Extra-Label Drug Use Requirements

Extra-label drug use (ELDU) is common in backyard poultry given the limited number of FDA-approved drugs for non-commercial poultry. The Animal Medicinal Drug Use Clarification Act (AMDUCA) of 1994 permits veterinarians to use/prescribe medications in an extra-label manner under certain conditions. Those conditions can be found in 21 CFR 530 and include: the veterinarian must have a valid veterinary-client-patient relationship; ELDU is limited to situations where the health of the animal is threatened or where the animal may die or suffer without treatment; only Food and Drug Administration (FDA)-approved animal or human drugs may be used ELDU; there is no animal drug approved for the intended use, or the approved drug for intended use does not contain the needed active ingredient/dosage form/concentration, or the veterinarian has found the FDA-approved drug to be clinically ineffective; a scientifically based extended withdrawal interval is required.

Additionally, the FDA has prohibited certain drugs from extra-label use if an acceptable analytical method has not been or cannot be established or the extra-label use poses a risk to human health, such as allergic reactions or antimicrobial resistance. Drugs and drug classes that are prohibited from extra-label drug use in poultry include:

• Chloramphenicol
• Clenbuterol
• Diethylstilbestrol
• Fluoroquinolones (i.e., enrofloxacin, ciprofloxacin, etc.)
• Nitroimidazoles (i.e., ipronidazole, dimetridazole, metronidazole, etc.)
• Glycopeptides (i.e., vancomycin)
• Nitrofurans (i.e., furazolidone, nitrofurazone, etc.)
• Cephalosporins and adamantane and neuraminidase inhibitors (i.e., amantadine, oseltamivir, etc.).

Common ELDU Questions and Cases in Poultry

Indexed Drugs

Case 1: A veterinarian has a patient considered to be a pet chicken by the owner and would like to administer deslorelin 4.7 mg implant SC to stop egg production due to reproductive disease.

In the United States, the deslorelin 4.7 mg implant is an indexed drug for use in ferrets. Indexed drugs are drugs for use in minor species who have had their animal safety and effectiveness confirmed through an alternate FDA review process. This process allows the indexed drug to obtain legal marketing status; however, they are not FDA approved. Since indexed drugs are not FDA approved, under the guidelines of AMDUCA they are not permissible for extra-label drug use. Additionally, all indexed products carry the warning statements: “Extra-label use is prohibited” and “This product is not to be used in animals intended for use as food for humans or other animals.” Although the patient in this case is considered to be a pet by the owners, because it is a chicken (a FDA-designated major species), it is still considered a food-producing animal. Information regarding FDA-indexed drugs can be found at www.fda.gov/animal-veterinary/minor-useminor-species/drug-indexing.

Products Listed as Generally Regarded as Safe (GRAS) or Not on the FDA GRAS List

Case 2: An owner applied a topical spray containing gentian violet on the foot of a chicken and is asking their primary veterinarian to provide a withdrawal interval recommendation.

One issue with this case is that topical sprays containing gentian violet are not FDA approved, and, therefore, not permissible under AMDUCA to be used in an extra-label manner. Additionally, FDA has determined that gentian violet is not a product that is considered generally recognized as safe and effective for any veterinary drug use in food animals (Title 21 CFR part 500.30). Information regarding FDA’s designation as generally regarded as safe can be found at: www.fda.gov/food/food-ingredients-packaging/generally-recognized-safe-gras, and a database of these products can be found at www.cfsanappsexternal.fda.gov/scripts/fdcc/?set=SCOGS.

Prohibited Drugs for Use in Food Animals

Case 3: A pet layer presented with severe pododermatites of the left third digit. Unfortunately, despite trimethoprim-sulfa and amoxicillin trihydrate/clavulanic acid, the infection spread and the digit was amputated. The infection spread to the carpal/metacarpal region, and the patient is worsening. A culture was done and the results are listed below. This indoor pet chicken was never intended for the food chain, and the owner was very attached.

• Isolate 1: E. coli 4+
• Isolate 1 MIC:
  • Amoxicillin R 2
  • Amoxicillin-clavulanic acid R 2
  • Cephalexin R 8
  • Cefpodoxime S <=0.25
  • Cefovecin S <=0.5
  • Ceftazidime S <=0.12
  • Ceftiofur S <=1
  • Imipenem S <=0.25
  • Amikacin S <=2
  • Gentamicin S <=1
  • Ciprofloxacin S <=0.06
  • Enrofloxacin S <=0.12
  • Marbofloxacin S <=0.5
  • Doxycycline R 1
  • Chloramphenicol S <=2
  • Trimethoprim/sulfamethoxazole S <=20

Based on the isolated organism’s sensitivity panel, the only available options for oral treatment were cephalosporins, fluoroquinolones, chloramphenicol, and trimethoprim/sulfa, which had already been tried. Since this patient was a chicken, it was considered a major species food-producing animal and, therefore, FDA’s rules and regulations regarding drug use in food animals must be adhered to. In addition, there aren’t any exceptions for food animals that are considered by owners as “companion animals” or “pets.” Chloramphenicol is a prohibited drug and cannot be used in food-producing animals and was not an option. Extra-label use of both fluoroquinolones and cephalosporins are also prohibited in major food animal species such as chickens. Many of the prohibitions on ELDU are related to antimicrobial resistance, and backyard flocks can become a source of resistant bacteria. Another concern is the end fate of the bird, as there could be a transfer of ownership or the owner dies and the heir is unaware of the drug use history.

Under the provisions of 21 CFR 530, the FDA recognizes the professional judgment of veterinarians and permits the extra-label use of drugs by veterinarians under certain conditions. Extra-label use of drugs may only take place within the scope of a valid veterinary-client-patient relationship and is limited to circumstances when the health of an animal is threatened or suffering or death may result from failure to treat. Given ELDU options, for this case, amikacin could be considered for treatment.