Annex 8: proposal to waive in vivo bioequivalence requirements for WHO Model List of Essential Medicines immediate-release, solid oral dosage forms.(World Health Organization)

 
Introduction 
 
1. Background 
 
2. WHO revisions to the criteria for Biopharmaceutics Classification 
   System classification 
 
3. WHO extensions to the scope of application of the biowaiver 
 
4. WHO additional criteria for application of the biowaiver procedure 
 
5. Explanation of the tables 
 
6. Biowaiver testing procedure according to WHO 

Introduction

This proposal is closely linked to the Multisource (generic) pharmaceutical products: guidelines on registration requirements to establish interchangeability (WHO Technical Report Series, No. 937, Annex 7). It aims to give national authorities sufficient background information on the various orally administered active pharmaceutical ingredients (APIs) on the WHO Model List of Essential Medicines (EML), also taking into account local usage of the API, to enable them to make an informed decision as to whether generic formulations should be subjected to in vivo bioequivalence (BE) studies or whether a biowaiver can be granted. In light of scientific work and discussion in the last decade, some of the criteria used to evaluate the API in terms of potential for a biowaiver have been revised to allow a broadened scope of application. The result is that many APIs on the EML can now be considered for the biowaiver procedure, subject to the usage and risks in the national setting.

1. Background

1.1 Initiatives to allow biowaivers based on the Biopharmaceutics Classification System

In 1995 the American Department of Health and Human Services, US Food and Drug Administration (HHS-FDA) instigated the Biopharmaceutics Classification System (BCS), with the aim of granting so-called biowaivers for scale-up and post-approval changes (SUPAC) (www.fda.gov/cder/ guidance/cmc5.pdf). A biowaiver means that in vivo bioavailability and/or bioequivalence studies may be waived (i.e. not considered necessary for product approval). Instead of conducting expensive and time-consuming in vivo studies, a dissolution test could be adopted as the surrogate basis for the decision as to whether two pharmaceutical products are equivalent. At that time the biowaiver was only considered for SUPAC to pharmaceutical products.

More recently, the application of the biowaiver concept has been extended to approval of certain orally administered generic products (www.fda.gov/ cder/guidance/3618fnl.htm).