In vitro bioequivalence: an opportunity for the development and commercialization of national generic medicines

Abstract

Introduction: The replacement of in vivo bioequivalence studies with in vitro dissolution assays, based on the Biopharmaceutical Classification System, has emerged as an important tool for demonstrating the therapeutic interchangeability of generic products.

Objective: Assess the chances and potentialities of the national pharmaceutical industry for the development and commercialization of effective and safe generic medicines, based on the application of in vitro bioequivalence studies.

Methods: An analysis of the international and national regulations on in vitro bioequivalence was carried out. A new provisional biopharmaceutical classification system was proposed and its application to the classification of oral solid forms of the 2019 Basic Chart of Medicines of Cuba was demonstrated.

Results: The analysis of the national regulation on in vitro bioequivalence and its comparison with the international regulatory show that since 2007 the regulatory one in Cuba has not been updated, which allows the demonstration of therapeutic interchangeability for drugs with high permeability and low solubility. Similarly, there is limited application of this regulation. The proposed consensus method for predicting permeability adequately classifies more than 95% of human permeability and allows for better interim biopharmaceutical classification. The model identified that more than 66% of the drugs included in oral formulations of immediate release of the Basic Chart of Medicines could be exempted from bioequivalence studies in humans and demonstrate their interchangeability through in vitro dissolution assays.

Conclusions: The Cuban pharmaceutical industry has the capacity and possibility to promote the development of interchangeable generics, with the application of in vitro bioequivalence studies, at a lower cost, which makes it possible to register and market them in the most demanding markets.