The FDA's Willful Evasion of Science

Decisions about drug safety should depend on the evidence, not agency resources.

The Food and Drug Administration (FDA) is now 0 for 2. In March, a United States magistrate judge ordered the agency to begin withdrawing approvals for most uses of penicillin and tetracycline antibiotics in animal feed. On Monday, the same judge ordered the FDA to reconsider its recent denial of two petitions submitted by public health advocates in 1999 and 2005. The petitions urge FDA to withdraw approvals not just for penicillin and tetracycline, but also for a wide range of antibiotics needed to treat human infections.

In covering the decision, the media have highlighted a few pithy quotes from the judge's opinion. "For over thirty years," he wrote, "the Agency has been confronted with evidence of the human health risks associated with the widespread subtherapeutic use of antibiotics in food-producing animals...[but] the Agency has done shockingly little to address these risks."

Why has a key public health agency done so little despite so much scientific evidence of a public health threat? An old proverb--you can lead a horse to water but you can't make it drink--comes to mind. The FDA certainly has been confronted with scientific evidence of the human health risks, but the agency has routinely set aside the science when making decisions. The ruling does not guarantee that the FDA will do what the petitioners have asked of the agency, but it does require the agency to base its decisions on science.

A Call to Inaction

Notable in the debate over the misuse of antibiotics in food animal production is that the medical and public health communities have long agreed on the science. Decades of research have demonstrated that misuse of these drugs by the food animal industry promotes the development of antibiotic-resistant bacteria that can contaminate the food we eat and the air, water, and soil surrounding the industrial operations that produce these animals.

Many of these bacteria can cause human infections that are harder and more expensive to treat, and in some cases, no effective treatments are available. One resistant pathogen, methicillin-resistant Staphylococcus aureus (MRSA), causes more than 94,000 invasive infections and kills more than 18,000 people each year in the U.S. Long associated with hospitals, MRSA is now increasingly acquired in the community, and emerging evidence has associated proximity to industrial food animal production sites with increased risk of infection. Health economists estimate that antibiotic resistance adds between $16.6 and 26 billion to the nation's health care bill each year.

In 1999, advocates urged the agency to withdraw approvals for the use of key antibiotics to make food animals grow faster and reduce infections linked to the overcrowded and unsanitary conditions in which most food animals are raised. In 2005, advocates sought the withdrawal of approvals for agricultural uses of antibiotics that even the FDA does not consider safe. Both petitions cited the scientific literature extensively, building strong cases for agency action.

Under federal law, the FDA must withdraw its approvals for uses of animal drugs if the agency finds those uses are no longer safe within the meaning of the law. To withdraw an approval, the agency must compile evidence about the safety of the use in question and hold a hearing at which the company that manufactures the drug can contest the withdrawal. If the company cannot convince the presiding administrative law judge that the use in question is safe, the approval is withdrawn.

That is how the FDA is supposed to regulate drugs: assess the scientific evidence to determine whether an approved use is safe or not, and withdraw the approval if it is not. That is what the agency routinely does with human drugs, and it is precisely what the 1999 and 2005 petitions sought.

Unfortunately, the FDA took a different route. The agency did not issue final responses to either petition until last year--more than a decade after the first petition was filed--when it denied both. In letters to the petitioners, the FDA evaded the scientific evidence that advocates had presented, justifying its decision on other grounds. The agency said it would not withdraw approvals for growth promotion because doing so would "take many years and would impose significant resource demands on the Agency." Instead, the FDA is asking the pharmaceutical industry to voluntarily withdraw these approvals.

Arbitrary and Ironic

The Natural Resources Defense Council (NRDC) sued the FDA on behalf of the petitioners early last year, first to force the agency to respond to the petitions and then, when the agency denied both, to require the FDA to reconsider the petitions on their scientific merits, not whether the agency believes it has enough time to do the right thing.

In court, the agency seemed to contest almost every point except the science. More than anything, the FDA reiterated the arguments it made when it denied the petitions: withdrawing approvals takes too much time and it hopes industry will voluntarily withdraw the approvals anyway. The agency never disputed what is well known: many current uses of antibiotics in food animal production pose a major public health threat.

The Court was not persuaded by these arguments. In a sharply worded opinion, the judge noted that although the petitions, accompanied by more than 3,000 pages of research and other documentation, contain "numerous scientific studies of the risks of antibiotic resistance from the use of antibiotics in food-producing animals, the Agency did not address or even mention the scientific evidence in its responses." The FDA had failed to meet the requirements of federal law, under which a "decision whether to initiate formal withdrawal proceedings must be based on an evaluation of the scientific evidence of a drug's safety."

The judge seemed impatient with FDA's arguments that withdrawing approvals "would take many years," calling this argument "ironic and arbitrary" as the agency had essentially ignored the two petitions for 12 and seven years, respectively. "Had the Agency addressed the Petitions in a timely fashion," he wrote, "withdrawal proceedings could have been commenced and completed by now."

Furthermore, the FDA's reliance on a voluntary program undercut its claim that the withdrawal process would be too time-consuming for the agency to undertake. "[If] any credence is to be given to the Agency's position that the drug industry intends to comply with the voluntary program, then it is unclear why the industry would contest formal withdrawal notices or require time consuming hearings."

The judge ordered the agency to reconsider both petitions, this time on their merits. Importantly, the Court did not order the FDA to reach a certain conclusion, only to base whatever decision it makes on the available scientific evidence. Both petitions make strong cases that using antibiotics for growth promotion and disease prevention does not meet the standard for safety set by law. If the FDA agrees--and one wonders how the agency cannot--the law requires it to withdraw approvals for such uses.

Last week the agency gave notice it would appeal the March ruling on penicillins and tetracyclines, and it will almost certainly do the same with the latest decision. If the NRDC and the petitioners win on appeal, the FDA may still find ways to deny the petitions yet again, although this will be hard to do if the agency takes a careful look at the science. Despite the challenges that lie ahead, however, the court decision this week was welcome news. The ruling puts the focus back on science--where it should have been all along.