FDA's Position on Extra-Label Use of FDA Approved Drugs in Aniimals

Animal Medicinal Drug Use Clarification Act of 1994 (AMDUCA)

The Animal Medicinal Drug Use Clarification Act of 1994 (AMDUCA) allows veterinarians to prescribe extralabel uses of certain approved 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. The key constraints of AMDUCA are that any extralabel use must be by or on the order of a veterinarian within the context of a veterinarian-client-patient relationship, must not result in violative residues in food-producing animals, and the use must be in conformance with the implementing regulations published at 21 CFR Part 530. A list of drugs specifically prohibited from extra-label use appears in the Code of Federal Regulations.
Extra-Label Use of FDA Approved Drugs in Animals
"Extra-label 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."

Under the provisions of the Animal Medicinal Drug Use Clarification Act of 1994, the FDA recognizes the professional judgment of veterinarians, and allows the extra-label use of drugs by veterinarians under certain conditions (21 CFR 530). Any drug used in an extra-label manner is by definition a prescription drug since the involvement of a veterinarian is required. Extra-label use of drugs may only take place within the scope of a valid veterinarian-client-patient relationship (VCPR) [4]. 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 and therefore adulterated under the Act (21 U.S.C. 351(a)(5)).
An approved new animal drug or human drug intended to be used for an extra-label purpose in an animal is not unsafe under the Act (21 U.S.C. 360b) and is exempt from the labeling requirements 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 veterinarian-client-patient relationship and such use complies with the extra-label use regulation (21 CFR Part 530). Extra-label 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 extra-label use to enhance production is prohibited. Extra-label use of drugs may be considered by food animal veterinarians only when:

1. There is no approved new 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 veterinarian client patient relationship, that the approved new animal drug is clinically ineffective for its intended use.
   
2. Before prescribing or dispensing an approved new animal or human drug for an extra-label 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 extra-label 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.
  Extra-label 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 extra-label manner for the particular use.

The prescribed or dispensed extra-label drug (prescription legend or over-the-counter) must bear labeling information which is adequate to assure the safe and proper use of the product.
Labeling of drugs prescribed for extra-label use
At a minimum, the following label information is recommended:

1. The name and address of the prescribing veterinarian.
2. The established name of the drug (active ingredient), or if formulated from more than one ingredient, the established name of each ingredient.
3. Any directions for use specified by the practitioner (including class/species or identification of the animals; dosage, frequency, and route of administration; and, duration of therapy).
4. Any cautionary statements specified by the veterinarian.
5. The veterinarian's specified withdrawal/discard time(s) for meat, milk, eggs, or any food which might be derived from the treated animals.

Because extra-label use of animal and human drugs in nonfood-producing animals (companion, sporting, exotic, etc) does not ordinarily pose a threat to the public health, extra-label use of animal and human drugs is permitted in nonfood-producing animals except where the public health is threatened.
Extra-label use of drugs in treating animals is allowable only by licensed veterinarians within the context of a valid veterinarian-client-patient relationship, and does not include drug use in treating animals by the layman (except under the supervision of a licensed veterinarian).
Lay persons cannot be expected to have sufficient knowledge and understanding concerning animal diseases, pharmacology, toxicology, drug interactions, and other scientific parameters to use drugs in any way other than as labeled.
Limitations to Extra-Label Use Provisions of AMDUCA
In addition to uses which do not comply with the provision set forth in Sec. 530.10, the following specific extra-label uses are not permitted and result in the drug being deemed unsafe within the meaning of section 512 of the Act:

1. Extra-label 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);
2. Extra-label use of an approved new animal drug or human drug in or on an animal feed;
3. Extra-label use resulting in any residue which may present a risk to the public health; and
4. Extra-label use resulting in any residue above an established safe level, safe concentration, or tolerance.

Prohibitions Under AMDUCA
FDA may prohibit the extra-label use of an approved new animal or human drug or class of drugs in animals if FDA determines that:

1. An acceptable analytical method needs to be established and such method has not been established or cannot be established; or
2. The extra-label use of the drug or class of drugs presents a risk to the public health.

A prohibition may be a general ban on the extra-label 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.
Compounding Under AMDUCA
The extra-label drug use regulation also provides for the legal compounding of animal drugs from approved animal drugs and approved human drugs. The compounding must be in compliance with the provisions of the regulation as presented above. The regulation provides additional requirements for extra-label compounding (21 CFR 530.13).
The extra-label drug use regulation does not allow for legal animal drug compounding from active pharmaceutical ingredients (bulk drugs).

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Additional Information

• Sec. 530.41 Drugs prohibited for extralabel use in animals¹

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Page Last Updated: 09/20/2011; source found here