Medical Devices

Getting a Humanitarian Use Device to Market

Getting a Humanitarian Use Device (HUD) to market is a two-step process. The applicant must first obtain an HUD designation from the FDA’s Office of Orphan Products Development (OOPD) and then submit a Humanitarian Device Exemption (HDE) application to the appropriate FDA premarket review center.

To be eligible to submit an HDE application, an applicant must have obtained HUD designation and there cannot be another comparable device that is legally marketed for the same intended use (other than another approved HUD). In determining whether a comparable device exists, FDA will consider:

  • The device's indications for use and technological characteristics.
  • The patient population to be treated or diagnosed with the device.
  • Whether the device meets the needs of the identified patient population.

Note that a comparable device may not be identical in design, specifications, or other characteristics.

HUD Designation

Prior to submitting an HDE application, an applicant must first obtain HUD Designation from the Office of Orphan Products Development.

Per Section 3052 of the 21st Century Cures Act (Pub. L. No. 114-255) (December 13, 2016), the population estimate required to qualify for Humanitarian Use Device (HUD) designation is “not more than 8,000.”

Applicants who wish to obtain HUD designation should submit one original paper copy and one duplicate copy (another paper copy or an electronic copy on compact disc) to the following address:

Office of Orphan Products Development
Food and Drug Administration
10903 New Hampshire Ave., WO32-5295
Silver Spring, MD 20993

For information about how to obtain HUD designation, please refer to:

If you have additional questions, you may contact the Office of Orphan Products Development:

Telephone: 301-796-8660
Fax: 301-847-8621
Email: orphan@fda.hhs.gov

HDE Application

After a device is designated as an HUD, the applicant then submits an HDE application to the proper FDA Premarket Review Center: either the Center for Devices and Radiological Health (CDRH) or the Center for Biologics Evaluation and Research (CBER), depending on which Center has jurisdiction of the device.

HDE approval authorizes marketing of an HUD device for its specified indication for use. The regulation (21 CFR 814, Subpart H) describes the submission, review, and post-approval regulatory requirements for HDEs.

HDE approval is based upon, among other criteria, a determination by the FDA that the HUD will not expose patients to an unreasonable or significant risk of illness or injury and the probable benefit to health from use of the device outweighs the risk of injury or illness from its use (while taking into account the probable risks and benefits of currently available devices or alternative forms of treatment).

The law exempts HDE devices from demonstrating a reasonable assurance of effectiveness, and instead requires demonstration of probable benefit. This difference in determination of effectiveness is a key difference between applications for premarket approval (PMA) and HDE devices. The table below compares some key aspects of HDEs and PMAs.

 

PMA

HDE

Indication for Use

Proposed by Applicant

Based on HUD Designation

Safety

Reasonable Assurance of Safety

Will not expose patients to an unreasonable or significant risk of illness or injury

Effectiveness

Reasonable Assurance of Effectiveness

Demonstration of Probable Benefit.  Exempt from demonstrating effectiveness.

FDA Review Days

180 days  – if no panel
320 days – if panel

75 FDA days to determine a decision*

Institutional Review Board (IRB) Oversight After Approval

No

May only be used at facilities that have IRB oversight

Restrictions on Profit

No

Yes

*For further information on review timeframes, please see the section on HDE Review

HDE Content

The content of an HDE application is described in (21 CFR 814.104). It includes the following:

  • A complete description of the HUD.
  • A copy of the HUD designation letter issued by OOPD.
  • An explanation of why the device would not be available unless an HDE were granted.
  • A statement that no comparable legally marketed device is available for the intended use (other than another approved HUD).
  • An explanation of why the probable benefit to health from the use of the device outweighs the risk of injury or illness from its use, taking into account the probable risks and benefits of currently available devices or alternative forms of treatment.
  • All of the information required under 21 CFR 814.20(b) except:
    • In lieu of the summaries, conclusions, and results from clinical investigations required under 814.20(b)(3)(v)(B), (b)(3)(vi), and (b)(6)(ii), include the summaries, conclusions, and results of all clinical experience or investigations (whether adverse or supportive) reasonably obtainable and are relevant to an assessment of the risks and probable benefits of the device.
    • Additional HDE labeling considerations are discussed in the “Labeling” section below.
  • Sufficient technical information* to demonstrate that the HUD will not expose patients to an unreasonable or significant risk of illness or injury and the probable benefit to health from use of the device outweighs the risk of injury or illness from its use while taking into account the probable risks and benefits of currently available devices or alternative forms of treatment. The technical information is usually divided into non-clinical studies and clinical investigations.
    • Non-clinical studies may include information on microbiology, toxicology, immunology, biocompatibility, stress, wear, shelf life, and other laboratory or animal studies.
    • Clinical investigations include study protocols, safety and probable benefit data, adverse reactions and complications, device failures and replacements, patient information, patient complaints, results of statistical analyses and any other relevant information from the clinical investigations. Any investigation conducted under an Investigational Device Exemption (IDE) should be identified as such.
      • Include Form FDA-3674, which is the Certification of Compliance with the Requirements of ClinicalTrials.gov Data Bank.
  • Quality Systems information including the methods, facilities, and controls used for the design, manufacture, labeling, packaging, storage, and where appropriate, installation of the device.
  • The amount of money to be charged, and if requesting to make a profit, the request for an exception to the profit prohibition.
  • The physician labeling and, if applicable, the patient labeling.

*For information on the non-clinical and clinical evidence that may be expected in your submission, refer to the applicable guidance documents and standards identified in the Product Classification database for your device.

Applicants are encouraged to contact the FDA to obtain further guidance prior to the submission of an HDE application. The applicant may request a "Pre-Submission" meeting with the FDA. The pre-submission program provides the applicant with the opportunity to obtain FDA feedback prior to the submission of a marketing application. Through the pre-submission program the applicant will interact directly with the appropriate review branch. The applicant may request a formal written response, a face-to-face meeting, or a teleconference to address their concerns, questions, etc. Details regarding how to submit a pre-submission request to the FDA for feedback are provided in the Guidance for Industry and FDA Staff: Requests for Feedback on Medical Device Submissions: The Pre-Submission Program and Meetings with Food and Drug Administration Staff.

HDE Review

The FDA review timeframe is 75 FDA days to determine a decision. (e.g., original submission, applicable amendments) (21 CFR 814.114).

Upon receipt of an HDE application, the FDA conducts a filing review that consists of an administrative and limited scientific review (21 CFR 814.112). The FDA will notify the applicant within 30 days of receipt of the application whether or not the HDE was filed. If the submission is not filed, the FDA will identify what is needed in order to file the application. Once the application is filed, the FDA review team begins the substantive review of the submission (21 CFR 814.116), which consists of the in-depth scientific, regulatory, and quality systems reviews. During the substantive review, FDA may interact with the applicant to address and resolve deficiencies that can be addressed during the review cycle.

FDA Actions

Once the FDA completes the substantive review of an HDE application, the FDA will make a decision and notify the applicant by issuing one of the following:

  • Approval Order
    • Allows device to be legally marketed
    • Lists the approved indication for use and any conditions of approval
    • Provides the Annual Distribution Number (ADN), if the FDA determines that the HDE holder is eligible to sell the device for profit.
  • Approvable Letter
    • Identifies minor deficiencies, such as items associated with the labeling or a postapproval study, that must be resolved in order for the application to be approved.
  • Major Deficiency Letter
    • Identifies major outstanding deficiencies that must be resolved in order for the application to be approved. Generally issued if deficiencies cannot be resolved interactively but do not require new clinical and/or substantive nonclinical evidence.
  • Not Approvable Letter
    • Identifies significant deficiencies that must be resolved in order for the application to be approved, usually involving new clinical and/or substantive nonclinical evidence.

HDE User Fees

There are no User fees for HDE applications.

HDE Labeling

Labeling and materials should be truthful and not misleading (section 502(a) of the FD&C Act). In accordance with 21 CFR 814.104(b)(4)(ii), the labeling of Humanitarian Devices also requires the following disclaimer: “Humanitarian Device. Authorized by Federal law for use in the [treatment or diagnosis] of [specify disease or condition]. The effectiveness of this device for this use has not been demonstrated.” In addition, the labeling should also meet the additional requirements in 21 CFR 814.20(b)(10).

Clinical Trials Information for ClinicalTrial.gov Database

ClinicalTrials.gov is a database of publicly and privately supported clinical studies of human participants conducted around the world. Title VIII of the Food and Drug Administration Amendments Act of 2007 (FDAAA) included a provision that all HDE applications are required to be accompanied with certification that all applicable clinical trial information has been submitted to the ClinicalTrials.gov data bank.

In order to fulfill this requirement, HDE applications should include Form FDA-3674 which is the Certification of Compliance with the Requirements of ClinicaTrials.gov Data Bank. If the HDE includes data from a clinical trial, the applicant should determine if the study is applicable for entry into the clinical trial registry data bank at ClinicalTrials.gov. An applicable device clinical trial is a prospective clinical study of health outcomes comparing an intervention with a device against a control in human subjects (other than a small clinical trial to determine the feasibility of a device, or a clinical trial to test prototype devices where the primary outcome measure relates to feasibility and not to health outcomes). See Title VIII - Clinical Trial Databases.

Information on how to register clinical trial(s) in the ClinicalTrials.gov data bank is available on the National Library of Medicine (NLM) Protocol Registration System (PRS) web site.

HDE Amendments

An applicant may submit an HDE amendment during the ongoing review of an HDE application in order to add additional information pertinent to the review (21 CFR 814.106). Submission of a major amendment may reset the FDA review clock to 75 days.
An applicant may also submit an HDE amendment to report a change in contact information, applicant address, or ownership, either during HDE review or after approval.
 

Page Last Updated: 11/13/2017
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