The level of scrutiny surrounding animal medicinal products has strengthened more adverse events (AEs) associated with such products have emerged in animals. Indeed, AEs and adverse drug reactions (ADRs) is a cause of concern for veterinarians. Several cases of toxicity from commonly used drugs have been reported, in canines, for example. These include licosamides that cause vomiting; penicillin and beta-lactam antibiotics that lead to allergies & hypersensitivity; and aminoglycosides that are associated with nephrotoxicity [1]. As a result, regulatory agencies, like the US FDA provides stringent approval pathway for new animal drugs. This ensures that the approved animal drug is safe, effective, and of high-quality per its label which is specifically written for a particular species. It also ensures that the FDA continues to evaluate and monitor the product after they’re on the market, as post-approval surveillance can often uncover new safety and risks associated with the product that were unknown at the time of approval.
A New Animal Drug
A new animal drug can be for companion animals or pets (cats, dogs, horses) or “food-producing” animals (chickens, pigs, and cattle). The FDA’s Center for Veterinary Medicine (CVM) classifies dogs, cats, horses, chickens, pigs, cattle, and turkeys as “major” species. All other animals are minor species- i.e., fish, goats, ferrets etc. A New animal drug can be used for minor species or for a minor use in one of the major species where the condition isn’t as frequent and only occurs in a small number of animals a year, or the condition occurs in a limited part of the country and in small number of animals each year. An example of this is a drug being used to control pain in dogs that have bone cancer- only a few dogs get bone cancer each year [2].
Types of New Animal Drug Applications
The US FDA has 3 different types of new animal drug applications [3]:
- New Animal Drug Application (NADA): used to seek approval of a new animal drug.
- Conditional Approval (CNADA): used to seek conditional approval of a new animal drug.
- Abbreviated NADA (ANADA): used to seek approval of a generic new animal drug.
The ANADA process enables the approval of generic versions of safe and effective animal drugs without the need for conducting new safety and efficacy studies with the generic drug. The generic drug must have the same active ingredient, concentration, dosage form, and administration route as the reference new animal drug. Information that satisfies the following technical aspects must also be included in the ANADA with reference to the reference listed new animal drug [4]:
- Bioequivalence (BE) studies
- Proposed generic products require a BE study; in-vivo BE study protocols should be submitted as an e-submission in question-based review format for each major species approved for use. Sponsors that plan on conducting blood-level BE studies should submit the bioanalytical method validation report in an H submission for review before the study begins.
- Requirement for in-vivo BE study may be waived for certain generic products such as parenteral solutions intended for injection, oral solutions or other solubilized forms, topically applied solutions, and inhalant volatile anaesthetic solutions [5].
- Patent certification & marketing exclusivity [6],
- CMC [7],
- Environmental impact [8]
- Human food safety (provided the drug is to be used in a food-producing animal) [9].
The ANADA process can be completed as a full application or through phased review where the latter involves technical sections to be reviewed under the established generic investigational new animal drug file by the appropriate CVM review group. An administrative ANADA can then be filed once these technical sections are complete. It is important to note that foreign sponsors who wish to submit an ANADA must have a U.S. agent in place- one who resides in the country- that can submit the applications [4].
Did You Know?- Insight into the Global Veterinary Medicine Market
The global veterinary medicine market is experiencing significant growth, with an estimated size of USD 44.59 billion in 2022. It is expected to expand at a lucrative compound annual growth rate (CAGR) of 8.2% over the forecast period. The market’s growth is primarily attributed to the rise in livestock population and production in developing countries. Additionally, increased spending on animal healthcare and pet ownership rates in North America and Europe contribute to the market’s expansion. The Asia Pacific region is also witnessing rapid growth due to rising disposable incomes, increasing pet adoption, and the development of animal husbandry practices [10].
As a leading regulatory consulting organization, DDReg has supported its customers in filing generic animal drug applications to the US FDA via the ANADA pathway for several medicinal products that treat a variety of conditions in animals such as pain, inflammation, bacterial infections, etc. In addition to veterinary products, DDReg’s diverse regulatory affairs portfolio covers generics & complex generics, biologics, biosimilars, medical devices & combination products, vaccines, and consumer products.
References and Further Reading
[1] Arunvikram K, Mohanty I, Sardar KK, Palai S, Sahoo G, Patra RC. Adverse drug reaction and toxicity caused by commonly used antimicrobials in canine practice. Vet World. 2014 May 1;7(5):299-5.
[2] US FDA. From an Idea to the Marketplace: The Journey of Animal Drug through the Approval Process. United States Food and Drug Administration. 2020
[3] US FDA. New Animal Drug Applications. United States Food and Drug Administration. 2023
[4] US FDA. Abbreviated New Animal Drug Applications. United States Food and Drug Administration. 2023
[5] US FDA. Bioequivalence. United States Food and Drug Administration. 2023
[6] US FDA. Patent Certification for Generic Animal Drugs. United States Food and Drug Administration. 2023
[7] US FDA. Chemistry Manufacturing and Controls (CMC) Guidance for Industry (GFIs) and Questions and Answers (Q&As). United States Food and Drug Administration. 2023
[8] US FDA. Environmental Impact Considerations. United States Food and Drug Administration. 2023
[9] US FDA. Human Food Safety Guidance. United States Food and Drug Administration. 2023
[10] GrandView Research. Veterinary Medicine Market Size Report. 2022