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No research participant may be enrolled in a human gene transfer clinical study until IBC and IRB approvals and applicable regulatory authorizations are obtained.
Human gene transfer experiments involve the "deliberate transfer of recombinant or synthetic nucleic acid molecules, or DNA or RNA derived from recombinant or synthetic nucleic acid molecules, into human research participants."
Human Gene Transfer (HGT) is a type of human subjects research. Proposals for HGT clinical trials at U-M are submitted via an IRB application (HUM) instead of an IBC application, which you will start in the eResearch Regulatory Management (eRRM) system. In section 7, indicate that your project involves human gene transfer. eRRM will then prompt you to complete the section of the IRB application specific to human gene transfer.
IBC Review Process
IBC review of the gene transfer-related sections of the IRB application and uploaded documents is required. In this case, the IBC functions as an "Ancillary Committee" in the IRB review process, with an IBC determination occurring prior to final review and approval by the IRBMED. IBC review is subject to the committee’s meeting schedule. Allow four weeks prior to an IBC meeting for the preliminary staff review of your human gene transfer proposal.
The IBC will review the following documents, which you should upload to your IRB application (relevant sections noted in parentheses below):
- Scientific abstract (Section 23-2.8)
- Non-technical abstract (Section 23-2.8)
- Clinical protocol including tables, figures and relevant manuscripts (Section 5)
- Summary of preclinical studies conducted in support of the proposed clinical trial OR reference to the specific seciton of the protocol providing this information (Section 23-2.7).
- A description of the product as a stand-alone document (Section 23-2.7):
- The derivation of the delivery vector system including the source (e.g., viral, bacterial, or plasmid vector); and modifications (e.g., deletions to attenuate or self-inactivate, encapsulation in any synthetic complex, changes to tropisms, etc.). Please reference any previous clinical experience with this vector or similar vectors.
- The genetic content of the transgene or nucleic acid delivered including the species source of the sequence and whether any modifications have been made (e.g. mutations, deletions, and truncations). What are the regulatory elements contained in the construct?
- Any other material to be used in preparation of the agent (vector and transgene) that will be administered to the human research subject (e.g., helper virus, packaging cell line, carrier particles).
- The methods for replication-competent virus testing, if applicable.
- The intended ex vivo or in vivo target cells and transduction efficiency.
- The gene transfer agent delivery method.
- Investigator's brochure (Section 15)
- Proposed informed consent document(s) (Section 10)
Submission of the IRB application informs the IBC of the need to review the proposal and allows the IBC staff access to the uploaded documentation. The IBC may request additional documentation in the course of its review.
The reporting requirements for adverse events that occur on human gene transfer clinical trials at U-M differ from those described in the Standard IRBMED Adverse Event Reporting Timetable. Principal Investigators involved in this type of clinical trial at U-M must follow the U-M IBC Adverse Event Reporting Requirements for Human Gene Transfer Clinical Trials, which explains the criteria, the timing, and the process for reporting human gene transfer AEs to the U-M IBC.
- Adverse events meeting certain criteria on human gene transfer clinical trials at U-M must be reported to the U-M IBC.
- Reporting adverse events to the U-M IBC occurs through the IRB AE/ORIO reporting function.
- These requirements are in addition to any reporting requirements imposed by the study sponsor or other regulatory bodies.
- Your IRB application should indicate at Section 32-1 that you will be following a Study-Specific AE Reporting Plan (U-M IBC Adverse Event Reporting Requirements for Human Gene Transfer Clinical Trials).
References and Resources
Questions about the U-M IBC Adverse Event Reporting Requirements for Human Gene Transfer Clinical Trials, or other matters regarding IBC oversight of human gene transfer clinical trials, can be directed to the IBC at 734-936-3934 or IBCstaff@umich.edu.
Please contact the IRBMED (763-4768) regarding the full process for human subjects review and approval.