On this page:
- Novel Approaches
- Continuous Manufacturing and Other Advanced Manufacturing Technologies
- Flexibilities in the Review Process
- Legislative Authorities
- Meeting Emerging Public Health Challenges
- Communication with Stakeholders to Increase Transparency and Predictability
- Research to Support Approval
The FDA’s Center for Veterinary Medicine (CVM) protects and promotes public health by ensuring that animal drug products are evaluated for safety and effectiveness; manufactured under quality standards; and properly labeled. While CVM evaluates new animal drug products according to existing laws and regulations that define the critical regulatory standards for approval (e.g., substantial evidence of effectiveness, reasonable certainty of no harm), CVM has flexibility in how these standards are met.
CVM does more than review animal drug applications. Promoting public health also requires the Agency to take steps that can help facilitate access to safe, effective, and innovative products, that can address existing, novel, and emerging animal health challenges. CVM takes a proactive approach to ensuring we have the tools and flexible processes to bring these innovations to the market.
CVM is committed to the identification and use of novel approaches to bring innovative products to the market while meeting 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.
Some other examples include:
- In 2014, CVM approved Folltropin, the first drug that relied on a systemic review of the literature and meta-analysis for the determination of effectiveness. CVM plans to update its current guidance for industry to further encourage this innovative approach.
- 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.
Continuous Manufacturing and Other Advanced Manufacturing Technologies
One of today’s most important tools for modernizing the animal pharmaceutical industry is a process known as continuous manufacturing. This advanced form of manufacturing transforms the traditional, step-wise manufacturing processes into a single system that’s based on modern process monitoring and controls. CVM supports and encourages the adaptation of advanced manufacturing technologies for animal drug products and encourages any sponsor interested in incorporating advanced manufacturing to meet with CVM to discuss the best regulatory filing strategy for the process. Advanced manufacturing is still new and developing. Harnessing the full potential of these innovations will require us to invest time and resources in developing scientific standards and policy and supporting implementation.
Flexibilities in the Review Process
CVM’s scientists regularly look for ways to move regulatory science forward and identify and fill gaps. For example:
- CVM recognizes that there are many critical drugs used by veterinarians that are not approved. CVM published a review of the scientific literature on the safety of one such drug, potassium bromide, in 2012. This innovative approach enabled a drug company to complete the target animal safety standard without performing prospective animal studies, supporting the conditional approval of KBroVet in January 2021.
- In 2018, CVM published a Federal Register notice seeking comments on how to improve the standard design of heartworm effectiveness studies. CVM recognized the limitations of the current recommended laboratory and field effectiveness studies for heartworm preventatives for use in dogs and sought stakeholder input on alternative approaches to these study designs that would reduce the limitations of such studies while also ensuring that the studies generate data to support substantial evidence of effectiveness.
Veterinary Innovation Program (VIP)
Veterinary regenerative medicine products (e.g., stem cells) and intentional genomic alterations (IGAs) in animals are fast-growing sectors of the animal health and agricultural industries and an active area of animal health research. The FDA initiated the Veterinary Innovation Program (VIP) in 2019 to facilitate advancements in development of these types 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 market for cell- and tissue-based products and IGAs in animals. As of August 2022, there were more than 40 products enrolled in the VIP.
Intentional Genomic Alterations (IGAs) in Animals
IGAs in 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 intentional genomic alteration (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 GalSafe pigs were the first products approved under the VIP, demonstrating the impact of this initiative in supporting the sponsor throughout the product review process.
Animal Cells, Tissues, and Cell- and Tissue-Based Products
In 2015, CVM published Guidance for Industry #218, Cell-Based Products for Animal Use, to clarify the regulatory pathway for different types of cellular products. In September 2021, CVM published additional draft guidance on good manufacturing practices and donor eligibility for animal cell- and tissue-based products. To help animal owners, veterinarians, researchers, and the public with access to information on clinical field studies investigating the use of these products in veterinary patients, CVM maintains a listing of Clinical Field Studies for Animal Cells, Tissues, and Cell- and Tissue-Based Products.
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 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 2021. 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.
Meeting Emerging Public Health Challenges
The COVID-19 pandemic showcased how CVM innovates when faced with a public health emergency, as it significantly impacted ongoing animal drug development. To help minimize the impact of the pandemic on new animal drug development, CVM issued two animal drug-specific guidances. In April 2020, CVM issued guidance providing recommendations for sponsors conducting ongoing studies to support new animal drug development. These recommendations were designed to help ensure the safety of animals, their owners, and study personnel; maintain compliance with good laboratory practice regulations and good clinical practices; and maintain the scientific integrity of the data. In May 2020, CVM issued guidance providing recommendations on the information drug sponsors should submit to the Agency to report and mitigate animal drug shortages during the public health emergency. CVM also collaborated with other FDA centers to publish several joint guidances on topics impacting both the human and animal health industry impacted by COVID-19, including guidance on statistical considerations for clinical trials conducted during the emergency, resuming normal manufacturing operations, and good manufacturing considerations.
A critical part of animal drug availability is having a robust program to minimize drug shortages’ impact on access to critical drugs, which came to the forefront during COVID-19. In additional to the guidance issued in May 2020, CVM continues to take proactive steps with the animal pharmaceutical industry to prioritize and expedite mission critical FDA inspections, reviews of submissions, and other regulatory actions for drugs that are in shortage or are at risk of going into shortage.
Communication with Stakeholders to Increase Transparency and Predictability
CVM takes a collaborative approach to working with its industry stakeholders to increase regulatory transparency and provide a more predictable pathway to approval. CVM regularly engages in dialogues with organizations that represent the animal drug industry and more targeted animal drug sectors. CVM also invites drug companies to meet periodically with us as part of portfolio overview meetings to share projections of their upcoming projects. Drug companies can meet with FDA early in drug development to discuss the regulatory pathway and work with CVM on solutions to challenges specific to their drug.
While communication with each drug company is a valuable tool, the FDA can often best communicate to the industry through guidance providing the Agency’s best and current thinking on how to navigate aspects of the approval process. In October 2021, the FDA published four significant final guidance documents that point specifically to our commitment to innovative approaches. The guidance documents provide pathways for 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 the US approval.
Research to Support Approval
In keeping with the goals of reducing, replacing, and/or refining the use of animals in research, CVM is 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.
FDA laboratories continue to investigate and define parameters for the culture and characterization of cellular based new animal drugs (including stem cells) to inform the development and evaluation of these products. CVM is engaged in cooperative research and discovery agreements (CRADAs) with corporate partners to develop a human intestine on-a-chip model that incorporates a multiple species bacterial microbiome for use in evaluating the potential impact of human consumption of animal drug residues in food derived from treated animals, and to develop physiologically-based in-silico models for the evaluation of new animal drug oral bioavailability and pharmacokinetics. CVM also collaborates with university experts to investigate the potential use of intestinal organoids on the evaluation of new animal drugs.
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.