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 new law, known as GADPTRA, amends the Federal Food, Drug, and Cosmetic Act to provide for the approval of generic copies of animal drug products that have been previously approved and shown to be safe and effective when used in accordance with their labeling. Under GADPTRA, a generic animal drug product may be approved by providing evidence that it has the same active ingredients, in the same concentration, as the approved animal drug product, and that it is bioequivalent to the approved animal drug product.

1. What is an Abbreviated New Animal Drug Application?

   The information necessary to obtain approval to market a generic animal drug is submitted to FDA in the form of an Abbreviated New Animal Drug Application, or ANADA. This information includes, but is not limited to, the following:

   • Identification or Basis - The proposed generic product and the approved (listed) product that will be copied are identified.
   • Patent Information - The application provides certification by the applicant that a patent does not exist, that a patent has expired or will soon expire, 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 applicant or sponsor must then notify the sponsor of the approved product application and the owner of the patent that he or she has filed an abbreviated application claiming invalidity or noninfringement of the patent.
   • Labeling - The application contains copies of the proposed labeling for the generic product and of the approved labeling for the listed product. The labeling of the proposed product must contain all of the same indications, warnings, cautions, directions for use, etc., as that of the approved product. It may differ only in tradename, logo, name and address, etc., that would be specific to the generic 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 product and their concentration in the final product. The active ingredients must be the same as those of the approved product unless they are the subject of an approved "Suitability Petition" (See Question 8). The finished product must also be the same strength, dosage form, and route of administration as the approved product, unless it is the subject of an approved Suitability Petition.
   • Bioequivalence - The application contains information to show bioequivalence between the proposed generic product and the approved product. The applicant may request that in vivo bioequivalence testing be waived, or refer to an earlier letter approving a request for waiver.
   • Human Food Safety - A tissue residue depletion study may be required for the proposed generic 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 product, the manufacturing facilities, key personnel, analytical methods, specifications, quality control procedures, etc. All animal drugs, whether generic or not, must be manufactured in accordance 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 application must contain either an environmental assessment (EA) or a request for categorical exclusion from an EA. Regulations for reporting environmental information 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 application, is required.

2. What animal drug products are eligible to be copied as generics?

   All 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 provisions of the GADPTRA, unless the animal drug has been subsequently withdrawn from the market for safety or effectiveness reasons, or unless it is the subject of a Notice of Hearing that has been published in the FEDERAL REGISTER. To meet requirements of the GADPTRA, the Center for Veterinary Medicine has arranged for the publication of a list of animal drug products that are eligible to be copied as generics (Green Book).

3. What is exclusivity?

   The GADPTRA provides for a period of 3 years of marketing exclusivity for a new use of an animal drug (a use that required reports of new clinical or field investigations for its approval), during which time no abbreviated application for a generic copy may be approved for the new use.

   The law provides for a period of 5 years of marketing exclusivity for an animal drug that has not been previously approved in any new animal drug application. During this period, no abbreviated application may be submitted. (Exception: An abbreviated application may be submitted after 4 years if the generic applicant claims noninfringement of a listed patent that is claimed for the approved product or its use.) The law also provides for another form of marketing exclusivity, known as patent term restoration. This type of exclusivity extends the period of protection by U.S. patent for an animal drug, or its method of use, that was approved after November 16, 1988, to compensate for the time that was required for investigation and regulatory review of the animal drug prior to its approval. Patent term restoration is not related to the exclusivity periods described above and may overlap those exclusivity periods.

4. When can I request a waiver from in vivo bioequivalence studies?

   For certain animal drug products or types of products, in vivo bioequivalence studies may not be necessary. Generally, these products are solutions intended for oral or parenteral use. They will have the same components and composition as the listed animal drug product, or they will have only minor differences in inert ingredients from those of the listed product. Ordinarily, other more complex dosage forms, i.e., tablets, capsules, etc., and medicated feeds or feed premixes will not be granted a waiver. A request for waiver for any product can be submitted at any time prior to submission of an ANADA. It will be assigned an Investigational New Animal Drug (INAD) application number and evaluated. The request for waiver should contain enough information on the composition of the proposed generic product and its differences from the listed product to allow a determination of whether bioequivalence studies would be needed.

5. How do I perform a bioequivalence study?

   A bioequivalency study must be performed in accordance with the FDA's Good Laboratory Practices (GLP) regulations. This also applies to a Clinical End Point study when such a study is accepted in lieu of a blood-level bioequivalence study. The FDA recommends that protocols be submitted for review before any study is begun.

6. What is a Suitability Petition and what kind of differences between an approved product and a proposed generic product can be considered in a Suitability Petition?

   A Suitability Petition is much the same as a Citizens Petition. It is a public document and may be viewed by the public at large. It must be submitted to:

   Dockets Management Branch, HFA-305
   Room 1-23
   Food and Drug Administration
   12420 Parklawn Drive
   Rockville, MD 20857

   A Suitability Petition may only request permission to submit an ANADA for a proposed generic product that is claimed to be bioequivalent to the listed product but that differs from the listed product in certain specific ways. The proposed generic product may only differ from the listed product if it is (1) a different dosage form, (2) a different strength or (3) a different route of administration, or it contains (4) more than one active ingredient and one of the active ingredients is different than that of the listed drug product, or if it is (5) 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 listed products 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 animal drug product?

   The statutory limit for approval of an ANADA is 180 days, as it is for a New Animal Drug Application (NADA). Seldom, however, is an application approved on the first submission. When an incomplete letter is sent to an applicant, the 180-day clock restarts upon receipt of the applicant's response. This process may continue, in some cases for several cycles. Generally, an ANADA will have a shorter average overall approval time than an NADA because of the relatively lesser complexity of the generic application. The time of approval, to a large extent, depends upon the quality and completeness of the original application and its subsequent amendments.