BIOEQUIVALENCE CRITERIA

RESEARCH PROGRAM

DRAFT 2

November 1, 2001

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I. INTRODUCTION

On September 23, 1999, the Advisory Committee for Pharmaceutical Science met to discuss the use of different criteria to allow comparison of bioavailability (BA) measures in bioequivalence (BE) studies. These criteria and their use in specified BE studies have been described in two draft FDA guidances entitled, respectively, Average, Population, and Individual Approaches to Establishing Bioequivalence (Criterion Guidance) and Bioavailability and Bioequivalence Studies for Orally Administered Drug Products (General Guidance). The Committee=s deliberations focused on six discussion topics. The last of these discussion topics and the Committee=s recommendations were:

Discussion Topic:

The Advisory Committee is asked to comment on plans for further research programs and projects associated with the use of average and individual criteria to allow comparison of bioavailability measures.

Committee Response:

The Committee endorsed plans proposed by FDA for better mechanistic understanding, clinical pharmacology studies (>proof of concept= and >goalpost= studies) and other approaches as well. The Committee recommended that outliers should be studied as a means of identifying important causes for a subject-by-formulation interaction. The Committee endorsed creation of a research document to guide the interim study period and to request a review of this document by the Expert Panel.

This draft research program has been prepared by the Population and Individual Bioequivalence Working Group/Replicate Design Technical Committee of the Biopharmaceutics Coordinating Committee in accordance with the requests of the Advisory Committee.

II. Program Overview

 

III. PROJECTS

A. Criteria for BE Comparisons

Primary Objectives

Secondary Objectives

B. Data Analyses and Statistical Methodology

The objectives of this research project are to assess the performance of proposed criteria (individual, population, average, other).

Primary Objectives

Secondary Objectives

C. Mechanistic Understanding of Mean/Variance T/R Differences

The objectives of this research project are to develop mechanistic understanding for: