Bioavailability and bioequivalence studies (BABE studies) are the pillars of successful generic drug approval. BABE studies establish therapeutic equivalence among a test drug and its reference counterpart. If two drugs are equivalent, then they are considered the same in all other aspects. BE studies evaluate the in vivo equivalence between two different drug products.

Sponsors achieve biological equivalence when the extent and absorption rate between two pharmaceutical products does not differ significantly. If bioavailability is similar at the same molar concentrations, the two drug products are considered bioequivalent. Different approaches such as comparative bioavailability studies, comparative clinical trials, and comparative pharmacodynamics studies are available to study the bioequivalence of drug products. Let us focus on how to design a bioequivalence study for rapid progression through different stages and its final approval.

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Design of Bioequivalence studies

The main objective while designing BE studies is to limit any experimental variables and try to avoid a study bias. Parallel design and cross-over design are two study designs mainly employed in bioequivalence clinical trials.

Parallel study design involves the administration of two formulations to two different sets of volunteers. Researchers avoid study bias by administering the formulations randomly among the volunteers. As this design does not address intersubject variability, a cross-over study is usually used in bioequivalence studies. In a cross-over design, the test drug and the reference drug are studied in healthy subjects who alternately receive both the test and reference drugs. Researchers separate the two treatments by a washout period which mainly depends on the half-life of the drug.

In a cross-over design, the study subjects receive the treatment randomly but are equally divided, among the groups. As both the medication is studied on the same study subject, intrasubject variability is much smaller between the volunteers, and therefore, cross-over design is the preferred choice in bioequivalence studies. Although different in performance, both parallel and cross-over study designs largely depend on the replication, randomization, and error control in a study setting.

For regulatory approvals, the test drug is generally compared with a reference standard drug to select the best dose or formulation among different study results obtained during in vitro analysis. The comparisons required are usually fulfilled with single-dose studies. This is because the relative bioavailability of drug products can be efficiently determined through single-dose studies and can then be used to predict its performance at multiple dose levels. Ideally, study samples should be analyzed as soon as they are collected. But often, samples are stored for several days. Therefore, it is crucial to take appropriate care of study samples.


BABE studies in clinical research have been a routine protocol adopted by all concerned pharmaceutical parties for more than 20 years. Such a surge in BABE studies is mainly contributed to a rise in generic drugs and drug products. Therefore, bioavailability and bioequivalence testing for generic drugs are conducted following stringent regulatory guidelines. Today bioequivalence studies need continuing efforts from different authorities and organizations for the development of robust and reliable approaches in designing bioequivalence studies.