The Ins and Outs of Extra-Label Drug Use in Animals: A Resource for Veterinarians

As a practicing veterinarian, you’ve likely prescribed a drug for an extra-label use. What does that mean? What gives you the legal ability to do so? What conditions must you meet? By explaining FDA’s requirements for extra-label drug use in animals, this article answers these questions and more.

In 1994, Congress enacted the Animal Medicinal Drug Use Clarification Act (AMDUCA), adding provisions to the Federal Food, Drug, and Cosmetic Act (FD&C Act) that give veterinarians the legal ability - with certain restrictions - to use approved human and animal drugs in an extra-label manner. This means, in some cases, you can use an approved drug in a way that isn’t listed on the drug’s labeling. Information about extra-label drug use is not on the approved label - it is a use that's "off of the label".

As a veterinarian who prescribes drugs in an extra-label manner, you need to understand FDA’s requirements for extra-label drug use, as stated in the FD&C Act and FDA regulations. You should also educate your clients, particularly food animal producers, on these requirements.

Extra-Label Drug Use in Animals

Before Congress passed AMDUCA in 1994, federal law did not permit extra-label drug use in animals. The AMDUCA provisions amended the FD&C Act to allow the use of approved human and animal drugs for extra-label uses in animals under specified conditions. The key points addressed in AMDUCA and the regulations established by FDA are:

Valid Veterinarian-Client-Patient Relationship
General Conditions for Extra-Label Drug Use
Conditions for Extra-Label Drug Use in Food-Producing Animals
Compounding
Drugs Prohibited from Extra-Label Uses in Animals

We’ll look at each point separately.

Valid Veterinarian-Client-Patient Relationship

The AMDUCA provisions of the FD&C Act allow extra-label drug use only on the lawful order of a licensed veterinarian in the context of a valid veterinarian-client-patient relationship. FDA regulations in Title 21 of the Code of Federal Regulations Part 530.3 (21 CFR 530.3) define a valid veterinarian-client-patient relationship as one in which:

you have assumed responsibility for making medical judgments about the health of an animal, or animals, and the need for medical treatment. In turn, the client (the owner or other animal caretaker) has agreed to follow your instructions;
you have sufficient knowledge of the animal, or animals, to form at least a general or preliminary diagnosis of the medical condition; and
you are readily available for follow-up in case of adverse reactions or treatment failure.

The definition states that such a relationship can exist only when you have recently seen and are personally acquainted with the keeping and care of the animal or animals by virtue of examination of the animal or animals and/or medically appropriate and timely visits to the premises (usually the case for food-producing animals), where the animals are kept.

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General Conditions for Extra-Label Drug Use

FDA’s requirements for extra-label drug use in animals limits this use to situations where an animal’s health is threatened or where the animal may suffer or die without treatment. This means that you cannot use a drug for a non-therapeutic purpose (i.e., production purpose) in an extra-label use manner. Also, the regulations limit extra-label use to situations where there is no approved new animal drug that is labeled for such use and that contains the same active ingredient in the dosage form and concentration that is required, except in situations where you find the approved new animal drug is clinically ineffective for its intended use.

Be aware that extra-label use is prohibited for conditionally approved and indexed animal drugs. You cannot prescribe these drugs for any extra-label use.

Thorough recordkeeping is vital. You must maintain records that identify the treated animal or animals. For food-producing animals, this can be done on a group, herd, flock, or per-client basis. The records must include the:

established name of the drug and its active ingredient, or if formulated from more than one ingredient, the established name of each ingredient. Ordinarily, the established name of the drug is the name listed in the United States Pharmacopeia (USP) and is made up of the active ingredient, route of administration, and dosage form (for example, “fenbendazole oral suspension”);
condition treated;
animal species treated;
dosage administered;
treatment duration; and
number of animals treated.
For food-producing animals, the records must include the specified withdrawal, withholding, or discard time(s), if applicable, time for food products made from treated animals, such as meat, milk, and eggs.

You must keep these records for two years or as otherwise required by federal or state law, whichever is longer and permit FDA to, at all reasonable times, have access to, permit copying and verify such records.

Thorough labeling is critical. The labeling for a drug dispensed on your order for an extra-label use must state your name and address. If the drug is dispensed by a pharmacy on your order, the labeling must state your name and the name and address of the dispensing pharmacy. The labeling must also include information similar to what is required in the record:

established name of the drug or, if formulated from more than one ingredient, the established name of each active ingredient. As mentioned above, the established name of the drug typically is the name listed in the USP and is made up of the active ingredient, route of administration, and dosage form (for example, “fenbendazole oral suspension”);
directions for use, including: the class/species or identification of the animal or herd, flock, pen, lot, or other group of animals being treated; the dosage, frequency, and route of administration; and the duration of the therapy; and
any cautionary statements (for example, “Not for use in veal calves”).
For food-producing animals, the drug labeling must also include your specified withdrawal, withholding, or discard time for meat, milk, eggs, or any other food which might be derived from the treated animal or animals.

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Conditions for Extra-Label Drug Use in Food-Producing Animals

If you’re a food animal veterinarian, you should be aware of the additional requirements for extra-label drug use in food-producing animals. Before prescribing or dispensing any approved human or animal drug for an extra-label use in food-producing animals, you must:

carefully diagnose and evaluate the condition for which the drug is to be used;
institute procedures to ensure the identity of the treated animal or animals is carefully maintained;
establish a substantially extended withdrawal period supported by appropriate scientific information. You may get this information from such sources as scientific literature, academia, or the Food Animal Residue Avoidance Databank (FARAD); and
take measures to assure withdrawal periods are met and no illegal drug residues occur in the treated animal or animals.

If you want to use a drug approved for people or a drug approved only for companion animals in food-producing animals, you must have:

an appropriate medical rationale doing so, and
scientific information on the safety of the drug in food products for people. If you do not have scientific information on the safety of the drug in food products for people, then you must take appropriate measures to assure the animal and its food products will not enter the human food supply.

Remember, you may not prescribe an approved human drug for food-producing animals if there’s an animal drug approved for food-producing animals that you can prescribe instead.

The FD&C Act doesn’t allow the extra-label use of any drug in animal feed. However, for some minor species, you may determine that the extra-label use of a drug in animal feed is needed to prevent suffering and death in these animals. (Minor species are all animals that aren’t one of the seven major species: cattle, horses, swine, chickens, turkeys, dogs, and cats.) Please refer to FDA’s Compliance Policy Guide, which describes FDA's current thinking on the extra-label use of over-the-counter and Veterinary Feed Directive medicated feeds for minor species.

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Compounding

FDA’s extralabel use regulations also address the compounding of animal drugs from an approved animal or human drug. This compounding is permitted under specific circumstances listed in 21 CFR 530.13(b). Animal drugs compounded from already approved animal and human drugs are considered an extra-label use and, as such, as long as the regulations in part 530 are met, would not result in the compounded drug being considered “unsafe” and therefore adulterated under the FD&C Act. However, FDA’s extralabel use regulations specifically state that, “[n]othing in this part shall be construed as permitting compounding from bulk drugs.” Thus, compounding animal drug from bulk drug substances results in an unapproved animal drug.

For more information about FDA’s policy regarding animal drugs compounded from bulk drug substances, see "Guidance for Industry #256, Compounding Animal Drugs from Bulk Drug Substances." More information may also be found at Animal Drug Compounding.

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Drugs Prohibited from Extra-Label Uses in Animals

Under certain circumstances, FDA can prohibit extra-label uses of certain drugs in animals. The following drugs (both human and animal), families of drugs, and substances are prohibited from extra-label uses in all food-producing animals:

Chloramphenicol
Clenbuterol
Diethylstilbestrol (DES)
Dimetridazole
Ipronidazole and other nitroimidazoles
Furazolidone and nitrofurazone
Sulfonamide drugs in lactating dairy cattle, except for the approved use of sulfadimethoxine, sulfabromomethazine, and sulfaethoxypyridazine
Fluoroquinolones
Glycopeptides
Phenylbutazone in female dairy cattle 20 months of age or older
Cephalosporins (not including cephapirin) in cattle, swine, chickens, or turkeys:
- For disease prevention purposes;
- At unapproved doses, frequencies, durations, or routes of administration; or
- If the drug is not approved for that species and production class.

The following drugs, or classes of drugs, that are approved for treating or preventing influenza A are prohibited from extra-label uses in chickens, turkeys, and ducks:

Adamantane
Neuraminidase inhibitors

The above list can be found in Section 530.41 of Title 21 of the Code of Federal Regulations (Drugs prohibited for extra-label use in animals). Currently, no approved drugs are prohibited from extra-label uses in companion animals.

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Conclusion

The Animal Medicinal Drug Use Clarification Act of 1994 added provisions to the Federal Food, Drug, and Cosmetic Act authorizing the extra-label use of approved human and animal drugs in animals under certain conditions. You can ensure proper extra-label use by complying with FDA’s requirements and by understanding what’s allowed and what’s not under the law.

For more information, please call FDA’s Center for Veterinary Medicine at 240-402-7002, or email AskCVM@fda.hhs.gov.

Relevant Guidance Documents

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