1. Monitoring, Audits, and Inspection Oh my! Rachel Sheppard Regulatory Director, OCRSS

2. Types of Review Routine monitoring Quality assurance audit IRB Audit Services Sponsor Routine investigation For cause investigation

3. Key parties PI Data coordinator/study coordinator Research nurse Investigational pharmacist IRB Parts of Hospital Contracts office

4. Monitoring Planned review of documentation and data 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

5. Monitoring continued Important relationship Good monitor vs. bad monitor Collaborative works best Open items must be reviewed again Documentation of all requests

6. IRB audit 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

7. FDA Audit Routine- verification of data quality, compliance and subject protection High enrollment First in data High profile study Directed – for cause Patient complaint Whistle blower Offshoot of other investigation Serious events Credentials and 482

8. Steps to prepare Do not panic Get all the information Timeline Scope Type of audit Notify all parties Designate contact for auditor Assign duties to staff for audit Arrange workspace and meeting space Prepare staff for questions

9. Responding to questions 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)

10. Documents Regulatory files CRFs and source documents Ensure access to eCRFs SOPs IP accountability records List of all projects PI has ongoing Request medical records

11. Close out meeting 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

12. Best Practices 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

13. Best Practices 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

14. Reference material 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)