Questions and Answers Regarding EPA/FDA Whitepaper: “A Modern Approach to EPA and FDA Product Oversight”

In February 2023, EPA and the U.S. Food and Drug Administration (FDA) released a new whitepaper, “A Modern Approach to EPA and FDA Product Oversight” that describes possible approaches for updating the agencies’ oversight of various products for animals regulated as either pesticides or new animal drugs. This webpage responds to some of the public’s questions and comments about the whitepaper, including those received during the public comment period and the public meeting. All comments can be found in docket EPA-HQ-OPP-2023-0103.

Questions Related to FDA’s Regulatory Process

1. What types of products does FDA’s Center for Veterinary Medicine (CVM) currently regulate?
   • FDA regulates new animal drugs, which are defined in part as articles intended to diagnose, treat, cure, mitigate, or prevent disease in animals and articles intended to affect the structure or any function of animals.
   • FDA regulates drugs given to animals by a variety of different routes of administration, including topical (such as topically applied products for external and internal parasites), oral, injectable, and products for all categories of animals, including pets, livestock, honeybees, and aquaculture.
   • FDA already regulates many products containing the same ingredients as the topically applied products the agencies are discussing moving from EPA to FDA.
2. What expertise does FDA have to regulate animal drugs?
   • FDA has a wide variety of scientific and regulatory expertise to regulate animal drugs, including but not limited to veterinary, environmental, aquaculture, toxicology, animal science, biology, chemistry, pharmacology, epidemiology, entomology, policy, and legal expertise.
   • FDA is a founding member of the International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH), which aims to establish and implement harmonized technical requirements for the registration of veterinary medicinal products that meet high quality, safety and efficacy standards and minimize the use of test animals and costs of product development.
3. Does FDA regulate both prescription and over-the-counter products for animals?
   • Yes, FDA regulates both prescription and over-the-counter (OTC) products. An animal drug is a prescription drug if it is not safe for animal use except under the professional supervision of a licensed veterinarian or if it is limited to prescription use during the approval process.
4. What does FDA review in order to approve animal drugs?
   • Effectiveness – the drug achieves its intended effect in the target animal species when it is used according to the label.
   • Target Animal Safety – the drug is safe to the target animal species when it is used according to the label.
   • Human User Safety— the drug is safe to people exposed to the drug, such as people administering the drug and people who are in contact with the animals, including children.
   • Human Food Safety – food products (such as milk, eggs, or meat) from treated animals are safe for people to eat, when the drug is used according to its label.
   • Environmental Impact– evaluates whether the investigational use and approval of a new animal drug will result in significant environmental impacts as required under the National Environmental Policy Act. See next question for more information about FDA’s environmental review.
   • Chemistry, Manufacturing, and Controls – correct tests, equipment and methods are in place to consistently produce a high-quality and safe drug.
   • Labeling – the labeling includes all necessary information to use the drug safely and effectively and identifies risks associated with the drug.
   • All Other Information – all information pertinent to the evaluation of safety and effectiveness the sponsor has received or otherwise obtained from any source for the new animal drug, has not previously been submitted for review (e.g., published scientific literature or foreign experience if the drug is approved in a country outside of the United States).
5. What does FDA’s environmental review look like?
   • Under the National Environmental Policy Act of 1969 (NEPA), FDA evaluates all major agency actions (including approval of new animal drugs or supplemental applications for existing animal drugs) to determine if the action will have a significant impact on the human environment.
   • FDA experts in the environmental sciences evaluate whether the action (e.g., an approval) may have a significant impact on the environment. There are three tools used by FDA to evaluate the potential for environmental impacts. Categorical exclusions are categories of actions that have been predetermined do not individually or cumulatively impact the human environment. Environmental assessments (EA) allow FDA to determine whether significant impacts may occur. If significant impacts occur, then an environmental impact statement (EIS) must be prepared. Most actions for animal drugs result in a claim of categorical exclusion or preparation of an EA.
   • Drugs intended for use in non-food animals, including dogs and cats, normally meet the criteria for a categorical exclusion (21 CFR 25.33) because, based on previous evaluations and experience, they generally are not expected to result in significant environmental impacts. However, CVM always evaluates the potential for extraordinary circumstances to exist that indicate that a specific proposed action that ordinarily would be excluded may significantly affect the quality of the human environment. If extraordinary circumstances exist, then an EA will be required (21 CFR 25.15 and 25.21), even for actions that normally would be categorically excluded. Examples of extraordinary circumstances include actions where there is the potential for serious harm to the environment and actions that adversely affect a threatened or endangered species (21 CFR 25.21).
   • Drugs for use in food animals, including cattle, swine, poultry, and aquaculture, often require the preparation of an EA. Directions for preparing an EA can be found at 21 CFR 25.40 (Environmental assessments), and guidance can be found in GFI #89, “Environmental Impact Assessments (EIA’s) for Veterinary Medicinal Products (VMP’s) I– Phase I,” and GFI #166, “Environmental Impact Assessments (EIA’s) for Veterinary Medicinal Products (VMP’s) – Phase II” (both of which are internationally harmonized VICH guidelines). An EA adequate for approval is one that contains sufficient information to enable the Agency to determine whether the proposed action may significantly affect the quality of the human environment (21 CFR 25.15(a)).
6. How does FDA review potential adverse incidents reported to the agency? o CVM Adverse Event Report (AER) data provide an early warning or signaling system to CVM for safety issues not detected during pre-market testing of FDA-approved animal drugs, detection of product manufacturing-related problems, or detection of a problem occurring because of inappropriate or incorrect use of a drug used in animals.
   • CVM scientists use the AER data to identify potential safety risks and make decisions about product safety, which may include changes to the label or other regulatory action.
   • When analyzing the AER data, CVM’s reviewers thoroughly evaluate all safety information included in the reports. CVM receives adverse event reports from animal owners, veterinarians, and drug manufacturers. CVM continuously monitors the adverse event database to identify potential safety signals and validate them by analyzing and interpreting the data. When combined with other scientific information, this information is used to generate meaningful data that can be used to help make decisions on potential safety issues.
   • CVM also supplies AER data to openFDA.gov so that the public can access information about clinical signs that have been reported for these drugs used in animals.
7. How do the agencies address potential environmental effects from products to treat external parasites that may end up in water?
   1. Based on the comments received, the agencies are discussing what they could do to better coordinate and collaborate on water quality challenges and questions.

Questions Related to Scope of a Modernized Process

8. Would the agencies need to update the 1973 Memorandum of Understanding (MOU) to better reflect a more modernized framework, including what the agencies are currently regulating and any potential changes?
   • Yes, the agencies may need to publish an updated version of the 1973 MOU that adds clarity on which agency regulates which products. The agencies anticipate maintaining the status quo for most products (except topically applied products for external parasites).
9. Are genetically modified animals produced for food included in the scope of this discussion?
   • No, only pest animals that are genetically engineered for population control uses are included in the scope of the whitepaper.
10. Are the agencies considering moving feed-through pesticides from EPA to FDA?
    • No, at this time the agencies are not planning to move feed-through pesticides. Feed-through products are those pesticide chemicals that are fed to livestock, travel through the digestive tract, and are excreted into the manure for the purpose of controlling flies or other insects that land or feed on the manure.

11. Are livestock pesticide products being considered in the transfer of jurisdiction/regulatory oversight from EPA to FDA?

    • The agencies have no immediate plans to transfer jurisdiction on products used on livestock to control external parasites.
    • The whitepaper discusses the transfer of oversight from EPA to FDA of topically administered products for external parasites of animals, which are currently regulated as pesticides.
    • While this category can include products used on pets and livestock, at this time, the agencies’ primary focus is on animal safety concerns related to products used on pets and ensuring that these products are with the agency that has the resources and expertise needed to best evaluate the safety of these products.
    • Again, no changes are imminent, and stakeholders will have more opportunities to make their views known before any potential future changes in product oversight. 
12. Are miticides and other bee related products also being considered in the transfer of jurisdiction/regulatory oversight from EPA to FDA?
    • EPA and FDA do not have immediate plans to transfer miticides or other products used to control external parasites of bees from EPA to FDA.
    • The agencies have received numerous comments from beekeepers and industry during the public hearing and whitepaper public comment period regarding concerns related to transfer of these products.
    • EPA and FDA have heard these comments, and as we continue to discuss realigning regulatory oversight in a way that protects humans, animals, and the environment, we commit to doing so through a transparent and participatory process.
    • Again, no changes are imminent, and stakeholders will have more opportunities to make their views known before any potential future changes in product oversight.

Questions Related to EPA/FDA Transfer Process

13.  Would Good Manufacturing Practices (GMPs) be required for EPA products that move to FDA jurisdiction?
    • FDA is interested in discussing what manufacturing practices would be required and in working collaboratively on this issue in the future. FDA anticipates working with industry to develop risk-appropriate manufacturing standards – many of which we anticipate industry is already performing – to ensure the quality of the product they are producing.
14. Would consumer access to pet and livestock products moved from EPA to FDA be interrupted? What measures would the agencies take to ensure that access is not interrupted?
    • EPA and FDA agree that many of these products are important to animal and public health. To that end, the agencies are striving to develop a process in collaboration with stakeholders that would preserve access to these important products if they are transitioned from EPA to FDA.
15. Would products used on pets and livestock to control fleas, ticks, and other external parasites remain available over-the-counter (OTC)?
    • Yes, FDA expects that most of these products would remain available over-the-counter, without the need for a veterinary prescription, unless serious safety concerns are identified.
16. Would the submission of additional data be required for products to move from EPA to FDA?
    • FDA and EPA would like a process that minimizes burden for stakeholders, possibly by enabling the agencies to rely mostly on existing registration files and publicly available information.
17. How long does it take to get a New Animal Drug Application (NADA) approval with FDA?
    • FDA CVM has a phased review process for animal drug approvals that allows drug developers to begin seeking FDA approval and having discussions with FDA experts early in drug development.
    • Many developers open files with FDA when products are still in the investigational research and development stages, often years before all of the studies and information necessary to ensure a drug is safe, effective, appropriately manufactured and properly labeled have been generated.
    • Total time to approval includes both the time it takes the sponsor to generate the required data and information to support approval as well as FDA’s review time, which may be an iterative process.
    • Therefore, while it may take years to obtain FDA approval of a new animal drug, because of FDA’s flexible phased review process, this timeframe includes the investigational/research and development phase when developers may still be generating data and information to support approval of their product.