FDA extends comment period on animal drug compounding draft guidance to June 17

Pharmacists who compound veterinary medications have another month to respond to revised draft guidance on the compounding of animal drugs from bulk drug substances (BDS). The revised draft of Guidance for Industry (GFI) #256, Compounding Animal Drugs from Bulk Drug Substances, if finalized, will describe FDA’s current thinking about the practice and identify circumstances under which the agency does not intend to take regulatory action against the compounding of drugs from BDS when no other medically appropriate treatment options exist.

The draft guidance pertains to compounding patient-specific prescriptions for nonfood-producing animals, office stock for nonfood-producing animals, and antidotes for food-producing animals.

Comments and criticism

Some pharmacies that specialize in the compounding of medications for animal health are critical of the guidance, challenging FDA’s authority to regulate veterinary compounding and claiming that such compounding is not subject to the Federal Food, Drug & Cosmetic (FD&C) Act. The FD&C Act was designed to regulate drug manufacturers, not veterinary compounders, they say. The guidance also infringes on the professional judgment of veterinarians and will ultimately have a negative impact on animal health.

According to FDA, comments may be submitted electronically or on paper. Submissions must include the Docket No. FDA-2018-D-4533 for “Compounding Animal Drugs from Bulk Drug Substances.” Electronic comments can be submitted through the Federal eRulemaking Portal, https://www.regulations.gov. Instructions on submitting comments are available at the portal. Mail paper comments to

Dockets Management Staff (HFA-305)
Food and Drug Administration
5630 Fishers Lane, Rm. 1061
Rockville, MD 20852

Interview with FDA spokesperson

APhA spoke with Siobhan DeLancey, MPH, team leader of strategic communications at FDA’s Office of Foods and Veterinary Medicine, about the revised draft guidance.

Pharmacy Today: With the deadline postponed, pharmacists have more time to submit comments on the guidance. What kinds of comments are you looking for? What areas would you most like pharmacists to weigh in on?

DeLancey: FDA issued this new draft guidance to state our enforcement priorities related to drugs compounded from BDS and to clarify for veterinarians, pharmacists, and others concerned with treating sick animals the circumstances in which we do not intend to take action against drugs compounded from BDS. As the draft describes, we intend to prioritize action against drugs compounded from BDS that present risks to human or animal health; are copies of approved or indexed products; are compounded as office stock and not on the list reviewed by FDA; or are for food producing animals. It also details how we do not generally intend to take action when a drug is compounded from BDS because the treating veterinarian has concluded no approved or indexed product can be used to treat an animal. The comment period has been extended an additional four months to allow impacted stakeholders, including pharmacists, veterinarians, sponsors of approved animal drugs, etc., to provide feedback and context on how the draft guidance might impact their usual practices.

Pharmacy Today: What are FDA and the Center for Veterinary Medicine’s concerns with compounding animal drugs from bulk drug substances? What are the goals?

DeLancey: The FDA encourages veterinarians to always first consider an FDA-approved drug, when available, as these products have met the agency’s rigorous standards for safety, effectiveness, and manufacturing. In addition to FDA-approved drug products, some drugs for nonfood-producing minor species have been evaluated for safety and effectiveness through an alternative FDA review process called indexing. Animal drug compounding is not meant to circumvent these processes, but instead provide veterinarians with additional tools to care for their patients.

Veterinarians provide medical care for a wide variety of conditions in a diverse range of species, including exotic and zoo animals, wildlife, and reptiles, and the availability of FDA-approved, conditionally approved, or indexed animal drugs may be limited for some conditions or in these categories of species. In the limited circumstances where there is no FDA-approved, conditionally approved, or indexed drug that can be used to treat an animal with a particular condition, an animal drug compounded from bulk drug substances may be a medically appropriate treatment.

Compounded drugs can serve an important medical need for patients, but they do not have the same safety, quality, and effectiveness assurances as FDA-approved drugs. Because compounded drugs are not FDA-approved, FDA does not verify their safety, effectiveness, or quality before they are marketed. In addition, FDA does not review the manufacturing methods used to make them or the accuracy of their labeling.

Poor compounding practices can result in serious drug quality problems, such as bacterial or fungal contamination of a drug that is intended to be sterile, or a drug that has either too much or too little of the active ingredient(s). Such quality problems can lead to serious patient injury and death. For example, on July 23, 2019, FDA published an alert to horse owners and veterinarians about a compounded drug product that contained approximately 18 to 21 times the amount of the active ingredient stated on the label and led to the death of three horses. A similar incident occurred in 2014 involving a different compounding pharmacy. Further, compounding drugs under insanitary conditions could lead to widespread patient harm, especially when the compounder engages in compounding office stock. FDA also has concerns about the stability of compounded drugs, especially when they are retained in inventory as office stock and not used immediately.

In developing this draft guidance, FDA has attempted to balance its concerns about the safety, effectiveness, and quality of animal drugs compounded from bulk drug substances with the need for options when no FDA-approved, conditionally approved, or indexed drug can be used to treat an animal.

Pharmacy Today: Anything else you think is important for our pharmacist readers to know?

DeLancey: The FD&C Act grants FDA the authority to approve and regulate drugs for use in animals. Under the FD&C Act, legal pathways to the marketplace for animal drugs are Approval, Conditional Approval, or listing on the Index of Legally Marketed Unapproved New Animal Drugs for Minor Species. In contrast, compounded animal drugs from bulk drug substances are unapproved, and therefore are not legally marketed. However, because FDA recognizes that in some situations a drug compounded from bulk drug substances may be the only appropriate treatment option for a particular animal, it has released this draft guidance to describe the agency’s proposed thinking on when it does not intend to take enforcement action against a compounded animal drug. This draft guidance, if finalized, would provide more flexibility to veterinarians and pharmacies:

  • FDA’s draft guidance discusses only the compounding of animal drugs from BDS. Compounding from approved animal or human drugs is legal when performed within the framework of extra-label use.
  • Under the draft guidance, the “List of Bulk Drug Substances for Compounding Office Stock Drugs for Use in Nonfood-Producing Animals or Antidotes for Food-Producing Animals” (the “Office Stock List”) is only for office stock, which are drugs compounded from BDS without a patient-specific prescription. The Office Stock List would not be relevant for pharmacists filling individual patient-specific prescriptions for nonfood-producing animals.
  • The draft guidance outlines expectations for veterinarians to provide with the prescription a brief explanation of why a compounded drug is needed only under specific circumstances: when the prescription is for a copy of an approved or indexed product (that is, when it has the same active ingredient as an approved or indexed product, is in the same route of administration, and is the same, similar, or readily substituted strength).

We would also like to differentiate between draft guidance #256 and the Requests for Nominations: List of Bulk Drug Substances for Compounding Office Stock Drugs for Use in Nonfood-Producing Animals or Antidotes for Food-Producing Animals. Although the comment period for the draft guidance closes on June 17, 2020, there is no end date for nominations to the BDS List. We will review nominations to the BDS list on a rolling basis.