Generic Animal Drug and Patent Term Restoration Act (GADPTRA)
On November 16, 1988, the President signed into law the Generic Animal Drug and Patent Term Restoration Act. The law, known as GADPTRA, amended the Federal Food, Drug, and Cosmetic Act (FD&C Act) to provide for the approval of generic copies of new animal drug products that have been previously approved and shown to be safe and effective when used according to their approved labeling. Under the FD&C Act, a generic sponsor must demonstrate, among other things, that its proposed generic new animal drug product has the same active ingredients, in the same concentration, as the approved reference-listed new animal drug product, and that it is bioequivalent to the reference-listed new animal drug product.
1. What is an Abbreviated New Animal Drug Application?
In order to legally market a generic new animal drug product, the generic sponsor must have an approved Abbreviated New Animal Drug Application, or ANADA for the product. The application must include, among other things, the following information:
- Reference-listed new animal drug product (RLNAD) - The approved RLNAD that the generic sponsor intends to copy must be identified.
- Patent Information - The application provides certification by the applicant that a patent does not exist, that a patent has expired or will expire on a certain date, or that a patent claimed for the approved product is invalid or will not be infringed upon by approval of the abbreviated application. In the latter-case, the generic sponsor must then notify the sponsor of the approved RLNAD and the owner of the patent that it has filed an ANADA claiming invalidity or noninfringement of the patent.
- Labeling - The application contains copies of the proposed labeling for the generic new animal drug product and of the approved labeling for the RLNAD. The labeling of the proposed generic new animal drug product must contain all of the same indications, warnings, cautions, directions for use, etc., as that of the approved RLNAD. It may differ only in tradename, logo, name and address, etc., that would be specific to the generic new animal drug product itself.
- Ingredients - The application identifies all of the active and inactive ingredients and any other components used in the manufacturing process of the proposed generic new animal drug product and their concentration in the final product. Unless FDA has granted an appropriate "Suitability Petition" (See Question 8), the finished product must also contain the same active ingredient(s), and be of the same strength, dosage form, and route of administration as the approved RLNAD.
- Bioequivalence - The application contains information to show bioequivalence between the proposed generic new animal drug product and the RLNAD or refers to an earlier letter approving a request for a waiver.
- Human Food Safety - A tissue residue depletion study may be required for the proposed generic new animal product if it is intended for use in food-producing animals.
- Manufacturing Methods, Facilities, and Controls - The application describes in detail the manufacture of the proposed generic new animal product, including, among other things, the manufacturing facilities, key personnel, analytical methods, specifications, and quality control procedures. All animal drugs must be manufactured in compliance with FDA's Good Manufacturing Practice regulations (GMPs). An FDA inspection for compliance with GMPs will be required. Current GMP regulations are found in Title 21, Code of Federal Regulations, Parts 210 to 226.
- Samples - Samples should be provided only if specifically requested by FDA.
- Environmental Impact - Every ANADA must contain either an environmental assessment (EA) or a request for categorical exclusion from the requirement to prepare an EA. Regulations regarding the environmental assessment are codified in Title 21, Part 25 of the Code of Federal Regulations.
- FOI Summary - An FOI Summary, which summarizes the studies forming the basis of approval of the ANADA, is required.
2. What new animal drug products are eligible to be copied as generics?
All new animal drugs that were approved for safety and effectiveness on November 16, 1988, or have been approved since that date, and are not protected by patent or exclusivity are eligible for copying under the FD&C Act, unless the new animal drug has been subsequently withdrawn from the market for safety or effectiveness reasons. A list of new animal drug products that are eligible to be copied (“the Green Book”) is maintained here.
3. What is marketing exclusivity?
Marketing exclusivity is the period of time during which we will not approve a generic copy of the approved RLNAD. The FD&C Act provides for five years of marketing exclusivity for a new animal drug product that has not been previously approved in any new animal drug application. During this period, no ANADA may be submitted (Exception: An ANADA may be submitted after four years if the generic sponsor claims noninfringement of a listed patent that is claimed for the approved RLNAD or its use). Under the FD&C Act, a pioneer sponsor may also qualify for a period of three years of marketing exclusivity for a new approved use of a RLNAD.
4. Under what circumstances may I request a waiver from in vivo bioequivalence studies?
An in vivo demonstration of bioequivalence may not be necessary for certain new animal drug products. Generally, these products are true solutions intended for oral or parenteral use. The proposed generic new animal drug product must have the same components and composition, except potentially minor differences in inert ingredients, as the approved RLNAD. Ordinarily, other more complex dosage forms, i.e., tablets, capsules, etc., and medicated feeds or feed premixes will not be granted a waiver. Such a request for waiver must be submitted and granted before an ANADA for that proposed generic animal drug product is submitted. The request for waiver should contain enough information on the composition of the proposed generic new animal product and its differences from the RLNAD to allow a determination of whether bioequivalence studies would be needed. The waiver request should be directed to a Generic Investigational New Animal Drug file (JINAD) established for the proposed generic new animal drug product.
5. How do I perform a bioequivalence study?
The generic sponsor is encouraged to seek our concurrence on a protocol for a bioequivalence study before beginning work on it. The conduct of a bioequivalence study (including a clinical endpoint study) must comply with the FDA's Good Laboratory Practices (GLP) regulations.
6. What is a Suitability Petition? What kind of differences between an approved product and a proposed generic product can be considered in a Suitability Petition?
A Suitability Petition is a public document (viewable by the public at large) that asks (petitions) the agency to affirm that the proposed generic new animal drug product and the RLNAD are sufficiently similar to permit submission of an ANADA. A Suitability Petition may only contain a request to submit an ANADA for a proposed generic new animal drug product that is claimed to be bioequivalent to the RLNAD but that differs from it in certain specific ways. The proposed generic new animal drug product may only differ from the RLNAD in:
- dosage form;
- route of administration;
- or if it contains more than one active ingredient and one of the active ingredients is different than that of the RLNAD
- or if it is a product intended for use in combination with another product in animal feed and the active ingredient of one of the products is different from the active ingredient of one of the RLNADs approved in combination.
No active ingredient of a single active ingredient animal drug product may be substituted for another.
7. How long will it take to get approval to market my generic new animal drug product?
The statutory limit for approval of an ANADA is 180 days. Under the Animal Generic Drug User Fee Act enacted in 2008 and reauthorized in 2013 (“AGDUFA II”) goals letter, FDA agreed to certain performance goals related to the review of ANADAs. The time of approval, to a large extent, depends upon the quality and completeness of the original application and its subsequent amendments.