Human Gene Therapy Institutional Review Procedures

1. Human Gene Therapy Institutional Review Procedures March 6, 2019 Institutional Biosafety Committee (IBC)& Institutional Review Board (IRB)

2. Introduction Review and proper registration of Human Gene Transfer protocols is very complex. A protocol goes through rigorous review by multiple internal Committees. Due to this complexity, we have developed this guidance to assist researchers navigate the process. • FDA • Hospital Service Lines • Institutional Biosafety Committee (IBC) • Committees on Human Research (IRB)

3. Investigator-Initiatedvs Industry Sponsored • Investigator-Initiated - If this is an investigator-initiated gene transfer project, then all of the requirements as outlined in this power point are the local investigator’s responsibility. • Industry-Sponsored - Some of the requirements as outlined in this power point are to be completed by the local investigator while some are to be completed by the sponsor. We will address where there are differences.

4. Step 1: Obtain FDA Approval FDA approval is required prior to submission for any institutional review. This will be the responsibility of the local investigator for investigator-initiated protocols and the sponsor for industry-sponsored projects.

5. Step 2: Obtain Approval from the Following Hospital Services Local Investigator is responsible to obtain feasibility approvals from the following hospital services, regardless of sponsorship: • UVMMC Investigational Drug Pharmacy • UVMMC Environmental Health and Safety Dept • UVMMC Infectious Disease • UVMMC Infection Prevention

6. Materials Required for Each Service Review Each service will require the following materials for review: • Clinical Trial Protocol • Investigational Drug Brochure • Standard Operating Procedures for Drug Preparation • Standard Operating Procedures for Transport of Drug • Standard Operating Procedures for Handling of Drug by Clinical Staff

7. All hospital service line reviews must be complete prior to submission to the IBC.

8. Step 3: Institutional Biosafety Review

9. IBC REVIEW • Local investigator is responsible for submission to the IBC. • Gene transfer protocols will require a full Committee review. • All Service Line reviews must be complete prior to submission to the IBC. • A site risk assessment must be completed prior to submission to the IBC. This would typically be done by the UVMMC Environmental Health and Safety staff and UVM Biosafety Officer or designate.

10. Documents Required for IBC Review IBC project will be entered into the Click-IBC system. Uploads will include but are not limited to: • SOPs for Drug Preparation, Transport, and Handling as approved by the Services Lines • Draft of Human Subjects IRB Consent Form • Clinical Protocol • Investigational Drug Brochure *Review of these materials satisfies the requirement to meet the Points to Consider Section, M-I-A, of the NIH Guidelines.

11. Step 4:Recombinant DNA Advisory Committee (RAC) Review The Recombinant DNA Advisory Committee is a federal advisory committee that has historically provided recommendations to the NIH Director related to basic and clinical research involving recombinant or synthetic nucleic acid molecules.  On August 16, 2018, the NIH released a proposal for comment to remove the NIH protocol submission, review, and reporting requirements under Appendix M of the NIH Guidelines. Changes to the roles and responsibilities of the RAC are also proposed. During this comment period and effective immediately, the NIH will no longer accept new human gene transfer protocol for the registration process or convene the RAC to review individual human gene transfer protocols.

12. Step 5:IRB REVIEW

13. IRB Review • Local investigator is responsible for submission to the IRB. • Gene transfer protocols will require a full Committee review. • Initial IBC review has to be completed with an approved-type status.

14. Documents forIRB Review IRB protocol will be entered into the Click-IRB system. Uploads will include but are not limited to: • Draft of Human Subjects IRB Consent Form (revised after IBC changes) • Clinical Protocol • Investigational Drug Brochure • Data Management and Security Plan • IBC Materials • Approval • Copy of Clarification Memo and PI Response *Review of these materials satisfies the requirement to meet the Points to Consider Section, M-I-A, of the NIH Guidelines.

15. CONCLUSION This presentation was designed to inform the audience on the local review of gene therapy experiments. Please do not hesitate to contact the RPO office for assistance with obtaining review and approval of a gene therapy protocol.