The Federal Food, Drug, and Cosmetic Act (FFDCA) authorizes the Food and Drug Administration (FDA) to regulate the safety and effectiveness of animal drugs. FDA's review of brand-name and generic a nimal drug applications is funded through a combination of annual discretionary appropriations from Congress and user fees collected from the regulated industry. Congress first authorized FDA's collection of user fees for brand-name animal drugs for FY2004 in the Animal Drug User Fee Act of 2003 (now called ADUFA I, P.L. 108-130 ), generally following the model established for human drugs a decade earlier. At that time, representatives of brand-name animal drug research and development companies said that an animal drug could take 7 to 10 years to develop, at a cost of $100 million or more, and that review of these products had not always been timely or predictable. Authority to collect user fees for brand-name (pioneer) animal drugs has been written to sunset at five-year intervals, and was reauthorized in 2008 and 2013 in laws referred to as ADUFA II and ADUFA III, respectively. This authority is due to sunset at the end of FY2018. As required by law, FDA has published the results of negotiations with animal drug sponsors, which it refers to as ADUFA IV. Congress first authorized FDA's collection of user fees for generic animal drugs for FY2009 in the Animal Generic Drug User Fee Act of 2008 (AGDUFA I, P.L. 110-316 ), coincident with ADUFA II. AGDUFA was reauthorized in 2013 as AGDUFA II, and, like ADUFA III, is also due to sunset at the end of FY2018. As required by law, FDA has published the results of negotiations with generic animal drug sponsors, which it refers to as AGDUFA III. Appendix A provides a snapshot of the legislative histories, statutory citations, and key statistics for both user fee programs. Under both its brand-name and generic animal drug authorities, FDA shall use fee revenue for the costs of "the process for the review" of the respective animal drug type, which includes the following: review of applications and other submissions; facility inspections; oversight of research to support the application/submission; issuance of regulations, policies, standards, and action letters; and review of labeling and advertising prior to approval. Neither authority permits postmarket review activities under current law. Sunset provisions, which are found in other FDA user fee authorities (such as those for human drugs and devices), may set a more strict reauthorization timeline for Congress and the agency than do the more common expirations of authority for appropriations. Despite a lapsed authorization of appropriations, HHS agencies may invoke general authorities to continue their work on a matter as the authority to conduct the activity remains. A sunset, in contrast, bars the agency from continuing such work beyond the sunset date, unless or until Congress reauthorizes the provision or otherwise lifts the sunset. The key consequence for FDA and drug sponsors of a lapse in user fee authority is that continued payment of FDA review personnel is prohibited, and the agency may have to lay off animal drug review staff. These personnel are highly specialized and not easily replaced. As a result, user fee reauthorizations are often considered "must pass," and Congress has consistently reauthorized ADUFA and AGDUFA before their sunset dates. Authorities governing FDA's review of animal drugs are found in FFDCA Section 512, which cross-references additional sections of the Act. Regulations are at 21 C.F.R. Chapter I, Subchapter E, which also cross-references other regulations. FDA does not oversee veterinary biologics (e.g., vaccines), which are regulated by the Department of Agriculture's Animal and Plant Health Inspection Service (APHIS). The FDA's Office of New Animal Drug Evaluation (ONADE) determines whether or not a new animal drug application (NADA) should be approved for marketing. According to ONADE, in order to approve and sustain a new animal drug for commercial use, five standards must be met. 1. The drug must be safe for the animal, for humans consuming food derived from a treated food-producing animal, and for the person administering the drug. 2. The drug must be effective for its intended uses, i.e., the uses prescribed, recommended or suggested in the labeling of the product. 3. The drug must be a quality manufactured product, being the result of a validated manufacturing process conducted in accordance with current Good Manu facturing Practice (GMP) regulations. 4. The drug must be properly labeled to inform the user of the product not only how to use the product but also safety considerations, procedures for use in food-producing animals, and procedures for storage and handling. 5. Under the National Environmental Policy Act, FDA must consider, during the review process, the environmental impact of an animal drug's postmarket use (e.g., medicated feed waste and potential runoff). In 2004 Congress addressed concerns about the availability of some animal drugs that are not commercially attractive, and enacted the Minor Use and Minor Species Animal Health Act (MUMS, P.L. 108-282 ), modeled after the authority for "orphan" human drugs. A minor use is a use in a major species (horses, dogs, cats, cattle, pigs, turkeys, and chickens) for a disease that occurs infrequently, involving only a small number of animals annually. Minor species are all other nonhuman animal species (except for the above listed major species )—such as zoo animals, fish, and pet birds and rodents—including some species of food-producing animals—such as sheep, goats, catfish, game birds, and honey bees, among others. MUMS allows conditional approval (marketing before all effectiveness data are available) and a period of marketing exclusivity, during which FDA may not approve an application for the generic copy of the approved brand-name drug. FDA may waive user fee requirements under ADUFA and AGDUFA for MUMS drugs. As with human medical products, it is the responsibility of the drug sponsor to conduct the necessary tests to demonstrate a product's safety and effectiveness for review purposes. Once the drug is on the market, FDA continues to monitor the animal drug's safety and effectiveness, manufacturing processes, labeling, and marketing communications. For the basic types of applications and other submissions in the review of a brand-name animal drug, as well as commonly used acronyms, see text box, above. Like brand-name animal drugs, authorities governing FDA's review of generic animal drugs are found in FFDCA Section 512, and regulations are at 21 C.F.R. Chapter I, Subchapter E. The Generic Animal Drug and Patent Term Restoration Act of 1988 ( P.L. 100-670 ) created an expedited pathway for the review of generic animal drugs. This pathway allows a sponsor to submit an abbreviated new animal drug application (ANADA) to FDA for premarket review rather than the full NADA required for a brand-name animal drug. The process is called "abbreviated" because instead of conducting new safety and effectiveness testing, the ANADA sponsor establishes that the generic animal drug is the same as the reference-listed new animal drug product (RLNAD, which is the brand drug), thereby relying on FDA's determination that the brand drug is safe and effective. In the ANADA, the generic drug sponsor must show: that the generic copy has the same active ingredient, strength, dosage form, dosing regimen, and route of administration as the RLNAD; that it is bioequivalent (or that the bioequivalence requirement has been waived); and that it is the same in identity, strength, purity, and quality. The labeling for the generic animal drug also must be the same as the brand, with some exceptions (e.g., company name and address). An ANADA also must contain an environmental assessment (EA) or a request for categorical exclusion from the EA, among other information. For basic types of applications, other submissions, and product references in the review of a generic animal drug, as well as commonly used acronyms, see text box, above. As noted, FDA must consider public health and environmental impacts in its safety assessment of a proposed new animal drug. This is most evident in FDA's regulation of drugs used in food-producing animals, where use of drugs can affect the safety of meat and milk products consumed by humans or other animals. FDA applies the following approaches, among others, to the review, approval, and use of these drugs. Tolerances and Withdrawal /Withholding/Discard Periods . Drug sponsors are required to study the persistence of a drug (called a "residue") in the tissues of food-producing animals and demonstrate a safe management approach, such as the minimum number of days after drug treatment ends that an animal must be held untreated before it can go to slaughter (called a "withdrawal period"), or that a cow's milk must be discarded rather than marketed. Limitations on " Extra-Label " Prescribing . Veterinarians are generally permitted to prescribe and/or dispense medications for indications not stated on the label (referred to as "off-label" in human medicine) and for species not stated on the label. This provides the basis of authority for veterinarians to prescribe or dispense human medications for use in animals. However, this practice is limited in a number of ways for uses in food-producing animals, in order to keep the food supply free of potentially harmful drug residues. Judicious Use of Medically Important Antimicrobial Drugs . According to FDA, "Antimicrobial use in animals can contribute to the emergence of antimicrobial resistance in bacteria that may be transferred to humans, thereby reducing the effectiveness of antimicrobial drugs for treating human disease."