1. Regulation of Medical Devices Celia M. Witten, Ph.D., M.D. Director Division of General, Restorative and Neurological Devices Office of Device Evaluation Food and Drug Administration RHAIR Society for Academic Emergency Medicine Boston, Massachusetts May 31, 2003

2. 2 Outline Outline Who we are Who we are Device types Device types Paths to market Paths to market Temperature control devices Temperature control devices Clinical study regulation Clinical study regulation

3. 3 FDA CVMCFSCANCDRH OSTOSMOSBODE DAGID DCD *DGRND DOED DRARD OHIPOCOIVD CBERCDER Who We Are

4. 4 Device Examples Neuroembolization devices Neuroembolization devices Deep brain stimulators Deep brain stimulators Neurodiagnostic devices (EEG, EMG) Neurodiagnostic devices (EEG, EMG) Neurosurgical shunts Neurosurgical shunts Muscle stimulators Muscle stimulators Neurovascular stents Neurovascular stents

5. 5 Regulatory Review: Pathways to Market Regulatory Review: Pathways to Market Premarket Notification 510(k) Premarket Notification 510(k) Premarket Approval Application (PMA) Premarket Approval Application (PMA) Product Development Protocol (PDP) Product Development Protocol (PDP) Humanitarian Device Exemption (HDE) Humanitarian Device Exemption (HDE) De Novo Classification De Novo Classification

6. 6 Premarket Notification 510(k) Substantial Equivalence Substantial Equivalence Predicate Device (legally marketed, not subject to PMA) Predicate Device (legally marketed, not subject to PMA) Comparison Comparison – same intended use and – same technological characteristics or – different technological characteristics and – as safe and effective as predicate

7. 7 Premarket Application (PMA) …reasonable assurance of safety and effectiveness…

8. 8 Regulatory Path Examples

9. 9 Hydrocephalus Shunts 510(k) (substantial equivalence) 510(k) (substantial equivalence) Comparison to predicate Comparison to predicate Standards: Standards: – ASTM F647 – ISO 7197 Materials/biocompatibility Materials/biocompatibility For new/unusual designs, may need a For new/unusual designs, may need a clinical study for – Infection – Revision/causes – Failures/failure modes

10. 10 Intracranial Neurovascular Stents Class III (PMA/HDE/PDP) Class III (PMA/HDE/PDP) 2 HDEs approved 2 HDEs approved

11. 11 Deep Brain Stimulation Class III Class III PMA approval for essential tremor and Parkinsons disease symptoms PMA approval for essential tremor and Parkinsons disease symptoms

12. 12 Clinical Study Regulation Clinical Study Regulation FFD&C Act gives FDA the authority to regulate investigational devices: To encourage the discovery and development of new devices To encourage the discovery and development of new devices Maintain optimum freedom for scientific investigations Maintain optimum freedom for scientific investigations

13. 13 Section 520(g) of the Act Requires IRB approval for all clinical investigations Requires IRB approval for all clinical investigations Requires informed consent from all subjects unless emergency use Requires informed consent from all subjects unless emergency use

14. 14 IDE Regulation (Part 812) Allows an unapproved device to be shipped for clinical evaluation: Identifies sections of the Act from which IDEs are exempt Identifies sections of the Act from which IDEs are exempt Identifies exempted investigations (e.g. cleared devices, IVDs) Identifies exempted investigations (e.g. cleared devices, IVDs) Defines SR and NSR investigations Defines SR and NSR investigations

15. 15 Significant Risk (SR) Study Presents a potential serious risk to the health, safety, and welfare of a subject and is: 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 FDA approval required FDA approval required

16. 16 Non-significant Risk Studies FDA approval not needed FDA approval not needed Examples: Examples: – MRI < 4 Tesla – Urologic catheters – Low level biostimulation lasers – Laparoscopes NSR devices can be SR studies NSR devices can be SR studies

17. 17 Informed Consent: Emergency Use Must be reviewed and approved by the IRB and the FDA prior to use Must be reviewed and approved by the IRB and the FDA prior to use May be waived when there is a life- threatening situation May be waived when there is a life- threatening situation – the subject cannot communicate – time is not sufficient – no available alternative – two physicians certify in writing

18. 18 Informed Consent: Emergency Research Certain studies may not require informed consent when IRB agrees that Certain studies may not require informed consent when IRB agrees that – there is a life-threatening situation and current treatments are unsatisfactory treatments are unsatisfactory – no time – cant identify subjects prospectively – community consultation – public disclosure

19. 19 When Are Clinical Data Needed? To support: PMA, PDP or HDE (almost always) PMA, PDP or HDE (almost always) 510(k) (<10%) 510(k) (<10%) New indication for an approved device (e.g., BPH for a urologic laser) New indication for an approved device (e.g., BPH for a urologic laser) Significant change to device, especially Class III devices Significant change to device, especially Class III devices

20. 20 Types of Studies Types of Studies Sponsor-investigator Sponsor-investigator Manufacturer-sponsored Manufacturer-sponsored –Feasibility –Pivotal, including sites outside the US –Post-approval

21. 21 Feasibility Trial Feasibility Trial Answer design-related questions that cannot be addressed by bench/animal testing Answer design-related questions that cannot be addressed by bench/animal testing Modify device design &/or instructions for use Modify device design &/or instructions for use Preliminary safety data Preliminary safety data No control No control Limited # pts/limited follow-up Limited # pts/limited follow-up

22. 22 Pivotal Trial Pivotal Trial Final design, indication for use, and protocol Final design, indication for use, and protocol Controlled Controlled Masked, if possible Masked, if possible Primary/secondary endpoints Primary/secondary endpoints Develop information for labeling Develop information for labeling Statistical validity to show S & E Statistical validity to show S & E

23. 23 Post-Approval May be required for PMA approval May be required for PMA approval Designed to address specific question Designed to address specific question # of patients and duration specified by FDA # of patients and duration specified by FDA

24. 24 Cooling Devices: Clinical Study Questions How soon? How soon? How cold? How cold? How fast? How fast? How long? How long? How measured? How measured? Speed of rewarming? Speed of rewarming? Other treatments provided? Other treatments provided? Local versus systemic? Local versus systemic?

25. 25 Temperature Control Devices Tool? Tool? Treatment? Treatment?

26. 26 Temperature Control Devices Cooling Blankets Cooling Blankets Endovascular Devices Endovascular Devices

27. 27