Monitoring, Audits,
and Inspection
Oh my!
Rachel Sheppard
Regulatory Director, OCRSS
Types of Review
• Routine monitoring
• Quality assurance audit
• IRB
• Audit Services
• Sponsor
• Routine investigation
• For cause investigation
Key parties
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PI
Data coordinator/study coordinator
Research nurse
Investigational pharmacist
IRB
Parts of Hospital
Contracts office
Monitoring
• Planned review of documentation and data
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ICF documentation
Screening documentation
Diagnostic test review documentation
Source documentation
Reporting of events to IRB/sponsor
IP inventory and dispensation
• Changes in monitoring
• High turnover
Monitoring continued
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Important relationship
Good monitor vs. bad monitor
Collaborative works best
Open items must be reviewed again
Documentation of all requests
IRB audit
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Review of regulatory and clinical files
Different levels
Full board review
Cause and not for cause
Not for Cause triggered by
• New investigator
• Random
• For Cause triggered by
• External governing agency audit
• CAR document review
• Excessive deviations
FDA Audit
• Routine- verification of data quality, compliance and subject
protection
• High enrollment
• First in data
• High profile study
• Directed – for cause
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Patient complaint
Whistle blower
Offshoot of other investigation
Serious events
• Credentials and 482
Steps to prepare
• Do not panic
• Get all the information
• Timeline
• Scope
• Type of audit
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Notify all parties
Designate contact for auditor
Assign duties to staff for audit
Arrange workspace and meeting space
Prepare staff for questions
Responding to questions
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Understand question – ask for clarifications
Take your time answering (think first)
Answer only what is asked
Tell the truth
Do not argue and be positive
Tell the auditor/investigator if you do not know
Take notes on what was asked (after)
Documents
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Regulatory files
CRFs and source documents
Ensure access to eCRFs
SOPs
IP accountability records
List of all projects PI has ongoing
Request medical records
Close out meeting
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Discussion of findings
Notify investigator/auditors of any corrective actions taken
FDA 483
Clarify any discrepancies on 483
Involve university offices in any written responses
Best Practices
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Document, document, document
Keep a binder of ICF copies
Consistency of documentation
Have and know SOPs
Have isolated workspace to limit access
Control copy access
Only supply requested information
Designate an escort/assistant
Be helpful
Best Practices
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Don’t wait for an audit to have good records
Identify and report problems
CAP (correct and prevent)
Document correction methods
Evaluate that CAP works
Reference material
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21CFR50, 21CFR56, 21CFR312, ICH E:6
21CFR: 312.68 Part 312 -- Investigational New Drug Application/Inspection of
investigator's records and reports
FDA: Bioresearch Monitoring: Clinical Investigators and Sponsor Investigators Guidance for FDA staff
FDA: Bioresearch Monitoring: FDA/ORA Bioresearch Monitoring
FDA: Compliance Program Guidance Manual (CPGM) (Chapter 48)
FDA Guidance: Computerized Systems Used in Clinical Investigations
FDA Guidance: FDA Inspections of Clinical Investigators
FDA: Form 483 Frequently Asked Questions
Sheet: Guidance for IRBs, Clinical Investigators, and Sponsors: FDA
ICH: International Committee on Harmonization (ICH) E: 6 Good Clinical
FDA: Investigations Operations Manual
FDA Guidance: Investigator Responsibilities — Protecting the Rights, Safety, and
Welfare of Study Subjects
FDA Guidance: Part 11, Electronic Records, Electronic Signatures – Scope and
FDA: Preparing for a Clinical Investigator Inspection
FDA: Regulatory Procedures Manual (RPM)