A nonprofit group that has been using the courts to pressure the Food and Drug Administration into exerting more control over farm antibiotic overuse has done a deep review of FDA documents prised loose through Freedom of Information Act requests — and concludes that by allowing the drugs to remain on the market as formulated, the agency isn’t meeting its own internal safety standards.
Instead of only making that assertion, the Natural Resources Defense Council took the unusual step of showing its evidence in detail. NRDC published its analysis, Playing Chicken with Antibiotics, alongside a selection of the raw documents it received from the FDA. You’ll have to be a document-obsessive to take it on: The file (cached in a Dropbox and requiring download to view) is 306 mb and 971 pages. But even without considering its content, the file’s heft makes clear how much discussion there has been at the FDA over this issue, and suggests how much evidence has been accumulating over the problem of antibiotic resistance emerging from livestock production. Also telling: The FDA has been attempting to put some controls on livestock production since 1977; these documents cover only reviews of antibiotic feed additives that were conducted between 2001 and 2010.
NRDC’s conclusion, in its report:
FDA’s scientific reviewers’ findings show that none of these products would likely be approvable as new additives for nontherapeutic livestock use if submitted today, under current FDA guidelines. Eighteen of the 30 reviewed feed additives were deemed to pose a “high risk” of exposing humans to antibiotic-resistant bacteria through the food supply, based on the information available. The remainder lacked adequate data for the reviewers to make any determination and their safety remains unproven. In addition, FDA concluded in their review that at least 26 of the reviewed feed additives do not satisfy even the safety standards set by FDA in 1973.
The documents that NRDC obtained were generated within the FDA from a program that was created in 2001 and discontinued in 2010. It evaluated feed additives (the main route of routine administration for antibiotic doses used for weight gain or protection from farm conditions), already on the market, against two existing standards: safety standards set in 1973, and guidelines for evaluating new animal drugs that were published in 2003.
NRDC’s findings, first on the 1973 standards:
Of the 30 reviewed antibiotic feed additives, 26 have never met the safety criteria established by FDA in 1973… Three other antibiotic additives were found not to have met the 1973 safety requirements (and thus were not proven to be safe), although the requirements may not have applied. Of the 30 reviewed feed additives, only one was found by FDA (in 1986) to meet the 1973 safety standards; however it was found to have failed the agency’s standard for efficacy.
And on the 2003 standards:
When these previously approved antibiotic feed additives were evaluated against the FDA’s 2003 antimicrobial safety guidelines (Guidance #152) for the evaluation of a new animal drug, the agency found that 18 of the 30 antibiotic feed additives posed a high risk of exposing humans to antibiotic-resistant bacteria through the food chain… For the remaining 12 additives, the drug manufacturers had not provided sufficient evidence for FDA to even determine the level of risk for human health posed by the additives, let alone to determine that the additives are safe as used. Thus, none of the 30 reviewed feed additives could likely be approved in their current forms today.
Within the report, NRDC pieces together document trails for the feed additives, tracing the back-and-forth in which FDA’s reviewers asked for additional data from manufacturers and did not receive it. Here’s one (“sponsor” refers to the manufacturer; in the report, each sentence is footnoted to a separate document):
In 1997, the FDA asked the sponsor to voluntarily withdraw (the formulation Penicillin G Procaine 50/100) due to increased concern from public officials and members of the health care community regarding the emergence of antimicrobial resistance. In the same letter, the FDA stated that the product failed to meet antimicrobial-resistance safety criteria. In its review, FDA noted increased microbial resistance was observed when the antibiotic feed additive was administered in feed to animals. The sponsor apparently disputed this finding, yet the FDA documents do not contain any other studies to address the safety issue. FDA sent another letter to the sponsor in 2004 laying out its concerns about resistance. The record does not show that the sponsor submitted any new studies. FDA never required the sponsor to take the antibiotic feed additive off the market, and it is still sold as a growth promoter in feed.
The obvious important point made by this report is that compounds are being used in agriculture about which federally contracted scientists — usually a conservative bunch — have raised repeated concerns. But what is also important — and you could view this as reassuring, or scandalous, or both at the same time — is precisely that those concerns were raised over years. It’s been clear that some of the inaction over misuse of farm antibiotics has been due to Congressional interference with the FDA’s mission (see the timeline in this post for details). These documents establish the degree to which drug manufacturers were resisting the FDA as well.