Bioavailability and Bioequivalence

Question 1

What is bioavailability?

Answer 1

“ .. the extent and the rate at which a substance or its active moiety is delivered from a pharmaceutical form and becomes available in the general circulation.”

Question 2

What is Absolute bioavailability?

Answer 2

• Comparison of the bioavailability of a particular dosage form with that following intravenous administration (100%)
• requires I. V. administration

Question 3

What is Relative bioavailability?

Answer 3

• comparison AUC values (ratio) of different dosage
• No IV reference required
• Determines the effect of formulation difference on drug absorption

Question 4

What are factors affecting Bioavailability studies?

Answer 4

• Body weight
• Sex and age of the test subjects
• Disease states
• Genetic differences in drug metabolism
• Excretion and distribution
• Concomitant administration of other drugs
• Stress
• Time of administration of the drug

Question 5

What is a generic drug?

Answer 5

“A drug product that is comparable to a brand/reference listed drug product in dosage form, strength, route of administration, quality and performance characteristics, and intended use”

-Ideally it must have the same efficacy, same quality and same efficiency

Question 6

When are Drug products are considered to be pharmaceutical equivalents?

Answer 6

If they contain the same active ingredient(s), are of the same dosage form, route of administration and are identical in strength or concentration

Question 7

When are drugs considered to be Pharmaceutical alternatives?

Answer 7

Drug products are considered pharmaceutical alternatives if they contain the same therapeutic moiety, but are different salts, esters, or complexes of that moiety, or are different dosage forms.

Question 8

When are Drugs considered to be Therapeutic Equivalent?

Answer 8

Drug products are considered to be therapeutic equivalents 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.

Question 9

What is Bioequivalence?

Answer 9

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

Question 10

What are approaches to determine Bioequivalence?

Answer 10

1) Pharmacokinetic (PK) studies
2) Pharmacodynamic (PD) studies
3) Comparative clinical trials
4) In vitro studies:Dissolution/drug release testing
5) Any other approaches deemed appropriate by FDA

Question 11

What is the acceptance criteria for Bioequivalence?

Answer 11

• Bioequivalence is based on a comparison of ratios where the ratio of generic to innovator for each pharmacokinetic parameter does not differ by more than 8:10, this is how the range for the confidence intervals is defined:
• The 90% confidence intervals for the ratios of both Cmax and AUC should be contained within the limits 0.80–1.25