Humanitarian Use Devices – HUDs and Humanitarian Device Exemption - HDEs

1. Humanitarian Use Devices – HUDs and Humanitarian Device Exemption - HDEs National Institutes of HealthProduct Life Cycle of anInvestigational Device Exemption Eric Chen Director Humanitarian Use Devices Designation Program Office of Orphan Products Development Food and Drug Administration June 24, 2010

2. Intent of HDE Provision Provide incentive for development of devices intended for treatment or diagnosis, in small patient populations where otherwise a device manufacturer’s R&D costs would exceed market returns NIH

3. Section 520(m) of the Food, Drug and Cosmetic Act “… to encourage the discovery and use of devices intended to benefit patients in the treatment and diagnosis of diseases or conditions that affect fewer than 4,000 individuals in the United States.” [yearly] NIH

4. Statutory Conditions • Device not otherwise available • No comparable device available • Device: • Does not pose unreasonable risk of illness or injury [i.e., safety], AND • Probable benefit outweighs the risk (i.e., exempt from effectiveness requirements of a PMA) NIH

5. Statutory Conditions • Approval authorizes marketing of HUD • IRB approval required before device used • Local IRB may approve or defer • Labeling must clearly identify device as HUD, and that effectiveness for that indication has not been demonstrated • Amount charged cannot exceed cost of research, development, manufacturing and distribution • Pediatric HUDs can make a profit (FDAAA) NIH

6. Statute to Regulation • Post-Safe Medical Devices Act (SMDA) of 1990, proposed rule based on modified IDE regulation • Final rule June 1996 - new subpart H added to existing PMA regulation (21 CFR 814) • Effective October 1996 • Modified by Food and Drug Modernization Act (FDAMA) November 1997 NIH

7. 21 CFR 814 Subpart H • Modeled after PMA regulation • Submission format similar to PMA • Amendments/supplements • Annual reports • GMP/MDR requirements • Approval thresholds differ: • PMA: safety and effectiveness • HDE: safety and probable benefit • No regulatory definition of probable benefit but we encourage sponsors to work with FDA to develop an appropriate level of benefit for their device NIH

8. HUD Designation by OOPD(21 CFR 814 Subpart H) Part 1 of the two part review/approval process: • Request submitted to FDA’s Office of Orphan Products Development (not CDRH) • Designates the intended population for the device • Incidence must be < 4000/year in the U.S. • If subset of a larger population, must be “medically plausible” subset • 45 day review NIH

9. “Medically Plausible Subset” If the disease or conditions occurs in >4,000 pts./yr., the device could be used in a subset of the disease or condition AS LONG AS the sponsor shows the subset is medically plausible (NOT just "readily identifiable“). A medically plausible subset is one in which use of the device is limited to that subset because of some inherent property of the device and/or the disease. That is, the sponsor must explain why the device couldn't also be used in all pts. with disease or condition. NIH

10. HDE review by CDRH Part 2 of the two part review/approval process must include the following: • HUD designation (granted by Office of Orphan Products) • Explanation why device would not otherwise be available • Statement that no comparable device exists • Device description Approved indications for use may be narrower than HUD designation NIH

11. HDE review by CDRH con’t • Preclinical information • Clinical experience: data, literature, OUS, data gained from same device in different patient population • Clinical trials are usually not randomized or controlled due to small sample size and lack of a comparable marketed device • Clinical trial data is help to describe device performance and adverse events • Clinical trial data may clearly define patient population and patient management protocols NIH

12. HDE review by CDRH con’t. • Manufacturing information: Quality Systems Regulation (QSR) applies (unless elements waived) • Labeling (physician and patient), including HUD statement (that no effectiveness demonstrated) NIH

13. Key Points • HDE is marketing approval • Exempt from effectiveness requirements but not safety requirement • IRB approval required • Informed Consent not required by FDA • No requirement to submit PMA/510(k) • Can have multiple HDEs for same indication from different sponsors NIH

14. Since 1996 • 50 approved HDEs • 155 designated HUDs • 239 submitted HUD applications • List of approved HDEs and their Summaries of Safety and Probable Benefit (SSPB) available at: http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/HDEApprovals/ucm161827.htm NIH

15. Thank you • Contact information: Sheila Brown – IDE/HDE staff (301) 796-6563 Sheila.brown@fda.hhs.gov Lynn Henley – IDE/HDE staff (301) 796-6120 Lynn.henley@fda.hhs.gov Eric Chen – Director of HUD Program, OOPD (301) 796-6327 Eric.chen@fda.hhs.gov NIH