Extralabel Use of FDA Approved Drugs in Animals
Limitations to Extralabel Use Provisions of AMDUCA
Extralabel Use in Food-Producing Animals
Labeling of Drugs Prescribed for Extralabel Use
Prohibitions Under AMDUCA
Compounding Under AMDUCA
The Animal Medicinal Drug Use Clarification Act of 1994 (AMDUCA) permits veterinarians to prescribe extralabel uses of certain approved new animal drugs and approved human drugs for animals under certain conditions. Extralabel use refers to the use of an approved drug in a manner that is not in accordance with the approved label directions. Under AMDUCA and its implementing regulations published at Title 21, Code of Federal Regulations, Part 530 (21 CFR 530), any extralabel use of an approved new animal or human drug must be by or on the lawful order of a veterinarian within the context of a veterinarian-client-patient relationship (VCPR). Extralabel use must also comply with other provisions of 21 CFR 530. A list of drugs specifically prohibited from extralabel use appears in 21 CFR 530.41.
"Extralabel use" is defined as:
"Actual use or intended use of a drug in an animal in a manner that is not in accordance with the approved labeling. This includes, but is not limited to, use in species not listed in the labeling, use for indications (disease and other conditions) not listed in the labeling, use at dosage levels, frequencies, or routes of administration other than those stated in the labeling, and deviation from labeled withdrawal time based on these different uses." (21 CFR 530.3(a))
Under the provisions of 21 CFR 530, the FDA recognizes the professional judgment of veterinarians, and permits the extralabel use of drugs by veterinarians under certain conditions. Extralabel use of drugs may only take place within the scope of a valid VCPR. In the absence of a valid VCPR, if an approved new animal drug is used for a use for which it is not labeled, such use has caused the drug to be deemed unsafe under the Federal Food, Drug and Cosmetic Act (“the Act”) (21 U.S.C. 360b), and therefore adulterated under the Act (21 U.S.C. 351(a)(5)).
An approved animal drug or approved human drug intended to be used for an extralabel use in an animal, other than a use in or on animal feed, is not unsafe under the Act (21 U.S.C. 360b) and is exempt from the labeling requirements under the Act (21 U.S.C. 502(f)), if such use is by or on the lawful written or oral order of a licensed veterinarian within the context of a valid VCPR and such use complies with the extralabel use regulation (21 CFR 530). Extralabel use is limited to circumstances when the health of an animal is threatened, or suffering or death may result from failure to treat. This means that extralabel use to enhance production is not permitted.
In addition to uses which do not comply with the conditions for permitted extralabel use set forth in 21 CFR 530, the following specific extralabel uses included in 21 CFR 530.11 are not permitted and result in the drug being deemed unsafe within the meaning of section 512 of the Act (21 U.S.C. 360b):
- Extralabel use in an animal of an approved new animal drug or human drug by a lay person (except when under the supervision of a licensed veterinarian);
- Extralabel use of an approved new animal drug or human drug in or on an animal feed;
- Extralabel use resulting in any residue which may present a risk to the public health; and
- Extralabel use resulting in any residue above an established safe level, safe concentration, or tolerance.
There are additional specific conditions that must be met for extralabel use of approved animal and approved human drugs in food-producing animals. The following conditions appear in 21 CFR 530.20:
- There is no approved animal drug that is labeled for such use and that contains the same active ingredient in the required dosage form and concentration, except where a veterinarian finds, within the context of a valid VCPR, that the approved animal drug is clinically ineffective for its intended use.
- Before prescribing or dispensing an approved animal drug or approved human drug for an extralabel use in food animals, the veterinarian must:
- Make a careful diagnosis and evaluation of the conditions for which the drug is to be used;
- Establish a substantially extended withdrawal period prior to marketing of milk, meat, eggs, or other edible products supported by appropriate scientific information, if applicable;
- Institute procedures to assure that the identity of the treated animal or animals is carefully maintained; and
- Take appropriate measures to assure that assigned time frames for withdrawal are met and no illegal drug residues occur in any food producing animal subjected to extra-label treatment.
The following additional conditions must be met for a permitted extralabel use, in food producing animals, of an approved human drug, or of an animal drug approved only for use in animals not intended for human consumption:
- Such use must be accomplished in accordance with an appropriate medical rationale; and
- If scientific information on the human food safety aspect of the use of the drug in food producing animals is not available, the veterinarian must take appropriate measures to assure that the animal and its food products will not enter the human food supply.
Extralabel use of an approved human drug in a food producing animal is not permitted if an animal drug approved for use in food producing animals can be used in an extralabel manner for the particular use.
Any drug prescribed and dispensed for extralabel use by a veterinarian or dispensed by a pharmacist on the order of a veterinarian must bear or be accompanied by labeling information adequate to assure the safe and proper use of the drug. (21 CFR 530.12) At a minimum, such information shall include the following:
- The name and address of the prescribing veterinarian. If the drug is dispensed by a pharmacy on the order of a veterinarian, the labeling shall include the name of the prescribing veterinarian and the name and address of the dispensing pharmacy, and may include the address of the prescribing veterinarian.
- The established name of the drug (active ingredient), or, if formulated from more than one active ingredient, the established name of each ingredient.
- Any directions for use specified by the veterinarian (including class/species or identification of the animal(s) being treated; dosage, frequency, and route of administration; and the duration of therapy).
- Any cautionary statements.
- The veterinarian's specified withdrawal, withholding, or discard time(s) for meat, milk, eggs, or any food which might be derived from the treated animal(s).
Under the AMDUCA provisions, FDA has the right to prohibit extralabel uses of certain drugs in animals.
FDA may prohibit the extralabel use of an approved animal drug or approved human drug or class of drugs in food-producing animals if FDA determines that:
- An acceptable analytical method needs to be established and such method has not been established or cannot be established; or
- The extralabel use of the drug or class of drugs presents a risk to the public health.
A prohibition may be a general ban on the extralabel use of the drug or class of drugs or may be limited to a specific species, indication, dosage form, route of administration, or combination of factors. 21 CFR 530.21
FDA may prohibit the extra-label use of an animal or human drug in nonfood-producing animals if FDA determines that such extra-label use presents a risk to the public health. 21 CFR 530.30
A list of drugs, families of drugs, and substances prohibited for extra-label use in animals appears in 21 CFR 530.41.
21 CFR 530.13 provides specific conditions under which extralabel use from compounding of approved animal drugs or approved human drugs is permitted. The compounding must be in compliance with all relevant provisions of 21 CFR 530. The extralabel drug use regulation does not permit animal drug compounding from active pharmaceutical ingredients (bulk drugs).