Background:
Bioequivalence studies are a vital part of drug development. The average bioequivalence
approach is the standard method of assessment to conclude whether the generic product is bioequivalent to the innovator
product. Of late, debates are on whether the average bioequivalence approach adequately addresses drug interchangeability
as it considers only population mean for the evaluation especially when highly variable drug products
and narrow therapeutic index drugs are dealt with. Hence, the alternative approaches like population bioequivalence
and individual bioequivalence assessment approaches emerge as they consider inter/intra-subject variance and subject-
by-formulation variance along with population mean.
Objectives:
The objective of the study was to apply different bioequivalence assessment approaches in a replicate
bioequivalence study to evaluate the drug interchangeability.
Methods:
This was an open-label, single-dose, randomized, balanced, two-treatment, three-period, three-sequence,
partial replicate crossover bioequivalence study of omeprazole enteric-coated tablet 20 mg conducted on 48 normal
healthy subjects under fed conditions. The plasma concentration of omeprazole was analyzed by a validated bioanalytical
method to determine the pharmacokinetic and statistical parameters to assess average bioequivalence,
population bioequivalence, and individual bioequivalence.
Results:
In this study, test formulation was shown to be bio-inequivalent to the reference formulation by average
bioequivalence, population bioequivalence, and individual bioequivalence approaches.
Conclusion:
The outcome of the evaluation clearly states that the bioequivalence outcome of all these approaches are
the same. Obviously, it does not mean that these three approaches provide the same outcome though the consideration
of variances varies. Certainly, population bioequivalence and individual bioequivalence approach will be more
accurate for the assessment of drug interchangeability.