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U.S. Department of Health and Human Services

Training and Continuing Education

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Presentation: Preparing for an FDA Institutional Review Board Inspection

(This presentation is also available in video format with captioning and PDF printer-friendly format.)

Presented by Allen Lou

Consumer Safety Officer
Division of Bioresearch Monitoring
Office of Compliance
Center for Devices and Radiological Health

FDA Is Coming!

FDA BIMO Program

  • FDA Bioresearch Monitoring (“BIMO”) program
    • To protect human research subjects from undue hazard or risk
    • To ensure the quality and integrity of data submitted in support of device applications
  • BIMO inspections

Objectives

  • Describe FDA IRB inspections
  • Describe inspection procedures
  • Discuss common inspectional observations and how to respond to them
  • Provide points to consider

Topics

  • Institutional Review Board Inspections
  • Pre Inspection Process
  • Preparing for a FDA Inspection
  • Inspection Day
  • What do we inspect?
  • Inspection Conclusion
  • Common IRB Deficiencies
  • Post Inspection Process
  • Inspection Classification
  • Written Response
  • Points to Consider
  • Summary

FDA IRB Inspections

  • A type of FDA inspection designed to determine compliance with FDA regulations and statutory requirements
  • Inspections conducted on-site at an IRB
  • Inspections typically involve:
    • Interviewing
    • Review of policy and procedures
    • Evaluation of performance via tracked studies
    • Facility tours
    • Determining compliance with regulations
    • Copying of study records

Pre-Inspection Process

  • Inspection assignments are issued by CDRH to district offices
  • FDA investigator may pre-announce inspection
  • Types of FDA inspections:
    • Routine/Surveillance
    • For Cause/Directed

Inspection Preparation

  • Have available
    • Most responsible person or designee available on inspection day to accept FDA 482
    • Personnel knowledgeable about all aspects of IRB and the study
    • A quiet area to conduct inspection with access to a photocopier
  • Have available and organized
    • All study documents including electronic records if applicable
    • Standard Operating Procedures (SOPs)

Inspection Day

  • FDA personnel (Field Investigators, Center personnel, etc.) will present his or her credentials
  • Issuance of Form FDA 482, Notice of Inspection
  • Request that a summary of any inspectional findings be provided at the end of each day
  • Inspection is conducted during normal business hours

What Do We Inspect?

  • Policy and procedures
  • Records of IRB membership
  • IRB reports
  • IRB approvals and corresponding documentation
  • Study folders
  • Meeting minutes
  • Significant risk versus non significant risk device determination
  • Correspondences to and from clinical sites, the sponsor, and FDA
  • Organizational charts
  • Emergency use
  • Complaints
  • Training/Qualification records
  • Collaborative research
  • IRB study databases

Inspection Conclusion

  • FDA Investigator conducts a close out meeting with management
  • FDA Investigator issues a Form FDA 483, Inspectional Observations for significant deviations from the regulations
  • Form FDA 483 does not represent a final Agency determination
  • Opportunity to respond to observations

Common CI Deficiencies

  • Inadequate meeting minutes
  • Inadequate/not following written procedures
  • Failure to have a majority of members present during convened meetings
  • Inappropriate use of expedited review
  • Failure to conduct continuing review
  • Failure to have a nonscientific member during IRB meetings
  • Failure to maintain IRB member rosters
  • Failure to make SR/NSR determinations
  • Failure to make prompt reports to FDA

Post Inspection Process

  • The FDA investigator completes Establishment Inspection Report (EIR)
  • The EIR, FDA 483 (if issued), supporting documentation, and the preliminary district classification is forwarded to CDRH
  • CDRH evaluates the report and determines the final classification for the inspection
  • Inspection findings and preliminary recommendations are reported to the appropriate CDRH review division
  • Consult with other FDA Centers such as CBER or CDER

Inspection Classification

  • No Action Indicated (NAI)
    • No objectionable conditions or findings
  • Voluntary Action Indicated (VAI)
    • Objectionable conditions or findings
    • But not at threshold to take or recommend administrative or regulatory action
  • Official Action Indicated (OAI)
    • Serious objectionable conditions found
    • Regulatory action recommended

Written Response

FDA recommends that your IRB respond in writing to the FDA 483

  • An evaluation of the extent of the problem
  • Assessment of the root cause of the problem
  • Any corrective actions
    • Not just a statement that you will correct or plan to correct the problem
    • What was corrected?
    • When was it completed?
    • Is the problem systemic?
  • Preventive actions to prevent recurrence of the problem in future studies
  • Time frame for training
  • Supporting documentation

The FDA 483 cited the following: The IRB failed to make a SR/NSR determination for study “ABC”

The IRB provided the following response:

  • “We agree that the IRB should have made a risk determination for study ABC. A procedure was not in place for determining whether an investigational device initially presented as non significant risk was truly as such. We have requested documentation from the Sponsor regarding the determination for this particular study and will consult with FDA. As a preventive action, we have developed and implemented written procedures that require IRB members to make this determination for device studies. This procedure also gives guidance on how IRB members are to make this determination. We have performed a risk assessment on all ongoing medical device studies. All IRB members have already been trained on this procedure. We have attached copies of the procedure, risk assessment forms for ongoing device studies, and training records for your review. After 6 months, we will conduct an audit of our device studies to determine if this preventive action is adequate.”

Points to Consider

  • Be courteous and responsive to FDA personnel
  • Keep study files organized at all times.
  • Maintain ALL correspondence - Clinical Investigators, Sponsors, and FDA
    • letters, faxes, e-mails, memos, phone contacts
  • Maintain detailed written procedures for all aspects of overseeing research

If it is not documented, it didn’t occur!

Summary

  • Described FDA IRB inspections
  • Described the inspection process
  • Discussed common inspectional observations and how to respond to them
  • Provided points to consider