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The FDA's New Animal Drug Application Process: 5 Best Practices for Ensuring Compliance


    Comply with FDA rules governing the new animal drug application process (NADA) to ensure product approval and avoid warning letters and other enforcement actions.

    The FDA has strengthened its scrutiny of animal drug products as public awareness of the issues surrounding their use and adverse events have increased. A number of manufacturers have been warned about marketing products with treatment claims without first obtaining approval from the agency. The approval process for a veterinary drug is as complicated and rigorously analyzed by the FDA as the one for human medicines. This article details what is considered an animal drug, the different types of applications and finally explains five best practices that manufacturers can adopt in order to ensure better compliance with the application process for a new animal drug.


    the-veterinary-drug-approval-process-and-fda-regulatory-oversight

    What is a New Animal Drug?

    According to the FDA, a new animal drug is any drug intended for use in animals other than man. This includes any drug intended for use in animal feed (though not the animal feed itself). The FD&C Act states that an animal drug cannot be sold into interstate commerce unless it has been approved through the new animal drug application (NADA), abbreviated NADA (ANADA), or conditional approval (CNADA).

    New Animal Drug Application

    There are three different types of new animal drug applications as mentioned above:

      NADAs and supplements - NADA is used to seek approval of a new animal drug and includes any subsequent supplemental applications made to an approval.

      ANADAs and supplements - An ANADA is used to seek approval for a generic new animal drug and includes any subsequent supplements to an approved ANADA.

      CNADAs - Applications for conditional approval allow a drug sponsor to legally market a new animal drug intended for a minor use or a minor species after proving it is safe, but before collecting all the necessary effectiveness data. The drug sponsor can keep the product on the market for up to five years, while collecting effectiveness data, if FDA approves the sponsor's annual renewal requests.

    The approval process for a new animal drug is similar to that of a human drug. The drug sponsor has to show that the drug is safe and effective when used as directed on the label. In the case of a NADA, the drug sponsor has to submit the application along with all supporting data, including all adverse effects associated with the drug product's use. The sponsor must show that

    • It can manufacture the drug so that the product's composition is consistent from batch to batch,
    • The product's active ingredients come from reliable sources
    • It follows good manufacturing practices while making the product.

    In case the drug is to be used in a food-producing animal, residues in food products from that animal should be shown to be safe for human consumption.

    The Center for Veterinary Medicine (CVM), the division of the FDA that oversees the regulation of animal drugs, also looks at environmental impact of the drug and the safety of the people who will give the drug to the animal or who may come in contact with the drug during the NADA process.

    Why Compliance is Important

    Compliance with the FDA's new animal drug application process is important as bypassing the agency's approval can result in Warning Letters and withdrawal of the product from the market, thus affecting the manufacturer's reputation and eroding public trust. Companies that violate the rules can also be faced with monetary penalties.

    5 Best Practices for Ensuring Compliance with the NADA Process

    The NADA process can be complex and time consuming, but manufacturers can ensure compliance with the FDA's regulatory requirements by adopting the following best practices:

    1. Show that the drug is safe and effective
    2. When preparing the NADA submission, the sponsor should include information that shows the drug is safe when administered to the target animal species in accordance with the uses detailed in the labeling. The studies should meet the following two goals:

      • Identify any harmful side effects of the drug; and
      • Establish a margin of safety for the drug.

      Information related to evaluation of safety and effectiveness of the new animal drug such as:

      • Information derived from other studies that involved similar drugs or the same drug in another country/region
      • Information obtained from commercial marketing of similar drugs
      • Reports in published scientific literature (favorable and unfavorable) that involves the product

      Certain drugs will require additional safety data - like those that will be administered to breeding animals.

    3. Include full details of product labeling
    4. The application must include three copies of each piece of all labeling that will be used on the product - that is, a total of nine copies. The following information should also be included:

      • Label identification showing the position of the label on the product or the way in which it will accompany the market package
      • Nonprescription animal drugs should include adequate directions for use under all conditions explained in a way that a layman can understand
      • Prescription veterinary drugs should have adequate information for use that allows the veterinarians to use the new animal drug safely and for the purposes for which it is intended
      • Any necessary use restrictions should be prominently and conspicuously displayed
      • Labeling for new animal drugs intended for use in the manufacture of medicated feeds must include:
        • Specimens of labeling to be used for such a drug with adequate directions for the manufacture and use of finished feeds for all conditions
        • Representative labeling that will be used for Type B and Type C medicated feeds containing the new animal drug in the case of drugs to be used in manufacture of medicated feeds, draft labeling can be submitted for preliminary consideration of an application. Final labeling will, however, be required prior to application approval.
    5. Prove that human food will be safe
    6. Human food made from treated animals has to be safe therefore drug sponsors must include information in their application that proves this and which has been obtained through human food safety studies. The application must also include the methods used to determine the level of residues that remain in the food made from an animal that has been treated with the drug. Ideally the application should include the complete experimental protocols as a well as complete details of the residual studies carried out under various conditions.

    7. Describe the chemistry, manufacturing and controls
    8. The chemistry section of the application should include the following:

      • Chemical structural formula or description for any new animal drug substance.
      • Relationship to other chemically or pharmacologically related drugs.
      • Description of dosage form and quantitative composition.
      • Scientific rationale and purpose the new animal drug is to serve:
        • Clinical purpose. o Highlights of laboratory studies
        • Highlights of clinical studies
        • A short statement of conclusions combining the major points of effectiveness and safety as they relate to the use of the new animal drug.

      The application should also include complete details of:

      • The person(s) responsible for manufacture, processing, packaging, labeling and control operations of the drug product if the applicant did not perform these
      • Qualifications, including educational background and experience, of the technical and professional personnel responsible for quality assurance
      • Facilities used in manufacturing, processing, packaging, labeling, storage, and control operations - Methods used in the synthesis, extraction, isolation, or purification of any new animal drug
      • Precautions taken to ensure proper identity, strength, quality, and purity of the raw materials, whether active or not
      • The instructions used in the manufacturing, processing, packaging, and labeling of each dosage form of the new animal drug
      • The analytical controls used during the various stages of the manufacturing, processing, packaging, and labeling of the new animal drug
      • Batch control numbers used in the manufacturing, processing, packaging, and labeling of the new animal drug
      • Characteristics of and the test methods employed for the container, closure, or other component parts of the drug package
      • Stability studies of the new animal drug in the final dosage form
      • Procedures designed to prevent contamination
    9. Prepare an environmental assessment
    10. An environmental assessment evaluates the potential risk for the drug or feed additive to cause significant environmental impacts. The evaluation is done taking into consideration fate, exposure, and effects data, and focuses on relevant environmental issues relating to the use and disposal of veterinary drugs or feed additives.

      The FDA along with other agencies in the US and EU has issued guidance documents that sponsors can use to create a concise environmental impact assessment - these are to be carried out in two stages: Phase 1 and Phase 2.

      If the CVM concludes that the drug has no significant impact on the environment based on the information in the EA, it will prepare a Finding of No Significant Impact (FONSI). If, on the other hand, the CVM decides that the drug will have a significant impact on the environment, it will issue an Environmental Impact Statement (EIS).

      The sponsor can ask for a categorical exclusion or CE from preparing an environmental assessment for a drug that is unlikely to cause an environmental impact.

    Comply with the FDA's New Animal Drug Application Rules to Avoid Citations

    As the incidents of food made from animals causing widespread illnesses and fatalities and issues related to the manufacture of pet food and drugs increase, the FDA has escalated its enforcement actions against those companies found to be violating the law. Animal drug manufacturers can no longer avoid regulatory scrutiny and those found to be non-compliant with regulations such as the ones governing marketing of new drugs have been held to account. Making treatment and/or prevention claims when marketing a product without having taken approval from the FDA can result in warning letters and product seizures. Negative headlines relating to a company's animal drug product can tarnish its reputation and public trust will be hard for it to regain. Following the regulators' rules to the letter and adopting the best practices related to the new animal drug approval process detailed on this web page can help companies better comply with the law.

    The areas highlighted above are just a small part of the wide range of practices and processes that ensure drug manufacturers comply with regulations. Subjects such as drug compliance are multi-faceted and complex and can be better understood after attending a training course such as the ones offered by ComplianceOnline. Our courses are available as webinars, training recordings, and seminars. We also offer customized training courses developed in conjunction with organizations that wish to train large groups of their employees.

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