BEBAC  Ing. Helmut Schütz

International Council for Harmonisation – ICH

Multidisciplinary Guideline

On 27 June 2018 the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) published a Draft Endorsed Guideline (i.e., step 2 of the process).

1.1. Background and Objective

Two drug products containing the same active substance are considered bioequivalent if their bioavailabilities (rate and extent of drug absorption) after administration in the same molar dose lie within acceptable predefined limits. These limits are set to ensure comparable in vivo performance, i.e., similarity in terms of safety and efficacy. In in vivo bioequivalence studies, the pivotal pharmacokinetic parameters AUC (the area under the concentration time curve), and Cmax (the maximum concentration), are generally used to assess the rate and extent of drug absorption.

The BCS (Biopharmaceutics Classification System)-based biowaiver approach is intended to reduce the need for in vivo bioequivalence studies i.e., it can provide a surrogate for in vivo bioequivalence. In vivo bioequivalence studies may be exempted if an assumption of equivalence in in vivo performance can be justified by satisfactory in vitro data. The BCS is a scientific approach based on the aqueous solubility and intestinal permeability characteristics of the drug substance. The BCS categorizes drug substances into one of four BCS classes as follows:

Class I: high solubility, high permeability
Class II: low solubility, high permeability
Class III: high solubility, low permeability
Class IV: low solubility, low permeability

This guidance will provide recommendations to support the biopharmaceutics classification of drug substances and the BCS-based biowaiver of bioequivalence studies for drug products.

1.2. Scope

BCS-based biowaivers may be used to demonstrate bioequivalence for example between products used in early clinical development through commercialization, for line extensions of the same pharmaceutical form of innovator products, in applications for generic drug products, and post-approval changes that would otherwise require in vivo bioequivalence evaluation, in accordance with regional regulations.

The BCS-based biowaiver is only applicable to immediate release, solid orally administered dosage forms or suspensions designed to deliver drug to the systemic circulation. Drug products having a narrow therapeutic index are excluded from consideration for a BCS-based biowaiver in this guidance. Fixed-dose combination (FDC) products are eligible for a BCS-based biowaiver when all drug substances contained in the combination drug product meet the criteria as defined in sections 2 and 3 of this guidance.

Public consultation is planned for August 2018 and adoption of the final guideline in May 2019.


On 20 Nov 2019 the final version (step 4) together with a Questions & Document was published.