FDA CVM Explained: Animal Drug Approval

When a research team tests a drug in dogs, cattle, horses or laboratory animals, the question of which federal agency has a say is easy to overlook, and the answer is often the FDA’s Center for Veterinary Medicine (CVM). CVM is the part of FDA that regulates products for animals, and it works from a different set of application types and a different vocabulary than the human-drug side of the agency. This guide explains what CVM regulates, how a new animal drug reaches the market, how investigational use is handled before approval, what the minor use and minor species (MUMS) programs are for, and what a research institution should check before an investigational animal drug enters a study. It is a regulatory orientation, not veterinary advice, and it does not replace the agency’s own pages or a conversation with the sponsor’s regulatory staff.

The broader field this regulation serves is covered in What Is Veterinary Science?. That page describes research areas, funding and careers; this one is narrower and picks up where it stops, at the regulatory pathway a veterinary product has to travel.

What CVM Is and What It Regulates

CVM is a center within the U.S. Food and Drug Administration. FDA’s animal and veterinary pages describe its mission as assuring that animal drugs and medicated feeds are safe and effective and that food from treated animals is safe to eat. The product areas it lists are:

Animal drugs. Products that act through a chemical or biological effect in or on an animal’s body. These are regulated under the Federal Food, Drug, and Cosmetic Act (FD&C Act), which defines a drug broadly as a product intended for the diagnosis, cure, mitigation, treatment or prevention of disease in humans or other animals.
Medicated animal feed and animal food. CVM’s remit includes medicated feeds, the Veterinary Feed Directive, and food additive petitions for animal food. The safety question is partly about the animal eating the product and partly about food derived from that animal.
Animal medical devices. FDA draws a functional line between drugs and devices. A product that relies on a chemical action in or on the animal’s body to achieve its primary intended effect is a drug, not a device. Syringes, surgical instruments and X-ray equipment are the agency’s own examples of devices; antibiotics and anesthetics are examples of drugs. CVM’s animal device page is largely a notice board for device recalls and safety alerts, and this guide does not describe a device clearance pathway. Anyone developing an animal device should read FDA’s device-specific pages directly.

Two points about scope are worth stating plainly. First, FDA explains that practically all animal drugs qualify as “new animal drugs,” because the statutory test (a drug whose composition is not generally recognized as safe and effective for use under the prescribed conditions) is almost never met. In practice, a drug intended for animals is a new animal drug unless an exemption applies. Second, CVM is not the only authority touching animal research. Welfare rules for animals in research come from the USDA and from the Public Health Service, and are administered locally through the Institutional Animal Care and Use Committee (IACUC). CVM regulates the drug; the IACUC oversees the animal use. A study can need both.

The Legal Ways a New Animal Drug Can Reach Animals

FDA’s page on animal drug regulation lists the lawful routes by which a new animal drug may enter interstate commerce: an approved new animal drug application (NADA) or abbreviated application (ANADA), conditional approval, indexing for minor species, emergency use authorization, and investigational exemptions. A drug on none of these routes lacks legal marketing status. The sections below take the main ones in turn.

Full Approval: NADA and ANADA

The new animal drug application (NADA)

A NADA is the application used to seek approval of a new animal drug. FDA evaluates the sponsor’s submission to determine that the drug is safe and effective for its intended use and that it is properly manufactured. The regulations governing these applications are in 21 CFR part 514. Section 514.1 lists what an application contains. As summarized from the current regulation, the content includes:

identification of the drug and a table of contents with a summary;
chemistry data, including the composition of the dosage form and a full list of components;
a description of manufacturing methods, facilities and quality controls;
the evidence establishing safety and effectiveness, including study highlights and the scientific rationale;
specimens of proposed labeling;
analytical methods for detecting residues in food, where relevant to food-producing animals; and
an environmental assessment or a claim of categorical exclusion.

That list shows how the animal side differs in shape from a human-drug application. A sponsor is not only proving the drug works in the target species. For a drug used in food-producing animals it must also address the people who eat the meat, milk or eggs, and it must address the environment. The human-drug analogue is 21 CFR Part 314.

The abbreviated application (ANADA)

The ANADA is the generic pathway. It was established by the Generic Animal Drug and Patent Term Restoration Act of 1988. After a brand-name drug has been on the market for the periods the law specifies, a competitor can start the approval process for a generic copy by filing an ANADA instead of repeating the full safety and effectiveness program.

Supplements and post-approval obligations

Approval is not the end of the file. Under 21 CFR 514.8, changes to an approved application are sorted into three tiers: major changes (for example, a formulation change or a new indication) need FDA approval before distribution; moderate changes need advance notice to FDA before distribution (the regulation specifies 30 days); and minor changes are reported in annual reports. Section 514.80 requires applicants to keep indexed files of safety and effectiveness information and to submit reports on a fixed schedule: three-day field alert reports for product or manufacturing defects, fifteen-day alert reports for serious, unexpected adverse events, and periodic reports every six months for the first two years and annually after that. FDA may withdraw approval if an applicant fails to keep required records, refuses FDA access to them or submits false information. For an institution running a post-approval study with an approved product, the adverse event pathway runs through the applicant, so coordinate with the sponsor before assuming a finding is reportable by you.

Conditional Approval

Conditional approval is for a drug that has been through the approval process except that it has not yet met the effectiveness standard for full approval. It allows a sponsor to market a drug before complete effectiveness data are collected, provided safety has been shown and effectiveness is reasonably expected. According to FDA, a conditionally approved product may remain on the market for up to five years, through annual renewals, while the remaining effectiveness data are gathered. FDA states that this authority was expanded in 2018 to cover serious or life-threatening conditions in major species; it was originally part of the MUMS Act.

Investigational Use: Notices, Exemptions and Records

Before a drug is approved, it can still be lawfully given to animals for testing under an investigational exemption. The statutory basis is section 512(j) of the FD&C Act and the operative regulation is 21 CFR part 511, titled new animal drugs for investigational use. Part 511 treats two situations differently, and the difference matters to institutions.

Laboratory research animals and in vitro tests

Section 511.1(a) exempts new animal drugs used solely for tests in vitro or in animals used only for laboratory research purposes. The exemption comes with conditions rather than a clinical filing: the label must carry a caution statement that the product contains a new animal drug for investigational use only in laboratory research animals or for tests in vitro and is not for use in humans; a distributor must exercise due diligence to assure that the recipient is regularly engaged in conducting such tests; and shipment records (recipient name, address, date and quantity) are kept for two years. For a university lab this is the situation behind much ordinary preclinical work, such as a pharmacology study in rodents.

Clinical investigations in the target species

Section 511.1(b) governs a new animal drug intended for clinical investigational use in animals, meaning studies in the species the drug is meant to treat, often client-owned or production animals. Here the sponsor submits a “Notice of Claimed Investigational Exemption for a New Animal Drug” to FDA before shipping the drug to investigators. The notice covers the identity of the drug, its labeling, the names and addresses of investigators, the number of animals, dosing information and, for food-producing animals, withdrawal times. In CVM practice the resulting file is commonly called an INAD (investigational new animal drug) file, though the regulation itself speaks of the notice. Additional conditions in the regulation include:

Labeling. The drug must be labeled for use only in investigational animals in clinical trials, not for use in humans, and edible products of investigational animals are not to be used for food unless authorization has been granted.
Records. Sponsors and distributors retain investigation records for two years, and investigator reports are retained for two years after the investigation. The sponsor must monitor for safety hazards and promptly report significant findings to FDA and to all investigators.
Investigators. Investigators have to be scientifically qualified, keep complete records and report to the sponsor in a timely way.
Food-producing animals. Edible products from investigational animals cannot enter the food supply unless the sponsor shows either that the edible product is safe at the maximum dose with a minimum withdrawal period, or that it contains no drug residue, and FDA or USDA authorizes the food use.

The human-drug counterpart is the Investigational New Drug application; see Investigational New Drug (IND) and Do You Need an IND Application?.

Minor Use and Minor Species (MUMS)

The Minor Use and Minor Species Animal Health Act, signed on August 2, 2004, was passed to make more medications legally available to veterinarians and animal owners where the market is too small to carry a conventional development program. FDA defines the terms this way. The major species are horses, dogs, cats, cattle, pigs, turkeys and chickens. A minor use is treatment in a major species of a disease that occurs infrequently or in limited geographic areas and in only a small number of animals each year. A minor species is any animal other than humans that is not one of the major species; FDA gives zoo animals, ornamental fish, ferrets, sheep, goats and honeybees as examples. The act has three core provisions:

Conditional approval, described above.
Designation, modeled on the Orphan Drug Act for human medicine. A designated sponsor that obtains approval receives seven years of exclusive marketing rights, and designated sponsors become eligible for grants to support safety and effectiveness testing.
Indexing, which lets FDA add an unapproved drug to an index of legally marketed products for minor species where adequate and well-controlled studies are impractical. It is limited to non-food minor species, which is why it matters most for zoo and endangered animals.

FDA also lists user fee waivers for minor use and minor species projects, and an enforcement-priority policy (Compliance Policy Guide 615.115) that deprioritizes action against extra-label medicated feed use in minor species under stated conditions. For researchers, MUMS matters for two reasons. It is often the realistic route for a drug aimed at an uncommon species, and designation-linked grant eligibility is something a grants office may want to know about. If your lab works on such a species, ask the sponsor early whether designation has been sought.

Guidance for Industry (GFI) Documents

CVM publishes its policy interpretations as Guidance for Industry documents, referred to by a GFI number. FDA is explicit that these documents represent its current thinking, do not create or confer rights on any person, and are nonbinding: an alternative approach can be used if it satisfies the applicable statutes and regulations. CVM sorts its guidance by subject, including new animal drug applications, labeling, antimicrobial resistance, MUMS and VICH. In practice this means three things:

The Code of Federal Regulations is the binding text; a GFI explains how CVM expects to apply it.
A sponsor or investigator who departs from a GFI should be able to explain how its approach still meets the statute and regulations, ideally after talking with CVM.
Guidance changes. Cite the specific GFI number and check the FDA guidance database for the current version before relying on a PDF someone saved years ago.

Veterinary Clinical Trials: GCP and VICH

Clinical studies of veterinary products in target species are expected to follow Good Clinical Practice. The standard reference for CVM is GFI #85, the VICH GL9 guideline on good clinical practice. VICH is the international program for harmonizing technical requirements for veterinary product registration; GFI #85 was developed under it to create common standards across the European Union, Japan and the United States and to support mutual acceptance of clinical data between regulators. FDA lists it as a final guidance issued in May 2001 (the page was last updated on August 15, 2018). According to FDA, the guideline is meant to ensure that studies in target species are conducted and documented in accordance with GCP, and it applies to everyone involved in design, conduct, monitoring, recording, auditing, analysis and reporting. The principles it stresses are scientific quality, data integrity, animal welfare, and safety for personnel, the environment and the food chain.

Veterinary GCP shares a spirit with the human-trial standard described in What Is Good Clinical Practice (GCP)?, but the participants differ. The “subject” is an animal, often owned by someone other than the investigator, and the food-chain question has no human-trial equivalent. Nonclinical laboratory studies are a different category; see GCP vs. GLP, Good Laboratory Practice (GLP) and 21 CFR Part 58 GLP requirements.

The unit of analysis is a design question too; see pseudoreplication and the experimental unit in animal studies. For food-producing animals, the budget should also cover withdrawal periods or disposal, since edible products cannot go to food without authorization.

Considerations for Research Institutions

An academic lab or veterinary teaching hospital usually meets CVM in one of three roles: as an investigator in a sponsor-run clinical trial, as the sponsor of its own investigational use, or as a user of a product that is already approved. A practical checklist follows.

Identify who holds the exemption

If a company supplies an investigational drug for a field or clinical study, the company is normally the sponsor that filed the notice with FDA. Confirm in writing that the exemption is in place, that your site and investigator are covered, and what the sponsor expects from you for records and safety reporting. If the institution or an individual faculty member is the sponsor, the institution takes on the sponsor duties in part 511, including the notice, labeling, monitoring and record retention.

Match the study to the right exemption pathway

Work in animals used only for laboratory research falls under the laboratory research animal provisions. A study in the target species to support a label claim is a clinical investigation. A study that blurs the line, such as a pilot in client-owned animals, should be classified by regulatory staff before it begins, not afterward.

Settle the animal welfare review separately

FDA’s exemption does not replace IACUC approval. The protocol still needs local review, and it has to describe the investigational agent, dose, monitoring and endpoints. See The IACUC Protocol, Animal Research Ethics: The 3Rs, IACUC Oversight, and the Law and IRB vs. IACUC. For pain and distress classification, see USDA Pain and Distress Categories, and for the methods side, AVMA euthanasia guidelines in lab practice. Grant applications that use vertebrate animals have their own narrative; see Vertebrate Animals Section (VAS).

Keep the records the regulation asks for

Two years is the retention period stated in part 511 for shipment and investigation records, but sponsor contracts, institutional retention schedules and funder terms often require longer. Use the longest applicable period.

Frequently Asked Questions

What does FDA CVM regulate?

Animal drugs, medicated animal feeds and animal food, and animal medical devices. Its stated mission is to assure that animal drugs and medicated feeds are safe and effective and that food from treated animals is safe to eat.

What is the difference between a NADA and an ANADA?

A NADA seeks approval of a new animal drug on the basis of the sponsor’s own safety, effectiveness and manufacturing data. An ANADA is the generic pathway, available after the brand-name drug has been marketed for the periods the law specifies, under the 1988 Generic Animal Drug and Patent Term Restoration Act.

What is an INAD?

It is the common name for the investigational file a sponsor opens by submitting a Notice of Claimed Investigational Exemption under 21 CFR 511.1(b) before shipping an unapproved drug to investigators for a clinical study in animals.

What does conditional approval mean?

The drug has met the requirements except the effectiveness standard for full approval. It may be marketed for up to five years, through annual renewals, while the remaining effectiveness data are collected.

Which GCP standard applies to veterinary trials?

CVM’s reference is GFI #85, the VICH GL9 guideline on good clinical practice, developed with the European Union and Japan.

Does the IACUC still review a study if FDA has an investigational exemption in place?

Yes. The exemption addresses the legal status of the drug; the IACUC reviews the animal use. They are separate requirements.

FDA Center for Veterinary Medicine (CVM) Explained: Animal Drug Approval and Veterinary Trials