For all inquiries, complaints and questions regarding potential Unapproved Animal Drugs, please e-mail: CVMUnapprovedDrugs@fda.hhs.gov.
What are Unapproved Animal Drugs?
FDA considers an “unapproved animal drug” to be a drug that:
- Is intended for use in animals; and
- Meets the definition of “new animal drug” in the Federal Food, Drug, and Cosmetic (FD&C) Act; but
- Does not have legal marketing status, meaning FDA has not approved, conditionally approved, or indexed the drug.
To better understand this, a couple of definitions are in order.
First, what’s a drug? The FD&C Act defines “drug” to include, among other things, “articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals” and “articles (other than food) intended to affect the structure or any function of the body of man or other animals.”1
The intended use of a product determines if it’s a drug. Here are a few examples to illustrate this concept:
- When a company sells bottled water for people to drink as a beverage, the water is not a drug. But if the company sells those same bottles of water as a cure for cancer in dogs, then the water is a drug under the FD&C Act because the intended use is to cure a disease (cancer) in dogs.
- When a company sells formaldehyde for a car manufacturer to use to make automotive parts, it’s not a drug. But when a company sells formalin—a solution of formaldehyde—for a fish biologist to use to kill external parasites on finfish, it’s a drug under the FD&C Act because the intended use is to treat a disease (parasitism) in fish.
- When a company sells a product claiming it makes cows ovulate at the same time, the product is a drug. Although it’s not treating or preventing a disease in the cows, the product’s intended use is to change how their bodies function, which makes it a drug under the FD&C Act.
Second,what's a new animal drug? The FD&C Act defines “new animal drug” as a drug intended for use in animals that is not Generally Recognized As Safe and Effective (GRASE) by qualified experts for the uses listed on the label.2 Taken in the reverse, if a drug is GRASE, then it’s not a new animal drug under the FD&C Act. For an animal drug to be GRASE, the experts must generally agree that, based on published studies, the drug is safe and effective for its intended uses.
There is a very narrow exception to the definition of a new animal drug and that is grandfathered drugs. For an animal drug to be grandfathered, it must have been approved under the 1906 Food and Drug Act and before June 25, 1938 (the date President Franklin Roosevelt signed the FD&C Act into law), and its label and composition have not changed since that time. If a drug is grandfathered, then it’s a not a new animal drug under the FD&C Act.
FDA thinks it’s very unlikely that any currently marketed animal drug would be considered GRASE or would qualify for the “grandfather” exception. And so, if a drug is intended for use in animals, it’s almost certain to be a new animal drug.
The entire term “new animal drug” is defined by law and applies to any product which fits that definition. The adjective “new” doesn’t mean the drug just went on the market; some “new animal drugs” have been marketed for years. For example, the drug ivermectin has existed for decades and even though FDA originally approved it to prevent heartworm disease in dogs in March 1987,3 ivermectin is still a “new animal drug” under the FD&C Act.
FDA Pre-Market Review & Legal Marketing Status
As required by the FD&C Act, new animal drugs must be reviewed by FDA for safety and effectiveness and obtain legal marketing status before they can be marketed. The pre-market review is integral to FDA’s ability to protect animal and public health. During the review, the agency evaluates information submitted by the drug company to make sure the drug is safe and effective for its intended use and that the drug is properly manufactured and properly labeled.
The FDA pre-market review is also necessary for the drug to obtain legal marketing status through an approval, conditional approval, or indexed listing.4 After the drug company gets a new animal drug approved, conditionally approved, or indexed by FDA, the company can legally market it for the uses listed on the label.
Unapproved Animal Drugs
Unapproved animal drugs are new animal drugs that don’t have legal marketing status. They have not been approved, conditionally approved, or indexed by FDA. It’s illegal to market unapproved new animal drugs because they haven’t gone through the FDA pre-market review and obtained legal marketing status under the FD&C Act. Unapproved animal drugs may not meet the agency’s strict standards for safety and effectiveness and may not be properly manufactured or properly labeled and packaged. Unapproved animal drugs include animal drugs compounded from bulk drug substances.
Three Pathways to Legal Marketing Status
An approved animal drug has gone through the New Animal Drug Application (NADA) process, or for an approved generic animal drug, the Abbreviated New Animal Drug Application (ANADA) process. If the information in the application meets the requirements for approval, FDA approves the animal drug. FDA’s approval means the drug is safe and effective when it is used according to the label. FDA’s approval also ensures that the drug’s strength, quality, and purity are consistent from batch to batch, and that the drug’s labeling is truthful, complete, and not misleading.
Learn more about the drug approval process by visiting the following webpage:
Conditional approval is only available for some animal drugs for use in a minor species or in a major species under special circumstances. A conditionally approved animal drug has gone through FDA's drug approval process except the drug has not yet met the effectiveness standard for full approval. FDA’s conditional approval means that when used according to the label, the drug is safe and has a “reasonable expectation of effectiveness.” FDA's conditional approval also means that the drug is properly manufactured.
The conditional approval is valid for one year. The drug company can ask FDA to renew the conditional approval annually for up to four more years, for a total of five years of conditional approval. During the 5-year period, the drug company can legally sell the animal drug while collecting the remaining effectiveness data. This early marketing is good for two reasons: first, the drug is available sooner to be used in animals that may benefit from it; and second, the company can recoup some of the investment costs while completing the full approval.
After collecting the remaining effectiveness data, the company submits an application to FDA for full approval. The agency reviews the application and, if appropriate, fully approves the drug.
Minor species are all animals, other than people, that are not major species. The seven major species are cattle, horses, pigs, chickens, turkeys, dogs, and cats. Ferrets, eagles, fish, and sheep are examples of minor species.
A minor use in a major species is using a drug in a major species for a disease or condition that occurs in only a small number of animals each year.
For example, using a drug to control pain in dogs with bone cancer is a minor use in a major species because relatively few dogs get bone cancer each year.
Learn more about minor species and minor uses by visiting the following webpages:
Learn more about the conditional drug approval process by visiting the following webpage:
An indexed animal drug is a drug on FDA’s Index of Legally Marketed Unapproved New Animal Drugs for Minor Species, referred to simply as “the Index.” As the name says, a drug listed on the Index is unapproved but has legal marketing status. It can be legally sold for a specific use in certain minor species. Indexing is allowed for drugs for:
- Non-food-producing minor species, such as pet birds, hamsters, and ornamental fish. These animals are typically not eaten by people or by other animals that produce food for people to eat; and
- An early non-food life stage of a food-producing minor species, such as oyster spat (immature oysters). Because people do not generally eat oyster spat, a drug to treat a disease in spat can be indexed, but a drug to treat a disease in adult oysters, which people commonly eat, cannot be indexed.
Indexing a drug is quite different from the drug approval process. Indexing relies heavily on a panel of qualified experts outside FDA. The experts review the drug’s safety in the specific minor species and the drug’s effectiveness for the intended use. All experts on the panel must agree that, when used according to the label, the drug’s benefits outweigh the risks to the treated animal. If FDA agrees with the panel, the agency adds the drug to the Index.
Learn more about indexing by visiting the following webpage:
- What You Need to Know: FDA-Approved vs. Unapproved Animal Drugs
- FDA Issues Warning Letters to Manufacturers of Unapproved Levothyroxine Drugs for Hypothyroidism in Dogs