Lessons Learned and Subsequent Changes Following an FDA Audit of the IRB

1. Lessons Learned and Subsequent Changes Following an FDA Audit of the IRB Clinical Research Compliance Office and Human Subjects Office November 2012

2. Background Information: FDA Audit of the IRB • In Sept. 2011, an FDA auditor reviewed several IU IRB-approved studies • No findings were noted at the exit interview, but a copy of a study that was not reviewed on site was taken by the auditor • Letter from FDA was received this past summer (2012) identifying several issues regarding that particular study

3. Main Issues Identified • Expedited review of a study that should have been considered greater than minimal risk • Randomization of test articles (drugs) • Waiver of informed consent granted for a clinical investigation • Waiver of consent not permitted under FDA regulations for clinical investigations • The IRB did not consider this to be an FDA-regulated study and thus granted the waiver **Though not specifically noted by the FDA, it was also determined that the study should have been conducted under an IND

4. Main Issues (Cont’d) • Expedited review of a study that should have been considered greater than minimal risk

5. Main Issues (Cont’d) • Waiver of informed consent for a clinical investigation

6. Subsequent IRB Changes • IRB Operations SOP Revision: • Expedited Studies:  Research that meets certain criteria may be reviewed and approved under expedited review procedures as per 45 CFR 46.110(a) and 21 CFR 56.110(a).  Expedited research applications are reviewed and approved by an IRB Chair or IRB member designated by the Chair who does not have a conflicting interest in the project under review. … Studies involving randomized use of drugs, biologics, or devices do not meet the definition of minimal risk and thus do not quality for expedited review.  All such studies will be reviewed by the full IRB.  

7. Subsequent IRB Changes (Cont’d) • Changes to the Summary Safeguard Statement (SSS): • Section III (formerly Section XIV), Test Articles: A tool to analyze and document whether a study is FDA-regulated: • Are you studying a drug or device? • Is the use of that drug or device dictated by the research protocol? • Section XII, Informed Consent Process: Updated to note that FDA regulated studies are not eligible for waivers of informed consentand refers investigators back to SSS, Section III, Test Articles to determine if the study is FDA regulated

8. Identifying FDA Regulated Studies: SSS

9. Identifying FDA Regulated Studies: SSS

10. Subsequent IRB Changes (Cont’d) • New IRB Forms: • Drug or Biological Product Form • Medical Devices Form • These should be completed for FDA-regulated studies based on responses to Section III of the SSS • Serve as tools to analyze and document whether an IND/IDE is needed • Contain some information that was previously on the SSS and replace IND/IDE Checklists • These forms will be required with new study and CR submissions (when applicable) in November 2012

11. New IRB Forms: A Closer Look • Drug and Biological Product Form • A tool to (1) document information about the drug or biological product (2) when necessary, determine whether an IND is needed • Form is based on FDA IND-related regulations and guidance: • Most investigations of drugs or biological products require submission of an Investigational New Drug Application (IND) to the FDA • If the study involves a drug used in humans in any way other than in the course of medical practice, an IND generally is required, unless certain exemptions apply • IND Exemptions: • Some studies of already approved drugs, • Some studies of diagnostic biological products and in vitro drug tests, and • Some bioavailability or bioequivalence studies

12. Drug or Biological Product Form Section I: Basic Information

13. Drug or Biological Product Form Sections II-IV: Exemption Categories

14. New IRB Forms: A Closer Look (Cont’d) • Medical Device Form • A tool to (1) document information about the device (2) when necessary, determine whether an IDE submission to the FDA is needed • Form is based on FDA IDE-related regulations and guidance: • When the principal intent of the medical device (or other product regulated as a device) is to develop information about the product's safety or efficacy, an IDE submission to the FDA is generally required, unless certain circumstances apply • Device investigations fall into one of three categories: • Exempt from IDE requirements • Custom Devices • Modifications, Combinations, or Preference Testing of Devices • Non-Invasive Diagnostic Devices • Already Approved or Cleared Devices • Studies of nonsignificant risk (NSR) devices subject to abbreviated IDE requirements • Significant risk (SR) devices subject to full IDE requirements

15. Medical Device Form, Section I: Basic Information

16. Medical Device Form Section II, A.-D.: Exemption Categories

17. New IRB Forms: A Closer Look (Cont’d) • Medical Device Form (Cont’d) • IRB Device Risk Determination • If a study involves a device and is not exempt from the IDE requirements per the SSS and Device Form, the IRB then must determine if the device is nonsignificant or significant risk • The Medical Device Form, Section III, includes a table of criteria provided by the FDA to help make that determination • Additionally, FDA has posted guidance and a list of examples of the devices that generally fall into each category • For some FDA guidance on devices, see http://www.fda.gov/downloads/regulatoryinformation/guidances/ucm126418.pdf and http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM127067.pdf.

18. Medical Device Form Section III: Risk Determination

19. Lessons Learned • This is a complex and high-risk area of research for investigators, HRPP, research compliance, and institution • Careful and thoughtful analysis/documentation of all parties involved is necessary to ensure compliance, minimize risk, and ultimately, protect subjects • Do not hesitate to ask questions and seek guidance early and often • FDA • CRCO • HSO • CTSI

20. Contact Information • IU Clinical Research Compliance Office (CRCO) (317) 278-9265 • IU Human Subjects Office (HSO) (317) 274-8289 irb@iu.edu

21. Applications When / What to Submit

22. New Expedited and Full Board Studies • Forms now available and required • Summary Safeguard Statement (v10/01/12) ** • Drug or Biological Products Form (v10/01/12) • Medical Device Form (v10/01/12)

23. Continuing Reviews: Open to Enrollment, Closed to Enrollment, and Data Analysis Only • Forms now available and required • Continuing Review Form – Open to Enrollment (v10/01/12) • Continuing Review Form – Closed to Enrollment (v10/01/12) • Test Articles Supplement (v10/01/12) NEW FORM required for all active biomedical studies involving drugs, biological products, or devices which have a currently approved Summary Safeguard Statement (v01/01/12) or earlier.