FDA’s Orange Book and AB Ratings of Pharmaceutical Drug Products: a Guide to Community Pharmacist
Vijay M Kale*
Department of Pharmaceutical Sciences, Roseman University of Health Sciences College of Pharmacy, South Jordan
Received: December 29, 2015 | Published: December 31, 2015
Vijay M Kale, Assistant Professor of Pharmaceutical Sciences, Roseman University of Health Sciences, College of Pharmacy, 10920 S Riverfront Parkway, Utah 84095, South Jordan, Tel: 801-878-1078; Email:
Kale VM (2016) FDA’s Orange Book and AB Ratings of Pharmaceutical Drug Products: a Guide to Community Pharmacist. MOJ Bioequiv Availab 1(3): 00013. DOI:
One of the major sources of error in filling prescription in community pharmacy is that not equivalent drug product substitution. Pharmacist often relies on orange book codes for therapeutic substitution when permitted by prescriber. In this mini review, we made sincere efforts to explain Orange book, therapeutic equivalent codes and how to interpret each code.
Keywords: Orange Book; Therapeutic equivalence; AB ratings
FDA orange book
The official name of FDA’s orange book is Approved Drug Products with Therapeutic Equivalence Evaluations. Originally this book was published in October 1980 with orange cover and thus the name “orange book”. The orange book is published annually and the 2015 edition is 35th edition of orange book . It is freely available for download and it has search options available on website. This book contains the list of all drugs approved in the United States as safe and effective. It is also the authoritative source of information on the therapeutic equivalence of drug products. The orange book consist of five main sections: an introduction, a “how to use” section, the drug product lists, appendices and a patent and exclusivity information addendum.
Before understanding different drug ratings it is necessary to understand bioavailability and bioequivalence. Bioavailability refers to the rate and extent to which the active ingredient or therapeutic ingredient is absorbed from a drug product and becomes available at the site of drug action. Bioequivalence refers to equivalent release of the same drug substance from two or more drug products or formulations. These two definitions give three different classes of equivalent drugs.
These are the drug products that contain the same active ingredients in the same strength and dosage form delivered by the same route of administration.
Bioequivalent drug products
These are the drug products that have shown comparable bioavailability when studied under similar conditions (e.g. the rate and extent of absorption of a test drug does not significantly differ from that of the reference drug) .
These are the drug products that are pharmaceutical equivalents that are bioequivalent.
Therapeutic Equivalence Evaluations Codes
There are broadly two types of therapeutic equivalent codes A-rated and B-rated drugs or codes.
“A” codes: A-rated drugs are those, which the FDA considers to be therapeutically equivalent and, therefore, substitutable where permitted by the prescriber. Various codes and their interpretations are described in table 1. The second letter (A, B, C, D, E, N, O, P, R, S, T or X) provides information about the dosage form, and in some cases, about the results of the FDA’s evaluation of actual or potential bioequivalence problems.
AA: ingredients and dosage forms presenting neither actual nor potential bioequivalence problems (e.g., oral solutions).
AB: actual or potential bioequivalence problems have been resolved through adequate in vivo and/or in vitro testing. Often some therapeutic codes are followed by a number, such as AB1, AB2, AB3 etc. This is particularly when there are two or more drug products, containing the same ingredient, with the same strength and dosage form, which are not bioequivalent to each other. For example, a generic rated AB1 can be substituted for a brand rated AB1, but cannot be substituted for a brand rated AB2.
“B” codes: B-rated drugs are those, which the FDA considers not to be therapeutically equivalent due to actual or potential bioequivalence problems, which have not been resolved. This section is often related to pharmacokinetic differences, which arises due to product dissolution, disintegration, and absorption or metabolism and linked to specific delivery forms rather to safety and efficacy. For example the calcium channel blocker verapamil is AB-rated but its extended release formulation Covera-HS is BC-rated and thus not substitutable .
No bioequivalence problems in conventional dosage forms
Meets necessary bioequivalence requirements
Meets bioequivalence requirements to AB1 rated reference drug
Meets bioequivalence requirements to AB2 rated reference drug
Meets bioequivalence requirements to AB3 rated reference drug
Meets bioequivalence requirements to AB4 rated reference drug
Solution or powder for aerosolization
Injectable oil solutions
Injectable aqueous solutions
Controlled-release tablet, capsule, or injectable
Documented bioequivalence problems
Enteric coated oral dosage forms
Product in aerosol-nebulizer delivery system
Potential bioequivalence problems
Suppository or enema for systemic use
Testing standards are insufficient for determination
Topical products with bioequivalence issues
Insufficient data to confirm bioequivalence
Requires further FDA investigation and review
This entry has been evaluated by the FDA, but a rating is not available for this labeler’s product
FDA standard with no orange book code
Table 1:Summary of FDA’s Orange Book Therapeutic Equivalence Codes.
Besides teaching, author also works as a community pharmacist at Harmons Grocery.
Conflict of Interest
We declare that author has no conflicting interest.