m8 : Bioavailability and Bioequivalence

Bioavailability studies

are drug product performance studies used to define the effect of changes in the physicochemical properties of the drug substance, the formulation of the drug, and the manufacture process of the drug product (dosage form)

Bioequivalence studies

are drug product performance tests that compare the bioavailability of the same active pharmaceutical ingredient from one drug product (test) to a second drug product (reference).

Bioavailability studies

Drug product performance studies are used in the development of new and generic drug products

in vivo

Bioavailability and bioequivalence can be considered as measures of the drug product performance in __

Reference Listed Drug (RLD)

Generic drugs are multisource products approved by the FDA as therapeutically equivalent to a __ — usually the brand or innovator product.

Bioavailability

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

Bioequivalence

is defined as 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.

Absolute bioavailability

This compares the bioavailability of the active drug in the systemic circulation following extravascular administration with the bioavailability of the same drug following intravenous administration. Intravenous drug administration is considered 100% absorbed

Relative Bioavailability

In a relative bioavailability study, the systemic exposure of a drug in a designated formulation (generally referred to as treatment A or reference formulation) is compared with that of the same drug administered in a reference formulation (generally referred to as treatment B or test formulation).

1. plasma drug concentration

2. urinary drug excretion

3. in vivo pharmacodynamic (PD) comparison

4. clinical endpoint study

5. in vitro studies

in vivo measurements of active moiety or moieties in biological fluids (decreasing accuracy or sensitivity and reproducibiiiiii)

Reference Listed Drug (RLD).

In bioequivalence (BE) studies, one product is chosen as the reference standard — this is the __

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The RLD is usually the original brand-name product approved under a New Drug Application (NDA) with proven safety and efficacy data. Generic (test) drugs must show bioequivalence to this RLD.

Orange

The FDA __ Book lists all RLDs officially recognized for comparison.

• Replicated Crossover Study Designs

• Narrow Therapeutic Index Drugs

• Reference Scaled Average Bioequivalence

• Parallel Study Designs

• Multiple-Dose (Steady-State) Study Design

• Clinical Endpoint Bioequivalence Study

• Determination of Bioequivalence of Drug Products in Patients Maintained on a Therapeutic Drug Regimen

Crossover Study Designs

. Pharmaceutical Equivalents:

Drug products in identical dosage forms that contain the same active ingredient(s), that is, the same salt or ester, are of the same dosage form, use the same route of administration, and are identical in strength or concentration. But different in excipients.

Pharmaceutical Alternatives

Drug products that contain the same therapeutics moiety but as different salts, esters, or complexes. Also differ in dosage for and strength

• Drug products containing different active ingredients that are indicated for the same therapeutic (drug class) or clinical objectives

naproxen

alternative for ibuprofen

therapeutic equivalents

Drug products are considered to be __ only if they are pharmaceutical equivalents and if they can be expected to have the same clinical effect and safety profile when administered to patients under the conditions specified in the labelling.

• Both pharmaceutical equivalent and bioequivalent.