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U.S. Department of Health and Human Services

Training and Continuing Education

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Presentation: Institutional Review Board Responsibilities in making the Significant Risk and Non-significant Risk Device Determination

(This presentation is also available in video format with captioning and PDF printer-friendly format.)

Presented by Janette Collins-Mitchell, MS RN

Nurse Consultant
Division of Bioresearch Monitoring
Office of Compliance
Center for Devices and Radiological Health

Learning objectives

  • Make distinction between significant risk (SR) and non-significant risk (NSR) device studies
  • Describe three criteria IRBs should consider when making the SR/NSR determination
  • Identify how IRBs document their determination

Topics

  • Background
  • Define SR and NSR device studies
  • IRB Responsibilities
  • What IRB's consider when making the SR/NSR determination
  • Documentation of IRB determination

Background

  • Investigational Device Exemption (IDE) Regulation is found Title 21 CFR 812
    • Sponsor and IRB responsibilities for NSR device determination
  • Why provide this information?
    • Improve IRB understanding of responsibility
    • Improve compliance with FDA regulation
  • IRB serves as FDA surrogate for NSR investigations
    • Initial and continuing review

What is a Significant Risk Device?

  • Definition
    • Intended as an implant and presents a potential for serious risk to the health, safety, or welfare of a subject
    • Purported or represented for supporting or sustaining human life and presents a potential for serious risk to the health, safety, or welfare of a subject

What is a Significant Risk Device?

  • Definition
    • Used for substantial importance in diagnosing, curing, mitigating, or treating disease and presents a potential for serious risk to the health, safety, or welfare of a subject
    • Otherwise presents a potential for serious risk to health, safety, or welfare of a subject
  • Examples: Dental lasers, embolization devices for urological use, and collagen and bone replacements

What is a Non-Significant Risk Device?

  • One that does not meet the definition of a significant risk device
  • Examples: External monitors for insulin reactions, general biliary catheters, MRI within specified parameters

Who Decides Whether a Device is SR or NSR?

  • Sponsors
    • Make the initial risk determination
    • Presents the IRB with this information
  • IRBs
    • Required to determine whether the NSR device study involves a SR or NSR device
  • FDA
    • Available to help
    • Final arbiter

What are the Requirements in 21 CFR 812 for NSR Device Studies?

  • Abbreviated requirements at 21CFR 812.2(b)
    • Labeling, IRB approval, informed consent, monitoring, record keeping, reports, and prohibition against promotion.
  • NSR studies are considered to have an approved IDE therefore no IDE to FDA
  • Sponsors and IRBs do not have to advise FDA of NSR device studies
  • IRBs must make a SR or NSR determination for every NSR study (21 CFR 812.66)

What is the sponsor’s responsibility to the IRB for NSR device studies?

  • Provide reviewing IRBs with a brief explanation of why the device is not a SR
  • Any other information requested by the IRB
    • Description of device
    • Reports of prior investigations
    • Proposed investigational plan
    • Subject selection criteria
  • Inform IRB if FDA determined the study to be NSR

What is the IRB responsibility for NSR device studies presented for review?

  • IRBs should make the SR or NSR determination about a study by reviewing relevant information at a convened meeting.

What Should IRBs Consider When Making the SR or NSR Determination?

For studies presented as NSR device studies, IRBs should consider:

  • What is the basis for the risk?
    • Proposed use of device
  • What is nature of harm that may result from the use of the device?
  • Any additional procedures?
    • Potential harm from procedures

Let’s Put This into Practice

Study of a change in a component of a device. For example: new leads, battery pack, or software of an approved pacemaker

  • Basis for risk: Any change to a component is a change to the device itself
  • This study is significant risk and requires IDE approval by FDA

More Practice

Study of a 510k, non-significant risk, daily wear lens device to be used as overnight lens. Design changes.

  • Proposed use and nature of harm: Potential for injury not normally seen with daily wear lens
  • This study is significant risk and requires IDE approval by FDA

What Happens When the Sponsor and IRB Determination Disagree?

  • If the IRB determines that a NSR device study involves a SR device
    • IRB must inform the clinical investigator and where appropriate the sponsor
    • The study cannot start until sponsor obtains an IDE

What Happens When the IRB Agrees with the Sponsor’s NSR Determination?

  • If IRB determination of NSR agrees with sponsor’s NSR
    • IRB can review the study using criteria at 21 CFR 56.111
    • The study may begin without notice to FDA or IDE application to FDA

How do IRBs Document the SR or NSR Determination?

  • Write determination in minutes
    • Give reason for determination
  • NSR studies
    • Maintain all materials reviewed

References

FDA Information Sheets
http://www.fda.gov/ScienceResearch/SpecialTopics/RunningClinicalTrials

Procedures for Handling Inquires
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/ Overview/BioresearchMonitoring/default.htm

Summary

  • Made distinction between significant risk (SR) and non-significant risk (NSR)
  • Described criteria IRB should use when making SR or NSR determination
  • Described how to generate documentation of IRB’s determination of SR or NSR