Bioequivalence Studies

The United States Food and Drug Administration (FDA) has defined bioequivalence as, "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 in an appropriately designed study."

In other words, bioequivalence is the property wherein two drugs with identical active ingredients (e.g., brand-name drug and its generic equivalent) or two different dosage forms (as tablet and oral suspension) of the same drug possess similar bioavailability and produce the same effect at the site of physiological activity.

(Pharmaceutical equivalence implies the same amount of the same active substances, in the same dosage form, for the same route of administration and meeting the same or comparable standards.

Pharmaceutical alternative is used to define pharmaceutical products that have the same active moiety but that may differ in chemical form (i.e., salt, ester etc.) of that active compound or in dosage form or strength.)

Need of Bioequivalence studies

These studies are required by regulations to ensure therapeutic equivalence between a pharmaceutically equivalent test drug and a reference drug. Most often, these studies are used for generic drugs or when a formulation of a drug is changed during development.

It means generic product possesses the same active ingredient, dosage form, strength, and route of administration under the same conditions of use and shows no significant difference in the rate and extent of absorption of the active pharmaceutical ingredient.

Thus, generic drug can become a substitute for its RLD by possessing same safety and efficacy as its reference RLD. On the other hand, when a generic drug is not bioequivalent to the RLD, it will not be approved as a substitute for its brand version but it may be approved for another use.

In general, generic drug does not need to go through the full process of clinical trial to get approval. It just need to show bioequivalence with the brand drug. However, in case of generic version of biologics (called “biosimilars”), clinical trial may be required to get approval.

Determination of Bioequivalence

The selection of the method used to determine bioequivalence depends upon the purpose of the study, the analytical methods available, and the nature of the drug product.