Human Clinical Trials

Oversight

The Institutional Biosafety Committee (IBC) must review and approve all clinical trial research involving potentially hazardous biological agents before they may be initiated. Typically, the use of agents subject to IBC oversight are investigational products (IPs) consisting of or containing recombinant or synthetic nucleic acid molecules (r/sNA), infectious agents, or biological-derived toxins.

Many clinical trials involving r/sNA IPs fit the NIH term Human Gene Transfer (HGT), which is a type of research with a specific definition. HGT, as a term, should not be equated to the use of an IP that transfers genetic material into the genome of study participants or only the use of human genes.

HGT is specifically defined (NIH Guidelines) as the deliberate transfer into human research participants of:

• Recombinant nucleic acid molecules, or DNA or RNA derived from recombinant nucleic acid molecules
• Synthetic nucleic acid molecules, or DNA or RNA derived from synthetic nucleic acid molecules, that meet any of the following criteria:
• Contain more than 100 nucleotides
• Possess biological properties that enable integration into the genome (e.g., cis elements involved in integration)
• Have the potential to replicate in a cell
• Can be translated or transcribed

Examples of HGT research include (but are not limited to) CAR-T cell therapies, the use of recombinant AAV in patients, and the use of recombinant attenuated infectious agents in patients. An example of a clinical trial that does not meet the definition of HGT but still requires IBC review would be the use of an anti-sense oligonucleotide therapy.

The IBC review is for compliance of proposed activities with the NIH Guidelines, the BMBL, and some University policies (e.g. factors that impact the safety of University faculty, staff, students, and the environment). All clinical trials subject to IBC oversight also require approval from the Institutional Review Board (IRB) before patient enrollment in the study begins.
 

eProtocol Application Guidance for Clinical Trials

Please note that all clinical trials subject to IBC oversight, even those that do not meet the definition of HGT, must select HGT in the Activities and use section 5 (Human Clinical Trials) for the basic information on the trial and the investigational product. 

Please note that the questions and wording in section 5 (Human Clinical Trials) have been updated as of June 2022.

1. At the Personnel Section, other than the Principal Investigator, please add only University of Minnesota personnel associated with the clinical trial that are handling the IP or require application access.
   a) Verify that the appropriate training has been completed by personnel. If necessary, add training records manually for individuals in the box for “training that is not indicated above.”
   b) Non-UMN Nurses and clinical staff do not need to be accounted for as personnel on the application.
2. In the Activities Include section, select the box for “Human Gene Transfer-Human Subjects/Clinical Trial.”
3. In the Study Objectives section (1a and 1b), include a description of the project and briefly describe the goals/specific aims of the clinical trial.
4. Fill in the Human Clinical Trials sections 5a through 5h as appropriate. Please note that the questions and wording of this section have been updated as of June 2022. If the investigational product does not meet the definition of HGT, please still complete section 5 and modify your responses to fit the product being used. We are working to change the wording in the section to fit all potential IPs (not just HGT).
5. Complete the Safety section (7) of the application.
   a) If the investigational product will be stored at a University of Minnesota location, identify the lab work location in Table 7a)i.
   b) Identify the location the investigational product will be prepared in section 7a)iii. The room number section can be used to provide further details if the building location options are not descriptive enough to match your location.
   c) Identify the location that the investigational product will be administered to patients in section 7a)iv. This location must be specific enough for the IBC to determine if it is appropriate for the required biosafety level. The room number section can be used to provide further details if the building location options are not descriptive enough to match your location.
6. Please consider that the information provided to the IBC is intended to describe protection of staff, the public, and the environment. In the Attachments section, disregard the table information and attach (from NIH Points to Consider for HGT (pdf):
   a) Clinical Protocol
   b) Investigator’s Brochure
   c) A procedure describing packing, labeling, and transportation procedures for the IP between its storage location, the location that it will be prepared at (e.g., pharmacy), and the location it will be administered to patients. This SOP should include descriptions of PPE and physical containment.  Name how that material is contained (ie, for transport on the road, through public areas),
   d) A procedure (if not covered by other attachments) for administration of the IP (including other risks, like the use of sharps).
   e) If relevant, include the Pharmacy Manual or other relevant SOP describing the preparation of the investigational product before administration to patients.  Clearly state what PPE is used when handling biohazardous materials (as relevant; ie. preparation - mixing, pipetting, diluting, loading into syringes or infusion bags and administration),
   f) A Biological Decontamination and Spill Clean-up Plan and Biological Waste Disposal Plan specific to your administration/clinic/hospital location. Or standardized forms are also available for your use.  Describe how to decontaminate spills or dispose of waste (solid/liquid) that is contaminated with product. (ie, a syringe and needle contaminated with IP after use)(what is used to decontaminate).
7. The P.I. should read and complete the assurance page of the application.