Human Research Protection Program 101

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Human Research Protection Program 101

• January 29-30, 2008
• Los Angeles, California

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The Device Side of FDA Regulations
C. Karen Jeans, MSN, CCRN COACH Project Analyst
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Medical Device Definition

• Defined, in part, as any health care product that
  does not achieve its primary intended purposes by
  chemical action or by being metabolized

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Investigational Device Definition

• A medical device which is the subject of a
  clinical study designed to evaluate the
  effectiveness and/or safety of the device.

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Clinical Study Regulation

• Federal Food, Drug, and Cosmetic Act gives FDA
  the authority to regulate investigational
  devices
• To encourage the discovery and development of new
  devices
• Maintain optimum freedom for scientific
  investigations

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Section 520(g) of the Act

• Requires IRB approval for all clinical
  investigations
• Requires informed consent from all subjects
  unless emergency use

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IDE Regulation(Part 812)

• Allows an unapproved device to be shipped for
  clinical evaluation
• Identifies sections of the Act from which IDEs
  are exempt
• Identifies exempted investigations (e.g. cleared
  devices, IVDs)
• Defines SR and NSR investigations

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IDE Regulation(Part 812)

• Clinical investigations undertaken to develop
  safety and effectiveness data for medical
  devices must be conducted according to the
  requirements of the IDE regulations.
• Unless exempt from the IDE regulations, an
  investigational device studies must be
  categorized as
• Significant Risk (SR) or
• Nonsignificant Risk (NSR)

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Significant Risk (SR) Study

• 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
• FDA approval required
• Examples
• Extended wear contact lenses
• Cardiac stents

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Nonsignificant Risk Studies

• FDA approval not needed
• Not to be confused with the concept of minimal
  risk
• Examples
• Urologic catheters
• Low level biostimulation lasers
• Conventional implantable vascular access devices

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Chronology of an investigational device study

• Sponsor initially determines whether a device
  used in a clinical investigation represents a
  nonsignificant risk or significant risk
• Study is submitted to FDA for SR studies and to
  an IRB for NSR studies

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Chronology of an investigational device study

• SR studies
• Submission of an IDE application to FDA required.
  
• Study may not commence until FDA has approved the
  IDE application and the IRB has approved the
  study.
• NSR studies
• No submission of an IDE application to FDA
• Sponsor required to conduct the study in
  accordance with the abbreviated requirements of
  the IDE regulations

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Chronology of an investigational device study

• IRB decision
• If IRB agrees that a study is NSR, no submission
  to or review by FDA is necessary before starting
  studies in humans.
• If IRB considers the study to be SR, the sponsor
  must obtain an IDE from FDA before proceeding
  with clinical studies.
• NOT AN OPTION An IRB considers a study to be
  NSR with FDA approves an IDE for a SR device.

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Chronology of an investigational device study

• Deciding whether a device study is SR or NSR
• IRB written policies and procedures regarding
  device review
• Best abilities
• Information in regulations and guidelines
• Risk evaluation provided by applicant
• Reports of prior investigations
• Proposed investigational plan
• Subject selection criteria
• Monitoring procedures
• Outside assistance

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Required IRB policies and procedures

• When the IRB determines that an investigation
  presented for approval as involving an NSR device
  actually involves an SR device, the IRB is
  required to notify the investigator and, where
  appropriate, the sponsor.
• Written procedures for conducting its initial
  review of research.
• Written procedures for reporting its findings and
  actions to the investigator.
• Procedures for determining whether a study is SR
  or NSR should be included among the written
  procedures.

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Key Points to Remember

• IRBs may agree or disagree with a sponsors
  initial NSR assessment.
• Risk determination should be based on the
  proposed use of the device in an investigation,
  and not on the device alone.
• Criteria for deciding if SR and NSR studies
  should be approved by the IRB are the same as for
  any other human research study.
• FDA has the ultimate decision in determining
  whether a device study is SR or NSR.

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Emergency use of an approved device

• Three circumstances for emergency use of an
  unapproved device
• No IDE for the device
• Use of a device under an IDE where the physician
  wants to use it in a way not described in the IDE
• When the physician, who wants to use it, is not
  an investigator

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Criteria for emergency use

• Each of the following conditions must exist
• Life-threatening condition or serious disease or
  condition
• No generally acceptable alternative treatment is
  available
• No time to obtain FDA approval
• FDA expects the physician to determine whether
  these conditions have been met and must assess
  potential for benefit and have substantial reason
  to believe benefit will occur.

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Criteria for emergency use

• Each of the following conditions must exist
• Life-threatening condition or serious disease or
  condition
• No generally acceptable alternative treatment is
  available
• No time to obtain FDA approval
• FDA expects the physician to determine whether
  these conditions have been met and must assess
  potential for benefit and have substantial reason
  to believe benefit will occur.

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After the emergency use

• Physician must notify the IRB within 5 days
• If future use likely, immediately initiate effort
  to obtain IDE and IRB approval
• If device was under an IDE, physician notifies
  the sponsor, who must report to FDA within 5 days
• If no IDE exists, physician notifies FDA
• About the emergency use
• Patient protection measures
• Scientific results

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Other device terminology

• 510(k)
• Compassionate use
• Single patient/small group
• Custom Devices
• Treatment Use
• Humanitarian Use Device

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Humanitarian Use Device (HUD)

• Manufacturer responsibilities
• Obtain HUD determination from the Office of
  Orphan Products Development
• Treatment or diagnosis of rare disease or
  condition
• 4000 or fewer patients
• No comparable device is available

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Humanitarian Device Exemption (HDE)

• The manufacturer must return to the Center for
  Devices and Radiological Health (CDRH) for
  approval of the HDE application
• Bench and animal testing
• Clinical experience
• Approval based on probable benefit outweighing
  risk of injury from its use
• HDE label states the effectiveness of this
  device for this use has not been demonstrated
• The HDE allowing marketing distribution of the HUD

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HUD HDEIRB Responsibilities

• IRB Activities
• Approval before HUD is administered
• Initial review at a convened meeting
• Continuing review
• Receive Medical Device Reports (MDRs)
• Withdrawal of approval
• Safety reasons
• Failure to follow FDA regulation/IRB procedure

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HUD Issues What causes problems?

• No protocol
• No informed consent requirements under FDA human
  research regulations
• Not research
• IRB approval and continuing review required
• RD Committee

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Center for Devices and Radiological Health

• Medical Devices
• Division of Bioresearch Monitoring Office of
  Compliance Center for Device and Radiological
  Health (CDRH)Phone [phone]Fax
  240-276-0128Web site www.fda.gov/cdrh/comp/bimo.
  html

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QUESTIONS