This page will provide information to assist the pioneer new animal drug sponsor through the first steps to get started with the new animal drug approval process including establishing an Investigational New Animal Drug (INAD) file.
NOTE: For sponsors seeking approval for a drug that will be a copy of a previously approved drug, this is a generic new animal drug. Please contact the Division of Generic Animal Drugs at CVMDGADMGT@fda.hhs.gov. You may also refer to Abbreviated New Animal Drug Applications for more information on the generic new animal drug approval process.
If you aren’t sure whether your product is considered an animal drug, please contact Ask CVM at firstname.lastname@example.org with a description of the product and its intended use and attach any proposed labeling.
An INAD file is the investigational file under which studies to document the safety and effectiveness of a new animal drug are conducted. Studies under an INAD file can be used to support a New Animal Drug Application (NADA). The regulations regarding INADs are in 21 CFR Part 511.
The new animal drug application (NADA) process is a systematic way to document the safety, effectiveness, and proper manufacturing to support approval of the new animal drug.
The recommended approval pathway is the phased review process, where a sponsor submits data and information supporting technical section requirements for incremental review under the INAD file. Once all requirements have been met, a sponsor can file an administrative NADA, which is reviewed within a 60-day timeframe. CVM recommends using the phased review process, because this process allows for greater CVM and sponsor interaction that is particularly critical to the development of new, innovative products. Additional information about the approval process can be found at the links below.
The regulations for New Animal Drug Applications are in 21 CFR Part 514.
An overview of the animal drug approval process is at: From an Idea to the Marketplace: The Journey of an Animal Drug through the Approval Process.
CVM GFI #132: Administrative Applications and the Phased Review Process.
A CNADA is used to seek conditional approval of a new animal drug. A conditionally approved product has met all the requirements to support the full approval of the new animal drug except for a demonstration of “substantial evidence of effectiveness.” For a CNADA, the applicant must demonstrate a “reasonable expectation of effectiveness.” A conditionally approved product allows the applicant to legally market the new animal drug for up to 5 years, provided FDA approves the required annual renewal requests, while the applicant continues to collect the effectiveness data needed to meet the “substantial evidence” standard for full approval.
There are two types of new animal drugs that may qualify for the conditional approval pathway: (1) a new animal drug for a minor use (in a major species) or use in minor species and (2) a new animal drug for a major use in a major species for serious or life-threatening conditions or unmet animal or human health needs where demonstration of effectiveness would require a complex or particularly difficult study or studies (also referred to as “expanded use of conditional approval”). For information regarding CVM’s processes for determining conditional approval eligibility, please see CVM ONADE’s P&P 1243.5704 Process for Eligible Sponsors to Obtain Conditional Approval.
For more information about INADs, NADAs, and CNADAs, please visit New Animal Drug Applications.
The Animal Drug User Fee Act of 2003 (ADUFA), amended the Federal Food, Drug, and Cosmetic Act (FFDCA) and authorized FDA to collect fees for certain animal drug applications, and for the establishments, products, and sponsors associated with these and previously approved animal drug applications, in support of the review of animal drugs.
There are user fees associated with animal drug review. The first fee encountered would be the annual sponsor fee once you establish a qualifying file with us. Fiscal Year 2023 animal drug user fee rates can be found here.
Fee waivers are available in certain cases; that information is available in CVM GFI #170: Animal Drug User Fees and Fee Waivers and Reductions. Note that the small business waiver can only be applied to the first application fee; it would not waive the annual sponsor fee.
Waivers may be submitted before establishing an INAD file. Waivers can be submitted in paper following the instructions in CVM GFI #170. Waivers can also be submitted electronically if a sponsor has completed electronic submission registration.
Information about user fees is available at: Animal Drug User Fee Act (ADUFA).
For waiver related questions, please contact: CVMADUFA@fda.hhs.gov.
If you are a non-U.S. sponsor, you will need a U.S. agent. Please keep in mind that your U.S. agent must either reside in the U.S. or maintain a place of business in the U.S. The U.S. agent cannot use a post office box as an address. The U.S. agent cannot use just an answering service. They must be available to answer the phone or have an employee available to answer the phone during normal business hours. All of your submissions to INAD and NADA files should be submitted by your U.S. agent on your behalf.
For more information on how CVM’s ONADE interacts with U.S. agents, please see P&P 1243.2020: United States (U.S)-Based Employee and U.S. Agent Representation of Foreign Sponsors.
Sponsors are not required to work with a consultant. A sponsor new to animal drug approval may find it helpful to work with an experienced consultant. If you wish to have the consultant make submissions or consult with the agency on your behalf, a G submission, outlining those permissions, is required in addition to the consultant being registered and set up to use eSubmitter.
Submissions are made using the CVM eSubmitter tool.
The sponsor will appoint someone (e.g., regulatory staff, a consultant, or U.S. Agent) to make submissions via CVM’s eSubmitter tool. CVM recommends you have two assigned stakeholders who are capable of making submissions.
eSubmitter is the electronic submission platform in which all submissions are made to CVM.
Information about setting up eSubmitter and using eSubmitter to make electronic submissions is available at: CVM eSubmitter Program for Animal Drugs - Office of New Animal Drug Evaluation. Additional details are available through the “Resource Center” link at the bottom of the page.
The FDA Electronic Submissions Gateway (FDA ESG) is the conduit through which successful electronic submission of information to the CVM Electronic submission system (CVM ESS) for review and evaluation must occur. The FDA ESG is separate and distinct from the CVM ESS. The purpose of the FDA ESG is to provide a centralized, Agency-wide communications point for securely receiving electronic regulatory submissions. Stakeholders seeking to make electronic submissions to the CVM ESS must register separately both with the FDA ESG and the CVM ESS. Registration for both systems can be done simultaneously and may take at least 30 days.
FDA ESG: Registering with the FDA ESG includes several steps, including requesting a WebTrader account and the process may take up to 30 days to complete. Some helpful resources for getting set up with FDA ESG include:
- Setting up a WebTrader Account Checklist
- ESG Chapter 2 Overview of The Registration Process
- ESG overview: Electronic Submissions Gateway
- ESG User Guide: User Guide
- Section IV and Appendix 3 of GFI 108, “Registering with CVM Electronic Submissions System”
For FDA ESG and WebTrader support, contact: ESGHelpDesk@fda.hhs.gov.
CVM ESS: You can register with CVM ESS at the same time as you register for the FDA ESG. This process may take 30 days or more to complete. Some helpful resources for getting set up with CVM ESS include:
For CVM ESS support, contact: email@example.com.
CVM eSubmitter: CVM eSubmitter is a free, question-based tool that allows animal drug sponsors to electronically and securely submit information to the center. Once you are registered with FDA ESG and CVM ESS, you can use the CVM eSubmitter tool to create and send submissions. Some helpful resources for getting started with CVM eSubmitter include:
- CVM eSubmitter program download
- CVM eSubmitter quick guide
- CVM eSubmitter Program for Animal Drugs—Office of New Animal Drug Evaluation
- CVM Recommended File Specifications for eSubmitter
- Getting Started with eSubmitter
For CVM eSubmitter support, contact: firstname.lastname@example.org.
A request to establish an Investigational New Animal Drug (INAD) file should be submitted through eSubmitter.
General summary of the “INAD-A” eSubmitter template specific requirements:
- Screen: 6.0 Submission Type Code/Amendment Information
- Select “Establish INAD File (A), Other; Unclassified
- Select “Division of Companion Animal Drugs (HFV-110)” or “Division of Food Animal Drugs (HFV-130)”
- Screen: 7.0 Product Description
- Populate required fields: “Does the drug product have a USP monograph?”, product established name and details such as product dosage form, Route of Administration (ROA) and Target Animal designations.
- For specific information on completing the product related information fields, please see CVM eSubmitter Product Book Quick Guide.
EI is defined as “data and /or information which uniquely describes the general attributes of the new animal drug.” We recommend that EI be submitted as part of the initial request to open an INAD file.
For more information regarding CVM ONADE’s processes for accepting and reviewing EI, see CVM ONADE’s P&P 1243.2200 Submission and Review of Early Information (EI) to Presubmission Conferences and Protocol Review.
Yes, please refer to the CVM’s Guidances for Industry (GFI) for information about specific parts of the approval process. You are not required to follow these documents and you can propose alternative approaches, but they will provide insight on what is typically needed.
- CVM GFI #85 (VICH GL9) Good Clinical Practice
- CVM draft GFI #61 Special Considerations, Incentives, and Programs to Support the Approval of New Animal Drugs for Minor Uses and for Minor Species
- CVM GFI #106 The Use of Published Literature in Support of New Animal Drug Approvals
- CVM GFI #185 (VICH GL43) Target Animal Safety for Veterinary Pharmaceutical Products
- CVM GFI #3 General Principles for Evaluating the Human Food Safety of New Animal Drugs Used In Food-Producing Animals
- CVM GFI #152 Evaluating the Safety of Antimicrobial New Animal Drugs with Regard to Their Microbiological Effects on Bacteria of Human Health Concern
- CVM GFI #89 (VICH GL6) EIAs for Veterinary Medicinal Products - Phase I
- CVM GFI #166 (VICH GL38) Environmental Impact Assessments (EIA's) for Veterinary Medicinal Products (VMP’s) - Phase II
- Various Chemistry, Manufacturing, and Controls GFIs
After you have established the INAD, you should submit other requests, such as a pre-submission conference, a categorical exclusion request for investigational use of the product, and a food use authorization if applicable (authorization to slaughter animals for human consumption or use milk from lactating cattle).
A pre-submission conference is a meeting to discuss the proposed indication and requirements for drug approval. The regulation regarding pre-submission conferences is 21 CFR 514.5.
If you are going to request a food use authorization you will need to propose the number of animals that you think you will need to conduct studies and propose withdrawal periods for meat/milk. If you do this, you will need to provide as much residue information as you have so our residue chemists can assign a withdrawal period. Lack of information usually leads to long withdrawal periods. You must report the date and place of slaughter of all investigational animals to USDA/FSIS, unless you ask for a waiver of that requirement.
It is important to note that the proposed conditions of use included in your request for a food use authorization should be the same as those included with your claim of categorical exclusion for the investigational use of the new animal drug. If the conditions of use are not the same, then you should contact CVM because a new claim of categorical exclusion may be needed.
The shipment or delivery of a new animal drug within the United States (U.S.) intended for clinical investigations requires the submission of an environmental assessment (EA) or a claim of categorical exclusion (CE) from the requirement to prepare an EA [21 CFR 511.1(b)(10)]. In most cases, a claim of CE will likely be appropriate. Therefore, if clinical investigations or any shipments of the drug have occurred within the U.S. or are expected to occur prior to the new animal drug application (NADA) approval, then a claim of CE according to 21 CFR 25.33(e) should be submitted.
With a claim of CE, you must certify that to your knowledge, no extraordinary circumstances exist that may significantly affect the quality of the human environment as discussed under 21 CFR 25.21. If extraordinary circumstances are identified, you should contact CVM because the submission of an EA may be needed.
If you have questions regarding the environmental requirements for the investigational use of a new animal drug, please contact CVM. For more information on CVM ONADE’s processes regarding this topic, please see P&P 1243.7220: Processing Environmental Impact Submissions for New Animal Drugs.
The information provided above only addresses the investigational use of the new animal drug. Before submitting your administrative NADA, a separate EA or claim of CE to satisfy the Environmental Impact technical section of the NADA is required. Additionally, if you intend to pursue a conditional approval, a separate EA or claim of CE for the conditional approval will be needed.
The New Animal Drug Regulations, Sections 21 CFR 511.1(b)(3), 21 CFR 511.1(b)(4) and 21 CFR 511.1(b)(10) require the sponsor to submit specific information prior to each shipment or other delivery of the drug for clinical investigation in animals. You can do this in paper or electronically.
For more information on CVM ONADE’s processes regarding these notices, please see P&P 1243.4066: Notice of Claimed Exemption (NCIE).