Questions and Answers regarding Carbadox
1. What is carbadox?
Carbadox 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). 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.
2. What is the current status of the approved animal drug products containing carbadox?
There are three approved New Animal Drug Applications (NADAs) for animal drug products containing carbadox, all held by Phibro Animal Health:
- Mecadox Premix 10 (NADA 041-061); contains carbadox alone
- Banminth/Mecadox (NADA 092-955); contains carbadox plus pyrantel tartrate
- Mecadox/Terramycin (NADA 141-211); contains carbadox plus oxytetracycline
3. How does the FDA regulate carcinogenic animal drugs?
Under the Delaney Clause in section 512 of the Federal Food, Drug, and Cosmetic Act (FD&C Act), the FDA cannot approve a new animal drug application if it “is found to induce cancer when ingested by man or animal….” An exception to this general rule, referred to as the Diethylstilbestrol "DES" Proviso, allows for the approval of a carcinogenic drug if the FDA finds that, under the approved conditions of use, the drug will not adversely affect treated animals and no residues of the drug will be found by an approved regulatory method in any edible tissues of or foods from the animal. All animal drugs must also meet the standards of the General Safety Clause in 512 of the FD&C Act, which requires the agency to find that the drug is safe for both the animal it is intended for and humans who consume food products derived from that animal.
4. What are CVM’s concerns with respect to carbadox?
CVM reviewed data available at the time it approved the 1998 supplemental applications for carbadox 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. Because there is no established relationship between the noncarcinogenic residue quinoxaline-2-carboxylic acid (QCA) measured by the approved method and the residue of carcinogenic concern, the approved method measuring the concentration of QCA in animal tissue does not allow CVM to conclusively determine whether the residue of carcinogenic concern remains in the tissue.
5. Why did CVM propose to revoke the approved method for carbadox?
On July 17, 2020, CVM displayed a proposed order that would, if finalized, revoke the approved regulatory method for carbadox because of FDA’s concern that it does not provide adequate information about carcinogenic residues of the drug. Interested persons had 60 days to comment on the proposed order. On the same day, CVM withdrew a previously published Notice of Opportunity for Hearing (NOOH) in the Federal Register that proposed to withdraw the approval of the drug applications for products containing carbadox.
If the proposed order to revoke the currently approved method is finalized and the approved analytical method is revoked, CVM intends to publish in the Federal Register an NOOH proposing to withdraw approval of all new animal drug applications for use of carbadox based on the lack of an approved method to demonstrate that there is no residue of carcinogenic concern in the edible tissue of treated animals.
6. What is the expected impact of this action on the swine industry?
If the order is finalized and the applications for carbadox ultimately withdrawn, carbadox will no longer be available for use by the swine industry. If this happens, the FDA 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. Pork producers can also work with their veterinarian to implement preventative measures that reduce the need for a drug like carbadox, such as vaccination or changes in husbandry practices.
7. Should consumers stop eating pork products treated with carbadox?
As a general matter, the FDA continues to advise all consumers to eat a well-balanced diet for good nutrition and to minimize potential adverse consequences from consuming an excess of any one food.
The agency recognizes that pork is a common protein in American diets. Although the agency is not recommending that people make changes in their food choices during the time that CVM is working to remove the drug from the market, the agency offers this advice to consumers: Pork is a good source of protein; however, protein can also be found in other meat, poultry, seafood, beans and peas, eggs, processed soy products, nuts and seeds. Select a variety of protein foods to improve nutrient intake and health benefits.
8. Does FDA have information about which pork products come from pigs that were treated with carbadox?
No. Producers are not required to report to the FDA which drugs they use.
9. Why did FDA holding a Part 15 public hearing?
CVM proposed to revoke the approved method for carbadox, which measures quinoxaline-2-carboxylic acid (QCA) as a marker residue to detect the presence of any residue of carcinogenic concern. (Determination of Carbadox (as Quinoxaline-2-Carboxylic [QCA]) Residues in Swine Liver and Muscle Tissues After Drug Withdrawal.) CVM’s proposed order was based on its determination that the method is inadequate to monitor the residue of carcinogenic concern in compliance with FDA's regulations in 21 CFR part 500, subpart E. These regulations set out the requirements for demonstrating that no residues of the drug will be found by an approved regulatory method in any edible tissues of or in any foods obtained from the animal, as required to meet the requirements of the DES Proviso.
FDA regulations provide that the procedures in Part 15 apply when, among other things, the Commissioner concludes that it is in the public interest to permit people to present information and views at a public hearing on any matter pending before the Agency. On March 10, 2022, CVM held a Part 15 public hearing for the public to present scientific data and information related to the residue of carcinogenic concern for carbadox.