Safeguards for Gene Therapy
An Advisory Panel to the U.S. Food and Drug Administration (FDA) recently heard testimony on two important recommendations regarding the manufacturing and monitoring of gene therapy treatments.
In a meeting in Washington, DC, the FDA's Biologics Response Modifiers Advisory Committee urged that the same stringent quality control tests required for traditional pharmaceutical drugs should also be required for drugs developed through genetic testing. A second meeting called for sponsors of gene therapy clinical trials to follow-up with patients for as long as 20 years.
On September 14, 1990, a 4-year-old girl named Ashanthi DeSilva became the first human patient to participate in a clinical trial for human gene therapy. Doctors at the National Institutes of Health in Bethesda, Maryland gave the girl an IV containing her own white blood cells that had been genetically altered in the hopes of fixing an inherited birth defect.
In the decade since that revolutionary first genetic step, over 400 clinical trials to test gene therapy have been launched, mostly targeted at cancer treatments. Unfortunately however, amid great promise, there has been little actual clinical success to date.
Human gene therapy involves the replacement of a person's faulty genetic material with normal genetic material to treat or cure a disease. Human genes are pieces of genetic material recorded on a DNA molecule. Genes carry specific bits of information that determine physical characteristics-ranging from eye color to the oxygen-carrying capacity of the blood-that are passed on from parents to children. Genes are also 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.
Advances in human gene therapy will eventually allow doctors to treat a disease by turning off a faulty gene, stopping the growth of a cancerous tumor, or enabling the body to produce a missing protein or enzyme.
The FDA's Center for Biologics Evaluation and Research (CBER) is responsible for regulating human gene therapies, which fall under the legal definition of a "biologic." The FDA has not yet approved any human gene therapy product for sale. However, the amount of gene-related research and development continues to grow at an extraordinary rate.
As a result, the CBER is considering new regulations that will require the manufacturers of gene therapy products to conduct the same battery of tests (for sterility, potency, concentration, the presence of toxins, etc.) that are required for traditional drug makers.
"Regulations from 10 years ago [when the first genetic tests were performed] are no longer adequate," testified Dr. Joyce Frey-Vasconcells of the CBER's Division of Cellular and Gene Therapies. She said new measures are crucial to "increase public confidence and ensure proper reporting and oversight."
Simultaneously, the FDA's Biological Response Modifiers Advisory Committee recommended that sponsors of human gene therapy trials be required to conduct patient follow-ups for as long as 20 years after their initial participation.
"I don't think the public is willing to accept any kind of gene therapy where the sponsor has no follow-up responsibility," said Dr. Daniel Salomon of The Scripps Research Institute in La Jolla, California.
Panelists noted that the risks associated with altering genetic material are still unknown and, in some instances, side effects could take decades to develop. On the other hand, lower-risk gene therapies, involving the transfer of genes into cells with a lifespan of only weeks, might only require a follow-up period of five years or less.
Beyond the confusion of requiring different follow-up periods for different gene therapies, Dr. Jay Siegel, the Director of CBER's Office of Therapeutic Research and Review, pointed out the logistical difficulties of tracking patients for decades-and for getting the necessary funding for such long-term programs.
"If we go to 10- or 20-year follow-ups with the absence of adequate funding arrangements," he warned, "that will take many of us out of gene therapies."
Because of these and other uncertainties, the CBER is not expected to reach consensus agreement on developing new gene therapy guidelines for at least two years. Even then-given the explosion of research into genetic therapies-such guidelines could already be outdated.
SOURCES:
Meetings of the Advisory Committees to the Center for Biologics Evaluation and Research, April 5-6, 2001, Washington, DC
The U.S. Food and Drug Administration (http://www.fda.gov)
Center for Biologics Evaluation and Research, U.S. Food and Drug Administration (http://www.fda.gov/cber)
[Table of Contents] [Archived Issues / Search] [The Breast Center]