Human Gene Therapy and The Role of the Food and Drug Administration

September, 2000


One of the most exciting and highly publicized areas in biomedical research today is human gene therapy - the replacement of a person's faulty genetic material with normal genetic material to treat or cure a disease or abnormal medical condition. Over time and with proper oversight, human gene therapy might become an effective weapon in modern medicine's arsenal to help fight diseases such as cancer, diabetes, high blood pressure and heart disease. Also, for patients with presently incurable diseases, such as cystic fibrosis, hemophilia A and B, and other genetic disorders, human gene therapy offers hope of a cure, or at least a measure of relief.

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.

The FDA's authority includes any human gene therapy product sold in the United States. Because of FDA's strong involvement in the regulation of human gene therapy products, it is important for consumers to know what FDA is doing to protect them in this area, how FDA is doing it, and how the agency is responding to concerns that human gene therapy, instead of helping patients, may be dangerous and may put patients at risk.


Human genes are very small pieces of information recorded on a molecule called deoxyribonucleic acid, or DNA, that tells the body how to operate. Genes also determine certain physical characteristics, such as eye color, and are passed on from parents to children. Genes are believed to play a role in some cancers, either by stimulating the growth of cancer cells or by failing to stop them before they grow out of control.

To better understand how human gene therapy works, it may be helpful to review some facts about human genes and gene delivery techniques:

  • Every person's body is made up of trillions of cells. These cells are too small for you to see with your eye - you must use a microscope.
  • Every cell contains a nucleus, which is even smaller, but still visible under a microscope.
  • The cell nucleus contains an even smaller set of chromosomes, which can only be detected with special laboratory techniques.
  • Every chromosome contains DNA, the genetic material that is unique for each living creature.
  • Along the DNA lie thousands of genes, which are smaller yet.

We can detect genes only by advanced analytical techniques such as gene sequencing methods that are currently being used to map the entire human genome. In the future, gene doctors would use a variety of techniques, some similar to current vaccinations, to inject normal genes into a person's body. Other approaches might put genes into mechanical devices to deliver them into the body. Even nanotechnology - the use of very small, even microscopic particles could eventually be part of a gene therapy delivery system.


Human gene therapy is the use of normal genes or genetic material to replace or cancel out the "bad" or defective genes in a person's body that are responsible for a disease or medical problem. The "good" genes find their way to the right spot in the body and begin to do the work required. The eventual hope is that for some diseases, like hemophilia, the good genes will keep working throughout a person's lifetime. There may be other uses of gene therapy, for example, to repair a wound, or to grow new blood vessels, during which the effect of the gene would only need to be active for a short time.

Advances in human gene therapy may allow doctors to treat a disease or abnormal medical condition by turning off a faulty gene and stopping the growth of a cancerous tumor, for example. Or they may allow the body to begin producing a necessary protein or other substance, such as an enzyme, that the faulty gene cannot order the body to produce.

For example, a person with the disease cystic fibrosis (CF) has a faulty gene for handling lung development, which results in excess mucous in the lungs, leading to chronic coughing, choking and serious respiratory infections. Cystic fibrosis patients often die young from pneumonia or other life-threatening respiratory diseases. The current median life span for CF patients is now about 30 years (see For these persons, a doctor might inject a normal CF gene into a patient's bloodstream. The hope is that the CF gene would find its way into the patient's lungs, replace the faulty gene and help the patient's lungs to function properly.


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. However, gene-related research and development is continuing to grow and FDA is very involved in overseeing this activity. Since 1989, FDA has received about 300 requests from medical researchers and manufacturers to study gene therapy and to develop gene therapy products. Presently, FDA is overseeing approximately 210 active IND gene therapy studies.


FDA's number one priority is to have safe human gene therapy studies. FDA does not want to stand in the way of progress that may lead to effective therapies and cures, but the agency knows - as with any medical product or procedure - that new gene therapies may have unknown risks, even as they provide tremendous benefits to patients. Furthermore, FDA is aware of the public's concern about the safety of human gene therapy studies. Therefore, FDA wants to make sure that gene therapy products are as safe as possible, and that people now enrolled in gene therapy studies and those who eventually receive approved gene therapy products will not be harmed.

FDA has dedicated time and resources toward recruiting top-notch scientists, physicians, statisticians and other health professionals, all of whom are working hard to ensure that gene therapy products will be safe. These people are experts in the sciences associated with gene therapy, such as virology (the study of viruses), molecular biology (the study of living cells at the molecular level), pharmacology (the study of drug actions), and toxicology (the study of toxic or adverse reactions from drugs, chemical or other substances). These experts understand how to determine whether gene therapy studies are appropriate, taking into account the safety of the human subjects whom may participate in the studies. FDA staff are trained in how to properly analyze gene therapy study results. They are the people who decide whether or not a manufacturer may begin studying a gene therapy product and, ultimately, will decide if it is safe for human use.

A separate team of FDA professionals with expertise in manufacturing processes travels to a manufacturer's testing and production facilities to make sure that FDA's rules for making a gene therapy products are being followed. And yet another team is responsible for reviewing any problems, or adverse events, that happen to patients who are part of a gene therapy study. If a problem is serious and unexpected, a manufacturer or researcher is required by law to notify FDA no later than 15 calendar days from when he learns of the problem. If a patient in the study dies or is at risk of dying, the manufacturer must notify FDA within seven days. At that point, FDA will either demand changes to the human study, require more non-human laboratory studies, put the human study on hold, or stop the study.

FDA works with other scientific experts - in hospitals, medical schools and other medical settings - to better ensure the safety of gene therapy products. FDA consults and receives advice from its Biological Response Modifiers Advisory Committee on scientific issues related to gene therapy products. FDA also works closely with other government agencies, such as the National Institutes for Health (NIH), the major public funding agency for laboratory and clinical research on gene therapy vectors and models, and co-sponsors many meetings with NIH to discuss issues related to gene therapy.

FDA and NIH have complimentary responsibilities with respect to the regulation of human gene therapy. FDA's primary job is to make sure that manufacturers produce high-quality and safe gene therapy products, and that these products are properly studied in human subjects. NIH's primary job is to evaluate the quality of the science involved in human gene therapy research, and to fund the laboratory scientists who invent and refine the tools used for gene transfer clinical studies.

The Recombinant DNA Advisory Committee (RAC), a public advisory committee to the Director of the NIH, holds regular meetings on gene transfer research, and focuses on the scientific, safety, and ethical issues involved. RAC members include physicians, scientists, medical ethicists, consumer activists, and private citizens, as well as ex officio members of the federal government, including FDA and the Department of Health and Human Services new Office of Human Research Protection (OHRP).

It's also important to remember that keeping patients safe is not only the government's responsibility. FDA also expects manufacturers and medical researchers to be responsible and to use the highest-quality experimental products, practice good clinical medicine, and accurately communicate information to FDA and to patients.


Human gene therapy and its safe application to patients will continue to be a high priority for FDA. As advances in our understanding of human gene therapy grow, FDA will use this information to make the best scientific, clinical, and regulatory decisions possible. FDA also will continue to place a high value on the public's concerns and take steps to see that they are addressed appropriately. To accomplish these goals, FDA will strengthen both its educational and enforcement programs for manufacturers, spend more time discussing gene therapy with its own staff, organize gene therapy-based research projects, and continue working with the NIH RAC.

For related information on human gene therapy:

Updated: March 24, 2003