(ORANGE BOOK)Therapeutic Equivalence Codes

AO

*Injectable* "Parenteral" *Oil Solutions*, considered to be *Pharmaceutically* and *Therapeutically Equivalent* only when the *active ingredient* is *concentrated* and the type of oil used as a vehicle is all identical

AP

*Injectable*"Parenteral" *Aqueous* *Solutions,* in certain instances, Intravenous*(IV)* non-aqueous solutions

BD

*ACTIVE INGREDIENTS* and *DOSAGE*(mg/Kg) *FORMS* with *DOCUMENTED BIOEQUIVALENCE PROBLEMS*, products containing *active ingredients* w/ known *Bioequivalence* problems and adequate studies have *NOT* been submitted to *FDA* demonstrating *Bioequivalence*.

ZZ

*FDA* Standard with *NO ORANGE BOOK CODE*

BS

*Products having DRUG STANDARD DEFICIENCIES,* drug standards for an *active ingredient* in a particular dosage form are found by *FDA* to be *deficient* preventing an evaluation of *Pharmaceutical* or *Therapeutic Equivalence*, all drug products containing that active ingredient in that dosage form are coded *

AN

*SOLUTIONS* and *POWDERS* for *AEROSOLIZATION,* solutions or suspensions in a specific delivery system, *Bioequivalence* standard is based upon *"in vitro"* methodology.

BR

*Suppositories* or *Enemas* that Deliver Drugs for *SYSTEMIC ABSORPTION*(route of administration of medication into the circulatory system so that the entire body is affected) can vary significantly from product to product

BT

*TOPICAL PRODUCTS* with *BIOEQUIVALENCE ISSUES* (dermatologic, ophthalmic, otic, rectal, and vaginal) Evaluated as having acceptable clinical performance, but has no *Bioequivalence* to other *Pharmaceutical Equivalent* products or *LACK* sufficient evidence of *Bioequivalence.*

*"A" CODES*

Considered by the *FDA* as *Therapeutically Equivalent* to other *Pharmaceutically Equivalent* Products, *evidence supporting bioequivalence* by *in vivo,*"living within"(organisms, animals, humans, plants) and/or *in vitro,*"within glass."(partial or dead organism)

*Pharmaceutical Equivalents*

Contains the *SAME* *active ingredients*, *SAME* *dosage form*, *route of administration* and *identical* in *strength* or *concentration.* *{**May Differ In Characteristics;* (a) shape (b) scoring configuration (c) release mechanisms (d) packaging (e) excipients(colors, flavors, preservatives) (f) expiration time (g) labeling.*}*

*Pharmaceutical Alternatives*

Contains the *SAME* *therapeutic ingredient*, but *DIFFERENT salts, esters* or *complexes* of *ingredients* or *DIFFERENT dosage forms* or *strengths*. (Data is generally not available from the *FDA* to make the determination if *tablets* or *capsules* are *Bioequivalence*.) *DIFFERENT dosage forms* and *strengths* within a *product line* by a *single manufacturer* are *Pharmaceutical Alternatives*, as are *extended-release* products when compared w/ *immediate-* or *standard-release* formulations of the *SAME active ingredient*.

*Therapeutic Equivalents*

Drug products that are considered *Pharmaceutical Equivalents*{*SAME active ingredient*(s), *SAME dosage form*, *route of administration* and *IDENTICAL* in *strength* or *concentration*} and have the *SAME clinical effect* and *safety profile* when administered to patients UNDER the *conditions specified* in the *labeling*.

Approved Drug Products w/ *Therapeutic Equivalence* Evaluations *(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(1938) *(FDCA)*. Drugs on the market *approved* *"ONLY"* on the basis of *SAFETY*.

AB

Products *MEETING* necessary *BIOEQUIVALENCE REQUIREMENTS,* identical active ingredient(s), dosage form, and route(s) of administration and having the same strength. When other methods are not applicable *"in vivo"* or *"in vitro"* test methods to *demonstrate bioequivalence* may be appropriate

AA

Products In *Conventional Dosage* Forms *NOT PRESENTING BIOEQUIVALENCE PROBLEMS,* contain active ingredients and dosage forms without any drug quality or standards issues. (oral dosage forms must meet an appropriate *"in vitro"* bioequivalence standard by the FDA)

BN

Products in *AEROSOL* or *NEBULIZER Drug Delivery Systems*, drug solutions or powders are *ONLY* a component or compatible with, a specific drug delivery system. There may be *significant differences* in the *dose* of drug and *particle size* delivered by different products of this type.

*"B" CODES*

REQUIRES FURTHER *FDA* *INVESTIGATION* and *REVIEW,* drug products that the *FDA* at this time do not consider to be *Therapeutically Equivalent* to other *Pharmaceutically Equivalent* products.

EE

This *ENTRY* has been *EVALUATED* by the *FDA*, but a *RATING is NOT AVAILABLE for this LABELER'S PRODUCT.*

AT

*Topical Products,* considered *Therapeutically Equivalent* to other *Pharmaceutically Equivalent* products; dermatologic(skin), ophthalmic(eye; ocular), otic(ear; auricular), rectal, and vaginal administration

BP

*Active Ingredients* and *Dosage Forms* with *POTENTIAL BIOEQUIVALENCE Problems*, injectable suspensions containing *active ingredient* suspended in *aqueous*(like water) or *oleaginous*(oily; greasy) vehicle. Differences in *particle size,* structure or formulation can affect the *rate of release* and *absorption*

BC

*CONTROLLED-RELEASED DOSAGE* (mg/Kg) *Forms,* (capsules, injectables and tablets) the *FDA*, *DOES NOT* consider different *extended-release* dosage forms containing the *same active ingredient* in equal strength to be *Therapeutically Equivalent.*

BX

*DRUG PRODUCTS* for which the *DATA is INSUFFICIENT* to DETERMINE *THERAPEUTIC EQUIVALENCE,* Presumed to be *therapeutically inequivalent* until adequate information becomes available for full evaluation of *Therapeutic Equivalence.*

BE

*Delayed Release Oral* Dosage Forms,(*Enteric Coating*, polymer barrier applied on oral medication, protecting drugs from the acidity of the stomach) containing the same *active ingredients* are subject to differences in *absorption* and presenting a *potential bioequivalence* problem

*FDA* classifies *Therapeutic Equivalents* by meet the following criteria.

1.) *Approved as Safe and Effective.* 2.) *Pharmaceutical Equivalents* (a) contains identical amounts of the *SAME active drug ingredient* in the *SAME dosage form* and *route of administration.* (b) Strength, quality, purity, and identity. 3.) *Bioequivalent* (a) doesn't present a known or potential bioequivalence problem, and meet an acceptable in vitro standard (b) a known or potential problem, shown to meet an appropriate *Bioequivalence* standards 4.) *Adequately labeling,* 5.) Compliance w/ *Good Manufacturing Practice(GMP)* regulations. 6.) *May Differ in Characteristics* (a) shape (b) scoring configuration (c) release mechanisms (d) packaging, (e) excipients(colors, flavors, preservatives), (f) expiration date/time (g) minor aspects of labeling (h)storage conditions. 7.) *Substituted* w/ the expectation that the *substituted* product will *PRODUCE* the *SAME clinical effect* and *safety profile* as the prescribed product.

*Bioequivalence*

1.) *Under the Drug Price Competition and Patent Term Restoration Act(1984)* manufacturers seeking approval to market a *generic drug* product must submit data demonstrating that the generic drug product is *Bioequivalent* to the *Pioneer*(Innovator,Proprietary) drug product. 2.) Drug products containing a drug substance that is chemically identical and is delivered to the site of action at the *SAME rate* and *extent* as another drug product, then it is *equivalent* and *can be substituted* for that drug product. 3.) *Methods used to define Bioequivalence*; (a) *Pharmacokinetic(PK)* studies (b) *Pharmacodynamic(PD)* studies (c) comparative clinical trials (d)* in-vitro* studies.

*Bioequivalent* Drug Products

1.) Describes *Pharmaceutical Equivalent* or *Pharmaceutical* *Alternative* products that display *COMPARABLE* *Bioavailability* when studied under *SIMILAR* *experimental conditions.* 2.)*Therapeutically Equivalent* and *interchangeable.*

*Bioavailability*

1.) The *rate* and *extent* to which the *active ingredient* or *therapeutic ingredient*(active moiety) is *absorbed*(into systemic circulation) from a drug product and becomes *available* @ the *site of drug action*. 2.) Products that are *NOT* intended to be absorbed into the *bloodstream* are measured by the *rate* and *extent* to which the *active ingredient* or *therapeutic ingredient*(active moiety) *becomes available* @ the *site of action*.