Regulatory Science and Translational Research Clinical Trials for Medical Devices What do you need to know?

Transcription

1 Regulatory Science and Translational Research Clinical Trials for Medical Devices What do you need to know? Lynn M. Rose, PhD Research Associate Professor, Pediatrics Institute of Translational Health Sciences Preclinical Research and Development Network

2 Learning Objectives Definition and classification of medical devices Regulatory requirements for initiating clinical trials with non-significant risk devices Regulatory requirements for initiating clinical trials with significant risk devices Regulatory requirements for initiating clinical trials with drug/device combination products

3 Step 1: Definition of a Medical Device Instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including any component, part, or accessory, which is: Recognized in the official National Formulary, or USP Intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals, or; Intended to affect the structure or any function of the body of man or other animals, and which does not achieve its primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of its primary intended purposes.

4 Entering the US Device Market Clearance/Approval may not be primary reason for conduct of a clinical trial Two primary routes for obtaining authorization to market medical devices 510(k) premarket clearance Premarket approval (PMA) De Novo (no predicate device) Humanitarian Device Exempt Status

5 Device Classification Drives Clinical Testing Requirements for Marketing Approval Medical Device Classes: Additional Classification: Class I General Controls Most exempt from premarket submission Class II Special Controls Premarket Notification [510(k)] Class III Premarket Approval Require Premarket Application [PMA] De Novo Device "types" that have never been marketed in the U.S., but whose safety profile and technology are now reasonably well understood Humanitarian Device Exemption (HDE) Devices for orphan diseases Intended to benefit patients in diagnosis and/or treatment of disease or condition affecting or manifested in fewer than 4,000 patients per year in the United States

6 Device Classification Device Classification is Risk-Based Clearance to sell many devices based on equivalence with already cleared devices (predicate devices) Manufacturing controls increase with the class of the device Requirements for clinical studies increase with class of the device

7 Distribution of Generic Medical Devices Class I - General Controls (e.g., manual surgical instrument for general use) Class II - General Controls and Special Controls (e.g., sharps containers) Class III - General Controls and Premarket Approval (e.g., coronary stents) # Classified Devices Risk 782 Low 799 Medium 119 High Data Obtained from CDRH Learn 2009

8 Device Classification 1700 generic groups of devices Classified within 16 medical specialties 21 CFR Part

9 Device Medical Specialities 862=Chemistry/Toxicology 864=Hematology/Pathology 866=Immunology/Microbiology 868=Anesthesiology 870=Cardiovascular 872=Dental 874=Ear, Nose, and Throat 876=Gastro/Urology 878=General Plastic Surgery 880=General Hospital 882=Neurological 884=OB/GYN 886=Ophthalmic 888=Orthopedic 890=Physical Medicine 892=Radiology 21 CFR Part

10 Device Classification Regulation Number Classification Name - Medical Support Stocking Product Code FQL (General Purpose) Class I EXEMPT from 510(k) EXEMPT from cgmp Product Code DWL (Prevents Pooling of Blood) Class II and requires 510(k) NOT EXEMPT FROM cgmp

11 Class I Devices Subject to general controls Device listing Labeling FDA quality system regulations (QSR) compliance 510(k) premarket notification Most Class I Devices Exempt from 510(k) premarket notification In some cases, exempt from QSR compliance, other than minimal record keeping and reporting Clinical studies not generally required for marketing clearance Examples of Class I Devices: Elastic bandages, examination gloves, and hand-held surgical instruments

12 Class II Devices Subject to general and special controls Performance standards Postmarket surveillance FDA requirements specific to the device Most Class II Require 510(k) submission Specific Labeling QSR Compliance Device Listing Clinical studies may be required, particularly if lack predicate prior to marketing clearance Examples of Class II Devices: Powered wheelchairs, infusion pumps, and surgical drapes

13 Substantial Equivalence A device is substantially equivalent to a legally marketed predicate device if: Both have the same intended use; Same technological characteristics; or Different technological characteristics that do not raise any new questions of safety or effectiveness, and performance data that demonstrates the new device is as safe and effective as the predicate device Bench Animal Clinical data

14 Class III Devices Subject to general and special controls Life sustaining and life supporting Implantable devices New devices not found to be substantially equivalent to legally marketed devices Most Class III Devices Require approval of a PMA (unless marketed prior to 1976) Most stringently regulated Require clinical study to demonstrate safety and effectiveness prior to marketing approval Examples of Class III Devices: Replacement heart valves, silicone gel-filled breast implants, and implanted cerebellar stimulators

15 De Novo Petition Down classification for devices that do not qualify for the 510(k) due to lack of predicate device (avoids PMA) To qualify, the device must be Novel Low Risk

16 De Novo Requirements Within 30 days of being denied Description of the device Labeling Justification for recommendation classification Information to support the recommendation bench, animal, human clinical data Usually clinical data is required

17 Medical Device Studies Required To: Support a marketing application; Collect safety and effectiveness data for a new use of a legally marketed device; Conduct sponsor-investigator studies of uncleared or unapproved devices - even if no marketing application is planned; or De Novo Down Classification (foreign manufacturer)

18 Types of Investigational Device Studies FDA defines 3 types of Investigational Device Studies Significant Risk (Requires an IDE) Nonsignificant Risk (May require an IDE) Exempt (Does not require an IDE)

19 Significant Risk Device Is intended as an implant and presents a potential for serious risk to the health, safety, or welfare of a subject; Is purported or represented to be for use supporting or sustaining human life and presents a potential for.; If for use of substantial importance in diagnosing, curing, mitigating, or treating disease, or otherwise preventing impairment of human health and presents a.; Otherwise presents a potential for..

20 Nonsignificant Risk Devices An NSR Device is one that does not meet the definition of a Serious Risk Device

21 Who decides whether a device study is SR or NSR? Sponsors make initial determination and present to IRB Unless FDA has already determined risk level, it is the responsibility of the IRB to make the determination FDA is available to consult with sponsor or IRB In cases of disagreement, FDA trumps IRB

22 Regulatory differences between SR and NSR Studies SR Studies must follow all the IDE regulations in 21 CFR Part 812 SR Studies must have an IDE application approved by FDA before they can proceed NSR Studies must follow abbreviated requirements of 21 CFR Part 812.2(b) NSR Studies do not require an IDE NSR Studies are not reported to FDA IRB acts as surrogate of FDA for NSR studies

23 Sponsors Responsibility for Non- Significant Risk Devices Provide IRB with explanation of determination Sufficient data to help IRB evaluate the risk of the device Description of device Prior investigations with device Proposed investigational plan Subject selection criteria Follow reporting requirements of IRB

24 NSR Studies and FDA FDA considers an NSR device study to have an approved IDE after IRB approval and when sponsors meet the abbreviated requirements of 21 CFR 812.2(b). Labels device as investigational IRB Approval Obtains informed consent from subjects in study Monitors study Maintains required records Does not promote device

25 Sponsors Responsibility For Significant Risk Devices Submit an IDE Application to FDA and obtain approval for the study Advise clinical investigators of the SR status and obtain agreement to comply with applicable regulations (no Form 1571 for devices) Submit protocol to IRB for review and approval

26 Required Elements of an IDE U.S. Sponsor (manufacturer or investigator) Report of Prior Investigations Investigational Plan Manufacturing Information Investigator and IRB Information Sales Information Labeling Informed Consent

27 IDE Exempt Studies 510(k)-cleared and HDE- or PMA-approved devices, if used in accordance with approved label; Consumer preference testing of marketed device; Combinations of legally marketed devices; Custom devices (NARROWLY defined); Foreign Studies; Declaration of Helsinki Studies of diagnostic devices (with some caveats)

28 The Intersection of Devices and Drugs: Combination Products Gem 21S Dental Bone Graft with Growth Factor Daytrana Transdermal patch Primary Mode of Action: Repair periodontal defects Secondary Action: Drug promotes growth of new bone Regulated as a Device (PMA) Primary Mode of Action: Drug delivery for ADHD Secondary Actions Local drug delivery of drug by device Regulated as a Drug (NDA)

29 What is a Combination Product? Safe Medical Device Act (1990) 503(g)(1) Products that constitute a combination of a drug, device or biologic Drug Device Device Biologic Biologic Drug Drug Device Biologic Can t make assumptions about clinical path based on device classification Note: Drug Drug, or Device - Device combination not included here

30 Challenge of Combination Products Drug NDA, Device BLA PMA, 510(K) IND, IDE Biologic Different Frameworks Device Drug Biologic CDER CDRH CBER CDRH CDER CBER IND, NDA IDE, PMA, 510(k) IND, BLA Different FDA Reviews

31 Real World Examples Drug-eluting stent CDRH Drug-eluting disc (oncology) CDER Contact lens/glaucoma drug CDER Contact lens/glaucoma drug CDER Spinal fusion device/therapeutic protein CDRH Chemo drug/monoclonal antibody CDER Scaffold seeded with autologous cells CBER Interferon/Ribivarin therapy CDER Embolization implant device/chemo drug CDRH Vertebroplasty device/analgesic CDRH

32 Office of Combination Products Assigns an FDA center to have primary jurisdiction for review of both combination and single entity products where the jurisdiction is unclear or in dispute. Ensures timely and effective premarket review of combination products Resolves disputes regarding the timeliness of premarket review of combination products. Submits annual reports to Congress on the Office s activities and impacts.

33 Summary Unlike drugs, many devices require no clinical studies to support marketing. Clinical studies may be needed to support adoption by the clinical community Investigational studies of devices are characterized and classified by risk IDE required for Class III/Significant Risk devices Nonsignificant risk devices require approval by IRB or FDA. Conduct of studies vary with risk characterization Combination products require decision from FDA

34 Links and Resources FDA Center for Devices and Radiological Health (CDRH) FDA Office of Combination Products FDA US Agent FDA Establishment and Device Listing Forms cfrl/printforms.cfm

35 ITHS Preclinical Research and Development Network 35 Consulting on IND/IDE Content Review Development Programs Assist in identification of industry and academic partners Funding Program for Translational Research (Ignition Awards for Nonhuman Primate studies, Pharmaceutics, and Manufacturing)

36 Thank you For additional information contact: Lynn Rose