III. POLICY

Although numerous drugs are FDA-approved or indexed for use in animals, there are many different species of animals, each with a variety of diseases and conditions for which there are no FDA-approved or indexed drugs. While there are cases in which FDA-approved animal or human drugs can be used to treat an animal under the extralabel use provisions of the FD&C Act and related regulations, FDA recognizes that there are circumstances in which no FDA-approved or indexed drug (including the extralabel use of an FDA-approved animal or human drug) can be used to treat an animal with a particular condition. In those limited circumstances, an animal drug compounded from bulk drug substances may be a medically appropriate treatment.

This guidance balances FDA's concerns about the safety, effectiveness, and quality of animal drugs compounded from bulk drug substances, which have not gone through Agency premarket review, with the need for such drugs when no FDA-approved or indexed drug is medically appropriate to treat the animal. Because of the safety and effectiveness benefits and protections of the pre-market review process and post-market review process and post-market monitoring of FDA-approved and indexed drugs, veterinarians should only use drugs compounded from bulk drug substances if FDA-approved or indexed drugs are not medically appropriate to treat the animal.

This guidance describes:

• The types of drugs compounded from bulk drug substances that FDA has determined present the greatest risk to human and animal health and intends to make priorities for enforcement action; and
• The circumstances under which, at this time, FDA does not generally intend to take enforcement action against drugs compounded from bulk drugs substances for violations of the FD&C Act's requirements for approval, adequate directions for use, and CGMPs.

These circumstances are separately described below for drugs compounded:
• to fill patient-specific prescriptions for nonfood-producing animals (see section A. Compounding for Nonfood-Producing Animals: Patient-Specific Prescriptions);
• for office stock for nonfood-producing animals (see section B. Compounding for Nonfood-Producing Animals: Without Patient-Specific Prescriptions (“Office Stockâ€�); and
• for food-producing animals (section C. Compounding for Food-Producing Animals: Drugs for Use as Antidotes for Food-Producing Animals or Sedatives and Anesthetics for Free-Ranging Wildlife Species).
  
  Editors Note: The blue sub-sections will be covered in upcoming issues of this newsletter.

These policies are intended to address FDA's concerns about the compounding of animal drugs from bulk drug substances, including significant concerns with such drugs when they:

• Present particular animal or human safety concerns. Examples include superpotency, microbial contamination, and drug formulations that present safety risks for the treated animals or for people handling or administering the animal drug. To help FDA identify compounded drugs that present safety concerns and to prevent future harm, the FDA encourages veterinarians, pharmacists, and animal owners to report adverse events associated with compounding animal drugs from bulk drug substances on FDA's website using Form FDA 1932a.
• Are intended for use in food-producing animals. Drugs compounded from bulk drug substances for use in food-producing animals present safety concerns because of the potential for harmful residues in food from treated animals. However, FDA recognizes that in some cases of toxicoses in food-producing animals, which can be life-threatening and may affect large groups of animals, an antidote compounded from a bulk drug substance may be the only treatment option and may be urgently needed to prevent animal suffering or death. FDA also recognizes the need for wildlife health professionals to have immediate access to some sedatives and anesthetics compounded from bulk drug substances for the capture and immobilization of free-ranging wildlife. As described in section C. Compounding for Food-Producing Animals: Drugs for Use as Antidotes for Food-Producing Animals or Sedatives and Anesthetics for Free-Ranging Wildlife Species, this guidance describes circumstances in which, at this time FDA generally does not intend to take enforcement action for limited compounding of certain antidotes for food-producing animals, and sedatives and anesthetics for free-ranging wildlife. These drugs are identified by the veterinary community, reviewed by FDA and available on the FDA website, which includes only bulk substances to compound drugs for antidotes, and sedatives and anesthetics that cannot be met by onlabel or extralabel use of an FDA-approved or indexed drug. When using these drugs, we expect the prescribing veterinarian, acting within a valid VCPR, to establish scientifically-based withdrawal, withholding, and discard times to ensure that animals treated with these drugs do not contain residues of the antidote, sedative, or anesthetic, or alternatively, to ensure that the treated animals do not enter the food supply.
• Are copies of a marketed FDA-approved or indexed drug. FDA supports increased availability of legally marketed animal drugs that have demonstrated that they are safe and effective, properly manufactured to ensure drug quality, and accurately labeled. Compounding copies of such drugs presents a disincentive to submit a new animal drug application, an abbreviated new animal drug application for generic animal drugs, an application for conditional approval, or a request for indexing, further reducing the availability of legally marketed animal drugs. As described below in section A. Compounding for Nonfood-Producing Animals: Patient-Specific Prescriptions, this guidance explains the circumstances in which FDA generally does not intend to take enforcement action at this time for compounded drugs, including limited copies, dispensed under a patient-specific prescription.
• Are sold as office stock (as opposed to dispensed by a pharmacy upon receipt of a prescription for an identified patient. For purposes of this guidance, a prescription includes the species of the animal patient, and identifying information about the animal patient (e.g., patient name or identification number, room or cage number, etc.), and otherwise complies with applicable State law. A patient may be a single animal or a group of animals in a specific, identified location (e.g., cats in isolation ward X, dogs in kennel Y, or horses in stable Z). The Agency is concerned that compounded office stock potentially exposes large numbers of animals to drugs of unproven safety, effectiveness, and quality. However, FDA recognizes that in some limited cases an animal drug is urgently needed, and the time needed to compound a drug in response to an individual patient prescription may result in animal suffering or death. As described in section B. Compounding for Nonfood-Producing Animals: Without Patient-Specific Prescriptions (“Office Stockâ€�), FDA generally does not intend to take enforcement action for compounding office stock at this time. Drugs used to compound as office stock are nominated by the veterinary community, reviewed by FDA, and available on the FDA website, which includes bulk substances to compound drugs for urgent treatment needs that cannot be met by onlabel or extralabel use of an FDA-approved or indexed drug.

When pharmacies and veterinarians compound animal drugs from bulk drug substances as described below, the Agency generally does not intend to take enforcement action for violations of the FD&C Act's requirements for animal drug approval; adequate directions for use; and CGMP. Nevertheless, FDA intends to prioritize enforcement of these provisions when: (1) the animal drugs are compounded outside the circumstances described below; (2) the compounded drugs present particular human or animal safety concerns; or (3) the compounded drugs do not meet other manufacturing, product quality, labeling, or packaging requirements of the FD&C Act (e.g., if the product is made under insanitary conditions or the labeling is false or misleading). FDA will ordinarily rely on compounding pharmacies' home State licensing boards to provide day-to-day oversight of routine compounding practices (i.e., routine inspections for drug quality) but may provide concurrent oversight of compounding practices when considered appropriate by the Agency. Should FDA have cause for concern, the Agency may also refer a case to the appropriate State licensing board(s).

The overview of the “POLICY� section of this Guidance will continue in next week's Newsletter.

Loyd V. Allen, Jr., PhD, RPh
Editor-in-Chief
International Journal of Pharmaceutical Compounding
Remington: The Science and Practice of Pharmacy Twenty-second edition