Pharmacopeial Working Group Update

1. IV PAN AMERICAN CONFERENCE FOR DRUG REGULATORYHARMONIZATION Pharmacopeial Working Group Update Horacio Pappa, Ph.D. Secretariat Santo Domingo, Dominican Republic March 2-4, 2005

2. Pharmacopeial Working Group Information Exchange Meetings Argentina Brazil Mexico USP (Secretariat) Harmonization Activities Pharmacopeia of the Americas Training Extranet

3. Mission statement The mission of this working group is to create a forum for discussion and exchange of information which will facilitate the adoption of harmonized procedures. A possible objective of the PWG is to have a harmonized PHARMACOPEIA of the Americas.

4. PWG Meetings 1. Washington DC, April 14, 2000 2. Sao Paulo, May 1, 2000 3. Porto Alegre, August 1, 2000 4. Orlando, March 26, 2001 5. Washington DC, November 20, 2001 6. Buenos Aires, June 26, 2002 7. Washington DC, December 19,2002 8. Cancun, November 4-5, 2003 9. Washington DC, April 9, 2005 (planned)

5. PUBLIC MEETNGS • Strategic Decision - A workshop held in Sao Paulo, March 2001, sponsored and organized by Farmacopeia Brasileira. • The Impact of Pharmacopeias on the Production and Regulation of Medicines and on Global Harmonization. Argentine Association for Industrial Pharmacy and Biochemistry (SAFYBI) hosted this forum on November 2001 in Buenos Aires. • The Impact of Pharmacopeias in International Trade. FEUM. Mexico City, on January 31, 2002. • USP held formal meetings with pharmaceutical manufacturers through its Prescription/Non­Prescription Stakeholders Forum.

6. Pharmacopeial Discussion Group Representatives from United States Pharmacopeia, European Pharmacopeia, and Japanese Pharmacopeia. Pharmacopeial Working GroupRepresentatives from the four active pharmacopeias in the Americas: Farmacopea Argentina - Dr. Carlos Chiale Farmacopeia Brasileira - Dr. Celso Bittencourt Farmacopea de los Estados Unidos Mexicanos - Dra. Carmen Becerril US Pharmacopeia - Dr. Roger Williams Secretariat support is provided by USP - Dr. H. Pappa Pharmacopeial Harmonization

7. Harmonization Harmonized: A pharmacopeial general chapter or other pharmacopeial document is harmonized when a pharmaceutical substance or product tested by the document’s harmonized procedure yields the same results, and the same accept/reject decision is reached. Harmonized by Attributes: If a monograph or general chapter is not completely harmonized with the corresponding texts of the other Pharmacopeias it is considered to be harmonized by attributes.

8. Harmonization Process Step 1. By consensus, one monograph is selected to be harmonized. A Leader Pharmacopeia (LP) is also selected. Step 2. LP send a draft to the other members of PWG with all the information which may be shared in accordance to the LP’s by laws. Step 3. Each pharmacopoeia sends the draft to the corresponding Expert Committees for revision. Later on, those comments are sent to LP within 45 days from the date of reception. Step 4. LP reviews the comments and prepares a second draft and a summary report about the discrepancies and agreements about the subject. After approval of the Expert Committee of LP such draft is sent to all the other members within the 30 days of having received the comments (sent by each member).

9. Harmonization Process Step 5. The Expert Committee of each pharmacopeia reviews the summary report and suggests if the complete harmonization is possible or will continue by attributes or the harmonization should be suspended. Not later than 45 days a response should be sent to LP. Step 6. LP receives the comments and if any of the pharmacopeias suggest that the complete harmonization or by attributes is not feasible, the process is suspended. If the answer is positive, LP prepares a third draft which is sent then to the other members for public comment indicating the tests and/or specifications where discrepancies may arise. Step 7. Each pharmacopoeia writes the proposal in its language and style and submits this text for public review stating the intention of harmonization, the degree of agreement reached and all the differences. Later on, each pharmacopoeia sends a report to LP.

10. Harmonization Process Step 8. LP analyzes the reports and sends the results to all the other PWG members together with a third draft. If necessary, Steps 5, 6 and 7 may be repeated. Step 9. After two cycles of revision, an agreement is signed if the parties agreed to harmonize a specific monograph. Each pharmacopeia must not modify any harmonized monograph without previously notifying the other three pharmacopeias. When an amendment is proposed, the change will follow the procedures stipulated by this protocol.

11. General Chapters Bacterial Endotoxins Residue on Ignition Particle in Injections Monographs Amiodarone Cat’s Claw PWG Update

12. Working Plan • To reach a consensus and harmonize the following general procedures: • Dissolution (FA as the leader Pharmacopeia) • Uniformity of Dosage Units (FEUM as leader Pharmacopeia) • Disintegration (USP as the leader Pharmacopeia)

13. Working Plan • To reach a consensus and harmonize the following monographs: • Aspirin • Morphine • Acetaminophen • Cod liver oil • Hydrocortisone • Ferrous Sulfate • Hydrochlorothiazide

14. NEWS • FEUM: The 8th edition was officially presented last December. • FB: Supplement 6 of 4th edition in print. • FA: Second supp. of 7th edition in print. • USP: Is working in the Spanish version. USP 29 will be available in Spanish and English. The Pharmacist’s Pharmacopeia will be available in July 2005.