ICH Guideline for Biopharmaceutics Classification System-Based Biowaiver (M9): Toward Harmonization in Latin American Countries.

Claudia Miranda,Verónica Llauró,Yanina Rodríguez,Gustavo Mendes,Alexis Aceituno,Miguel Ángel Cabrera-Pérez,Mirna Fernández

doi:10.3390/pharmaceutics13030363

Claudia Miranda, Verónica Llauró + Show 5 more

Open Access

https://doi.org/10.3390/pharmaceutics13030363

Copy DOI

Abstract

The biopharmaceutical classification system (BCS) is a very important tool to replace the traditional in vivo bioequivalence studies with in vitro dissolution assays during multisource product development. This paper compares the most recent harmonized guideline for biowaivers based on the biopharmaceutics classification system and the BCS regulatory guidelines in Latin America and analyzes the current BCS regulatory requirements and the perspective of the harmonization in the region to develop safe and effective multisource products. Differences and similarities between the official and publicly available BCS guidelines of several Latin American regulatory authorities and the new ICH harmonization guideline were identified and compared. Only Chile, Brazil, Colombia, and Argentina have a more comprehensive BCS guideline, which includes solubility, permeability, and dissolution requirements. Although their regulatory documents have many similarities with the ICH guidelines, there are still major differences in their interpretation and application. This situation is an obstacle to the successful development of safe and effective multisource products in the Latin American region, not only to improve their access to patients at a reasonable cost, but also to develop BCS biowaiver studies that fulfill the quality standards of regulators in developed and emerging markets.

Highlights

The biopharmaceutical classification system (BCS) is a very important tool to reduce the need for in vivo bioequivalence (BE) studies during the development of new and generic drug products
It is remarkable that several authorities in the Latin American region do not specify, in their regulatory guidance documents, the solubility requirements for BCS
The results reveal that only Chile, Brazil, Colombia, and Argentina have a more comprehensive BCS guideline, including solubility, permeability and dissolution requirements

Summary

Introduction

The biopharmaceutical classification system (BCS) is a very important tool to reduce the need for in vivo bioequivalence (BE) studies during the development of new and generic drug products. 1995, to classify drug substance(s) from immediate release solid orally administered dosage forms, taking into account their aqueous solubility and intestinal permeability properties [1]. The combination of these properties with the dissolution rate of the drug product are considered the most important factors that modulate the rate and amount of the drug absorbed (bioavailability) [2]. A complete harmonization between them has not been achieved, as significant differences in this regulatory guidance still remain [4,5,6]

Objectives

Methods

Results

Discussion

Conclusion