Bioequivalence and Orange Book

bioavailability

rate and extent to which the active drug ingredient or therapeutic moiety is absorbed from a drug product and becomes available to the site of drug action

no

Is bioavailability a criterion for clinical effectiveness?

pharmacokinetics

bioavailability data provides fraction of drug absorbed from the formulation, and _________________________ of the drug

relative bioavailability

_________ _____________ studies compare two drug product formulations (brand vs generic)

vivo

bioavailability and bioequivalence can be considered as performance measures of the drug product in __________

bioequivalence

the absence of a significant difference in the rate and extent to which the active ingredient or active moiety becomes available at the site of drug action when administered at the same molar dose under similar conditions in an appropriately designed study

bioequivalence

a ________________________ study is a specialized type of relative bioavailability study

new

bioavailability concerns the amount and rate of a drug or active moiety appearing in systemic circulation and has to be determined for any _________ drug

comparable

bioequivalence addresses whether other drug products are __________________ to an already approved drug product with respect to biological performance

therapeutic

bioequivalence study helps to determine the __________________ equivalence between the pharmaceutically equivalent generic drug product a reference drug product

therapeutically equivalent

if two drugs are pharmaceutically equivalent and bioequivalents, the can be assumed to be ___________________________________

pharmaceutical equivalence

the same drug from different companies; have the same dose, same name, and same amount makes it to the blood

development

during drug _________________, bioequivalence studies are used to compare:

-early and late clinical formulations

-formulations used in clinical trials and stability studies, if different

-clinical trial formulations and to-be-marketed drug products, if different

-product strength equivalence, as appropriate

postapproval

___________________, in vivo bioequivalence studies may be needed to support regulatory approval of major changes such as formulation, manufacturing, or site, in comparison to reference formulation

generic

__________________ drug manufacturer must demonstrate that the drug product is pharmaceutically equivalent, bioequivalent, and therapeutically equivalent to the comparator brand-name drug product

oral

drug product performance comparison for ____________ generic drug products:

-in vivo bioequivalence studies in normal healthy adult subjects

-in vitro may also include comparative drug dissolution/release profiles

superimpose

plasma-time profiles of drugs that are bioequivalent should perfectly _________________ eachother

generic drugs

affordable alternative of the FDA-approved copies of brand-name "innovator" drugs; should comply the same high standards for quality as the innovator drug; represent 88% of drugs dispensed in the United States

orange book

Approved Drug Products with Therapeutic Equivalence Evaluations book; prepared to fulfill the mandate as per 505(c) of Federal Food, Drug, and Cosmetic Act

daily

website and app for the orange book update ____________

positive formulary approach

Substitution limited to a specific list of drugs

negative formulary approach

substitution allowed for all drugs except those prohibited by a particular list

orange book contents

includes prescription products, OTC, discontinued drug products, patents, and exclusivity

referenced listed drug (RLD)

an approved drug product to which new generic versions are compared to show that they are bioequivalent

reference standard (RS)

the previously approved drug selected by FDA that an applicant must use in conducting any in vivo bioequivalence testing required for approval

monthly, annual

____________ and ____________ updates of the orange book are on website, app, and in publication

pharmaceutical equivalents

drug products are considered ____________________________:

-if they contain the same active ingredients and the same amounts

-are the same dosage form

-have same route of administration

-are identical in strength or concentration

differ

pharmaceutically equivalent drugs may ___________ in:

-shape and scoring configuration

-release mechanisms

-packaging and excipients

-expiration time

-labeling

pharmaceutical alternatives

drugs are considered _____________________ if they contain the same therapeutic moiety BUT are different salts, esters, or complexes of that moiety, or are different dosage forms or strength

not pharmaceutically equivalent but produce same therapeutic effect

alternatives

Ex: tetracycline hydrochloride 250 mg capsules and tetracycline phosphate complex 250 mg capsules are considered pharmaceutical _______________________

equivalent

if drugs are pharmaceutically _____________________, permission is not needed from a physician to switch drugs

alternative

if drugs are pharmaceutically _____________________, permission is required from the physician to switch

therapeutic equivalent

pharmaceutical equivalents + same clinical effect and safety profile when administered to patients under the conditions specified in the labeling

equivalent

If the first letter in the orange book code is "A", the multisource drugs are therapeutically ______________________

inequivalent

If the first letter in the orange book code is "B", the multisource drugs are therapeutically __________________________

third

the ________ character in an orange book drug code is assigned when more than one reference listed drug of the same strength has been designated under the same heading (more than one branded drug on the market)

second

the ___________ character of the orange book drug code gives description such as whether or not they have bioequivalence problems

bioequivalent

drugs must have the same orange book code (ex: AB1) to be considered ____________________

therapeutic

although these two drugs are bioequivalent because the same amount reaches the blood, they are NOT __________________________ because their absorption rates are different