Bioequivalence Flashcards
What is the official name of the orange book?
Approved drug products with therapeutic equivalence evaluations
What is the purpose of the 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 (the
FD&C Act).
What is meant by formulary?
This is what is approved for sale or use in institution.
Therapeutic Equivalence-Related Terms
Define Pharmaceutical Equivalents.
Pharmaceutical equivalents are drug products in identical dosage forms and route of administration that contain identical amounts of the identical active drug ingredient,
i.e., the same salt or ester of the same therapeutic moiety
They may differ in characteristics such as shape, scoring configuration, release mechanisms, packaging, excipients (including colors, flavors, preservatives), expiration date/time, and, within certain limits, labeling
Therapeutic Equivalence-Related Terms
Define Pharmaceutical Alternatives.
Pharmaceutical alternatives are drug
products that contain the identical therapeutic moiety, or its precursor, but
not necessarily in the same amount or dosage form, or the same salt or ester
(e.g., tetracycline hydrochloride, 250 mg capsules vs. tetracycline phosphate
complex, 250 mg capsules; quinidine sulfate, 200 mg tablets vs. quinidine
sulfate, 200 mg capsules
Therapeutic Equivalence-Related Terms
Define Therapeutic Equivalents.
drug products are considered to be therapeutic equivalents if they are pharmaceutical equivalents for which bioequivalence has been demonstrated, and they can be expected to have the same clinical effect and safety profile when administered to patients under the conditions specified in the labeling.5
Therapeutic Equivalence-Related Terms
Define Strength.
Strength refers to the amount of drug substance contained in, delivered, or deliverable from a drug product
includes
1. the total quantity of drug substance in mass or units of activity in a dosage unit or container closure
2. the concentration of the drug substance in mass or units of activity per unit volume or mass
Therapeutic Equivalence-Related Terms
Define Bioavailability.
the rate and extent to which the active ingredient or active moiety is absorbed from a drug product becomes available at the site of drug action
Therapeutic Equivalence-Related Terms
Define Bioequivalence.
is the absence of a significant difference in the rate and extent to which the active ingredient or active moiety in pharmaceutical equivalents or pharmaceutical alternatives becomes available at the site of drug action when administered at the same molar dose under similar conditions
What are the two basic categories into which multisource drugs have been placed?
This is indicated by the first letter of the relevant therapeutic equivalence code
A and B codes
What type of drug products does the A code refer to
that FDA considers to be therapeutically equivalent to other pharmaceutically equivalent products.
The A code is broken into two further categories.
What are they and what are the codes for each?
there are no known or suspected bioequivalence problems. AA, AN, AO, AP, AT depending on the dosage form
actual or potential bioequivalence problems have been resolved with adequate in vivo and/or in vitro evidence supporting bioequivalence. AB
What type of drug products does the B code refer to?
Drug products that FDA at this time, considers not to be therapeutically equivalent to other pharmaceutically equivalent products.
drug products for which actual or potential bioequivalence problems have not been resolved by adequate evidence of bioequivalence. Often the problem is with specific dosage forms rather than with the active ingredients. These are designated BC, BD, BE, BN, BP, BR, BS, BT, BX, or B*.
AA
Products in conventional dosage forms not presenting bioequivalence problems.
Multisource drug products coded as AA contain active ingredients and are in dosage forms that are not regarded as presenting either actual or potential bioequivalence problems or drug quality or standards issues
AB, AB1, AB2, AB3…
Products meeting necessary bioequivalence requirements
Multisource drug products listed under the same heading (i.e., identical active ingredients(s), dosage form, and route(s) of administration) and having the same strength
AN
Solutions and powders for aerosolization
AO
Injectable oil solutions
AP
Injectable aqueous solutions and, in certain instances, intravenous non-aqueous solutions
AT
Topical products
B*
Drug products requiring further FDA investigation and review to determine therapeutic
equivalence
BC
Extended-release dosage forms (capsules, injectables and tablets)
BD
Active ingredients and dosage forms with documented bioequivalence problems
BE
Delayed-release oral dosage forms
BN
Products in aerosol-nebulizer drug delivery systems
BP
Active ingredients and dosage forms with potential bioequivalence problems
BR
Suppositories or enemas that deliver drugs for systemic absorption
BS
Products having drug standard deficiencies
BT
Topical products with bioequivalence issues
BX
Drug products for which the data are insufficient to determine therapeutic equivalence
What are therapeutic alternatives?
Therapeutic alternatives are medicines that are chemically different from the one prescribed (used) but which have the same clinical effect. Therapeutic alternatives are not to be confused with generics.
Abbreviated New Drug Application (ANDA)
A request to the FDA for approval of a generic drug. ANDA is abbreviated because it allows for approval based on the demonstration of bioequivalence to a branded drug, rather than requiring the expensive and time-consuming clinical trials that the brand name drug underwent.
What are the Methods for Assessing BA and BE?
- In vivo measurement of active moiety or moieties in biological fluid (PK study)
- In vivo pharmacodynamic (PD) comparison
- In vivo limited clinical comparison
- In vitro comparison
- Any approach deemed acceptable (FDA)
What is an Abbreviated New Drug Application (ANDA)?
An application for FDA approval of a generic drug, demonstrating bioequivalence to a brand-name drug without requiring full clinical trial.
What is bioavailability?
The rate and extent to which a drug’s active ingredient is absorbed and reaches systemic circulation.
What is a bioequivalence requirement?
A standard that ensures a generic drug has similar bioavailability to the brand-name drug, ensuring the same therapeutic effect.
What are bioequivalent drug products?
Drugs with the same active ingredient, dosage form, and strength that exhibit similar bioavailability when administered in the same way.
What is a biosimilar drug?
A biologic product that is highly similar to an FDA-approved biologic with no clinically meaningful differences in safety and effectiveness.
What is a brand-name drug?
The proprietary name given to a drug by its manufacturer, protected by trademarks.
What is the chemical name of a drug?
The name that describes the drug’s molecular structure, used in scientific and medical contexts.
What is a drug product?
A finished dosage form (tablet, capsule, injection) containing a drug substance and inactive ingredients.
What is drug product performance?
How well a drug delivers the active ingredient in terms of stability, bioavailability, and therapeutic effect.
What is a drug substance?
The active pharmaceutical ingredient (API) that produces the intended therapeutic effect.
What is equivalence in pharmaceuticals?
The similarity between two drug products in terms of quality, safety, and efficacy.
What is a generic drug name?
The official, non-proprietary name assigned to a drug, the same across all manufacturers.
What are multisource drug products?
Drugs available from multiple manufacturers, typically generic versions of brand-name drugs.
What is generic substitution?
Replacing a brand-name drug with an FDA-approved generic equivalent.
What is a Reference Listed Drug (RLD)?
The original brand-name drug used as the standard for generic approval.
What are pharmaceutical alternatives?
Drugs with the same active ingredient but in different dosage forms or strengths.
What are pharmaceutical equivalents?
Drugs with the same active ingredient, dosage form, and strength but possibly different inactive ingredients.
What is pharmaceutical substitution?
Dispensing a different pharmaceutical equivalent (e.g., tablet vs. capsule) for the prescribed drug.
What are therapeutic alternatives?
Drugs with different active ingredients but similar therapeutic effects.
What are therapeutic equivalents?
Drugs that are both pharmaceutical equivalents and bioequivalent, meaning they have the same clinical effect.
What is therapeutic substitution?
Replacing a prescribed drug with a different drug that has the same therapeutic effect.
What is relative bioavailability?
A comparison of drug absorption between different formulations or routes of administration.
What is absolute bioavailability?
The percentage of a drug that reaches systemic circulation compared to IV administration (100%).
What is the purpose of the Orange Book?
To provide FDA-approved drug products and therapeutic equivalence evaluations for generic substitution.
How do you interpret data in the Orange Book?
It includes active ingredients, dosage forms, therapeutic equivalence ratings, and patent/exclusivity details.
