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U.S. Department of Health and Human Services

Drugs

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Therapeutic Equivalence Code

FDA Data Element Number. None.

CDER Data Element Number. C-DRG-00701

Data Element Name. Therapeutic Equivalence Code.

Description. This standard provides format specifications for representing the therapeutic equivalence code (TE Code). The TE Code is used in CDER's publication, Approved Drug Products with Therapeutic Equivalence Evaluations, to allow comparisons between different brands of the same drug.

Source. Approved Drug Products with Therapeutic Equivalence Evaluations (aka The Orange Book).

Relationship.

FDA Specifications. None.

CDER Specifications. Therapeutic Equivalence Code is represented by alphabetic text of two characters, without punctuation.

FDA Approved Date.

CDER Approved Date. January 10, 1995.

FDA Revised Date.

CDER Revised Date.

Data Values.

NAME DEFINITION FDA CODE
Products in conventional dosage forms not presenting bioequivalence problems. Products coded as AA contain active ingredients and dosage forms that are not regarded as presenting either actual or potential bioequivalence problems or drug quality or standards issues. However, all oral dosage forms must, nonetheless, meet an appropriate in vitro test(s) for approval. AA
Products meeting necessary bioequivalence requirements. Products generally will be coded AB if a study is submitted demonstrating bioequivalence. Even though drug products of distributors and/or repackagers are not included in the List, they are considered therapeutically equivalent to the application holder's drug product if the application holder's drug product is rated AB or is single source in the List. The only instance in which a multisource product will be rated AB on the basis of bioavailability rather than bioequivalence is where the innovator product is the only one listed under that drug ingredient heading and has completed an acceptable bioavailability study. However, it does not signify that this product is therapeutically equivalent to the other drugs under the same heading. Drugs coded AB under an ingredient heading are considered therapeutically equivalent only to other drugs coded AB under that heading. AB
Solutions and powders for aerosolization Uncertainty regarding the therapeutic equivalence of aerosolized products arises primarily because of differences in the drug delivery system. Solutions and powders intended for aerosolization that are marketed for use in any of several delivery systems are considered to be pharmaceutically and therapeutically equivalent and are coded AN. Those products that are compatible only with a specific delivery system or those products that are packaged in and with a specific delivery system are coded BN, unless they have met an appropriate bioequivalence standard because drug products in their respective delivery systems are not necessarily pharmaceutically equivalent to each other and, therefore, are not therapeutically equivalent. AN
Injectable oil solutions The absorption of drugs in injectable (parenteral) oil solutions may vary substantially with the type of oil employed as a vehicle and the concentration of the active ingredient. Injectable oil solutions are therefore considered to be pharmaceutically and therapeutically equivalent only when the active ingredient, its concentration, and the type of oil used as a vehicle are all identical. AO
Injectable aqueous solutions

It should be noted that even though injectable (parenteral) products under a specific listing may be evaluated as therapeutically equivalent, there may be important differences among the products in the general category, Injectable; Injection. For example, some injectable products that are rated therapeutically equivalent are labeled for different routes of administration. In addition, some products evaluated as therapeutically equivalent may have different preservatives or no preservatives at all. Injectable products available as dry powders for reconstitution, concentrated sterile solutions for dilution, or sterile solutions ready for injection are all considered to be pharmaceutically and therapeutically equivalent provided they are designed to produce the same concentration prior to injection and are similarly labeled. Consistent with accepted professional practice, it is the responsibility of the prescriber, dispenser, or individual administering the product to be familiar with a product's labeling to assure that it is given only by the route(s) of administration stated in the labeling.

Certain commonly used large volume intravenous products in glass containers are not included on the List (e.g., dextrose injection 5%, dextrose injection 10%, sodium chloride injection 0.9%) since these products are on the market without FDA approval and the FDA has not published conditions for marketing such parenteral products under approved NDAs. When packaged in plastic containers, however, FDA regulations require approved applications prior to marketing. Approval then depends on, among other things, the extent of the available safety data involving the specific plastic component of the product. All large volume parenteral products are manufactured under similar standards, regardless of whether they are packaged in glass or plastic. Thus, FDA has no reason to believe that the packaging container of large volume parenteral drug products that are pharmaceutically equivalent would have any effect on their therapeutic equivalence.

AP
Topical Products There are a variety of topical dosage forms available for dermatologic, ophthalmic, otic, rectal, and vaginal administration, including solutions, creams, ointments, gels, lotions, pastes, sprays, and suppositories. Even though different topical dosage forms may contain the same active ingredient and potency, these dosage forms are not considered pharma- ceutically equivalent. Therefore, they are not considered therapeutically equivalent. All solutions and DESI drug products containing the same active ingredient in the same topical dosage form for which a waiver of in vivo bioequivalence has been granted and for which chemistry and manufacturing processes are adequate, are considered therapeutically equivalent and coded AT. Pharmaceutically equivalent topical products that raise questions of bioequivalence including all post­1962 topical drug products are coded AB when supported by adequate bioequivalence data, and BT in the absence of such data. AT
Extended-release dosage forms (capsules, injectables and tablets)

An extended­release dosage form is defined by the official compendia as one that allows at least a twofold reduction in dosing frequency as compared to that drug presented as a conventional dosage form (e.g., as a solution or a prompt drug-releasing, conventional solid dosage form).

Although bioavailability studies have been conducted on these dosage forms, they are subject to bioavailability differences, primarily because firms developing extended­release products for the same active ingredient rarely employ the same formulation approach. FDA, therefore, does not consider different extended­release dosage forms containing the same active ingredient in equal strength to be therapeutically equivalent unless equivalence between individual products in both rate and extent has been specifically demonstrated through appropriate bioequivalence studies. Extended­release products for which such bioequivalence data have not been submitted are coded BC, while those for which such data are available have been coded AB.

BC
Active ingredients and dosage forms with documented bioequivalence problems The BD code denotes products containing active ingredients with known bioequivalence problems and for which adequate studies have not been submitted to FDA demonstrating bioequivalence. Where studies showing bioequivalence have been submitted, the product has been coded AB. BD
Delayed­release oral dosage forms A delayed­release dosage form is defined by the official compendia as one that releases a drug (or drugs) at a time other than promptly after administration. Enteric­coated articles are delayed­release dosage forms.Drug products in delayed­release dosage forms containing the same active ingredients are subject to significant differences in absorption. Unless otherwise specifically noted, the Agency considers different delayed­release products containing the same active ingredients as presenting a potential bioequivalence problem and codes these products BE in the absence of in vivo studies showing bioequivalence. If adequate in vivo studies have demonstrated the bioequivalence of specific delayed­release products, such products are coded AB. BE
Products in aerosol­nebulizer drug delivery systems This code applies to drug solutions or powders that are marketed only as a component of, or as compatible with, a specific drug delivery system. There may, for example, be significant differences in the dose of drug and particle size delivered by different products of this type. Therefore, the Agency does not consider different metered aerosol dosage forms containing the same active ingredient(s) in equal strengths to be therapeutically equivalent unless the drug products meet an appropriate bioequivalence standard. BN
Active ingredients and dosage forms with potential bioequivalence problems

FDA's bioequivalence regulations (21 CFR 320.33) contain criteria and procedures for determining whether a specific active ingredient in a specific dosage form has a potential for causing a bioequivalence problem. It is FDA's policy to consider an ingredient meeting these criteria as having a potential bioequivalence problem even in the absence of positive data demonstrating inequivalence. Pharmaceutically equivalent products containing these ingredients in oral dosage forms are coded BP until adequate in vivo bioequivalence data are submitted.

Injectable suspensions containing an active ingredient suspended in an aqueous or oleaginous vehicle have also been coded BP. Injectable suspensions are subject to bioequivalence problems because differences in particle size, polymorphic structure of the suspended active ingredient, or the suspension formulation can significantly affect the rate of release and absorption. FDA does not consider pharmaceutical equivalents of these products bioequivalent without adequate evidence of bioequivalence.

BP
Suppositories or enemas that deliver drugs for systemic absorption The absorption of active ingredients from suppositories or enemas that are intended to have a systemic effect (as distinct from suppositories administered for local effect) can vary significantly from product to product. Therefore, FDA considers pharmaceutically equivalent systemic suppositories or enemas bioequivalent only if in vivo evidence of bioequivalence is available. In those cases where in vivo evidence is available, the product is coded AB. If such evidence is not available, the products are coded BR. BR
Products having drug standard deficiencies If the drug standards for an active ingredient in a particular dosage form are found by FDA to be deficient so as to prevent an FDA evaluation of either pharmaceutical or therapeutic equivalence, all drug products containing that active ingredient in that dosage form are coded BS. For example, if the standards permit a wide variation in pharmacologically active components of the active ingredient such that pharmaceutical equivalence is in question, all products containing that active ingredient in that dosage form are coded BS. BS
Topical products with bioequivalence issues This code applies mainly to post­1962 dermatologic, ophthalmic, otic, rectal, and vaginal products for topical administration, including creams, ointments, gels, lotions, pastes, and sprays, as well as suppositories not intended for systemic drug absorption. Topical products evaluated as having acceptable clinical performance, but that are not bioequivalent to other pharmaceutically equivalent products or that lack sufficient evidence of bioequivalence will be coded BT. BT
Drug products for which the data are insufficient to determine therapeutic equivalence The code BX is assigned to specific drug products for which the data that have been reviewed by the Agency are insufficient to determine therapeutic equivalence under the policies stated in this document. In these situations, the drug products are presumed to be therapeutically inequivalent until the Agency has determined that there is adequate information to make a full evaluation of therapeutic equivalence. BX