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