for a particular indication, but rather a designation for a rare disease or condition generally. Upon obtaining HDE approval, CDRH or CBER may limit the approval to certain indications.
When submitting a HUD request, the sponsor should carefully consider the particular disease or condition for which it is seeking HUD designation, namely, “specific aspects of the disease or condition relevant to the functionality of the device, as well as any information that assists in defining the patient population.” Because HUD designation depends on the affected patient population, identifying the appropriate disease or condition is very important. For example, the guidance discusses the difference between multiple myeloma, lytic lesions regardless of cause, or lytic lesions due to multiple myeloma. The device for which the sponsor is seeking the HUD designation may actually be lytic lesions due to multiple myeloma, not multiple myeloma itself. Sponsors should carefully characterize the disease when seeking a HUD designation.
Population Estimates. HUD designations are for those diseases or conditions that affect no more than 4,000 individuals in the United States per year. The method for estimating the affected population may vary depending on whether the device is intended for therapeutic or diagnostic purposes. As described in the guidance, for therapeutic devices, “the population estimate is generally the number of new patients per year diagnosed with the relevant disease or condition and eligible for treatment with the device.” For diagnostic devices, “the population estimate is generally the number of patients per year who would be subjected to diagnosis with the device, regardless of whether the test result is positive or negative.” Thus, a therapeutic HUD is based on the number of new cases, whereas as a diagnostic HUD is based on the number of people who are expected to be tested. Because of this difference, the guidance suggests that each applicant “identify in a HUD request whether the device is intended for therapeutic or diagnostic purposes.”
Orphan Subset of a Non-Rare Disease or Condition. “Orphan subset” describes “the subset of individuals with a non-rare disease or condition on whom use of a device is appropriate, where use of the device on the remaining individuals with that disease or condition would be inappropriate given some intrinsic feature of the device.” Of note, “an orphan subset does not simply mean any medically recognizable or clinically distinguishable subset of persons with a non-rare disease or condition.” (Emphasis in original.) Rather, device characteristics must preclude use in the remaining individuals with the non-rare disease or conditions. This is similar in concept to "orphan subsets" for orphan drug designation purposes (see here). The guidance gives several examples of when an orphan subset may be appropriate. For example, the adverse event profile may help determine the existence of an orphan subset by showing that the device should not be used on patients who have not failed drug therapy. The orphan subset would therefore be those patients who have previously failed drug therapy.
For those relatively few sponsors who seek HUD designations, perhaps this guidance will help lead to more successful submissions. Even if it helps clarify certain issues, however, it is unlikely that the guidance will go to the more fundamental issues that have limited use of the program.