Description
FDA developed thisguidance documentto provide clarity to industry and FDA staff about the current review practices for the Humanitarian Device Exemption (HDE) Program. This programmatic guidance addresses commonly asked questions about HDEs and Humanitarian Use Devices (HUDs), including FDA actions on HDE applications, post-approval requirements, and special considerations for devices marketed under the HDE Program. This guidance document reflects changes in the HDE Program resulting from statutory amendments made by the 21st Century Cures Act (Cures Act) and explains the criteria FDA considers to determine if “probable benefit” has been demonstrated as part of the Agency’s decision-making process regarding marketing authorization for a HUD. This guidance document also reflects amendments made to the HDE provision of the Federal Food, Drug, and Cosmetic Act (FD&C Act) by the FDA Reauthorization Act of 2017 (FDARA).
Scope & Applicability
Product Classes
3Medical devices intended to benefit patients in the treatment or diagnosis of diseases affecting not more than 8,000 individuals in the U.S. per year.; Devices intended for diseases occurring in fewer than 8,000 individuals; devices approved under an HDE
Medical device intended for small populations
Products combining drug, device, or biological constituents; Generally recommended for Enhanced Documentation; Requires 14971-based framework incorporating ICH Q9; A drug-device combination where the device constituent part detects ingestion.
Stakeholders
9Entity responsible for HDE submissions.
Care-partner perspectives may be considered where it is not feasible to obtain PPI.; Perspective considered during benefit and risk assessment
entity submitting marketing applications
Veterinarian responsible for selecting anesthetic regimens and conducting field studies
Governs top dose in clinical studies
consulting in advance with patient advocacy groups; Entities that may review consent forms to ensure they facilitate understanding
Entity submitting the HDE application
Alternative to IRB for approving HUD use at a facility; Standing committee for the facility that has expertise in clinical care
Prepares report verifying device costs
Regulatory Context
Attributes
10The standard used by FDA to determine if a HUD outweighs the risk of injury or illness.; Standard for HDE approval weighing benefit against risk; Standard for HDE approval where patients are likely to benefit
conformity with an FDA-recognized standard can help demonstrate that an NGS-based test developer has performed the activities necessary to identify the indications for use; number and types of samples used in the study should be statistically justified for the test’s indications for use; If a modification expands the indications for use beyond aiding in the diagnosis of symptomatic individuals; Acceptable performance levels depend on these
reasonably foreseeable risks or side effects
requirement from which HDEs are exempt
evaluation factor for HDE approval
Standard for data supporting an HDE
Determined based on stability data; Established through stability testing; also called dating period.; Established through formal stability studies; Establishing the period during which a drug product is expected to remain within specifications; Period for drug products; The period during which a drug product is expected to remain within specifications; Duration product remains within acceptance criteria; Period during which product remains within specifications; Established for intermediates pu
The IRB would need to make a SR/NSR determination
Risk classification for medical device clinical investigations.; A classification for medical device studies.; A risk determination for a clinical study.
Factor considered for 'highly impracticable' determination
Identified Hazards
Hazards
5Safety standard evaluated during substantive review
Risk assessment factor for diagnostic devices
Risk assessment factor for diagnostic devices
FDA must determine that the device will not expose patients to an unreasonable or significant risk of illness or injury.
Criteria for determining if pediatric development is unsafe
Related CFR Sections (12)
- 21CFR814.20§ 814.20 Application.
(a) The applicant or an authorized representative shall sign the PMA. If the applicant does not reside or have a place of business within the United States, the PMA shall be countersigned by an authorized representative residing or maintaining a place of business in the United States and shall identRead full regulation →
- 21CFR814.104§ 814.104 Original applications.
(a) United States applicant or representative. The applicant or an authorized representative shall sign the HDE. If the applicant does not reside or have a place of business within the United States, the HDE shall be countersigned by an authorized representative residing or maintaining a place of buRead full regulation →
- 21CFR860.7§ 860.7 Determination of safety and effectiveness.
(a) The classification panels, in reviewing evidence concerning the safety and effectiveness of a device and in preparing advice to the Commissioner, and the Commissioner, in making determinations concerning the safety and effectiveness of a device, will apply the rules in this section.Read full regulation →
- 21CFR812.28§ 812.28 Acceptance of data from clinical investigations conducted outside the United States.
(a) Acceptance of data from clinical investigations conducted outside the United States to support an IDE or a device marketing application or submission (an application under section 515 or 520(m) of the Federal Food, Drug, and Cosmetic Act, a premarket notification submission under section 510(k) Read full regulation →
- 21CFR25.20§ 25.20 Actions requiring preparation of an environmental assessment.
Any proposed action of a type specified in this section normally requires at least the preparation of an EA, unless it is an action in a specific class that qualifies for exclusion under §§ 25.30 , 25.31 , 25.32 , 25.33 , 25.34 , or 25.35 :Read full regulation →
- 21CFR814.112§ 814.112 Filing an HDE.
(a) The filing of an HDE means that FDA has made a threshold determination that the application is sufficiently complete to permit substantive review. Within 30 days from the date an HDE is received by FDA, the agency will notify the applicant whether the application has been filed. FDA may refuse tRead full regulation →
- 21CFR3.2§ 3.2 Definitions.
For the purpose of this part:Read full regulation →
- 21CFR814.126§ 814.126 Postapproval requirements and reports.
(a) An HDE approved under this subpart H shall be subject to the postapproval requirements and reports set forth under subpart E of this part , as applicable, with the exception of § 814.82(a)(7) . In addition, medical device reports submitted to FDA in compliance with the requirements of part 803 oRead full regulation →
- 21CFR56.111§ 56.111 Criteria for IRB approval of research.
(a) In order to approve research covered by these regulations the IRB shall determine that all of the following requirements are satisfied:Read full regulation →
- 21CFR814.124§ 814.124 Institutional Review Board requirements.
(a) IRB approval. The HDE holder is responsible for ensuring that a HUD approved under this subpart is administered only in facilities having oversight by an Institutional Review Board (IRB) constituted and acting pursuant to part 56 of this chapter , including continuing review of use of the deviceRead full regulation →
- 21CFR814.118§ 814.118 Denial of approval or withdrawal of approval of an HDE.
(a) FDA may deny approval or withdraw approval of an application if the applicant fails to meet the requirements of section 520(m) of the act or of this part, or of any condition of approval imposed by an IRB or by FDA, or any postapproval requirements imposed under § 814.126 . In addition, FDA may Read full regulation →
- 21CFR814.3§ 814.3 Definitions.
For the purposes of this part:Read full regulation →
Related Warning Letters (10)
- 2025-12-09
CGMP/QSR/Medical Devices/Adulterated
Envoy Medical Inc.
- 2025-11-25
CGMP/QSR/Medical Devices/Adulterated
Hong Qiangxing Shenzhen Electronics Limited
- 2025-10-28
CGMP/QSR/Medical Devices/Adulterated
Contec Medical Systems Co., Ltd.
- 2025-10-28
CGMP/QSR/Medical Devices/Adulterated/Misbranded
Royal Philips
- 2025-10-28
CGMP/QSR/Medical Devices/Adulterated/Misbranded
Qianjiang Kingphar Medical Material Co Ltd.
- 2025-10-21
CGMP/QSR/Medical Devices/Adulterated
LEVO AG
- 2025-10-07
CGMP/QSR/Medical Devices/Adulterated
Technological Medical Advancements LLC
- 2025-09-30
Medical Device Reporting/Misbranded
Insung Medical Co. Ltd.
- 2025-09-23
Medical Device/Adulterated/Misbranded/Lacks PMA and/or 510(k)
The Richline Group, Inc.
- 2025-09-16
Investigational Device Exemptions (IDE)/Premarket Approval Application (PMA) Adulterated Device
SeniorLife Technologies, Inc.
See Also (8)
- Pharmacogenetic Tests and Genetic Tests for Heritable Markers: Guidance for Industry and FDA Staff (Status: Final)
- New Contrast Imaging Indication Considerations for Devices and Approved Drug and Biological Products: Guidance for Industry (Status: Final)
- The Content of Investigational Device Exemption (IDE) and Premarket Approval (PMA) Applications for Artificial Pancreas Device Systems: Guidance for Industry and Food and Drug Administration Staff (Status: Final)
- Deciding When to Submit a 510(k) for a Change to an Existing Device: Guidance for Industry and Food and Drug Administration Staff (Status: Final)
- Multiple Function Device Products: Policy and Considerations: Guidance for Industry and Food and Drug Administration (Status: Final)
- Patient-Matched Guides to Orthopedic Implants: Draft Guidance for Industry and Food and Drug Administration Staff (Status: Draft)
- Marketing Submission Recommendations for a Predetermined Change Control Plan for Artificial Intelligence-Enabled Device Software Functions: Guidance for Industry and Food and Drug Administration Staff (Status: Final)
- Acceptance of Clinical Data to Support Medical Device Applications and Submissions: Frequently Asked Questions: Guidance for Industry and Food and Drug Administration Staff (Status: Final)