By: Steven M. Solomon, D.V.M., M.P.H., Director, Center for Veterinary Medicine
The U.S. Food and Drug Administration’s Center for Veterinary Medicine (CVM) plays a vital role in facilitating the development and availability of innovative medical products for animals. Our role in promoting public health drives us to take steps that can help facilitate access to safe, effective, and innovative products to address existing, new, and emerging animal health challenges. The FDA takes a proactive approach, using all of our available tools and flexible processes, to provide timely and efficient review approaches to ensure safety and effectiveness and help bring these innovations to the market.
Today the FDA released four final guidance documents that demonstrate our commitment to innovative approaches. The guidance documents describe pathways for animal drug sponsors to use new approaches like adaptive study designs, real world evidence and biomarkers to establish drug effectiveness and more detailed guidance on how to leverage data collected from foreign countries to support approval of their products in the U.S. These guidance documents encourage animal drug sponsors to consider these innovative approaches as they prepare data submissions related to new animal drug products for agency evaluation and review, as part of the FDA’s new animal drug approval process. The recommendations in these guidance documents closely align with those already issued by the FDA’s other medical product centers.
CVM is also committed to the identification and use of alternative methods to bring innovative products to the market by encouraging use of novel approaches to meet the regulatory standards. The typical process for demonstrating drug effectiveness is conducting a clinical trial; however, there are other ways to prove an animal drug works and alternative study designs to use when the standard design doesn’t fit the situation.
For example, CVM evaluated a range of data sources that demonstrate the safety of ThyroKare in dogs, a drug used to treat hypothyroidism, as an alternative to conducting laboratory animal studies. These sources included (1) a comprehensive review of publicly available literature on the use of levothyroxine in dogs; (2) pharmacovigilance data for ThyroKare that were voluntarily reported to the sponsor when it was previously marketed as an unapproved drug; and (3) reports to an animal poison control center of accidental overdoses of natural or synthetic thyroid hormone products in dogs.
In 2018, CVM approved Experior (lubabegron Type A medicated article), the first animal drug that when fed to beef cattle under specific conditions results in less ammonia gas released as a by-product of their waste. The drug sponsor collected data in special environmental chambers where gas emissions could be contained and accurately measured. These studies indicated that the product partially reduces ammonia gas emissions from manure from an individual animal or a pen of animals in semi-controlled conditions in enclosed housing.
Additionally, novel products, such as intentional genomic alterations (IGAs) in animals and animal cell and tissue-based products, offer the potential to treat or even cure diseases or conditions for which limited treatment options exist. The fields of veterinary regenerative medicine (e.g., stem cells) and IGAs in animals are fast-growing sectors of the industry and an active area of animal health research. While the same laws and regulations that apply to all other animal drugs also apply to these rapidly developing products, the FDA initiated the Veterinary Innovation Program (VIP) in 2019 to facilitate advancements in development of innovative animal products. The goals of the VIP are to provide greater certainty in the regulatory process, encourage development and research, and support an efficient and predictable pathway to approval for cellular products and IGAs in animals. As of September 2021, there were more than 40 animal drug products enrolled in the VIP program. IGA animals have potentially significant and broad applications to advance animal and human health including development of animal models of human disease, human pharmaceutical production, production of organs/tissues for xenotransplantation, improved animal health/husbandry and enhanced food production. Given the unique nature and evolving science associated with these products, the FDA uses a science- and risk-based review approach to assess the type and amount of information needed to support approval.
In December 2020, CVM approved a first-of-its-kind IGA in a line of domestic pigs, referred to as GalSafe pigs, which may be used for food or human therapeutics. This is the first IGA in an animal that the CVM has approved for both human food consumption and as a source for potential therapeutic uses. This approval underscores the success of the FDA in modernizing our scientific processes to optimize a risk-based approach that advances cutting-edge innovations in which consumers can have confidence. The developer of GalSafe pigs was the first product approved under the VIP program, demonstrating the impact of this initiative in supporting the sponsor throughout the product review process.
The FDA also helps support innovative product development by using legislative authorities designed to increase drug availability for minor animal species or minor uses in major animal species while ensuring critical standards are still met. One way the agency does this is through the conditional approval pathway for new animal drugs. Established as part of the Minor Use and Minor Species (MUMS) Animal Health Act in 2004, conditional approval allows a drug company to legally market a drug for use in a minor species, such as ornamental fish, ferrets, sheep, goats or honey bees, or for a use in a major species (horses, dogs, cats, cattle, pigs, turkeys and chickens) afflicted with an uncommon disease or condition (minor use) after proving the drug is safe and that there is reasonable expectation that it will be effective.
Recently, this program has helped facilitate development and approval of certain innovative canine cancer drugs. For example, in January 2017, the FDA conditionally approved the first drug to treat lymphoma in dogs, and this drug became the first conditionally-approved companion animal drug to achieve full approval in July of this year. In January 2021, the FDA conditionally approved the second drug and first oral tablet to treat lymphoma in dogs. The ability to utilize the MUMS conditional approval pathway enabled access to critical treatments for lymphoma in dogs before evaluation of all of the effectiveness data typical for a full approval had been completed.
In keeping with the goals of reducing, replacing, and/or refining the use of animals in research, CVM is also conducting a study at its research facility to validate an alternative in-vitro dissolution model approach for bioequivalence studies for certain animal drugs. If this study validates the bioequivalence model, this alternative approach will provide animal drug sponsors with a scientifically sound method to demonstrate bioequivalence of certain drugs that does not require that dogs be euthanized as part of the study.
CVM’s flexible, collaborative and proactive approach to the regulation of animal drugs has facilitated the availability of critically needed drugs for conditions like heart failure, hypertension, cancer, epilepsy and pain and brought a number of generic animal drugs to market to enhance competition and drive innovation. These approaches have also facilitated the introduction of novel technologies with One Health impacts beyond animal health like reduction in gas emissions from an animal’s waste and IGAs in animals that produce biopharmaceuticals used in the production of human drugs. We are committed to continuing our collaborations with a variety of stakeholders to ensure the efficiency of our review and approval process for new animal drugs, and that we are supporting innovative approaches that ultimately help safe and effective animal drugs reach the marketplace.
For more information: Innovation in Animal Drug Development