In a July 20 Federal Register notice, the Food & Drug Administration's Center for Veterinary Medicine (CVM) proposed an order to revoke the approved method for detecting residues of carbadox, a new animal drug used in swine feed.
CVM noted that an approved method is required by the Federal Food, Drug & Cosmetic Act (FD&C Act), as implemented by regulation, to show that no residue of carcinogenic concern from a new animal drug persists in any edible tissue or in any food derived from treated animals.
The currently approved method measures quinoxaline-2-carboxylic acid (QCA) as a marker residue to detect the presence of any residue of carcinogenic concern.
CVM said it is proposing to revoke the approved method for carbadox based on the agency's determination that it is inadequate to monitor residue of carcinogenic concern in compliance with FDA's operational definition of no residue because there is no established relationship between QCA measured by the approved method and the residue of carcinogenic concern.
In a related notice, CVM announced the withdrawal of a notice of opportunity for a hearing (NOOH) proposing to withdraw the approved uses of carbadox.
If the order to revoke the approved method is finalized, CVM said it intends to publish in the Federal Register an NOOH proposing to withdraw approval of all new animal drug applications for use of carbadox.
Carbadox, sold under the Mecadox trade names by Phibro Animal Health, is an animal drug used in swine (hogs and pigs) for production purposes (e.g., increased rate of weight gain and improved feed efficiency) and therapeutic purposes (e.g., to control swine dysentery and bacterial swine enteritis).
In a "Questions & Answers" post on the CVM website, CVM said carbadox is an animal drug shown to be carcinogenic in laboratory animals. While carbadox is also an antimicrobial, it does not pose the same resistance issues as other antimicrobials and is not considered important to human medicine.
CVM said when it approved the 1998 supplemental applications for carbadox, it reviewed data at that time and made several conclusions about carbadox tissue residues based on that information. However, subsequent human food safety information demonstrates that carcinogenic carbadox residues persist longer than previously known, CVM noted in its "Questions & Answers."
Those interested have 60 days to comment on the proposed orders published in the July 20 Federal Register.
CVM said if the order is finalized and the applications for carbadox is ultimately withdrawn, carbadox will no longer be available for use by the swine industry. If this happens, the agency said it "will work to minimize impacts on the swine industry to the extent possible while ensuring the safety of the food supply. Other drugs are available for controlling swine dysentery and bacterial swine enteritis."
CVM also suggested that pork producers work with a veterinarian to implement preventative measures that reduce the need for a drug like carbadox, such as vaccination or changes in husbandry practices.
In response, Phibro Animal Health noted that carbadox/Mecadox has been approved and sold in the U.S. for more than 45 years and is a widely used treatment for controlling bacterial diseases in swine, including salmonella and swine dysentery, resulting in improved health and welfare for newly born and young pigs.
In 2016, when FDA issued its original NOOH on carbadox, Phibro said it requested a hearing and, over the next four years, continued an ongoing process of responding collaboratively and transparently to CVM inquiries to provide extensive and meticulous research and data confirming the safety of carbadox.
Phibro believes that the evidence submitted to FDA:
- Concludes that no carbadox residues of carcinogenic concern can be detected at the end of the labeled withdrawal period;
- Confirms that carbadox remains a safe drug to control bacterial diseases in swine;
- Increases the collective understanding of the drug’s metabolism, residue characterization and depletion, and
- Reinforces and affirms prior FDA determinations that the use of carbadox is safe as approved.
According to Phibro, in the new published notice, FDA states that it does not agree with Phibro’s scientific conclusions and announced a new process for the review of carbadox, instead of following its own procedure and moving forward with a hearing that would resolve the parties’ differing interpretations of the science supporting the safety of carbadox.
Phibro said it disagrees with the agency’s conclusions, it is disappointed that FDA is taking these steps and the company "stands ready to discuss alternative regulatory methods if FDA believes that the current method is inappropriate."
Phibro has requested to the FDA Office of the Commissioner that the agency continue the process it started in 2016 and proceed with a hearing to review the substantial body of data supporting the safety of carbadox. In addition to the science proving the safety of carbadox, Phibro said it believes the therapeutic efficacy, which has significant animal health and welfare implications, supports the continued use of carbadox.
Phibro noted that it will continue to defend swine producers’ ability to use Mecadox, which remains available for use by swine producers.