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