1. Investigational Device Exemptions 21 CFR Part 812
A Review for OCRA US RAC Study Group
September 2005
Ginger Clasby, MS
Promedica International
x 25

2. IDE About the Regulation
Provides procedures for conduct of clinical studies for unapproved devices
Exempts products from 510(k) or PMA approval requirements:
Registration, listing, interstate distribution
Labeling
GMPs
Applies to most studies to determine device safety & effectiveness

3. When IDE Application Not Required Clinical Study Situations
Device legally marketed for indicated use
Marketing preference studies
Market seeding studies
Device is substantially equivalent to pre 1976 commercially distributed device
Device is non-significant risk & IRB has approved study
Many diagnostic devices
Veterinary devices
Custom device

4. Defining Device Types Significant or Non-Significant Risk?
Significant Risk: device has potential for serious risk to patient health, safety or welfare
Implants
Products supporting/sustaining life
Products with substantial role in diagnosing, curing mitigating or treating disease (or preventing impairment of human health)
Non-Significant Risk: all other devices

5. Defining Device Types Significant or Non-significant Risk?
How to decide?
Sponsor makes initial determination; IRB makes final call

6. Regulatory Differences Significant vs. Non-significant Risk
Significant Risk Devices require FDA (IDE) & IRB approval prior to clinical study initiation
Non-Significant Risk Devices require only IRB approval prior to clinical study initiation
IDE presumed, unless FDA notified Sponsor that application is required

7. IDE Application Contents Administrative Details
Sponsor responsibility
3 copies of submission required
All correspondence related to IDE sent by registered mail or by hand
IDE approval required prior to study initiation

8. IDE Application Contents An Overview
Sponsor name & address
Report of prior investigations & investigational plan
Description of methods, facilities, controls used for device manufacture, processing, packaging, storage & use
Names of proposed investigators & example of proposed investigator agreements
Certification that all investigators will sign agreement prior to study participation

9. IDE Application Contents An Overview
List of name, address & chairperson of each IRB reviewing study
If device will be “sold”, amount to be charged and rationale for why sale does not constitute commercialization
Environmental exemption/assessment
Proposed device labeling
“Caution – Investigational Device Limited by Federal (or US) Law to Investigational Use”
Copies of all informed consent documents

10. IDE Contents Report of Prior Investigations
Reports of all prior clinical, animal & lab testing of device – should be adequate to justify proposed study
Bibliography of related publications
Summary of unpublished info
Non-clinical lab studies (in compliance with GLP)

11. IDE Contents Investigational Plan
Study purpose
Proposed protocol
Risk analysis
Device description
Monitoring procedures
Labeling
Consent materials

12. IDE Contents Investigational Plan
IRB info
Info on core labs, reading centers, etc.
Add’l records & reports

13. IDE Review/Approval FDA’s Considerations
Approval/disapproval decision
Rendered in writing
Rendered  30 days of FDA receipt
Approval may be denied/rescinded if:
Sponsor fails to comply with applicable regulations
Sponsor is non-responsive to requests for add’l info
Subject risks outweigh benefits
Unreasonable to proceed due to inadequacy of investigational plan, manufacturing or monitoring

14. Prohibited Practices Under IDE Sponsors & Investigators
Promotion of investigational product
Representing device as safe or effective for use in the study
Commercializing device by charging more than cost-recovery
Unduly prolonging study
Enrolling more subjects than necessary

15. IDE Supplements Necessary When:
Changes made to investigational plan that may affect:
Scientific soundness of study
Rights, safety or welfare of study subjects
Changes in device design
Changes in device manufacturing
Addition of study investigators

16. “Treatment” IDE Appropriate When:
Device intended to treat or diagnose serious or life-threatening condition
No satisfactory alternative available
Controlled clinical trials in progress under IDE
Or when trials completed & FDA review of request to market is pending
Sponsor actively pursuing device marketing approval with FDA

17. Sponsor Responsibilities Subpart C
Selection of qualified investigators & maintenance of ongoing communications
Appropriate monitoring of study
Special emphasis on device-related adverse events
Confirmation of IRB review/approval
Submission of IDE application to FDA
Prompt notification of significant new information to FDA, IRB

18. Sponsor Responsibilities Subpart G – Records
Maintenance of records:
Study-related correspondence
Device shipment/disposition
Signed investigator agreements & financial disclosure info
Non-significant risk justification (if applicable)
Adverse device effects & complaints
Record retention ≥ 2 yr after study completion or date no longer required for PMA application
Record custody transferable with notice to FDA

19. Sponsor Responsibilities Subpart G – Inspections
Must permit access by FDA employees to inspect facility where devices are held
Must permit access by FDA employees to inspect & copy study-related records

20. Sponsor Responsibilities Subpart G – Reports
Unanticipated adverse device effects – 10 working days
Withdrawal of IRB approval – 5 working days
Withdrawal of FDA approval – 5 working days
Current investigator list – every 6 months
Progress reports – at least yearly
Device recalls & disposition – 30 working days

21. Sponsor Responsibilities Subpart G – Reports
Study completion (significant risk) - 30 working days
Final report - 6 months
Use of device without written consent – 5 working days
Significant risk determination – 5 working days

22. IRB Responsibilities Subpart D
Membership, duties & functions in accordance with 21 CFR 56
Review of research
Initial review prior to study initiation
Significant risk determination, if necessary
Continuing review throughout study

23. IRB Responsibilities Subpart G – Records & Reports
Records maintained in accordance with 21 CFR 56

24. IRB Responsibilities Subpart G – Inspections
Must permit access by FDA employees to inspect & copy study-related records

25. Investigator Responsibilities Subpart E
Compliance with:
Investigational plan
Investigator agreement(s)
Applicable FDA regulations
Protection of subject rights & welfare
Control of investigational devices
Obtaining consent in accordance with 21 CFR part 50
Repeated noncompliance with assigned responsibilities may result in investigator disqualification by FDA

26. Investigator Responsibilities Subpart G – Records
Maintenance of records:
Study-related correspondence
Product receipt, use, or disposition
Subject case records
Protocol & amendments
Record retention ≥ 2 yr after study completion or date no longer required for PMA application
Record custody transferable with notice to Sponsor, FDA

27. Investigator Responsibilities Subpart G – Inspections
Must permit access by FDA employees to inspect facility where devices are held
Must permit access by FDA employees to inspect & copy study-related records
Must permit access by FDA employees to inspect & copy records identifying subjects, if:
Suspicion that adequate consent was not obtained
Required investigator reports incomplete, inadequate, false

28. Investigator Responsibilities Subpart G - Reports
Unanticipated adverse device effects – 10 working days
Withdrawal of IRB approval – 5 working days
Progress reports – at least yearly
Deviations from investigational plan – 5 working days
Device use without documentation of consent – 5 working days
Final report - 3 months

29. IDE Regulation Reference Documents & Links (www.fda.gov/cdrh)
Guidance on IDE Policies & Procedures (1/1998)
Early Collaboration Meetings Under FDA Modernization Act (FDAMA), Final Guidance for Industry & CDRH Staff (2/2001)
Guidance on Significant & Non-Significant Risk Device Studies 7/25/86 (D86-1)
The Least Burdensome Provisions of FDA Modernization Act of 1997: Concept & Principles; Draft Guidance for FDA & Industry (5/3/2001)

30. IDE Regulation Reference Documents & Links (www.fda.gov/cdrh)
FDA Guidance for Financial Disclosure by Clinical Investigators
FDA Guidance for IRBs & Clinical Investigators
FDA Guidance for Monitoring Clinical Investigations
FDA/ORA Compliance Program Guidance for Bioresearch Monitoring of Clinical Investigations
FDA CDRH Device Advice