1. Bioavailability of Dietary Supplements: Key Issues in Defining the Research Agenda Impact of Formulation on Bioavailability? Discussion Leader: Stephen W. Hoag Ph.D. University of Maryland Rapporteur: Ajaz S. Hussain, Ph.D. CDER, FDA

2. Preface  Introductions  Background –Pharmaceutical Sciences –Nutritional Sciences –Nutraceuitical Sciences –Pharmaceutical formulations, bioavailability and bioequivalence –Food and Dietary Supplements – formulations, bioavailability, and bioequivalence

3. Questions for considerations  Key issues in defining the research agenda? –What is the question? Do two different pharmaceutical products containing the same drug provide the same “safety” and “efficacy” profile? –What are we willing to assume? Drug concentration time profile in plasma is a reliable surrogate for safety and efficacy profile –How sure do we want to be? The 90% confidence interval of the ratio of the peak concentration of drug in plasma, time to reach the peak concentration, and the area under the curve are within 80- 125%

4. Key Topics Discussed  Product Classification System  Identification of “Critical Variables” –Interactions –Modulation of Bioavailability –In vitro methods for assessing dissolution & absorption –Product Comparison –Optimal Product Use

5. Goals and Objectives  Improving Public Health –Better products –Safety  Enhance Scientific Knowledge  Develop General Methods for: –Formulation –Testing  Define Quality Standards  Prioritization –Health Issues –Market Prevalence

6. Identification of “Critical Formulation Variables”  For a given class –Critical Process and formulation variables that significantly impact Bioavaiable Stability  General strategies and/or methods need to be developed for formulation optimization of nutritional supplements  Data for Public Domain use –Improve quality and safety through better practices

7. In vitro methods for assessing dissolution & Absorption  USP Dissolution  Caco2  Etc.

8. Product Comparison  “Bioequivalence”  Comparison of bioavailability of different product types (including food) –Information for consumers and clinicians  Example –Natural vs. synthetic Ca supplements –Units of activity measurement