Clinical research with genetic material poses many safety and methodologic challenges not shared by other forms of human investigation. As a result, there are a number of regulatory requirements that must be satisfied before any human studies involving gene transfer can be initiated. Presented below are guidelines to assist the clinical investigator in opening a gene therapy study on the GCRC. The policy of the GCRC is to require that a gene therapy protocol be approved by all committees/agencies listed below before the first patient can be enrolled. Investigators may choose to submit a proposal to the National Gene Vector Laboratories (NGVL) for clinical grade vector for use in their clinical trials.

 REGULATORY REQUIREMENTS

  Clinical protocols that involve the administration of recombinant DNA products into human subjects must be approved by the following reviewing bodies:

FEDERAL REQUIREMENTS:

1. Food and Drug Administration (FDA)   http://www.fda.gov/cber/
   
   The pharmaceutical sponsor or the principal investigator must file an Investigational New Drug (IND) application with the Center for Biologics Evaluation and Research (CBER) for each new investigational agent intended for human study.  The format and requirements of the IND are provided in Title 21 of the Code of Federal Regulations.  The IND must include extensive documentation regarding methods of production and preclinical testing.  If an IND has already been filed for the agent, every new protocol must be submitted as an amendment to the IND.  Requests for a CBER IND Packet can be made by contacting:
   
   A Office of Communication, Training and Manufacturers Assistance (OCTMA)
   HFM-40  (301)827-1800
   
   The FDA has published a document entitled “Guidance for Human Somatic Cell Therapy and Gene Therapy” http://www.fda.gov/cber/gdlns/somgene.htm, which provides guidelines and recommendations relating to the clinical use of gene products.
   
2.   NIH-Office of Biotechnology Activities (OBA)/Recombinant DNA Advisory Committee (RAC)  http://www.nih.gov/od/oba/
   
   This application requires information about the disease under study, vector being used, and the nature of the proposal in addition to other items.  The NIH review process is open to the public so proprietary information should be withheld.  Approval must be obtained from the HIC and IBC before submission to OBA.

LOCAL REQUIREMENTS:

1. Institutional Biosafety Committee (IBC) http://keats.admin.virginia.edu/gene/home.html
   
   The mission of the IBC is to ensure that biologic agents, including genetic material, are being handled using appropriate safe techniques and that risk of transmission to others is minimal. Investigators planning to conduct gene therapy trials must submit both a gene therapy registration document http://keats.admin.virginia.edu/gene/gene_therapy_registration_document.html and a biosafety manual specific for their study that would include a complete set of instructions for the safe handling of the gene product and any specimens that are collected as part of the study.  The study protocol, which should also be included in the submission package, must also incorporate certain safety practices http://keats.admin.virginia.edu/gene/gene_therapy_safety_practices.html
   developed by the university biosafety officer. A model biosafety manual http://keats.admin.virginia.edu/gene/gene_therapy_biosafety_manual.html
   can be downloaded from the Internet. The IBC meets monthly.
   
2. Human Investigation Committee (HIC)
   
   The HIC is the University of Virginia’s Institutional Review Board and must approve all studies involving human subjects. The study protocol, a protocol summary, investigators brochure (if available) and a consent form are included in the submission. The HIC meets on the second and fourth Tuesday of each month except December where it meets only on the second Tuesday.
3. GCRC Advisory Committee
   
   The GCRC Advisory Committee review all protocols being proposed for the GCRC with regard to their scientific merit and methodology and feasibility. Protocols must be converted to the Turbo format before submission. The most recent version can be obtained by calling the GCRC administrator at 924-2073. 
4. Cancer Center Protocol Review Committee (for cancer trials only)
   
   The Cancer Center Protocol Review Committee (PRC) must review all cancer related clinical trials. The PRC meets once a month. Call the nursing director for the Cancer Center Clinical Trials Office, at 982-0039 for submission instructions.  
5. UVA HSC Infection Control - should be consulted for isolation guidelines if infectious vectors are involved.
6. UVA School of Medicine Gene Transfer Research Trials Information page is located at
   http://www.med.virginia.edu/medicine/admin/PolicyonGeneTransferResearchTrials.pdf

NGVL

http://www.ngvl.org/

The National Gene Vector Laboratories (NGVL) an extramural program of the National Institutes of Health (NIH), are composed of an interactive group of academic production laboratories whose purpose is to provide eligible investigators with clinical grade vectors (DNA plasmid, lentivirus, HSV, adenovirus, adeno associated virus, and retroviral vectors) for phase I and II gene therapy applications.  

Requests for vector production will be reviewed by the Scientific Review Board and Steering Committee of the NGL with selection based upon scientific merit, feasibility and availability of NGVL resources. If the application is approved through the Steering Committee, clinical grade material will be produced free of charge for use in human gene therapy trials. 

An application packet can be downloaded from the NGVL Web page.