Ensuring Drug Safety with USP Standards

1. Food and Drug AdministrationPublic MeetingMay 1, 2009Economically Motivated AdulterationAcademic/Government Panel Roger L. Williams, M.D. Chief Executive Officer Chair, Council of Experts rlw@usp.org

2. Topics • USP Convention • USP in Law • USP and Heparin • Issues and Summary

4. Convention Membership Councilof Experts & Expert Committees Board of Trustees & Board Committees USP Staff Stakeholder Forums & Project Teams Advisory Bodies USP Governing and Advisory Bodies Council of the Convention Advisory Panels

5. USP Global Laboratory Sites China India Rockville, Maryland Brazil

6. USP 32–NF 27 • Time-tested, international resource. USP standards are used in more than130 countries • More than 4,200 monographs • Official authority—FDA-enforceable for drugsmanufactured in, exported to, or marketed in the U.S. • Continuously updated—published annually in a main edition and two Supplements • Available in English (print, online, CD) and Spanish (print)

7. USP’s Legal Recognition (FD&C Act) • SEC. 201. For the purposes of this chapter - • (g)(1) The term ''drug'' means articles recognized in the official United States Pharmacopoeia, official Homoeopathic Pharmacopoeia of the United States, or official National Formulary, or any supplement to any of them • (j) The term ''official compendium'' means the official United States Pharmacopoeia, official Homeopathic Pharmacopoeia of the United States, official National Formulary, or any supplement to any of them.

8. USP’s Legal Recognition: FD&C Act Section 501(b) Adulteration • A drug or device shall be deemed to be adulterated if it purports to be or is represented as a drug the name of which is recognized in an official compendium, and its strength differs from, or its quality or purity falls below, the standards set forth in such compendium. • Such determination as to strength, quality, or purity shall be made in accordance with the tests or methods of assay set forth in such compendium… USP’s public standards can help assure the quality and safety of all drugs sold in U.S. market

9. 2005-2010 USP Council of Experts Food Ingredients Expert Committee

10. Expert Committee Chair: Jean Huxsoll, Ph.D. Members: Timothy Hayes, Ph.D. Christopher Bryant, Ph.D. Pamela Clark, M.D., J.D. Elaine Gray, Ph.D. Patrick McKee, M.D. Michael Passwater, BS John Sokolowski, MS Advisory Panel Chairs: Wesley Workman, Ph.D & Kristian Johansen, Ph.D. Members: Edward Chess, Ph.D. Neil Desai, Ph.D. Gyöngyi Gratzl, Ph.D. Elaine Gray, Ph.D. Hester Hasper-van Heusden, Ph.D. Craig Jackson, Ph.D. Robert Linhardt, Ph.D Barbara Mulloy, Ph.D. Zachary Shriver, Ph.D. Christian Viskov, Ph.D. FDA liaison: Ali Al-Hakim, Ph.D. Blood and Blood Products Expert Committee and Advisory Panel

11. Changes to USP Heparin Sodium Monograph

12. Prior Efforts to Revise • WHO – 1998 working group develops chromogenic anti-factor IIa potency test • 2004 Stimuli article in Pharmacopeial Forum (PF) 30(5) on the qualification of chromogenic test – proposes replacement of sheep plasma assay • 2006 Advisory Panel is formed • 2007 revision proposal in PF 33(2) to replace the sheep plasma clotting potency test with chromogenic anti-factor IIa potency test

13. Comparison of Monograph Requirements

14. Issues and Summary • Current USP View:An up to date public monograph in USP with careful attention to GMPs, including careful in-process testing, could have prevented access to commercially contaminated heparin drug substances in the US market • Many other USP monographs are either missing or out of date • The FDA-USP partnership created in law more than 100 years ago needs to be strengthened • No mechanism for ensuring that USP receives information it needs to create and update monographs • This will need involvement from all stakeholders

15. Thank you