Getting a Humanitarian Use Device to Market

On this page:

• HUD Designation
• HDE Application
  • HDE Content
  • HDE Review
  • HDE User Fees
  • HDE Device Labeling
  • Clinical Trials Information for ClinicalTrial.gov Database
  • HDE Amendments

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:

• Developing Products for Rare Diseases & Conditions
• Designating Humanitarian Use Device (HUD)
• Guidance for Industry and FDA Staff - Humanitarian Use Device (HUD) Designations

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 applications should be submitted in an electronic format (eCopy).

Online

Send eCopy premarket submission online through the CDRH Customer Collaboration Portal (CDRH Portal):

• Send and Track Medical Device Premarket Submissions Online: CDRH Portal

Mail

Once an HDE application is received by the FDA, we do not return the application or any copies to the applicant. 

Send applications to the appropriate Document Control Center (DCC). The current mailing address for CDRH’s DCC and a link to the CBER’s DCC mailing address are provided on the eCopy Program for Medical Device Submissions webpage.

We recommend submitting an HDE application to FDA by a method that will provide a signed receipt of delivery, e.g., registered mail with a return receipt or a commercial delivery service.

When CDRH or CBER receives an HDE application, the appropriate Center assigns the request a unique document number. For CDRH, an HDE number begins with “H” followed by six digits. For CBER, an HDE number begins with “BH” followed by six digits. The first two digits represent the calendar year in which the request was received and the last four digits represent the sequential request number for that year. For example, the first HDE request received in the calendar year 2018 would be H180001. The appropriate Center will provide an acknowledgment letter, including the HDE number, usually within 7 days of receipt of the HDE application.

For HDE requests submitted to CBER please contact them for further assistance at either 1-800-835-4709 or Industry.Biologics@fda.hhs.gov

HDE approval authorizes marketing of an HUD device for its specified indication for use. The regulation (21 CFR 814, Subpart H) describes the application, 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

For further information regarding the operational aspects of the HDE Program, including how the FDA determines whether to approve a humanitarian device exemption application, refer to the "Humanitarian Device Exemption (HDE) Program" guidance.

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.
    • For more information regarding the content and format of bench testing information, please see the FDA's guidance document, "Recommended Content and Format of Non-Clinical Bench Performance Testing Information in Premarket Submissions."
  • 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.
    • For more information regarding the FDA's acceptance of clinical data refer to our page on Acceptance of Data from Clinical Investigations for Medical Devices and the FDA guidance entitled "FDA Acceptance of Clinical Data to Support Medical Device Applications and Submissions Frequently Asked Questions."
• 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 feedback from the FDA through a Pre-Submission. Pre-Submissions provide the applicant with the opportunity to obtain the FDA's feedback prior to the submission of a marketing application. During the Pre-Submission, the applicant will interact directly with the appropriate review Division. The applicant may request a formal written response, a face-to-face meeting, or a teleconference to address their concerns, questions, etc. Details about how to submit a Pre-Submission to the FDA for feedback are provided in the FDA guidance Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program.

HDE Review

The FDA review timeframe is 75 FDA days to render a decision for original submissions and supplements (21 CFR 814.114 and 814.108).

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 as to whether 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 filing and the substantive reviews, FDA may interact with the applicant to address and resolve deficiencies that can be addressed during those review cycles.

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.

A valid eCopy is required for all types of HDE Amendments.

For further information regarding the HDE Program, including amendments, refer to the "Humanitarian Device Exemption (HDE) Program" guidance.