Dissolution Testing for Generic Drugs: An FDA Perspective

Abstract

In vitro dissolution testing is an important tool used for development and approval of generic dosage forms. The objective of this article is to summarize how dissolution testing is used for the approval of safe and effective generic drug products in the United States (US). Dissolution testing is routinely used for stability and quality control purposes for both oral and non-oral dosage forms. The dissolution method should be developed using an appropriate validated method depending on the dosage form. There are several ways in which dissolution testing plays a pivotal role in regulatory decision-making. It may be used to waive in vivo bioequivalence (BE) study requirements, as BE documentation for Scale Up and Post Approval Changes (SUPAC), and to predict the potential for a modified-release (MR) drug product to dose-dump if co-administered with alcoholic beverages. Thus, in vitro dissolution testing plays a major role in FDA's efforts to reduce the regulatory burden and unnecessary human studies in generic drug development without sacrificing the quality of the drug products.

Development of a Dissolution Method for Gliclazide Modified-Release Tablets Using USP Apparatus 3 with <i>in Vitro–in Vivo</i> Correlation

“…15,16) The United States Pharmacopeia (USP) Apparatus 3 (Reciprocating cylinder or BioDis) was specifically designed for dissolution evaluation of MR dosage forms because it can mimic physicochemical and mechanical changes experienced by a MR dosage form in the GIT. [17][18][19] In addition, this apparatus demonstrates superior hydrodynamic controls in comparison to USP apparatuses 1 and 2 and provides numerous options in terms of instrumental parameters, such as composition of the media, pH and agitation rate. 20,21) To describe a relationship between in vitro characteristics of a dosage form and the in vivo response, a predictive mathematical model is used to define the in vitro-in vivo correlation (IVIVC) level.…”

Medicamentos genéricos: su importancia económica en los sistemas públicos de salud y la necesidad de estudios in vitro para establecer su bioequivalencia

“…La FDA promueve reducir el trámite regulatorio y los estudios innecesarios en humanos sin sacrificar la calidad de los productos (Anand, Yu y Conner, 2011). Las pruebas de disolución han emergido como una herramienta en la industria farmacéutica de genéricos, especialmente para los procesos de formulación y desarrollo, en el monitoreo de procesos de manufactura y en pruebas de control de calidad; también son de gran utilidad para predecir el desempeño in vivo de ciertos productos.…”

Evaluation of the Bioequivalence Documentation Required For Registration of Generic Drug Products in Burkina Faso: Methodology of Implementation and Impact

“…The rates of in vivo pharmacokinetic studies and in vitro comparative dissolution tests found in the applications were respectively higher and lower in 2010, compared to those of 2011. The documentation of bioequivalence from in vivo trials is less advantage in terms of cost, time and safety and requires ethic and regulatory approbations, contrary to the in vitro dissolution studies that are more accessible, easier and shorter to achieve [5,17,18]. Therefore, the comparative in vitro dissolution studies were privileged by the majority of the applicants with some success.…”