Bioequivalence testing is an essential step during the development of generic drugs. Regulatory agencies have drafted recommendations and guidelines to frame this step but without finding any consensus. Different methodologies are applied depending on the geographical region. For instance, in the EU, EMA recommends using average bioequivalence test (ABE), while in the USA, FDA recommends using population bioequivalence (PBE) test. Both methods present some limitations (e.g., when batch variability is non-negligible) making it difficult to conclude to equivalence without subsequently increasing the sample size. This article proposes an alternative method to evaluate bioequivalence: between-batch bioequivalence (BBE). It is based on the comparison between the mean difference (Reference − Test) and the Reference between-batch variability. After presenting the theoretical concepts, BBE relevance is evaluated through simulation and real case (nasal spray) studies. Simulation results showed high performance of the method based on false positive and false negative rate estimations (type I and type II errors respectively). Especially, BBE has shown significantly greater true positive rates than ABE and PBE when the Reference residual standard deviation is higher than 15%, depending on the between-batch variability and the number of batches. Finally, real case applications revealed that BBE is more efficient than ABE and PBE to demonstrate equivalence, in some well-known situations where the between-batch variability is not negligible. These results suggest that BBE could be considered as an alternative to the state-of-the-art methods allowing costless development.