Kentucky News: Solving the Mystery of "Orange Book" Evaluation Codes

March 1, 2006 12:45 pm

Published in the March 2006 Kentucky Board of Pharmacy Newsletter.
 

With more than 10,000 drugs listed in the 25th edition of the “Orange Book,” it is not surprising that much can arise when trying to determine if and when a drug is substitutable. Substitution of levothyroxine products is just one example of how pharmacists can get caught in the middle of a bioequivalence debate among manufactures, physicians, and Food and Drug Administration (FDA).
There are two basic categories into which multisource drugs are placed. A listed drug products are considered therapeutically equivalent to other pharmaceutically equivalent drug products. B listed drug products are not considered therapeutically equivalent to other pharmaceutically equivalent drug products. The second letter of the therapeutic evaluation code (TE code) gives general information on why the drug is rated A or B. For example, two pharmaceutically equivalent AA rated drugs contain active ingredients and dosage forms that are not regarded as presenting either actual or potential bioequivalence problems or drug quality or standards issues. Drug products identified by FDA as having actual or potential bioequivalence problems will only be designated therapeutically equivalent after scientific evidence proves the two products to be bioequivalent. These products are generally assigned an AB rating.
A third character in the TE code is assigned when multiple sources of a single ingredient are available but not all of the sources are considered therapeutically equivalent to each other. The best example of this came about a few years ago when Procardia XL® and Adalat® CC both went off patent. Both products are listed in the “Orange Book” under the active ingredient nifedipine. These branded products are not bioequivalent to each other. In order to designate which generic products are equivalent to which brands, FDA has assigned Adalat CC a rating of AB1 and Procardia XL a rating of AB2.
The three-character system described above is the same system used to designate bioequivalence between levothyroxine drug products. Because there are multiple reference listed drugs of levothyroxine, FDA felt its traditional system of three-character TE codes could be potentially confusing and elected to provide an explanation and chart in the most recent edition of the “Orange Book.” Levothyroxine products are divided into three groups (AB1, AB2, AB3). Therapeutic equivalence has been established between products having the same three-character rating. More than one TE code may apply to some of the products, eg, levothyroxine sodium (Mylan Laboratories Inc) is rated as AB1, AB2, and AB3. A common TE code indicates therapeutic equivalence between products, eg, levothyroxine (Genpharm Inc) and Synthroid® (Abbott Laboratories)
have an AB2. It should be noted that Novothyrox®, Thyro-Tabs®, and Levolet® are currently BX rated. BX rated products are those that FDA considers not to be therapeutically equivalent to other pharmaceutically equivalent products. The first publication of the “Orange Book” in October 1980 was the result of many requests from the states for FDA to assist in preparation of both positive and negative formularies. The agency could not serve the needs of each state on an individual basis and decided to provide the states with a single list based on common criteria. The “Orange Book” is no longer published in paper form but can be found, along with monthly updates, online at www.fda.gov/cder/ob/default.htm. The online version of the “Orange Book” is an easy to use, valuable tool for pharmacists with generic substitution questions.