Bioavailability of Dietary Supplements Key Issues in Defining

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

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

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 80125%

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

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

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 formulation optimization of nutritional supplements ¨ Data for Public Domain use – Improve quality and safety through better practices

In vitro methods for assessing dissolution & Absorption ¨ USP Dissolution ¨ Caco 2 ¨ Etc.

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