1. Copyright 2009 1 FDA Inspections: Where Do Things Go Wrong? Diana Naser RN, MS, CCRP Executive Director Clinical Research Administration Clinical Research Development Office (CReDO)

2. Copyright 2009 2 FDA Inspections of Clinical Research Conducted when clinical investigation is FDA regulated (e.g. IND, IDE) The two most common types of FDA inspections are: 1. Routine or surveillance 2. Direct or for-cause

3. Copyright 2009 3 Why? FDA inspections are typically conducted at clinical sites to determine: – compliance with federal regulations and adherence to guidelines – to verify the validity and integrity of clinical data submitted in applications for approval – to assure that the rights and welfare of subjects participating in clinical studies have been protected.

4. Copyright 2009 4 FDA Inspections - Outcomes – The FDA will classify the inspection based on the evaluation finding and send a letter to the site – Classifications: No Action Needed (NAI) Voluntary Action Indicated (VAI) Official Action Indicated (OAI) also called “Warning Letters”

5. Copyright 2009 5 Review of FDA Warning Letters In the past 12 months 27 FDA warning letters have been issued to clinical investigators Five FDA warning letters issued in March 2009

6. Copyright 2009 6 Where Did They Go Wrong? Failure to conduct the studies or ensure they were conducted according to the signed investigator statement and investigational plan Failure to personally conduct or supervise the investigation

7. Copyright 2009 7 Where Did They Go Wrong? Failure to assure that an IRB was responsible for the initial and continuing review and approval of clinical study Failure to obtain IRB approval prior to implementing a change to the investigational plan

8. Copyright 2009 8 Where Did They Go Wrong? Failure to maintain, accurate, complete, and current case histories that record all observations and other data pertinent to the investigation

9. Copyright 2009 9 Where Did They Go Wrong? Failure to maintain adequate records of the disposition of the drug including dates, quantity, and use by subjects Failure to maintain accurate, complete and current device shipment records

10. Copyright 2009 10 Where Did They Go Wrong? Failure to prepare and submit complete, accurate, and timely reports of unanticipated adverse effects

11. Copyright 2009 11 Where Did They Go Wrong? Failure to obtain legally effective informed consent Failure to properly document informed consent

12. Copyright 2009 12 Where Did They Go Wrong? Failure to include written procedures for monitoring the investigation and failure to ensure proper monitoring of the investigation

13. Copyright 2009 13 Where Did They Go Wrong? Allowing subjects to participate in an investigation without FDA approval Failure to obtain FDA approval prior to implementing a change to the investigational plan.

14. Copyright 2009 14 Where Did They Go Wrong? Failure to prepare and submit progress reports to the FDA at least yearly Failure to submit final reports to the FDA

15. Copyright 2009 15 Conclusion FDA will hold investigators accountable for the commitments they agree to when signing the Form 1572 Statement of Investigator and for complying with current FDA regulations

16. Copyright 2009 16 References FDA Inspections of Clinical Investigators, Information Sheet Guidance, U.S. Department of Heath and Human Services, Food and Drug Administration, January 2006 http://www.fda.gov/OC/OHRT/IRBS/investigator.pdf FDA’s Electronic Reading Room, Warning Letters and Responses, http://www.fda.gov/foi/warning.htm