eparting from longstanding practice, the Food and Drug Administration will allow some drugs and vaccines designed to counter biological, chemical and nuclear terrorism to be approved without being tested in people to prove they work.
In an announcement yesterday, the agency said the new rule could spur development of drugs for use against biological, chemical and radioactive substances by eliminating a major stumbling block, the ethical barriers to exposing people to deadly substances like smallpox or nerve gas simply to prove that a drug works.
"We've been stymied for some products figuring out a way to show human efficacy, given the ethical issues," said Dr. Janet Woodcock, director of the Center for Drug Evaluation and Research at the F.D.A. "One of the reasons there wasn't commercial interest was that people were not at all certain their drugs could be approved if they developed them."
The agency normally requires three phases of clinical trials in people to prove a drug is safe and effective. The new rule would allow animals to be used to test effectiveness, providing there was no ethical way to test that in people.
Testing for safety and side effects would still have to be done on human volunteers because that requires exposing people only to the drug, not to the lethal agent.
The rule was first proposed in 1999 and there has been no real opposition to it, so the agency has faced criticism for dragging its feet in formally approving it, especially after the Sept. 11 attacks and the anthrax mailings last fall.
"It's been languishing," said Dr. Frank E. Young, a former chairman of the agency who is now a director of a biotechnology company, EluSys Therapeutics, that is developing a drug to treat people exposed to biological agents. "In the absence of this rule, companies cannot go forward."
Dr. Woodcock said it did not take unusually long to get the rule approved given federal procedures.
Dr. Sidney Wolfe of Public Citizen, an advocacy group in Washington, said the concept of the new rule was good but its application must be limited to cases of absolute necessity. "I'm very worried about this being abused" to win approval for drugs without adequate testing, he said.
The F.D.A. acknowledged that there was a risk in approving drugs based only on animal tests because many drugs that work in animals do not work in people. Under the new rule, the products would be labeled as having been tested only in animals. In most cases, at least two types of animals would be used. There also would have to be enough understanding of the mechanism of the disease and of the drug to reasonably conclude that the animal results reflect what would happen in people.
Dr. D. A. Henderson, the top bioterrorism adviser to the secretary of Health and Human Services, said yesterday that the F.D.A. move was logical and overdue.
"It only makes sense," he said. "There's no way we can possibly test against these diseases in man."
Still, it is not quite clear how much the rule will stimulate development of drugs and vaccines. Dr. Woodcock said she knew of a handful of drugs now in development that might eventually come up for approval based on animal studies. But the F.D.A. estimates that the new rule might be used only once every three years.
Stephan Lawton, a vice president of the Biotechnology Industry Organization, said there were many small companies working on drugs that could be used for biodefense. Dr. Michael A. Friedman, senior vice president for policy at the drug maker Pharmacia, said companies might now try to get the antibiotics they already sell approved for the additional use of treating anthrax infections.
But Dr. Friedman, who is also chief of biomedical preparedness for the drug industry's main trade group, the Pharmaceutical Research and Manufacturers of America, said that while the new rule would help spur development of such drugs, "it doesn't solve all the problems."
One problem, he said, is that there are long waits at the few laboratories that test lethal agents on animals. He also said that for some biological agents there are no animals that can be used for testing.
Charles L. Bailey, a former commander of the Army's laboratory at Fort Detrick, Md., said another problem was the shortage of research monkeys for such tests, although he said the government was now moving to address this issue.
Another factor that could inhibit development is that the drugs might have a limited market because a biological, chemical and radioactive attack might never come. "This is a niche market," Dr. Young said.
One of the biggest beneficiaries could be the Pentagon, which has already indicated it wants to use animal testing to win approval of a drug that has allowed mice in tests to survive normally lethal doses of radiation. The Army also has many vaccines for biological agents that it has never been able to win approval for but which are given as experimental drugs to protect scientists who work with lethal agents at Fort Detrick and other laboratories.
"Now both the civilian population and the military population will be able to get these products out in a straightforward fashion," said Dr. Arthur O. Anderson, the chief ethics officer of the biodefense program at Fort Detrick.
The F.D.A. has already approved one drug without human testing, the antibiotic Cipro, which was approved in 2000 for use against anthrax. In that case, the agency used a different rule that relaxes testing requirements for drugs meant for life-threatening diseases like cancer or AIDS.
In some cases, the microbes that might be used as biological agents have natural outbreaks, giving an opportunity for drugs to be tested. The anthrax vaccine currently in use was tested decades ago in textile mill workers, who were exposed to the spores in goat hair. But for many other agents natural outbreaks might never occur.
The F.D.A. could allow the use of unproven drugs as experiments. But that requires informed consent of each person treated, which might be hard to obtain in an emergency after a biological or chemical attack, Dr. Woodcock said. The new rule sprang in part from a controversy that arose when the military tried to have the informed consent rule waived so it could give botulism vaccine and a nerve gas antidote to soldiers in the Persian Gulf war.