The Food Animal Residue Avoidance Databank (FARAD) recently provided guidance to small ruminant producers and their veterinarians in an article titled “Extralabel drug use (ELDU) in small ruminants” in JAVMA, Vol 253, No. 8, Oct. 15, 2018, pp 1001-1009.

FARAD is a university-based national program that serves as the primary source for scientifically-based recommendations regarding safe withdrawal intervals of drugs and chemicals in food-producing animals. As such, FARAD is a key resource for protection of our nation’s food supply, including meat, milk and eggs, against accidental contamination of animal-derived foods with violative residues of drugs, pesticides or other agents that could compromise food safety.”

FARAD regularly provides guidance to the food animal producing industry and veterinarians regarding “the use of therapeutic drugs, pesticides and other agents that improve overall animal health and promote safe, efficient and humane production practices.”

The purpose of its latest digest, as stated, “was to provide US veterinarians guidance regarding ELDU in small ruminants. The lack of FDA-approved drugs for sheep and goats frequently necessitates ELDU in those species. When the FDA approves a drug for use in a particular species, it establishes a tolerance or that drug in the various tissues or products (eg, milk or eggs) of that species that might be consumed by people. When a drug not labeled for use in a small ruminant is administered in an extralabel manner, there is a zero tolerance for residues of the parent drug or its metabolites in the edible tissues or products of treated animals, and detection of the parent drug or metabolites in any product marketed for human consumption is considered a violation and subject to regulatory action. Given the lack of tolerance and pharmacokinetic and tissue depletion data for many drugs administered in an extralabel manner to small ruminants, extended meat and milk WDIs are generally required to ensure that drug residues are undetectable. Veterinarians need to be cognizant of the requirements for legal ELDU in food-animal species to safeguard the human food supply while continuing to promote the health and welfare of small ruminants.”

As a former owner of a veterinary large animal practice in which 50% of my patients were small ruminants (goats, sheep, alpaca and llama), it was imperative to be able to prescribe or administer drugs in an extralabel manner to provide humane care and prevent animal suffering.

Extralabel use means 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 or 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 the labeled withdrawal time based on these different uses.  21 CFR 530.3.

Some of these uses have included medications added to commercial feeds, that are now governed under the Veterinary Feed Directive that FDA enforces for use in major, but not minor species.

According to guidance from FDA, “many commercial medical feeds that require a VFD are not approved for use in minor species,” defined by FDA as all species other than cattle, horses, swine, chickens, turkeys, dogs, and cats.  Compliance Policy Guide Sec. 615.115 Extralabel Use of Medicated Feeds for Minor Species.  A veterinarian may consider ELDU of medicated feed in minor species if:

There are no approved treatment options available;

The health of the animals is threatened; and

Failure to treat the animals would result in suffering or death.

The veterinarian must provide a written recommendation that includes the medical rationale for ELDU of medicated feed.

Before a veterinarian can provide such professional guidance, a valid veterinarian-client-patient relationship (VCPR) must exist.  While state laws govern the practice of veterinary medicine, including such relationships, FDA has inserted itself in the equation by identifying which states do not require the elements of a VCPR that FDA considers sufficient for the purposes of enforcing its Veterinary Feed Directive and other federal laws.

These multilayered state and federal laws can be difficult for veterinarians and small ruminant producers to decipher—hence the necessity of FARAD and other agencies to provide more specific guidance.

FDA’s recent announcement that it is “withdrawing draft Guidance for Industry (GFI) #230, ‘Compounding Animal Drugs from Bulk Drug Substances’” reminded me that pet owners can become confused about what type of medications are available for treating their pets.  For example, while serving on the New Jersey State Board of Veterinary Medicine, I recall a fair number of consumer complaints that alleged that a veterinarian provided substandard medical care because the medication prescribed to a pet was labeled “for human use only.”  Consumers therefore concluded that the medication harmed their pet.

However, the fact that medication is not specifically approved for use in animals does not mean that it would necessarily be harmful to those animals.

In fact, the use of an approved drug in a manner that is different than stated on the label, has been a fundamental tool used in veterinary medicine since drugs were first labeled.  This “extralabel” drug use was memorialized by Congress in the Animal Medicinal Drug Clarification Act of 1994 (AMDUCA).  See AVMA’s description of AMDUCA.

As AVMA describes on it’s website, “Compounding: FAQ for Veterinarians,” “compounding for animal patients . . . [is] a subpart of  [the] Extralabel Drug Use (ELDU) Rules.”

The ability to use approved drugs in species, for treatments, or at dosages, frequencies, or routes of administration that are not included on the label, is a tool that veterinarians use on a daily basis.  Since obtaining drug approvals for all uses in all types of animal species is cost-prohibitive, the only way some animals can be treated is through the use of drugs in an extra-labeled fashion.

When used properly and pursuant to the standard of care in veterinary medicine, such use should be considered legal.

While FDA has stated that “[c]urrent law does not permit compounding of animal drugs from bulk drug substances,” whether, and to what extent FDA governs compounding in the veterinary space has been the subject of legal debate.

However, FDA’s withdrawal of its guidance document related to compounding animal drugs from bulk substances creates even more confusion and uncertainty for the regulated community.  The now withdrawn guidance document,  Guidance #230, had set forth the situations in which FDA had indicated that it would not take regulatory action against a pharmacy or veterinarian when “an animal drug compounded from bulk substances may be an appropriate treatment option.”

Now, instead of finalizing the draft guidance based on comments received, “FDA intends to publish the new draft in early 2018 for public comment.”

So, the regulated community will be without guidance for a short period of time.

Hopefully FDA’s new guidance will continue to permit compounding from bulk substances when needed to provide adequate medical care for animals in need thereof.

 

Livestock producers who fail to correct asserted violations of the Food, Drug, & Cosmetic Act face serious repercussions that may result in the permanent or temporary cessation of their operations.

Illegal residues of drugs in meat, milk, or eggs, identified by USDA and/or FDA are serious offenses that require the immediate attention of, and response by, the alleged violator.  When these acts are repeated, particularly egregious, or the response is deemed inadequate, the government may take additional measures, including filing complaints for permanent injunctions, to permanently restrain and enjoin producers from continuing operations that introduce or deliver into interstate commerce any article of food consisting of animals and their edible tissues.  Violators may also have to pay for the costs of any related investigations, in addition to any fines ordered by the court.

Needless to say, livestock producers should take extraordinary measures to remain squarely out of the cross-hairs of such government actions.  Those who do not may be accused of the following offenses:

  • Failing “to have a system to control drug administration,” specifically, failing “to document the drug usage or the withdrawal time,” resulting in “animals with illegal drug residues offered for slaughter for use as food.”[1]
  • Failing “to systematically review treatment records prior to offering an animal for slaughter for human food, to ensure that drugs have been used only as directed and that appropriate withdrawal times have been observed.”
  • Failing to maintain adequate medical records, including the treatment dosages, route of administration and withdrawal times.
  • Using a prescription drug in a manner not specified by the label, and without a prescription from a veterinarian, thereby resulting in illegal extra-label drug use.  The drugs used in this manner are considered unsafe and the food produced from the livestock treated is considered adulterated.

FDA and USDA ordinarily warn livestock producers, sometimes repeatedly, whose management practices are found to be deficient, in order to ensure compliance with the laws governing the medical treatment of livestock raised for food.  However, even without proof of actual harm to humans, those agencies will take remedial and punitive action to protect consumers from potential public health risks resulting from the consumption of food containing above-tolerance levels of antibiotics and other drugs.


[1] Representative offenses specified in U.S. v. Metzler & Sons, L.L.C., Case No. 3:13-cv-00283-KRG, (W.D. Pa. Dec. 18, 2013)

 

holstein

Dairy farmers, and other food animal producers, should be ever-vigilant in their use of medications to treat their herds and flocks, otherwise they may be at risk of violating certain federal laws.  Following through with its promise to increase its enforcement activities, FDA has already issued more warning letters to dairy farmers, for misuse of medications, in the first two months of 2014, than they had in all of 2013. (See FDA’s website).

A warning letter from the FDA requires an expedited written response-within 15 days-outlining the steps the farmer taken to come into compliance.  Farmers, who fail to respond timely or sufficiently, risk facing the threatened regulatory action of seizure or injunction.

The violations recently cited by the FDA in warning letters to dairy farmers resulted from:

  1. the presence of drugs approved for use in food animals, but identified in tissues at slaughter at levels which exceed those established by FDA; or
  2. the presence of drugs not approved for use in food animals and identified in tissues at slaughter.

The use of drugs in a manner that is not indicated on the label is considered an “extralabel use” and is only permitted under limited circumstances in food animals, and only “by or on the lawful order of a licensed veterinarian within the context of a valid veterinarian/client/patient relationship.”

If drug residues are identified at slaughter, FDA usually sends investigators to the farm to inspect the farming operation and interview farmers and their employees.  These unannounced on-farm investigations often occur months after the treated animal has been tested, and can result in additional violations cited.

To ensure that farm operations are in compliance with the law, dairy farmers should consult with their veterinarians about the proper use of medications approved for use in cattle, including the appropriate route of administration, dosage, documentation of treatment, separation of treated animals, and withholding times required to ensure that residues in meat and milk products will not exceed permitted levels.