Innovative in vitro methodologies for establishing therapeutic equivalence

ABSTRACT To improve the quality of pharmaceutical products in their markets, several Latin American countries have begun to require that new generic products demonstrate bioequivalence against innovator or reference products. However, given the number of products involved, it is not feasible to rely on clinical studies to comply with this requirement. Instead, it makes sense to adopt or develop strategies that are appropriate to the characteristics of the region. To streamline drug development and accelerate patients’ access to quality drug products, 15 years ago the United States Food and Drug Administration (FDA) decided to grant exemptions from clinical bioequivalence studies (i.e., biowaivers) for certain types of drug products based on the Biopharmaceutics Classification System (BCS). Biowaivers can significantly reduce development time and cost and can also prevent unnecessary human exposure to potentially dangerous drugs while providing a robust, consistent standard for therapeutic equivalence of generic drug products. In addition, the limited success of translating in vitro dissolution data into in vivo performance can be enhanced using innovative tools such as the in vitro dissolution and absorption systems (IDAS). By integrating in vitro dissolution and permeability tests, these systems can provide useful insights for formulation development. A thorough assessment of the potential of in vitro techniques, along with formalization of their use through regulatory science initiatives when appropriate, may lead to cost-effective tools to help address some of the quality and regulatory challenges faced in the Latin American and Caribbean region