Institutional Review BoarResponsibilities in making Significant Risk and Non-significant Risk DevicDetermination 

Institutional Review Boar

Institutional Review Boar

Responsibilities in making 

Responsibilities in making 

Significant Risk and Significant Risk and Non

-significant Risk Devic

significant Risk Devic

Determination Determination

Presented by Janette Collins-Mit

Presented by Janette Collins-MitNurse ConsultantDivision of Bioresearch MonitoringOffice of ComplianceCenter for Devices and Radiological Health

Nurse ConsultantDivision of Bioresearch MonitoringOffice of ComplianceCenter for Devices and Radiological Health
Learning objectives Learning objectives

z Make distinction between sign

(SR) and non-significant risk (device studies

z Describe three criteria IRBs s

consider when making the SRdetermination

z Identify how IRBs document t

determination
Topics

• Background• Define SR and NSR device • IRB Responsibilities • What IRB’s consider when m

SR/NSR determination 

• Documentation of IRB deter
Background Background

z Investigational Device Exemption 

Regulation is found Title 21 CFR 8

– Sponsor and IRB responsibilities for 

determination

z Why provide this information?

– Improve IRB understanding of respo– Improve compliance with FDA regula

z IRB serves as FDA surrogate for N

investigations

– Initial and continuing review
What is a Significant Risk 

What is a Significant Risk 

z Definition 

– Intended as an implant and pre

potential for serious risk to the hsafety, or welfare of a subject

– Purported or represented for su

sustaining human life and presepotential for serious risk to the hsafety, or welfare of a subject
What is a Significant Risk 

What is a Significant Risk 

z Definition

– Used for substantial importance in d

curing, mitigating, or treating disease a potential for serious risk to the heawelfare of a subject

– Otherwise presents a potential for se

health, safety, or welfare of a subjec

z Examples: Dental lasers, emboliza

devices for urological use, and cobone replacements
What is a Non-Significant Ri

What is a Non-Significant Ri

z One that does not meet the de

a significant risk device 

z Examples: External monitors 

reactions, general biliary cathwithin specified parameters
Who Decides Whether a Devor NSR? 

Who Decides Whether a Devor NSR?

z Sponsors

– Make the initial risk determination– Presents the IRB with this informatio

z IRBs

– Required to determine whether the N

study involves a SR or NSR device

z FDA 

– Available to help – Final arbiter 
What are the Requirements 21 CFR 812 for NSR Device 

What are the Requirements 21 CFR 812 for NSR Device 

z Abbreviated requirements at 21CF

– Labeling, IRB approval, informed con

monitoring, record keeping, reports, prohibition against promotion.

z NSR studies are considered to ha

approved IDE therefore no IDE to 

z Sponsors and IRBs do not have to 

FDA of NSR device studies 

z IRBs must make a SR or NSR det

for every NSR study (21 CFR 812
What is the sponsor’s resp

to the IRB for NSR device 

What is the sponsor’s respo

to the IRB for NSR device 

z Provide reviewing IRBs with a brie

explanation of why the device is n

z Any other information requested b

• Description of device• Reports of prior investigations• Proposed investigational plan• Subject selection criteria

z Inform IRB if FDA determined the 

NSR
What is the IRB responsibility device studies presented for 

What is the IRB responsibility device studies presented for 

z IRBs should make the SR or N

determination about a study breviewing relevant information convened meeting. 
What Should IRBs Consider Making the SR or NSR Deter

What Should IRBs Consider WMaking the SR or NSR Determ

For studies presented as NSR d

studies, IRBs should consider

z What is the basis for the risk?

– Proposed use of device

z What is nature of harm that m

from the use of the device?

z Any additional procedures?

– Potential harm from procedures
Let’s Put This into Practic

Let’s Put This into Practic

Study of a change in a compo

device. For example: new leapack, or software of an approvpacemaker

– Basis for risk: Any change to a 

is a change to the device itself

– This study is significant risk and 

IDE approval by FDA 
More Practice More Practice

Study of a 510k, non-significa

daily wear lens device to be uovernight lens. Design change

– Proposed use and nature of ha

Potential for injury not normally daily wear lens

– This study is significant risk and 

IDE approval by FDA 
What Happens When the Spand IRB Determination Disa

What Happens When the Spand IRB Determination Disa

z If the IRB determines that a N

study involves a SR device

– IRB must inform the clinical inv

and where appropriate the spon

– The study cannot start until spo

obtains an IDE
What Happens When the IRwith the Sponsor’s NSR Dete

What Happens When the IRwith the Sponsor’s NSR Dete

z If IRB determination of NSR a

sponsor’s NSR 

– IRB can review the study using 

21 CFR 56.111

– The study may begin without no

or IDE application to FDA
How do IRBs Document the NSR Determination? 

How do IRBs Document the NSR Determination?

z Write determination in minute

– Give reason for determination

z NSR studies

– Maintain all materials reviewed
References References

z FDA Information Sheets

– http://www.fda.gov/ScienceResea

pics/RunningClinicalTrials

z Procedures for Handling Inqu

– http://www.fda.gov/MedicalDevice

lationandGuidance/Overview/Biororing/default.htm
Summary Summary

z Made distinction between sign

(SR) and non-significant risk (

z Described criteria IRB should 

making SR or NSR determina

z Described how to generate 

documentation of IRB’s determSR or NSR