Bridging the Gap for Rare Diseases: The FDA’s Humanitarian Use Device Program and China’s Emerging Role (I)

FDA’s Humanitarian Use Device (HUD) program offers a crucial lifeline to patients with rare conditions who might otherwise be left behind in the march of technological progress. In recent years, this niche but vital program has expanded its global reach, welcoming new players into its fold. Notably, two Chinese firm—Pulnovo Medical and Super Vision Technology—have entered the arena with novel devices that reflect both scientific ingenuity and regulatory sophistication. This article explores the HUD program’s structure, its eligibility criteria, and showcases ten notable HUD-designated devices by medical indication. We close with a detailed look at the two HUDs from Chinese manufacturers, milestones both for the companies and for China’s medical device industry.

Background of HUD

The Humanitarian Device Exemption (HDE) program is a regulatory pathway established by FDA to facilitate the development and market approval of medical devices intended to treat or diagnose rare diseases or conditions. These devices, known as Humanitarian Use Devices (HUDs), serve small patient populations, typically where no comparable devices exist and conventional clinical trials may not be feasible.

The FDA established the HUD program through the Safe Medical Devices Act of 1990, with the goal of encouraging the development of medical devices for diseases and conditions affecting fewer than 4,000 individuals per year in the United States. This threshold was later expanded to 8,000 individuals under the 21st Century Cures Act in 2016, reflecting both evolving epidemiological data and an increased awareness of unmet medical needs. The core idea behind the HUD pathway is simple but powerful: to provide patients suffering from rare diseases access to potentially life-saving medical technologies, even when the patient population is too small to support the kind of large-scale clinical trials typically required for premarket approval (PMA).

FDA released the guidance document “Humanitarian Device Exemption (HDE) Program” in December 2019.

Eligibility and Approval Criteria

For a device to qualify for HDE approval, several core criteria must be met:

1. The target condition must affect no more than 8,000 individuals per year in the U.S.
2. The device must not pose unreasonable or significant risl of illness or injury.
3. There must be no comparable device available in the U.S., except other HUDs or investigational devices.
4. The probable health benefit must outweigh risks, considering the current treatment landscape.
5. Use of the device requires approval by an Institutional Review Board (IRB) or appropriate local committee, except in emergencies.
6. The applicant must obtain a HUD designation from the Office of Orphan Products Development (OOPD) before submitting an HDE application.

Application and Review Process

An HDE application closely resembles a Premarket Approval (PMA) submission in structure but is subject to relaxed efficacy requirements and shorter review timelines. The standard FDA review timeline for an HDE is 75 days, compared to 180 days for PMAs.

The HDE application must include:

1. Device description and intended use
2. Justification of the rare disease prevalence
3. Assessment of probable benefit-risk
4. Details of manufacturing and quality control
5. Clinical and non-clinical study results
6. Statement on device price and cost (profit is generally prohibited unless specific conditions are met)

The FDA may take several actions during review: issuing an approval order, a major deficiency letter, a not approvable letter, or a denial order.

Probable Benefit-Risk Assessment

Since HUDs are exempt from proving full effectiveness, the FDA evaluates them on the basis of probable benefit-risk, considering:

1. Type and magnitude of potential benefit
2. Probability and duration of benefit
3. Risks, severity, and duration of harm
4. Patient and caregiver perspectives
5. Availability of alternative treatments
6. Clinical data are encouraged but not always required. In certain cases, strong non-clinical data such as animal studies or simulations may suffice.

Post-Approval Requirements

Approved HUDs come with specific post-market responsibilities:

1. Continued IRB/local committee oversight of device use
2. Submission of Medical Device Reports (MDRs) to both FDA and the overseeing IRB
3. Submission of supplements for significant changes
4. Annual reports detailing device distribution and any adverse events
5. Re-evaluation of HDE status if a comparable device is later approved

The profit prohibition remains a key restriction, though exceptions apply. For example, devices for pediatric patients or for conditions meeting certain thresholds may be sold for profit up to the Annual Distribution Number (ADN)—a figure calculated to represent the number of devices needed to treat or diagnose 8,000 individuals per year.

Use of HUDs in Clinical and Emergency Settings

Use of HUDs in routine care must be pre-approved by an IRB or local committee. However, in emergencies, HUDs can be used without prior IRB approval, provided proper documentation follows. Emergency use is defined as situations where there is no approved alternative, and waiting for approval would present a serious threat to the patient’s life or health.

For investigational use (e.g., in new clinical trials), a separate IDE (Investigational Device Exemption) is required. HUDs may not be used in trials without this additional layer of oversight.