The purpose of this page is to provide information on the legal requirements for livestock producers to use drugs in food-producing animals to students enrolled in VMS 361 Agricultural Animal Health. I am not a lawyer and this page is not intended to provide legal advice to producers or veterinarians. This document may not be current in the specifics as this law changes over time when the FDA adapts to new scientific findings, changes in livestock husbandry and market conditions. Please note that some of the following is in part my attempt to interpret what some might call "gobbledygook".

Key Point:

Producers must use drugs according to the label on the container. Any usage contrary to the label by a producer is illegal under U.S. law. This label may be the manufacturer's label, which is approved by the FDA, or the label applied by the prescribing veterinarian.

Note that the FDA is responsible for the approval and licensing of livestock drugs and the USDA is responsible for the approval and licensing of livestock vaccines.

• Species the drug is approved for use in (cattle, swine, lactating cattle, etc.)
• Diseases or conditions for which the drug is approved
• Dosage (amount of drug to be used per treatment)
• Frequency (number of times to treat, i.e., once per day, three times per day, etc.)
• Route(s) of administration (e.g., oral, intramuscular, subcutaneous, intramammary, topical)
• Duration of treatment
• Withdrawal time (time from last treatment before products from the animal can be harvested)
• Precaution or warnings (possible adverse reactions)

OTC ("over-the-counter") drugs:

These drugs are available to producers from many sources, such as feed stores. However, they can be used only according to the manufacturer's label unless directions for extra-label use are given on another label by a veterinarian within a valid veterinary-client-patient relationship.

The key to the classification of a drug as OTC rather than prescription is whether or not the manufacturer can develop instructions that an animal owner can understand and follow without serious consequences to the owner, the animal or the consumer of animal products.

Note: Under the law if such instructions can be written, they must be and the drug must be classified as an OTC drug.

Prescription ("legend") drugs:

These drugs can only be purchased and used under the guidance of a licensed veterinarian in a valid VCPR (veterinary - client - patient relationship) with the producer. The producer can use these drugs only according to the label on the drug container, whether applied by the manufacturer or prescribing veterinarian.

By U.S. law, all such drugs have exactly the following legend on the container and the package insert:

Caution: Federal (US) law restricts this drug to use by or on the order of a licensed veterinarian.

Any other variation, such as "for sale to licensed veterinarians only", is for the company's marketing purposes only.

A valid VCPR exists when all of the three following conditions have been met:

1. The veterinarian has assumed the responsibility for:

Making clinical judgments regarding the health of animals and the need for medical treatment

The client has agreed to follow the veterinarian's instructions

2. The veterinarian has sufficient knowledge of the animals to initiate at least a preliminary diagnosis.

This means that the veterinarian must have recently seen and is personally acquainted with the keeping and care of the animals by either:

• Exam of the animal(s)
• Medically appropriate and timely visits to the premises of the animal.

3. The veterinarian is readily available for follow-up evaluation or has arranged for emergency coverage in case of adverse reactions or failure of the treatment regimen.

For the veterinarian to use or to prescribe the use of any drug "off-label" or "extra-label" in food animals, the following criteria must be met:

• The drug is an approved animal (NADA) or human drug.

Drugs that do not have a NADA or that are not approved human drugs cannot be used.

• Only when an animal's health is threatened or the animal is suffering.
• Only for therapeutic purposes or therapeutic preventive medicine.

Drugs cannot be used off-label for purposes of production or reproduction.

• A careful diagnosis or evaluation of the condition for which the drug will be used.
• Either:

No approved drug labeled for such use or that contains the same drug in the dosage form and concentration exists.

If an approved drug exists, the veterinarian must find within a valid VCPR that the approved drug is clinically ineffective for its intended use.

• The producer carefully maintains identity of the treated animals.
• Establish an extended withdrawal period supported by appropriate scientific information.

If nothing in the literature enables the veterinarian to predict withdrawal times, then either that drug cannot be used or the animal cannot be used to produce food.

• Treatment records, including animal identity and condition treated, are maintained by the producer for 2 years and, where possible, the veterinarian.
• May be used in water but not in or on feed.

On-line FDA AMDUCA Materials for further information:

• FDA Center for Veterinary Medicine AMDUCA
• Federal Register 61(217) Nov. 7, 1996 (Final AMDUCA Rule)

Note that under any circumstance the producer can only use a drug according to its label, whether the label is applied by the manufacturer or by the prescribing veterinarian.

• Name, Address, Phone number of veterinarian prescribing the drug.
• Identification of animals treated and species where possible.
• Date of treatment or dispensing of drug.
• Name and quantity of drug
• Dosage and duration directions for use.
• Cautionary statements
• Expiration date
• Slaughter withdrawal and/or milk withholding times.

• Chloramphenicol
• Clenbuterol
• Diethylstilbestrol (DES)
• Dimetridazole
• Fluroquinolones (except as specifically approved)
• Furazolidone 
• Ipronidazole
• Glycopeptides
• Nitrofurazone 
• Phenylbutazone (female dairy cattle 20 months of age or older)
• Sulfonamides in lactating dairy cows, except those specifically approved.

For examples of FDA's actions and resulting penalties when producers or veterinarians violate these provisions, see the "Regulatory Activities" section news items in the issues of the bi-monthly FDA Veterinarian

The treatment described in the article includes estradiol, progesterone, dexamethazone, prolactin, and placental lactogen, none of which are approved by the FDA for this use.

Is this extra-label drug use legal for producers and veterinarians under AMDUCA?

Response from an FDA Center for Veterinary Medicine official:

"These compounds are new animal drugs as defined by the Federal Food, Drug, and Cosmetic Act (the Act), and must have pre-market approval by the Food and Drug Administration (FDA) for commercial marketing and use. These drug compounds are not labeled and approved by the FDA to initiate mammary growth and lactation."

"AMDUCA allows veterinarians to prescribe extra-label uses of approved animal drugs and approved human drugs for animals. AMDUCA provides that the extra-label use of approved animal drugs and human drugs must be in accordance with conditions established by the Secretary of Health and Human Services." - - - "The purpose of those regulations is to establish the conditions for extra-label use. 21CFR Part 530.2 clearly states that extra-label use is limited to treatment modalities when the health of an animal is threatened or suffering or death may result from failure to treat."

"AMDUCA does not extend extra-label use to production or reproduction uses. Initiating mammary growth and lactation are production claims. Use of these products in this manner, whether under a veterinarian's control or not, is not permitted under AMDUCA and would cause the drugs to be adulterated in violation of the Act."

As Baytril 100 is a legend drug, it must be prescribed by a veterinarian in a valid VCPR. This drug is unusual in that the law expressly forbids any extra-label use under any circumstances by anyone. (21CFR530.41)

Label:

• Species Approved: Cattle only (not for use in cattle intended for dairy production or in calves to be processed for veal)
• Disease: Only for treatment of bovine respiratory disease associated with Pasteurella haemolytica, P. multocida, Haemophilus somnus
• Dosage: Only the approved dosage rates on the label
• Frequency of Treatment: Only those listed on the label
• Route of Administration: Subcutaneous injections only
• Withdrawal Time: Animals must not be slaughtered within 28 days of the last treatment
• Warning: Do not use in cattle intended for dairy production > 20 months of age or in calves to be processed for veal.

This product cannot be used in an extra-label manner by anyone!

• Can only be used as therapy for respiratory disease in cattle.
• Cannot be used to treat foot rot, pinkeye, calf scours, or other diseases.
• Can be used only according to the label.
• Cannot be used in sheep, dairy cows, etc.
• Cannot be given intramuscularly, or intravenously.
• Cannot be used at different dosage rates or frequency from those listed on the label.
• Cannot be used to treat calf scours or other diseases not listed on the label.

Note:

The FDA Milk Safety Branch Pasteurized Milk Ordinance (PMO) places additional requirements on how drugs are stored and used on dairy farms producing Grade A milk. For example, drugs for lactating cows must be stored separately from drugs for non-lactating animals and clearly marked as different.

The 2005 Grade A Pasteurized Milk Ordinances are available at as html  or Adobe pdf documents (table of contents)

Additional On-line Information:

For a general summary of FDA jurisdiction and the laws, see "FDA and the Veterinarian"

On-line FDA AMDUCA Materials for further information:

• FDA Center for Veterinary Medicine AMDUCA
• Federal Register 61(217) Nov. 7, 1996 (Final AMDUCA Rule)

Important FDA Updates:

• ECP Not Approved for Use in Animals
• FDA Order Prohibits Extralabel Use of Phenylbutazone in Certain Dairy Cattle
• EXTRA-LABEL USE OF BAYTRIL 100 PROHIBITED, INCLUDING USE IN DAIRY CATTLE OR VEAL CALVES
• HUMAN DRUG PRODUCT NOT EQUIVALENT TO VETERINARY CEFTIOFUR
• COLLOIDAL SILVER NOT APPROVED
• FDA ORDER PROHIBITS EXTRALABEL USE OF FLUOROQUINOLONES AND GLYCOPEPTIDES

Animal Drugs @ FDA - FDA NADA Database of Approved Animal Drug Products

FDA Approved Animal Drug Products Online Database System NADA / ANADA

MUMS - Animal Drugs for Minor Uses and Minor Species

FDA MUMS

Residue avoidance:

• The Judicious use of antimicrobials for dairy producers (FDA, pdf)
• Dairy 10-Point Quality Control Program Mastitis Treatment Records (NebGuide G1666 html)
• Milk and Dairy Beef Residue Prevention Protocol (ppt slides)
• DQA Milk & Dairy Beef Quality Assurance Program - catalog of materials

AVMA on-line information for veterinary practitioners

• AMDUCA Reference
• AMDUCA Algorithm
• Extra-label Drug Use brochure (pdf)
• MUMS Issues

Counterfeit Drugs:

• Counterfeit Drugs: Coming to a Pharmacy Near You (2006, html)
• The Global Threat of Counterfeit Drugs: Why Industry and Governments Must Communicate the Dangers (Cockburn, R et al., PLoS Medicine 1(4), 2005, html)
• Matrix of Drug Quality Reports in USAID-assisted Countries (7/06, pdf  USP page)

Note: Thanks to Dr. Mike Apley, then of Iowa State Univ. and now of Kansas State Univ., for his comments on the first version of this page. Please note that responsibility for any misinterpretations rests squarely with me.