With no notice other than a holiday-eve posting in the Federal Register, the US Food and Drug Administration has reneged on its long-stated intention to compel large-scale agriculture to curb over-use of agricultural antibiotics, which it had planned to do by reversing its approval for putting penicillin and tetracyclines in feed.
How long-stated? The FDA first announced its intention to withdraw those approvals in 1977.
From the official posting:
The Food and Drug Administration (FDA or the Agency) is withdrawing two 1977 notices of opportunity for a hearing (NOOH), which proposed to withdraw certain approved uses of penicillin and tetracyclines intended for use in feeds for food-producing animals based in part on microbial food safety concerns.1 … (1FDA’s approval to withdraw the approved uses of the drugs was based on three statutory grounds: (1) The drugs are not shown to be safe (21 U.S.C. 360b(e)(1)(B)); (2) lack of substantial evidence of effectiveness (21 U.S.C. 360b(e)(1)(C)); and (3) failure to submit required reports (21 U.S.C. 360b(e)(2)(A)).)
There is a lot of background to this, but here is the takeaway: For 34 years, the FDA has been contending that administering small doses of antibiotics to healthy animals is an inappropriate use of increasingly scarce drugs — a position in which it is supported by organizations as mainstream as the American Medical Association. With this withdrawal, it backs away from the actions it took to support that assertion — which may indicate there will be no further government action on the issue until after the 2012 election.
In the Federal Register, the FDA says that it plans instead to “focus its efforts for now on the potential for voluntary reform and the promotion of the judicious use of antimicrobials in the interest of public health.” That’s a reference to a draft guidance that the FDA put forward in the summer of 2010, which proposes that large-scale agriculture voluntarily stop using those “subtherapeutic” small doses, and also stop giving any antibiotic doses to animals unless veterinarians prescribe them.
Two things to note there: After 18 months, the guidance is still in draft, and has never been finalized; and even in draft, the industry opposes it, calling into question the likelihood of “voluntary” adherence if it were to become final. One example, from the National Cattlemen’s Beef Association, when the draft was first put forward:
NCBA supports the role that FDA plays in making science-based decisions regarding the safety and efficacy of antibiotics and antimicrobials used in animal agriculture… However, this (sic) is no conclusive scientific evidence indicating the judicious use of antibiotics in cattle herds leads to antimicrobial resistance in humans.
It is not correct that there is no such evidence: There are dozens of good scientific papers on the link between antibiotic use in animals and antibiotic-resistant illness in humans. (Good bibliographies are maintained by the Pew Charitable Trusts and by the group Keep Antibiotics Working.) The link is so robust that in Europe, subtherapeutic or “growth promoter” dosing of feed has been banned since 2005.
How did we get to this point? It’s a tangled history, but here is a recap:
- 1951 & 1954: The FDA approves penicillin, chlortetracycline and oxytetracycline as feed additives.
- 1969: The UK government’s “Swann Report,” formally the Joint Committee on the Use of Antibiotics in Animal Husbandry and Veterinary Medicine (headed by Dr. M. M. Swann), proposes that rising rates of multi-drug resistant bacteria are due to agricultural use.
- 1970: The FDA becomes concerned about the human health effects of subtherapeutic use of the drugs in animals, and convenes a task force, which concludes the drugs’ use fosters the emergence of antibiotic-resistant bacteria.
- 1973: On the basis of the task force’s findings, the FDA proposes to withdraw its 1951 and 1954 approvals, unless industry can prove they are safe.
- 1976: In the first influential US research, Tufts University researchers establish an experimental farm, give tetracycline-laced feed to chickens on it, and recover tetracycline-resistant bacteria from the farm workers.
- 1977: The FDA issues the “notices of opportunity for a hearing” that were withdrawn Thursday.
- 1978: The House of Representatives’ Committee on Appropriations orders the FDA to put a hold on its actions and conduct more research. The FDA asks the National Academy of Sciences to perform the research.
- 1980: The National Academy report says it cannot prove subtherapeutic use is safe. The House Committee asks for another round of research.
- 1981: The Senate Committee on Appropriations also asks for more research. The FDA asks the health department in Seattle and the surrounding county to perform it.
- 1983: Pharmaceutical companies ask the FDA to withdraw the 1977 hearings notices. The FDA refuses.
- 1984: The Seattle-King County Health Department finds that bacteria in chickens on farms using tetracycline, and the same bacteria in humans locally, have the same resistance fingerprints, and raises the possibility that the resistance DNA is moving into other bacterial species.
- 1988: The Institute of Medicine of the National Academy issues a report that resistance from subtherapeutic use of antibiotics is a “potential human health hazard.” The FDA tells the House and Senate committees that it has all the research it needs.
- 2001: The American Medical Association passes a resolution opposing growth-promoter drug dosing.
- 2003: The Institute of Medicine says in a second report: “Mounting evidence suggests a relationship between antimicrobial use in animal husbandry and an increase in bacterial resistance in humans.”
- 2004: The FDA tells feed manufacturers that it considers putting subtherapeutic doses of antibiotics into feed to be “high risk.”
- 2010: The FDA issues its draft voluntary guidance on limiting subtherapeutic dosing.
- 2011: After putting 34 years into pushing for removal of two of the main drug categories used for subtherapeutic dosing, the FDA backs off.
In the Federal Register posting, the FDA represents this move not as a retreat, but as a change in tactics. It says:
FDA remains concerned about the issue of antimicrobial resistance. 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, either with respect to the antimicrobial new animal drugs covered by the 1977 NOOHs or any others… This strategy leaves open the possibility of pursuing withdrawal proceedings at a later time if FDA’s proposed strategy does not yield satisfactory results.
At the end of the Federal Register posting, the FDA says it is taking public comment on this issue, via the docket established for the draft guidance issued in 2010. That docket number is FDA-2010-D-0094-0002, and the form for submitting comments is here.