Orange Book- Approved Drug Products with Therapeutic Equivalence Evaluations

The publication, Approved Drug Products with Therapeutic Equivalence Evaluations (the List, commonly known as the Orange Book),  identifies drug products approved on the basis of safety and effectiveness by the Food and Drug Administration (FDA) under the Federal Food, Drug, and Cosmetic Act (the Act).

The List is composed of four (4) parts:

(1) Approved prescription (Rx) drug products with therapeutic equivalence evaluations;

(2) Approved over-the-counter (OTC) drug products for those drugs that may not be marketed without NDAs or ANDAs because they are not covered under existing OTC monographs;

(3) Drug products with approval under Section 505 of the Act administered by the Center for Biologics Evaluation and Research; and

(4) A cumulative list of approved products that have never been marketed, are for exportation, are for military use, have been discontinued from marketing, or have had their approvals withdrawn for other than safety or efficacy reasons subsequent to being discontinued from marketing.

 Reference Listed Drug (RLD)

 A reference listed drug (21 CFR 314.94(a)(3)) means the listed drug identified by FDA as the drug product upon which an applicant relies in seeking approval of its ANDA.

 Therapeutic Equivalence Evaluations Codes:

The coding system for therapeutic equivalence evaluations is constructed to allow users to determine quickly whether the Agency has evaluated a particular approved product as therapeutically equivalent to other pharmaceutically equivalent products (first letter) and to provide additional information on the basis of FDA’s evaluations (second letter).  With few exceptions, the therapeutic equivalence evaluation date is the same as the approval date.

The two basic categories into which multisource drugs have been placed are indicated by the first letter as follows:

A: Drug products that FDA considers to be therapeutically equivalent to other pharmaceutically equivalent products, i.e., drug products for which:

(1) There are no known or suspected bioequivalence problems.  These are designated AAANAOAP, or AT, depending on the dosage form; or

AAProducts in conventional dosage forms not presenting bioequivalence problems

AN: Solutions and powders for aerosolization

AO: Injectable oil solutions

AP: Injectable aqueous solutions and, in certain instances, intravenous non-aqueous solutions

AT: Topical products

(2) Actual or potential bioequivalence problems have been resolved with adequate in vivo and/or in vitro evidence supporting bioequivalence.  These are designated AB.

B: Drug products that FDA at this time, considers NOT to be therapeutically equivalent to other pharmaceutically equivalent products, i.e.

Drug products for which actual or potential bioequivalence problems have not been resolved by adequate evidence of bioequivalence

Often the problem is with specific dosage forms rather than with the active ingredients.  These are designated BDBEBNBPBRBSBTBX, or B*.

BC: Extended-release dosage forms (capsules, injectables and tablets)

BD: Active ingredients and dosage forms with documented bioequivalence problems

BE: Delayed-release oral dosage forms

BN: Products in aerosol-nebulizer drug delivery systems

BP:  Active ingredients and dosage forms with potential bioequivalence problems

BR: Suppositories or enemas that deliver drugs for systemic absorption

BS: Products having drug standard deficiencies

BT: Topical products with bioequivalence issues

BX: Drug products for which the data are insufficient to determine therapeutic equivalence

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