Another DHHS agency, the National Institutes of Health (NIH), oversees the conduct of federally funded clinical trials through a series of guidelines that add additional requirements to those specified in the CFR.
NIH - OBA - RAC
The NIH established the Recombinant DNA Advisory Committee (RAC) on October 7, 1974 in response to public concerns regarding the safety of manipulating genetic material through the use of recombinant DNA techniques. Although the RAC’s responsibilities have evolved over time with scientific understanding and developments in this technology, it continues to serve the NIH as a critically important forum for open, public deliberation on the panoply of scientific, ethical, and legal issues raised by recombinant DNA technology and its basic and clinical research applications. A major responsibility of the RAC at present is to review human gene transfer research on behalf of the NIH. Human gene transfer trials conducted at, or sponsored by, institutions receiving NIH funding for recombinant DNA research are registered with the Office of Biotechnology Activities (OBA) and reviewed by the RAC. The OBA is responsible for the NIH system of oversight of recombinant DNA research. Clinical gene therapy protocols that raise novel or particularly important scientific, safety or ethical considerations are discussed by the RAC at one of its quarterly public meetings. RAC proceedings and reports are posted to the OBA website to enhance their accessibility to the scientific and lay publics.
The NIH also consults the RAC for advice concerning various advances in recombinant DNA technology, as well as ethical and safety considerations associated with novel or possibly risky forms of recombinant DNA research.
FDA - CBER
The U.S. Food and Drug Administration (FDA) is the primary government agency charged with protecting the health of U.S. citizens by ensuring that drugs, medical devices and biological products are safe and effective before they are used by doctors, nurses, other health care professionals, hospitals and consumers.
FDA's Center for Biologics Evaluation and Research (CBER) regulates human gene therapies, which fall under the legal definition of a "biologic." Manufacturers of gene therapy products must test their products extensively and meet FDA requirements for safety, purity and potency before they can be sold in the United States. A manufacturer who is considering selling a gene therapy product in the United States first must tell FDA of its intentions, and then must test the product in a laboratory and then in research animals. When a manufacturer is ready to study the gene therapy product in humans, it must obtain a special permission exemption from FDA before starting. This exemption is called an investigational new drug application or (IND). In the IND, the manufacturer explains how it intends to conduct the study, what possible risks may be involved and what steps it will take to protect patients, and provides data in support of the study. As part of the IND process, the manufacturer also must get approval from a committee of scientific and medical advisors and consumers (called an Institutional Review Board), which focuses on protecting persons who may participate in the study. Researchers also must inform the persons who may be part of the study about the study's potential risks and benefits, and obtain their consent.
When FDA's scientists receive an IND application for gene therapy, they review it carefully before permitting the manufacturer or researcher to begin the study. FDA may ask the study sponsor to do more laboratory tests and include more safeguards to ensure the safety of patients, such as giving patients smaller doses. As discussed in the next section, if unexpected problems arise, FDA may tell the manufacturer to change the study or stop it altogether.
FDA has not yet approved for sale any human gene therapy product.
Regulatory issues for clinical gene therapy trials. Hum Gene Ther. 2002; 13(10):1143-9. In this review, the basic tenets of human subject research are discussed in the context of the regulatory bodies which oversee this work. The challenges faced by academic research are outlined, including new and proposed regulations which impact human gene therapy investigators.
NIH Guidelines for Research Involving Recombinant DNA Molecules (September, 2009)
FDA Guidance for Industry: Supplemental Guidance on Testing for Replication Competent Retrovirus in Retroviral Vector Based Gene Therapy Products and using Follow-up of Patients in Clinical Trials Using Retroviral Vectors (November 28, 2006)
The Sponsor’s Guide to Regulatory Submissions For an Investigational New Drug. A practical guide for bench Scientists entering the clinical and regulatory realm (March, 2005)