February 15, 2012

 

 FDA cancels 1977 drug withdrawal bids

Posted on February 1, 2012
 

This past December, federal drug authorities canceled a 34-year-old proposal to withdraw approvals for some antimicrobial uses in feed.

The Food and Drug Administration had proposed in 1977 to end such uses of penicillins and tetracyclines in livestock feed. At the time, Congress ordered the agency to continue studying the matter. The agency contracted with outside organizations to study the issue through the late 1980s but did not proceed with or cancel the proposal.

A Dec. 22, 2011, Federal Register notice stated that the FDA was withdrawing its notices of opportunity for a hearing, or NOOHs, connected with the proposals. Such hearings, required in the process of withdrawing drug approvals, would have let drug manufacturers contest the agency proposals.

"Today's action should not be interpreted as a sign that FDA no longer has safety concerns or that FDA will not consider re-proposing withdrawal proceedings in the future, if necessary," the notice states. "FDA has not ruled out the prospect of future regulatory action, either with respect to the antimicrobial new animal drugs covered by the 1977 NOOHs or any others."

The Natural Resources Defense Council, Center for Science in the Public Interest, Food Animal Concerns Trust, Public Citizen, and Union of Concerned Scientists filed a federal lawsuit in May 2011 based on allegations the agency had unreasonably delayed action on the 1977 proposal and had unreasonably delayed ruling on two antimicrobial use–related citizen petitions filed in 1999 and 2005.

The petitions implored the FDA to withdraw its approvals for an array of antimicrobial uses for improving livestock production and preventing diseases, rather than for treating diagnosed maladies. The FDA denied the petitions last November. 

Changes in opinions, tactics, knowledge

In canceling the 1977 proposal, FDA officials noted their agency expects cooperation from the animal pharmaceutical industry to phase out livestock production uses of antimicrobials important for human medicine.

 

FDA officials have also indicated the agency intends to require greater veterinary oversight of antimicrobial use, which would involve removing the over-the-counter availability of many medicated feeds. Buying such feeds would instead involve veterinary feed directives, which require veterinarian oversight similar to that for prescription medications.

Even if the agency had not changed strategies since 1977, the 2011 Federal Register notice indicates the agency has changed its opinion on what uses are therapeutic. In addition to uses to increase rate of weight gain in livestock, the FDA had, in the 1970s, considered antimicrobial uses to prevent and control disease to be subtherapeutic.

 

"Today's action should not be interpreted as a sign that FDA no longer

has safety concerns or that FDA will not consider re-proposing

withdrawal proceedings in the future, if necessary. FDA has not ruled out

the prospect of future regulatory action ... "

FDA Federal Register notice published Dec. 22, 2011

 

"FDA's thinking on this issue has evolved over the last three decades, and FDA now generally considers disease control and prevention claims to be judicious uses," the 2011 notice states.

In addition, the notice indicates further analysis could find better targets for agency actions.

"It is possible that FDA would conclude that its judicious use goals would better be achieved by first pursuing withdrawals of drugs other than penicillins and tetracyclines," the notice states.

Actions considered since early '70s

A Federal Register notice published in 1972 indicated an FDA task force found that "growth promotant and subtherapeutic" antimicrobial uses in livestock favored development of antimicrobial resistance, and animals receiving such doses could become reservoirs of antimicrobial-resistant pathogens that could infect humans.

 

The notice stated that then FDA Commissioner Charles C. Edwards would propose revoking permission for such uses of antimicrobial agents in feeds when those drugs were also used in human medicine "unless data are submitted which establish their safety and effectiveness under specific criteria" based on guidelines from the task force.

In 1974, a subcommittee of the FDA's National Advisory Food and Drug Committee recommended withdrawal of growth-promotant and disease-control uses of penicillin in agriculture. It also recommended ending tetracycline uses for growth promotion when alternates exist, permitting disease-control uses when alternatives are absent, and increasing restrictions on distribution of the drugs.

In 1977, the FDA announced its plan to withdraw all penicillin uses in animal feed and all tetracycline uses for growth promotion and disease control, with exceptions for six tetracycline uses in chickens, turkeys, beef cattle, and sheep. Congress directed the agency to halt the proceedings pending further study.

The first study was conducted by the National Academy of Sciences, which reported in 1980 that then-current research was insufficient to conclude whether antimicrobial use in livestock feed risked human health. Such research may not be possible, according to background information in the December 2011 Federal Register notice. In 1984, the FDA arranged for further study by the Seattle-King County Health Department, which reported that bacteria in humans and retail poultry had similar antimicrobial susceptibility patterns. In 1987, the Institute of Medicine conducted a study for the FDA and found evidence that implied but could not prove that antimicrobial use in livestock could increase risks to human health.

The Federal Register notice states that further study occurred within the agency during the 1990s, and the agency changed its considerations and processes for approving new antimicrobials during the late 1990s and early 2000s. The current efforts to increase veterinarian oversight and ensure judicious use are connected with a draft guidance document published in June 2010; a final draft had not been published at press time.