FDA Veterinarian Newsletter March/April 2003 Volume XVIII, No 2, by Gillian Comyn, D.V.M., M.P.H., D.A.C.V.P.M.Introduction
Since 1994, when Congress passed the Animal Medicinal Drug Use Clarification Act of 1994 (AMDUCA), veterinarians in the U.S. have enjoyed legitimate extra-label use (ELU) privileges. Veterinarians can safeguard ELU privileges by following AMDUCA, and by educating clients (particularly food animal producers) on AMDUCA and prudent drug use principles. This article outlines key points of AMDUCA in plain language.
Animal Medicinal Drug Use Clarification Act
Extra-label drug use (ELU) refers to the use of an approved drug in a manner that is not in accordance with the approved label directions. ELU of new animal drugs was considered illegal and permitted only as a matter of enforcement discretion until the passing of AMDUCA. AMDUCA amended the Federal Food, Drug, and Cosmetic Act (the Act), legalizing extra-label drug use by and under the order of a licensed veterinarian within the context of a valid veterinarian-client-patient relationship, and became effective in 1996 when implementing regulations (21 CFR Part 530) were published.
AMDUCA allows veterinarians to prescribe extra-label uses of certain approved animal drugs and approved human drugs for animals under specified conditions.
The key components and conditions of AMDUCA1 are as follows:
- Veterinarian-Client-Patient Relationship (VCPR)
- General Conditions for Extra-Label Use Under AMDUCA
- Conditions for Extra-Label Use in Food Animals
- Compounding Under AMDUCA
- Prohibitions Under AMDUCA
The regulation defines a valid veterinarian-client-patient relationship as one in which:
- A veterinarian has assumed the responsibility for making medical judgments regarding the health of (an) animal(s) and the need for medical treatment, and the client (the owner of the animal or animals or other caretaker) has agreed to follow the instructions of the veterinarian;
- There is sufficient knowledge of the animal(s) by the veterinarian to initiate at least a general or preliminary diagnosis of the medical condition of the animal(s); and
- The practicing veterinarian is readily available for follow-up in case of adverse reactions or failure of the regimen of therapy. Such a relationship can exist only when the veterinarian has recently seen and is personally acquainted with the keeping and care of the animal(s) by virtue of examination of the animal(s), and/or by medically appropriate and timely visits to the premises where the animal(s) are kept.
- There is no animal drug approved for the intended use;
- Or, there is an animal drug approved for the intended use, but the approved drug is not in the required dosage form or concentration;
- Or, the approved drug has been found to be clinically ineffective when used as labeled;
- Or, if the intended use is in a non-food animal, an approved human drug can be used even if an approved animal drug is available.
- In food animals, use of approved human drugs is not permitted if (an) approved animal drug(s) can be used.
- RECORDKEEPING: The veterinarian must maintain records with animal identification (in food animal practices, on a group, herd, flock, or per-client basis). The records have to include: established name of the drug and its active ingredient, or if formulated from more than one ingredient, established name of each ingredient; condition treated; species of the treated animal(s); dosage administered; treatment duration; number of animals treated; and withdrawal, withholding, or discard time(s), for meat, milk, eggs, or any food from the animals treated. The veterinarian must keep these records for 2 years or as required by Federal or State law, whichever is greater. The records must be available at any reasonable times to FDA designated personnel, for copying and verifying.
- LABELING: The label on a drug dispensed for ELU,
whether by a veterinarian or dispensed by a pharmacist on the order of a
veterinarian, must have the following information: name and address of the
prescribing veterinarian (and the pharmacy if dispensed this way). Also, the
labeling must have on it the following:
- animal identification (individual for companion animals, or group or pen if food animal),
- indication (what condition is the drug being used to treat),
- number of animals treated (in the case of food animals),
- dosage, route, and duration of treatment,
- withdrawal intervals, and,
- any cautionary statements (for example: not for use in horses intended for food).
- AMDUCA does not allow extra-label drug use in animal feeds.
- AMDUCA does not permit veterinarians, or pharmacists, to compound unapproved finished new animal drug products from bulk drugs
- Before prescribing or dispensing an approved new
animal or human drug for an extra-label use in food animals, the veterinarian
- make a careful diagnosis and evaluation of the conditions for which the drug is to be used;
- provide an estimated, scientifically-based, withdrawal interval for the milk, meat, eggs, or other edible products from the treated animal (this information may be obtained by the veterinarian in context of a VCPR from among other sources, scientific literature, academia, or the Food Animal Residue Avoidance Databank (FARAD)2 ;
- make sure that the identity of the treated animal or animals is maintained;
- take measures to assure that assigned timeframes for withdrawal are met and no illegal drug residues occur in any food-producing animal subjected to extra-label treatment.
- When considering extra-label use of an approved
human drug in food animals:
- the veterinarian must have medical rationale for the use;
- the veterinarian may not use an approved human drug if an animal drug approved for use in food-producing animals can be used instead for the particular ELU; 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.
FDA defines compounding as the manipulation of drugs to obtain products that differ from the starting materials in an approved dosage form drug. Under AMDUCA, compounding is considered to be extra-label drug use, and must be done from approved finished dosage form human or animal drugs only. Like any extra-label use, compounded drugs should not be used if an approved drug can be used at its approved dose and dosage form. AMDUCA does not permit veterinarians, or pharmacists, to compound unapproved finished new animal drug products from bulk drugs. Unless conditions set forth in 21 CFR 530.13(b) are met, the compounding of a new animal drug from an approved human or animal drug results in an adulterated new animal drug.
Conditions for Compounding
- all relevant portions of the regulation have been complied with;
- there is no approved new animal or approved new human drug that when used as labeled or in the available dosage form and concentration, will properly treat the condition diagnosed. Compounding from a human drug for use in food-producing animals will not be permitted if an approved animal drug can be used for the compounding;
- the compounding is performed by a licensed pharmacist upon the order of a veterinarian or by a veterinarian within the scope of their professional practice;
- adequate procedures and processes are followed that ensure the safety and effectiveness of the compounded product;
- the scale of the compounding operation is commensurate with the established need for compounded products (e.g., similar to that of comparable practices); and
- all relevant State laws relating to the compounding of drugs for use in animals are followed.
As described above, AMDUCA allows FDA to place limits on certain extra-label drug uses in animals. These limits include prohibitions of certain extra-label uses. Though The Act provides a stepwise procedure leading to a prohibition, the Agency does not have to take all the steps before prohibiting an extra label use if it finds that the extra-label drug use “presents a risk”.
When assessing the risk from an extra-label drug use, the Agency may inspect a veterinarian’s records. The purpose of the inspection is to document the extent and nature of the extra-label use, not for enforcement reasons. The Agency provides informal public notice when it makes such a finding. If the Agency finds that an extra-label drug use presents a risk, or a required analytical method has not been developed, the Agency may prohibit the use. Any new prohibition ordered by the Agency will be published in the Federal Register, with a ninety-day delayed effective date and a sixty-day comment period. The order will be effective in ninety days, unless it is revoked or modified, or the comment period is extended. When a prohibition or any other important regulatory change is codified, the notice is posted immediately on the CVM web site and disseminated through printed media (FDA Veterinarian, veterinary and trade journals and other sources).
The Current List of Drugs Prohibited From Extra-Label Use (As listed in 21 CFR 530.41)
These drugs (both animal and human), families of drugs, and substances are currently prohibited for extra-label uses in all food-producing animals, (including horses intended for human food):
- Diethylstilbestrol (DES)
- Ipronidazole and other nitroimidazoles
- Furazolidone, Nitrofurazone, other nitrofurans
- Sulfonamide drugs in lactating dairy cattle (except approved use of sulfadimethoxine, sulfabromomethazine, and sulfaethoxypyridazine)
AMDUCA legalized extra-label use of approved animal and human drugs in animals when that use is under the supervision of a veterinarian and in accordance with FDA regulations. AMDUCA provided veterinarians with privileges comparable to those generally enjoyed by physicians. Veterinarians can protect these privileges by complying with AMDUCA, and understanding the permitted and prohibited extra-label drugs and uses (including compounding).
For more information on AMDUCA, other regulations and policies, and to request hard copies, please visit the CVM Home Page, and look under Quick Index. Notices of proposed rulemaking and final rules, such as additions to prohibited drug list, are announced by Federal Register notices and posted on the CVM Home Page and the FDA Dockets Advanced Publication Display website.
Dr. Comyn is a Consumer Safety Officer in CVM’s Division of Compliance.
Article is found at FDA website located here.