For the past eight years, the Food and Drug Administration has repeatedly asked pharmaceutical companies not to use materials from cattle raised in countries where there is a risk of mad cow disease.
But regulators discovered last year that five companies, including some of the world's largest drug concerns, were still using ingredients from those countries to make nine widely used vaccines.
Some of the companies say that they found the FDA's request unclear and do not believe they did anything wrong. Others say they could not keep up with the government's expanding list of countries where cattle could be infected. One, however, acknowledged that it could have moved more quickly.
The nine vaccines include some regularly given to millions of American children, including common vaccines to prevent polio, diphtheria and tetanus. They also include the anthrax vaccine, which the government requires for soldiers serving in the Persian Gulf.
Federal health officials stress that the vaccines are still considered safe. They calculate that the odds of these vaccines passing on the disease, in the worst eventualities, are between one in 40 million and one in 40 billion doses.
The officials say that the very slight chance that someone could be infected is far outweighed by the benefits that these vaccines bring in fighting disease and preventing death. Indeed, it is now only a scientific theory that a vaccine could infect someone with the human form of mad-cow disease — called new variant Creutzfeldt-Jakob disease. No one is known to have contracted the disease this way.
"Any risk is very remote," said Dr. Karen Midthune, director of the FDA's Office of Vaccine Research and Review. "But if we have the ability to bring this remote risk to zero, that is something we want to do."
Nonetheless, the fact that these suspect materials slipped into the nation's vaccine supply — and that the FDA did not discover it for seven years — raises questions about the agency's ability to ensure that all medicines are free of the infectious proteins that can cause mad-cow disease.
The FDA so far has only investigated the vaccine makers and has not looked to see whether other medicine is free of possible mad-cow contaminants. Some experts say they worry more about dietary supplements. Unlike drugs, supplements are largely unregulated. The FDA is not even sure how many supplement makers there are.
"It's just insane not to have greater safeguards" for supplements, said Dr. Paul W. Brown, chairman of the FDA's advisory committee on mad-cow disease. "The potential exists for abuse."
The five vaccine makers are GlaxoSmithKline, Aventis, American Home Products, Bioport and North American Vaccines (which was acquired by Baxter International last year). The five vaccine makers have now agreed to stop using the suspect materials, which include blood, fetal calf serum and meat broth.
But it will take a year or more to replace existing supplies with reformulated products, because it can take many months to grow cultures used in making vaccines. Both the companies and the FDA say that the current products are safe and should remain on pharmacy shelves.
They point out that the suspect ingredients, for the most part, are used only in the early stages of manufacturing, when cultures are grown. Blood, for instance, may be used to feed the bacteria and viruses in these cultures. The cultures are then significantly diluted in the final vaccine.