1. Device Research Presented by Marian Serge, R.N.

2. Goals Identify devices Recognize difference between significant risk (SR) and non- significant risk (NSR) devices Explain how an Investigational Device Exemption (IDE) is obtained for SR and NSR devices Discuss IRB responsibilities Discuss investigator responsibilities Recognize humanitarian use devices 2

3. Food, Drug and Cosmetic Act -Sec. 201 Device Definition An instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including any component, part, or accessory which is intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or intended to affect the structure or any function of the body and which does not achieve its primary intended purposes through chemical action within or on the body and which is not dependent upon being metabolized for the achievement of its primary intended purposes. 3

4. Types of Devices Radiation emitting devices Joint replacements Contact lenses Tissue adhesives Dialysis machines Urology catheters Stents Lasers Implantable vascular access ports Wound dressings CT Scans Collagen Infusion pumps 4

5. Devices Used in Research Investigational Device Exemption (IDE) What does Investigational Device Exemption (IDE) mean? Food, Drug and Cosmetic Act (a law) mandates that only devices with FDA approval can be shipped and used So, how can a device that does not yet have FDA approval be shipped and used in research? The device manufacturer or person conducting the research has to apply to FDA for an Investigational Device Exemption (IDE) from the Act The Act and FDA regulation, 21 CFR 812, describes the Investigational Device Exemption (IDE) process 5

6. Investigational Device Exemption(IDE) Regulation 21 CFR Part 812 This regulation describes: IDE application process so that a device not yet approved by FDA can be used in a clinical investigation Significant Risk (SR) Device Submission of an IDE application to FDA and IRB approval The entire regulation at 21 CFR 812 must be followed Non-Significant Risk (NSR) Device IRB acts as FDA’s surrogate and after IRB approval it is considered to have approved application for IDE Only parts of the regulation at 21 CFR 812 must be followed Sponsor responsibilities Clinical investigator responsibilities IRB approval IRB determination of SR or NSR for NSR devices 6

7. Two Types of Devices Significant risk Non-significant risk 7

8. Significant Risk (SR) Device Presents a potential serious risk to the health, safety and welfare of a subject and is: an implant; or life supporting or sustaining; or of substantial importance in diagnosing, curing, mitigating, or treating disease or preventing impairment of human health; or a device that presents a potential serious risk to the health, safety and welfare of a subject. 8

9. Significant Risk (SR) Device Investigational Device Exemption (IDE) IDE application submitted to FDA FDA Reviewer FDA reviews and sends the sponsor an approval letter Examples of SR devices: Extended wear contact lenses Stents – coronary, urinary, vascular/peripheral Cutting lasers 9

10. Non-significant Risk (NSR) Device No definition of non-significant risk (NSR) device in FDA regulation Any device that is not a significant risk (SR) device is a non-significant risk (NSR) device 10

11. NSR Device Investigational Device Exemption No IDE application to FDA is needed; rather, sponsor submits risk determination to the IRB. The IRB acts as FDA’s surrogate and after IRB approval (following 21CFR 56.111) the device is considered to have approved application for IDE. FDA will not know about NSR device investigations. Examples of NSR devices: Urologic catheters Low power lasers for pain relief MRI Simple wound dressings IRB meeting 11

12. Compare and Contrast Summary of SR and NSR Devices SR Device Meets FDA definition of significant risk device Submission of an IDE application to FDA required Study may start after FDA approves the IDE application and the IRB approves the study NSR Device No definition – NSR device is any device not a significant risk device No submission of an IDE application to FDA; rather, sponsor submits their risk determination to the IRB. The IRB also makes a risk determination. After IRB approval, the device is considered to have an approved application for IDE and the study may start 12

13. Exercise Is the device – SR or NSR? Coronary stents Dialysis delivery systems Sutures Implantable Vascular Access Devices (Ports) Contact lens Daily wear Extended wear Wound dressing Plain gauze Interactive wound or burn dressings 13

14. Exercise How is an IDE Obtained? Coronary stents Dialysis delivery systems Sutures Implantable Vascular Access Devices (Ports) Contact lens Daily wear Extended wear Wound dressing Plain gauze Interactive wound or burn dressings 14

15. IRB Responsibilities for Investigational Devices IRBs need to distinguish between SR and NSR devices IRBs may review a SR device study before FDA reviews it – However, SR device studies may not start until after both IRB and FDA approval IRBs must make a SR or NSR device determination for every NSR device study submitted to the IRB (21CFR 812.66) 15

16. IRB Determination: NSR Device: Is it SR or NSR? IRB written policies and procedures regarding initial and continuing review of research must have a procedure for IRB determination of device risk, to include: Sponsor’s brief explanation of why the device is not significant risk 21 CFR 812.2 Review definition of significant risk device Review a description of the device Review the protocol to find out the proposed use of the device in the study Review the informed consent form Review subject selection criteria Review FDA guidance on medical devices (FDA Information Sheets) Review reports of prior investigations, if any Obtain outside assistance or FDA’s assistance 16

17. How to Request FDA Assistance for Determining Whether Device is SR or NSR Send 3 copies of the following information to: Document Mail Center WO66 G609 FDA/CDRH 10903 New Hampshire Avenue Silver Spring, MD 20993-0002 Detailed description of the device(s) Study protocol Description how the device will be used in the study Population that will receive the device Sponsor’s name, contact persons, titles, address, phone, fax, email address 17

18. Non Significant Risk Device IRB Determination What happens after an IRB makes its determination? If the IRB’s determination of NSR agrees with the sponsor’s determination of NSR..... then the IRB may review the study for approval following 21 CFR 56.111 (Same as 38 CFR 16.111) However, if the IRB’s determination disagrees with the sponsor’s determination (i.e. IRB thinks the device is SR).... then the sponsor must obtain approval of an IDE application from FDA before beginning a clinical investigation (21 CFR 812.66) 18

19. IRB Required Documentation IRB written policy and procedure regarding review of devices Determine whether a NSR device is a SR or NSR device 21CFR 812.66 21CFR 56.108 Document the IRB’s determination in the meeting minutes or project file 21CFR 56.115 Report to the investigator or sponsor whenever the IRB’s determination disagrees with the sponsor’s NSR determination 21 CFR 812.66 Obtain FDA letter of approval of IDE application for SR device FDA Information Sheets Guidance 19

20. Key Points to Remember Devices are either SR or NSR IDE is required before a device investigation may begin IRB determination may agree or disagree with a sponsor’s initial NSR determination IRB risk determination should be based on the proposed use of the device in an investigation, and not on the device alone IRBs must have written procedures for review of device studies (21 CFR 56.108) and document their findings (21 CFR 56.115) FDA is the final arbiter in determining whether a device is SR or NSR 20

21. Title 21 CFR 812.100 Clinical Investigator Device Responsibilities FDA good clinical practice for device studies Follow signed agreement with sponsor Ensure Informed consent process and form complies with 21 CFR 50 Conduct study in accordance with IRB conditions of approval Follow the protocol Supervise the use of the device Ensure device studies have proper Investigational Device Exemption Maintain device accountability records and return or dispose of devices Recordkeeping: Correspondence, subjects’ case history, exposure, etc. Reports: Unanticipated adverse device effects, deviations, progress etc. Maintaining research records 21

22. Humanitarian Use Device (HUD) Why have HUDs? Congress enacted a law that would encourage device manufactures to develop devices for people who have rare diseases or conditions FDA approves humanitarian use devices for marketing 22

23. Humanitarian Use Device (HUD) 21 CFR 814 Subpart H FDA can grant an exemption from the effectiveness requirements of the Food, Drug & Cosmetic Act if it finds the HUD is designed to treat or diagnose a disease or condition that affects fewer than 4,000 patients in the U.S. and No comparable device available and Will not expose patients to an unreasonable risk of injury and the probable benefit outweighs the risk This is not research 23

24. Humanitarian Use Device (HUD) IRB Responsibilities Must approve the use at the facility May specify limitations on the use Based on one or measures of disease progression Prior use and failure of any alternative treatment Reporting requirements to the IRB or Chair Appropriate follow-up precautions/evaluations Any other criteria it determines appropriate Must perform continuing review Must review serious adverse events & deaths Must terminate for non-compliance 24

25. What Have We Learned? There are 2 types of devices: significant risk (SR) and non-significant risk (NSR) SR devices must have FDA approval of an IDE application and IRB approval NSR device must have IRB approval IRBs have a big role in device studies – risk determination for NSR devices Investigators of device studies must follow requirements at 21 CFR 812 Humanitarian Use Devices (HUD) require IRB approval, but are not research 25

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