Device Research

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Device Research

• Presented by Marian Serge, R.N.

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Goals

• Identify devices
• Recognize difference between significant risk
  (SR) and non-significant risk (NSR) devices
• Explain how an Investigational Device Exemption
  (IDE) is obtained for SR and NSR devices
• Discuss IRB responsibilities
• Discuss investigator responsibilities
• Recognize humanitarian use devices

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Food, Drug and Cosmetic Act -Sec. 201 Device
Definition

• An instrument, apparatus, implement, machine,
  contrivance, implant, in vitro reagent, or other
  similar or related article,
• including any component, part, or accessory
• which is intended for use in the diagnosis of
  disease or other conditions or in the cure,
  mitigation, treatment, or prevention of disease,
  or intended to affect the structure or any
  function of the body and
• which does not achieve its primary intended
  purposes through chemical action within or on the
  body and which is not dependent upon being
  metabolized for the achievement of its primary
  intended purposes.

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Types of Devices

• Radiation emitting devices
• Joint replacements
• Contact lenses
• Tissue adhesives
• Dialysis machines
• Urology catheters
• Stents
• Lasers
• Implantable vascular access ports
• Wound dressings
• CT Scans
• Collagen
• Infusion pumps

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Devices Used in Research Investigational Device
Exemption (IDE)

• What does Investigational Device Exemption (IDE)
  mean?
• Food, Drug and Cosmetic Act (a law) mandates that
  only devices with FDA approval can be shipped and
  used
• So, how can a device that does not yet have FDA
  approval be shipped and used in research?
• The device manufacturer or person conducting the
  research has to apply to FDA for an
  Investigational Device Exemption (IDE) from the
  Act
• The Act and FDA regulation, 21 CFR 812, describes
  the Investigational Device Exemption (IDE) process

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Investigational Device Exemption(IDE) Regulation
21 CFR Part 812

• This regulation describes
• IDE application process so that a device not yet
  approved by FDA can be used in a clinical
  investigation
• Significant Risk (SR) Device
• Submission of an IDE application to FDA and IRB
  approval
• The entire regulation at 21 CFR 812 must be
  followed
• Non-Significant Risk (NSR) Device
• IRB acts as FDAs surrogate and after IRB
  approval it is considered to have approved
  application for IDE
• Only parts of the regulation at 21 CFR 812 must
  be followed
• Sponsor responsibilities
• Clinical investigator responsibilities
• IRB approval
• IRB determination of SR or NSR for NSR devices

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Two Types of Devices

• Significant risk
• Non-significant risk

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Significant Risk (SR) Device

• Presents a potential serious risk to the health,
  safety and welfare of a subject and is
• an implant or
• life supporting or sustaining or
• of substantial importance in diagnosing, curing,
  mitigating, or treating disease or preventing
  impairment of human health or
• a device that presents a potential serious risk
  to the health, safety and welfare of a subject.

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Significant Risk (SR) Device Investigational
Device Exemption (IDE)

• IDE application submitted to FDA
• FDA Reviewer
• FDA reviews and sends the sponsor an approval
  letter
• Examples of SR devices
• Extended wear contact lenses
• Stents coronary, urinary, vascular/peripheral
• Cutting lasers

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Non-significant Risk (NSR) Device

• No definition of non-significant risk (NSR)
  device in FDA regulation
• Any device that is not a significant risk (SR)
  device is a non-significant risk (NSR) device

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NSR DeviceInvestigational Device Exemption

• No IDE application to FDA is needed rather,
  sponsor submits risk determination to the IRB.
  The IRB acts as FDAs surrogate and after IRB
  approval (following 21CFR 56.111) the device is
  considered to have approved application for IDE.
  FDA will not know about NSR device
  investigations.
• Examples of NSR devices
• Urologic catheters
• Low power lasers for pain relief
• MRI
• Simple wound dressings
• IRB meeting

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Compare and Contrast Summary of SR and NSR
Devices

• SR Device
• Meets FDA definition of significant risk device
• Submission of an IDE application to FDA required
• Study may start after FDA approves the IDE
  application and the IRB approves the study

• NSR Device
• No definition NSR device is any device not a
  significant risk device
• No submission of an IDE application to FDA
  rather, sponsor submits their risk determination
  to the IRB. The IRB also makes a risk
  determination.
• After IRB approval, the device is considered to
  have an approved application for IDE and the
  study may start

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ExerciseIs the device SR or NSR?

• Coronary stents
• Dialysis delivery systems
• Sutures
• Implantable Vascular Access Devices (Ports)
• Contact lens
• Daily wear
• Extended wear
• Wound dressing
• Plain gauze
• Interactive wound or burn dressings

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ExerciseHow is an IDE Obtained?

• Coronary stents
• Dialysis delivery systems
• Sutures
• Implantable Vascular Access Devices (Ports)
• Contact lens
• Daily wear
• Extended wear
• Wound dressing
• Plain gauze
• Interactive wound or burn dressings

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IRB Responsibilities for Investigational Devices

• IRBs need to distinguish between SR and NSR
  devices
• IRBs may review a SR device study before FDA
  reviews it However, SR device studies may not
  start until after both IRB and FDA approval
• IRBs must make a SR or NSR device determination
  for every NSR device study submitted to the IRB
  (21CFR 812.66)

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IRB Determination NSR Device Is it SR or NSR?

• IRB written policies and procedures regarding
  initial and continuing review of research must
  have a procedure for IRB determination of device
  risk, to include
• Sponsors brief explanation of why the device is
  not significant risk 21 CFR 812.2
• Review definition of significant risk device
• Review a description of the device
• Review the protocol to find out the proposed use
  of the device in the study
• Review the informed consent form
• Review subject selection criteria
• Review FDA guidance on medical devices (FDA
  Information Sheets)
• Review reports of prior investigations, if any
• Obtain outside assistance or FDAs assistance

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How to Request FDA Assistance forDetermining
Whether Device is SR or NSR

• Send 3 copies of the following information to
• Document Mail Center WO66 G609
• FDA/CDRH
• 10903 New Hampshire Avenue
• Silver Spring, MD 20993-0002
• Detailed description of the device(s)
• Study protocol
• Description how the device will be used in the
  study
• Population that will receive the device
• Sponsors name, contact persons, titles, address,
  phone, fax, email address

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Non Significant Risk DeviceIRB Determination

• What happens after an IRB makes its
  determination?
• If the IRBs determination of NSR agrees with the
  sponsors determination of NSR . . . . .
• then the IRB may review the study for
  approval following 21 CFR 56.111 (Same as 38 CFR
  16.111)
• However, if the IRBs determination disagrees
  with the sponsors determination (i.e. IRB thinks
  the device is SR). . . .
• then the sponsor must obtain approval of
  an IDE application from FDA before beginning a
  clinical investigation (21 CFR 812.66)

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IRB Required Documentation

• IRB written policy and procedure regarding review
  of devices
• Determine whether a NSR device is a SR or NSR
  device
• 21CFR 812.66
• 21CFR 56.108
• Document the IRBs determination in the meeting
  minutes or project file
• 21CFR 56.115
• Report to the investigator or sponsor whenever
  the IRBs determination disagrees with the
  sponsors NSR determination
• 21 CFR 812.66
• Obtain FDA letter of approval of IDE application
  for SR device
• FDA Information Sheets Guidance

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Key Points to Remember

• Devices are either SR or NSR
• IDE is required before a device investigation may
  begin
• IRB determination may agree or disagree with a
  sponsors initial NSR determination
• IRB risk determination should be based on the
  proposed use of the device in an investigation,
  and not on the device alone
• IRBs must have written procedures for review of
  device studies (21 CFR 56.108) and document their
  findings (21 CFR 56.115)
• FDA is the final arbiter in determining whether a
  device is SR or NSR

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Title 21 CFR 812.100Clinical Investigator Device
Responsibilities

• FDA good clinical practice for device studies
• Follow signed agreement with sponsor
• Ensure Informed consent process and form complies
  with 21 CFR 50
• Conduct study in accordance with IRB conditions
  of approval
• Follow the protocol
• Supervise the use of the device
• Ensure device studies have proper Investigational
  Device Exemption
• Maintain device accountability records and return
  or dispose of devices
• Recordkeeping Correspondence, subjects case
  history, exposure, etc.
• Reports Unanticipated adverse device effects,
  deviations, progress etc.
• Maintaining research records

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Humanitarian Use Device (HUD)

• Why have HUDs?
• Congress enacted a law that would encourage
  device manufactures to develop devices for people
  who have rare diseases or conditions
• FDA approves humanitarian use devices for
  marketing

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Humanitarian Use Device (HUD)21 CFR 814 Subpart H

• FDA can grant an exemption from the effectiveness
  requirements of the Food, Drug Cosmetic Act if
  it finds the HUD is designed to treat or diagnose
  a disease or condition that affects fewer than
• 4,000 patients in the U.S. and
• No comparable device available and
• Will not expose patients to an unreasonable risk
  of injury and the probable benefit outweighs the
  risk
• This is not research

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Humanitarian Use Device (HUD)IRB Responsibilities

• Must approve the use at the facility
• May specify limitations on the use
• Based on one or measures of disease progression
• Prior use and failure of any alternative
  treatment
• Reporting requirements to the IRB or Chair
• Appropriate follow-up precautions/evaluations
• Any other criteria it determines appropriate
• Must perform continuing review
• Must review serious adverse events deaths
• Must terminate for non-compliance

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What Have We Learned?

• There are 2 types of devices significant risk
  (SR) and
• non-significant risk (NSR)
• SR devices must have FDA approval of an IDE
  application and
• IRB approval
• NSR device must have IRB approval
• IRBs have a big role in device studies risk
  determination for NSR devices
• Investigators of device studies must follow
  requirements at
• 21 CFR 812
• Humanitarian Use Devices (HUD) require IRB
  approval, but are not research

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QUESTIONS