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Investigational Device Exemptions21 CFR Part 812
A Review for OCRA US RAC Study GroupSeptember 2005
Ginger Clasby, MSPromedica Internationalgclasby@promedica-intl.com714-799-1617 x 25
IDEAbout 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
When IDE Application Not RequiredClinical 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
Defining Device TypesSignificant 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
Defining Device TypesSignificant or Non-significant Risk?
How to decide?
Sponsor makes initial determination; IRB makes final call
Regulatory DifferencesSignificant 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
IDE Application ContentsAdministrative 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
IDE Application ContentsAn 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
IDE Application ContentsAn 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
IDE ContentsReport 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)
IDE ContentsInvestigational Plan
• Study purpose
• Proposed protocol
• Risk analysis
• Device description
• Monitoring procedures
• Labeling
• Consent materials
IDE ContentsInvestigational Plan
• IRB info
• Info on core labs, reading centers, etc.
• Add’l records & reports
IDE Review/ApprovalFDA’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
Prohibited Practices Under IDESponsors & 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
IDE SupplementsNecessary 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
“Treatment” IDEAppropriate 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
Sponsor ResponsibilitiesSubpart 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
Sponsor ResponsibilitiesSubpart 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
Sponsor ResponsibilitiesSubpart 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
Sponsor ResponsibilitiesSubpart 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
Sponsor ResponsibilitiesSubpart 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
IRB ResponsibilitiesSubpart 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
IRB ResponsibilitiesSubpart G – Records & Reports
• Records maintained in accordance with 21 CFR 56
IRB ResponsibilitiesSubpart G – Inspections
• Must permit access by FDA employees to inspect & copy study-related records
Investigator ResponsibilitiesSubpart 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
Investigator ResponsibilitiesSubpart 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
Investigator ResponsibilitiesSubpart 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
Investigator ResponsibilitiesSubpart 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
IDE RegulationReference 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)
IDE RegulationReference 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
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