Quality management in bioequivalence assessment: problems and prospects

Abstract

One of the main problems of modern drug production is the assessment of bioequivalence during the life cycle of the product at the stage of preliminary approval (the stage of clinical trials) and at the stage after approval.Getting a biowaiver is very important for pharmaceutical companies because of the significant savings in resources and time. However, if this is not done with scientific justification, safety and efficacy may be affected due to false positive decisions. Often differences in bioavailability are not found in pharmaceutical practice and hence are rarely reported.A search of original studies in the scientific databases of PubMed, Elsevier Science (Scopus) and Clarivate Analytics (Web of Science) was carried out to determine the distinguishing features of the biowaiver methodology, followed by analysis of the data obtained.In general, pharmaceutical development should relate in vitro dissolution to in vivo product efficacy. Under certain conditions, the results of a comparative bioavailability or clinical study can be extrapolated to all generic drugs. Biowaiver considerations include drug pharmacokinetics, dosage form type, manufacturing processes, and formulation proportionality. The article summarizes the unresolved issues associated with biowaiver based on the Biopharmaceutical Classification System (BCS), but also discusses the positive aspects of the prospect of further uses of the biowaiver procedure.Unresolved issues that have arisen in the analysis of examples of false negative and false positive results described in the literature require further adjustment of regulatory requirements. Possible ways to solve these problems are the use of modeling and simulation, as well as the improvement of in vitro biorelevant tests, which are able to distinguish dosage forms with unequal in vivo efficiency, which potentially effectively allows the use of the biowaiver procedure.