Ensuring Compounded Products Are Used Safely & Legally
The use of drugs approved by the U.S. Food and Drug Administration gives veterinarians and animal owners confidence that the drug is safe and will be effective.
Due to the large number of animal species and the relatively small number of FDA-approved animal drugs, a veterinarian will sometimes need a pharmacist to change a property of a drug to best treat an animal, a process called compounding. For example, a pharmacist may create a liquid formulation of an approved animal drug that was previously only made in tablet form or may change the concentration (amount of drug per volume) so that a pet owner can more easily measure the current dose for a tiny pet. Animal medicine compounding is the customized manipulation of an approved drug to meet the health needs of a particular patient. Examples of compounding include:
- Mixing two injectable drugs
- Preparing a paste or suspension from crushed tablets
- Adding flavoring to a drug
Compounding to meet animal health needs can be thought of in two broad categories:
- The manipulation of an approved drug for a specific patient under the supervision of a veterinary, as allowed by federal law.
- The use of bulk drug substances, or active pharmaceutical ingredients, to make a compounded product. This type of compounding is not legal because it creates a new animal drug and does not follow FDA guidelines for good manufacturing practices or adequate labeling and have not been evaluated for safety, efficacy or quality.
Compounding That is Legal
Compounding of animal drugs was first permitted by Congress under the Animal Medicinal Drug Use Clarification Act (AMDUCA). It is limited to the use of an approved animal or human drug that is compounded under the prescription of a licensed veterinarian for a specific patient in the context of a veterinarian-client-patient relationship.
Compounding That is Not Legal
There is no provision in federal law for compounding animal drugs from bulk substances, also known as active pharmaceutical ingredients (API), so this type of compounding is illegal. Compounding from bulk substances creates an unapproved new animal drug and does not follow good manufacturing practices or adequate labeling requirements. Importantly, there is no assurance to the veterinarian of safety, efficacy, or quality of these products.
Concerns About Compounding From Bulk Drug Substances
FDA/CVM has listed four major concerns with drugs compounded from bulk drug substances:
- Human and animal safety concerns. There is a great deal of literature documenting deficiencies in compounding products, including sub-potency (less than the amount of active ingredient on the label) or super-potency (more than the amount of active ingredient on the label). Both can be fatal for animal patients.Tragically, there are examples. In 2009, 21 polo ponies were killed by a compounding product with 100 times of amount of listed active ingredient. In 2014, two horses were killed and another six injured by a superpotent product; and in 2019, three horses in two different states were killed. In addition, there have been 39 voluntary recalls of compounded drugs since 2015.
- Compounded drugs used in food-producing animals. The food safety protections that come with approved drugs, including data-driven withdrawal times to ensure no violative residues, do not exist with compounded products. Since there is no data behind products compounded from bulk substances, these products should not be used in food animals.
- Copies of approved drugs. In recent years, many compounders have acted like drug manufacturers under the guise of compounding. Using bulk substances, they have compounded preparations in large quantities and advertised them as cheap alternatives to approved drugs. They have compounded drugs that mimic FDA-approved drug products. In addition to the safety concerns outlined above, this activity undermines the FDA drug approval process and actually results in fewer approved drugs for veterinarians. It is difficult for a drug manufacturer to justify the expense of millions of dollars and many years to get a drug approved by FDA only to find compounders will circumvent the drug approval process and make it from bulk so they can sell it cheaply.
- Compounded drugs sold as office stock with no patient prescription. Because these drugs are widely distributed and used in a large number of animals, the potential for animal harm is much greater.
The Exception: Limited Compounding From Bulk Drug Substances is Needed
It is widely recognized by FDA, the animal health industry, and others that a limited amount of compounding from bulk drug substances is needed for animal health. With seven major species, a large number of minor species, and a relatively small number of approved animal drugs, there are many medical needs in animal health that cannot be met with an approved drug. Additionally, in some cases the API needed to treat a condition may not be found in any approved animal or human drug. To allow for these exceptions, FDA exerts enforcement discretion – meaning it will not take action again these illegal compounds.
However, this enforcement discretion is limited. The specific circumstances under which FDA allows enforcement discretion are described in Guidance for Industry #256.
Patient-specific compounding for non-food producing species is allowed unless it is a copy of an approved drug. Copies can be made if the veterinarian can provide a medical rationale for why an approved product will not work for the animal patient.
Compounding from bulk for office stock for non-food producing animals, for antidotes for food producing animals, and for sedatives for wildlife is permitted only if the bulk drug substances appear on FDA’s list of bulk drug substances allowed for use for these purposes.
Abuse of These Rules Threatens Animal Health
Despite these rules, lack of enforcement has allowed some compounding pharmacies to act like drug manufacturers and produce mass quantities of compounded drugs without the guarantee of safety and effectiveness. These compounders typically import bulk drug substances which they use to produce large quantities of copies or near-copies of approved drugs and market them as low-cost alternatives to FDA-approved drugs.
Veterinarians and pet owners should be very cautious about the use of these products. These compounded products carry no assurance that they are safe or that they will even work as advertised. In addition, if an animal does suffer harm from one of these compounded products, the compounder has no obligation to report that adverse event to the FDA, unlike manufacturers of approved drugs who must report these events.
In addition to threatening animal health, this practice severely undermines the incentive for drug manufacturers to commit the time and resources necessary to bring an approved drug to market. On average it can take up to seven years and $100 million dollars to do this successfully. Manufacturers cannot risk such sums of money to produce a product that then must compete with a compounded product that is made without any of the same costs and requirements.
FDA can promote innovation in animal health by more aggressively enforcing its compounding guidance and leveling the playing field.
Compounding is Legal When…
Under federal law, compounding is legal when:
- The health of an animal is threatened or suffering or death may result from failure to treat.
- It is performed by a licensed veterinarian or licensed pharmacist on order of a veterinarian within the scope of professional practice.
- There is no approved animal or human drug that, when used as labeled or in conformity with the extra label drug use regulations, will, in the available dosage form and concentration, appropriately treat the condition diagnosed.
- Preparations are compounded from FDA-approved animal or human drugs for individual patients.
Compounding is Illegal When…
Animal drug compounding from bulk active, or raw pharmaceutical ingredients is not legal. Nevertheless, FDA does exert what is called “enforcement discretion” to allow some animal drug compounding from bulk substances. This is generally necessary when there is a need for a specific active ingredient and there is no approved human or animal drug with that active ingredient. The animal health industry also recognizes and supports these limited exceptions to the law in the interest of patient health.