Clinical Trials Administrative Start-Up Handbook

SECTION 7

HUMAN GENE TRANSFER REVIEW

The National and Local Review Process

Clinical trial protocols involving gene transfer or recombinant-DNA-based vaccines need both federal and local review and approval before a study participant can be enrolled.

1. Federal review is performed by:
   a) the Recombinant DNA Advisory Committee (RAC) in the Office of Biotechnology Activities (OBA) at the National Institutes of Health (NIH). Note that RAC review is required even if the trial will not be funded by federal dollars.
   b) the FDA under an Investigational New Drug (IND) application.
   
2. Local review is performed by the Institutional Biosafety Committee (IBC) at the site where the investigational agent will be administered. Both IBC and Institutional Review Board (IRB) review are required before enrolling subjects for human gene transfer, regardless of funding source.

About National Review

For an experiment involving human gene transfer (the deliberate transfer of recombinant DNA, or DNA or RNA derived from recombinant DNA, into human research participants) investigators may not enroll any research participants until both the national and local review processes - and any other regulatory obligations - have been completed. The following Websites are full of very helpful information:

• Frequently Asked Questions about the NIH Review Process for Human Gene Transfer Trials for quick answers and for links to critical information.
• Points to Consider... , especially Appendix M-I, "Requirements for Protocol Submission, Review, and Reporting - Human Gene Transfer Experiments."
• FDA's Investigational New Drug (IND) application requirements.

For sponsor-initiated gene transfer or recombinant-DNA-based vaccine trials, the RAC application and the IND application will normally be handled by the industry sponsor. For investigator-initiated gene transfer or recombinant-DNA-based vaccine trials, the RAC application and the IND application will normally be handled by the investigator.

Generally speaking:

If you are the initial site to conduct the *clinical trial (see italicized note below):

• Submit the protocol to NIH/OBA for RAC review. See Appendix M-1-A for details about submitting your protocol.
• Submit an IND application to the FDA. Note that the FDA may advise you first to submit a pre-IND.
• Consider how you wish to stage the various reviews and approvals. Normally, it is advisable to start with the RAC review, then follow with the IND, the IBC, and finally with the IRB. Consult with the various reviewers when planning your strategy. The IBC, for example, will not approve your study without the RAC's recommendations, and the IRB will not approve your study until the IBC has approved it.
• Report to the RAC that you have initiated your study no later than 20 working days after you have enrolled your first research subject. See Appendix M-1-C-1.

If your site is added after the RAC review process and the IND submission have already been filed by the initial site or by the study's sponsor:

• Obtain both IRB and IBC approval.
• Report to the RAC - or ensure that the sponsor/initial site has reported to the RAC - before you begin subject enrollment. See Appendix M-1-C-2.

*Note that certain vaccine trials are exempt from RAC review, per Appendix M-VI-A ; however, these vaccine trials are not exempt from local IBC or IRB review. Consult with the UW IBC Coordinator for more information about this. Studies exempt from the RAC review may or may not require an IND submission.

About Local Review

The UW Institutional Biosafety Committee (IBC) evaluates human gene transfer studies, including vaccines. The IBC focuses on public protection - for example, the protection of research personnel, care givers, and the general public. The IBC review complements the IRB review, and approvals by both the IBC and the IRB are required prior to enrolling subjects.

A general description of IBC roles and responsibilities can be found at the IBC page at the NIH Website. Site-specific UW information is at the UW EH&S Website.

To initiate review by the UW IBC, you will need to complete and submit the following information to EH&S Research and Biological Safety Office (RBSO)..

• For an experiment involving human gene transfer (the deliberate transfer of recombinant DNA, or DNA derived from recombinant DNA, into human research participants), complete and submit the items listed below. Note that before submitting this information to the UW IBC, you will need to wait until the RAC has completed its review of your trial.

  • UW Research Project Hazard Assessment.
  • RAC commentary from the RAC review of the protocol, plus and additional RAC-sponsor or RAC-investigator correspondence.
  • Copies of documents provided to the RAC in Appendix M-I-A.

• For human studies that are exempt from RAC review, per Appendix M-VI-A, complete and submit:
  
  • UW Research Project Hazard Assessment
  • Scientific abstract
  • Non-technical abstract
  • Proposed clinical protocol
  • Proposed consent form
  • Principal investigators' CVs

Send the package to the IBC Coordinator. After your protocol has been reviewed and approved, you will receive a Biological Use Authorization (BUA) letter with a protocol reference number.

If the hazards associated with your trial change during the approval period, call the UW IBC Coordinator to discuss what action you need to take. It's likely that you will need to submit changes for IBC review, but call the IBC Coordinator to be sure.

Best Practices for Expediting the Institutional Biosafety Committee Review

• Be sure to time carefully your submissions to the various national and local oversight committees. If the protocol for your trial was written by an industry sponsor, timing for your submissions will be determined by your classification either as (1) a first investigative site or as (2) an additional site. Ask the sponsor into which category you fall. If you are a first investigative site, your protocol will need to be reviewed by the RAC before local review can begin. (You and the sponsor will be partners in this national review process). If you are an additional site, you can proceed with local IBC and IRB reviews right away, then "register" with the national oversight committees by sending them the required local approvals. If you (not the industry sponsor) have written the protocol, call the IBC Coordinator for advice about timing your various submissions.

Administrative Start-Up Checklist
Institutional Biosafety Committee

Click to Download Checklist in Word

Key Contact

IBC Coordinator

Environmental Health and Safety

Research and Biological Safety Office
Box 357165
Phone: 206-221-7770
Fax: 206-221-3068

Timeline

UW IBC meetings will be held monthly beginning in July, 2009. Applications are screened and assigned continuously for review. You will be contacted within three days after your documents have been submitted. Allow 4-6 weeks for IBC review.