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Gene Therapy Legislation in the US

In the United States, the Department of Health and Human Services (DHHS) has been charged with oversight of clinical trials. Two organizations within DHHS, the Office for Human Research Protections (OHRP) and the U.S. Food and Drug Administration (FDA), have specific authority described in the Code of Federal Regulations (CFR). All investigators, must comply with these regulations when conducting clinical gene therapy trials. The OHRP mandates that all research involving human subjects undergo Institutional Review Boards (IRB) review and approval. An IRB is charged with evaluating research risk to subjects and must approve research protocols and informed consent documents prior to beginning a study.
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.

The Novel and Exceptional Technology and Research Advisory Committee (NExTRAC) is a federal advisory committee that provides recommendations to the NIH Director and a public forum for the discussion of the scientific, safety, and ethical issues associated with emerging biotechnologies like gene therapy. NExTRAC proceedings and reports are posted to the OSP Web site to enhance their accessibility to the scientific and lay public.

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.

Literature and Guidance Documents

Regulatory issues in human gene therapy. Blood Cells Mol Dis 2003; 31: 51–56. This paper will review the current oversight agencies and identify areas of evolving regulations that pose particular challenges to gene therapy investigators.

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: Gene Therapy Clinical Trials - Observing Subjects for Delayed Adverse Events (November 28, 2006)

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)