The Sponsor and Sponsor Investigator: Responsibilities in Medical Device Clinical Trials

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The Sponsor and Sponsor -InvestigatorResponsibi
lities in Medical Device Clinical Trials
Presented by Catherine Parker, RN
Consumer Safety Officer Division of Bioresearch
Monitoring Office of Compliance Center for
Devices and Radiological Health
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Disclaimer

• The contents of this presentation are my own,
  and do not necessarily reflect the views and/or
  policies of the Food and Drug Administration or
  its staff as per 21 CFR 10.85.

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Presentation Topics

• Regulatory Definitions
• Sponsor Responsibilities
• Sponsor-Investigator Responsibilities
• Lessons Learned

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A Sponsor Initiates a Study
21 C.F.R. 812.3(n)
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A Sponsor is a Person
21 C.F.R. 812.3(l)
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A Clinical Investigator conducts a Study
21 C.F.R. 812.3(i)

• A Clinical Investigator (CI) is an individual
  who actually conducts a clinical investigation,
  under whose immediate direction the test article
  is administered, dispensed, or used.

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A Sponsor-Investigator does both.
21 C.F.R. 812.3(o)
Initiates
Conducts
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Presentation Topics

• Regulatory Definitions
• Sponsor Responsibilities
• Sponsor-Investigator Responsibilities
• Lessons Learned

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General Sponsor Responsibilities
21 C.F.R. 812.40

• Select qualified investigators
• Provide them with the information they need to
  conduct the study

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General Sponsor Responsibilities
21 C.F.R. 812.40

• Ensure proper monitoring
• Ensure IRB review and approval
• Submit IDE application to FDA
• Ensure IRB and FDA are informed of significant
  new information about an investigation

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Sponsor Responsibilities
21 C.F.R. 812.43

• Ship investigational device(s) only to qualified
  investigator(s)
• Obtain signed investigator agreements and
  financial disclosure from all investigators
• Select qualified monitors

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Monitor
21 C.F.R. 812.3(j)

• An individual designated by a sponsor or CRO to
  oversee the progress of an investigation
• It is a sponsors responsibility to select
  monitors that are qualified by training and
  experience

21 C.F.R. 812.43(d)
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Monitoring
21 C.F.R. 812.3(j)

• The act of overseeing the progress of an
  investigation.
• Used to assure the protection of human subjects
  and data integrity
• Ongoing continuous process
• The task of monitoring can be delegated but, it
  is ultimately the sponsors responsibility

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Monitors Review

• IRB approvals
• Informed Consent Documents
• Source documents
• Case Report Forms (CRF)

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Monitoring Investigations
21 C.F.R. 812.46

• Secure investigator compliance
• Conduct an evaluation of any unanticipated
  adverse device effects
• Obtain FDA and IRB approval before resuming a
  terminated study

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Monitoring Investigations

• Does the sponsor-investigator need to ensure
  adequate monitoring of the investigation at their
  own site?

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• YES

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Monitoring vs. DMC
Data Monitoring Committee (DMC) Sometimes
referred to as a Data and Safety Monitoring Board

• Monitoring is a different process then oversight
  by a Data Monitoring Committee

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Data Monitoring Committee

• A group that reviews data from a trial
• They advise the sponsor regarding the continuing
  safety of trial subjects
• Evaluate data for continuing validity and
  scientific merit

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Sponsor Records
21 C.F.R. 812.140(b)

• All correspondence with another sponsor, monitor,
  CI, IRB, and FDA
• Shipment and disposition of the device

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Sponsor Records
21 C.F.R. 812.140(b)

• Shipment
• Name and address of consignee
• Type and quantity of device
• Date of shipment
• Batch number or code
• Disposition
• Batch number or code
• Reasons for
• Method of disposal

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Sponsor Records
21 C.F.R. 812.140(b)

• Signed investigator agreements financial
  disclosure information
• Non-significant risk device records

21 C.F.R. 812.140(b)(4)
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Sponsor Records
21 C.F.R. 812.140

• Adverse device effects and complaints
• Other records required by FDA

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Documentation

• If it is not documented, it never happened!

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Inspections
21 C.F.R. 812.145

• Permit access to FDA
• Permit inspection and copying of documents

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Sponsor Required Reports
21 C.F.R. 812.150(b)

• Unanticipated Adverse Device Effects (UADE)
• Withdrawal of IRB approval
• Withdrawal of FDA approval

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Sponsor Required Reports
21 C.F.R. 812.150(b)

• Investigator list
• Annual progress report
• Recall and device disposition
• Final report

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Sponsor Required Reports
21 C.F.R. 812.150(b)

• Use of device without informed consent
• Significant risk determination
• Other reports

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Presentation Topics

• Regulatory Definitions
• Sponsor Responsibilities
• Sponsor-Investigator Responsibilities
• Lessons Learned

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CI General Responsibilities
21 C.F.R. 812.100

• Follow the investigator agreement, the
  investigational plan, and applicable regulations
• Protect the rights, safety, and welfare of
  subjects
• Control devices under study
• Obtain informed consent

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CI Specific Responsibilities
21 C.F.R. 812.110

• Obtain IRB and FDA approval
• Follow investigator agreement, investigational
  plan, and conditions of approval imposed by IRB
  or FDA
• Supervise device use
• Disclose financial interests
• Dispose of device

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Disqualification
21 C.F.R. 812.119

• An investigators repeated or deliberate failure
  to comply with these requirements may result in
  disqualification from receiving investigational
  devices

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Investigator Records
21 C.F.R. 812.140(a)

• All correspondence with another investigator,
  Institutional Review Board (IRB), sponsor,
  monitor, or FDA

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Device Records
21 C.F.R. 812.140(a)

• Records of receipt, use, and disposition of
  device including
• Type and quantity of the devices, dates of
  receipt, and batch number or code mark
• Name of all persons who received, used, or
  disposed of each device
• Why and how many devices have been returned,
  repaired, or other wise disposed of

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Case Histories
21 C.F.R. 812.140(a)

• Exposure to the device
• CRFs and supporting data
• Informed consent documents
• Adverse device effects
• Any relevant observations

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Protocols
21 C.F.R. 812.140(a)

• All IRB approved amendments
• Including approvals
• Documentation of protocol deviations and IRB and
  sponsor approvals

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Record Retention
21 C.F.R. 812.140(d)

• Two years after study termination or completion
• Two years after records are no longer required to
  support marketing application

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Records Custody
21 C.F.R. 812.140(e)

• Withdraw responsibility to maintain records
• Transfer custody to any other person who will
  accept responsibility
• Notice of transfer to FDA not later than 10
  working days

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Documentation

• If it is not documented, it never happened!

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FDA Inspections
21 C.F.R. 812.145

• Occur at reasonable times and in a reasonable
  manner
• Permit records to be inspected and copied

http//www.fda.gov/ora/cpgm/default.htmbimo
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Investigator Reports
21 C.F.R. 812.150

• Unanticipated Adverse Device Effects
• Withdraw of IRB approval
• Progress reports
• Deviations from the investigational plan
• Informed consent
• Final report
• Other

Progress Report 2009
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Adverse Effect

• Any adverse medical occurrence that may or may
  not be related to the investigational device
• All adverse effects should be documented

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Unanticipated Adverse Device Effect
21 C.F.R. 812.3(s)

• Any serious adverse effect that is possibly
  caused by or related to the investigational
  device
• Not previously identified in nature, severity, or
  degree, or
• Any other unanticipated serious problem
  associated with a device

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Investigator Responsibilities-AEs and UADEs

• Report Unanticipated AEs to the sponsor and IRB
  within 10 working days
• Maintain records of all AEs (anticipated or
  unanticipated)
• Follow the sponsors requirements for reporting
  and recording of AEs and UADEs

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Study Deviations
21 C.F.R. 812.140(a)(4)

• Document dates and reasons for any deviations
  from the study protocol
• Emergency deviations must be reported to the
  sponsor and IRB within 5 days
• Obtain prior approval from the sponsor, IRB, and
  FDA for changes or deviations from the
  investigational plan

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Presentation Topics

• Regulatory Definitions
• Sponsor Responsibilities
• Sponsor-Investigator Responsibilities
• Lessons Learned

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The FDA inspection results are in
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Top 6 2008 Sponsor Deficiencies

• Monitor study
• Secure investigator compliance
• Analyze and report AE/UADE
• Inform investigators, FDA, or IRB
• Control of inv devices
• Obtain signed Inv Agreement

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Sponsor- Investigator Deficiencies

• Follow investigational plan, investigator
  agreement, or protocol
• Obtain adequate informed consent
• Submit an IDE application to FDA
• Monitoring
• Progress reports to FDA and IRB
• Accurate, current, and complete records

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Summary

• A sponsor initiates the investigation while a CI
  conducts the study and an SI does both
• The sponsor and CI responsibilities are designed
  to
• Protect human subjects
• Promote the collection of quality data