1. WHOs Normative Work in the Field of Pharmaceuticals - introduction Lembit Rägo, MD, PhD, Coordinator Quality Assurance and Safety: Medicines Essential Drugs and Medicines Policy Health Technology and Pharmaceuticals Cluster World Health Organization E-mail: ragol@who.ch November 2003

2. 2 WHO - EDM Meeting with FDA, Mar. 2002 Why normative work is needed? n Medicines are very specific category of products ä Patients/consumers limited capacity to assess their safety, efficacy and quality ä Pharmacists and medical doctors - the same n Medicines must meet three basic criteria ä SAFETY ä EFFECACY ä QUALITY

3. 3 WHO - EDM Meeting with FDA, Mar. 2002 To assess QUALITY, SAFETY and EFFICACY norms and standards are needed n New innovative medicines (NCE or NDA) ä QUALITY, SAFETY; EFFICACY n Multisource or generic medicine ä QUALITY, and proof of being therapeutically interchangeable

4. 4 WHO - EDM Meeting with FDA, Mar. 2002 WHO medicines strategy Normative work on pharmaceuticals - Health Technology and Pharmaceuticals Cluster n Essential Drugs and Medicines Policy ä Quality Assurance and Safety: Medicines (QSM) ä Policy, Access and Rational Use (PAR) ä Drug Action Programme (DAP) ä Traditional Medicine (TRM) n Vaccines and Biologics - in another cluster FCH n Blood Safety and Clinical Technology - Now Essential Technologies

5. 5 WHO - EDM Meeting with FDA, Mar. 2002 Quality Assurance and Safety: Medicines Team (QSM) --- areas of work n Norms, standards and guidelines for quality, safety and efficacy of pharmaceuticals ä International Pharmacopoeia, GMP, GCP etc. n Nomenclatures, classifications ä International Nonproprietary Names (INNs) ä Anatomical Therapeutic Chemical (ATC) classification and Defined Daily Dose (DDD) n Guidance for control and use of psychotropics and narcotics n Drug safety ä The WHO Programme for International Drug Monitoring etc. n Drug regulatory support ä WHO Certification Scheme, assessment of NDRAs, training for regulators etc.

6. 6 WHO - EDM Meeting with FDA, Mar. 2002 Norms and standards for pharmaceuticals n International Pharmacopoeia ä Simple, classical physicochemical techniques are used ä Priority given to essential drugs, especially to drugs that are important to WHO health programmes (anti-TB etc.) ä Based on international experience and tested in WHO Collaboration Centres n Basic tests ä Limited range of widely available reagents are used ä Can be applied when a fully equipped laboratory is not available ä Merely confirm identity, does not replace pharmacopoeial monograph n Reference substances and infrared reference spectra for pharmacopoeial analysis

7. 7 WHO - EDM Meeting with FDA, Mar. 2002 Guidelines for pharmaceuticals n Good Manufacturing Practices (GMP) ä including starting materials --> would be revised based on ICH Q7A. Step-wise approach to the implementation needed ä including specific products (sterile, biological, investigational, and herbal products) --> guidelines for radiopharmaceutical products newly adopted at the Expert Committee ä Model certificates adopted ä Guidance for GMP inspection report adopted n Inspection of manufactures and distribution channels n Good Storage Practices ä Adopted at the Expert Committee

8. 8 WHO - EDM Meeting with FDA, Mar. 2002 Guidelines for pharmaceuticals n Good Clinical Practice (GCP)--- under revision ä Development of ICH GCP ä Significant changes were made to Declaration of Helsinki (5th amendment in 2000) ä Publication of EU Directive on GCP in April 2001 ä Needs for harmonization ä Ethical aspects should be strengthened --> Informal consultation to review WHO GCP was held in September 2001

9. 9 WHO - EDM Meeting with FDA, Mar. 2002 Drug Regulatory Support n WHO Certification Scheme ä on the quality of pharmaceutical products ä on the quality of starting materials n Assessment of NDRAs --> evidence based interventions and training for regulators n WHO Basic Training Modules on GMP ä Training workshop for inspectors n Medical Products and the Internet: A Guide to Finding Reliable Information ä Guide to consumers n Model web site for drug regulatory authorities

10. 10 WHO - EDM Meeting with FDA, Mar. 2002 Drug Regulatory Support n International Conference of Drug Regulatory Authorities (ICDRA) ä promoting collaboration and exchange of information between DRAs ä discussing common regulatory challenges n Promotion of regulatory harmonization ä acting as a link between ICH and non-ICH countries ä regional harmonization (PAHO, ASEAN etc.) n SIAMED (computer-assisted drug registration system) ä jointly developed with PAHO

11. 11 WHO - EDM Meeting with FDA, Mar. 2002 Drug Regulatory Support n Marketing Authorization of Pharmaceutical Products with Special Reference to Multisource (Generic) Products ä A Manual for a Drug Regulatory Authority n Prevention of counterfeit drugs ä guideline published ä raising awareness ä information sharing ä cooperation between DRAs and other authorities needed

12. 12 WHO - EDM Meeting with FDA, Mar. 2002 Drug Safety n WHO Programme for International Drug Monitoring ä more than 70 countries participating countries (2002) ä Annual meetings of National Centres ä Database of 3 million case reports ä Free access to database by participating countries ä Data mining process included n Exchange of Information ä WHO Drug Information ä WHO Pharmaceutical Newsletter ä WHO Drug Alerts ä WHO Restricted List

13. 13 WHO - EDM Meeting with FDA, Mar. 2002 Drug Safety n Promoting pharamcovigilance ---Series of technical guidelines ä Safety Monitoring- Guidelines for setting up a Pharmacovigilance Centre ä The Importance of Pharmacovigilance ä Guidelines for Safety monitoring in Communities ä Guidelines to improve reporting by physicians ä Guidelines on Crisis Management ä Guidelines on Monitoring herbal medicines

14. 14 WHO - EDM Meeting with FDA, Mar. 2002 Drug Safety n Technical support to countries ä Support to the WHO Programme for International Drug Monitoring ä Regional training courses in Pharmacovigilance ä Strengthen spontaneous reporting systems ä Establish active surveillance programmes n Partnerships and cooperations with other organizations ä Collaborating centers ä CIOMS VI Working Group ä Collaboration with PIC/S, EDQM, USP ä Working with IPC partners - UNICEF, UNAIDS, UNFPA; WB ä Working with the Pharmaceutical Industry ä Working with Consumers

15. 15 WHO - EDM Meeting with FDA, Mar. 2002 Guidance for control and use of psychotropics and narcotics n Undertake medical and scientific review of psychotropic and narcotic substances before the UN Commission on Narcotic Drugs makes decisions ä under 1961 Single Convention on Narcotic Drugs and 1971 Convention on Psychotropic Substances ä through Expert Committee on Drug Dependence n Model Guidelines for the International Provision of Controlled Medicines for Emergency Medical Care (1996) ä - access to narcotic pain killers remains a big problem

16. 16 WHO - EDM Meeting with FDA, Mar. 2002 Nomenclatures, classifications n International Nonproprietary Names (INNs) ä Collaboration with WIPO to protect INNs against use as trademarks ä INNs for biotechnological / biological products --> need collaboration with experts n Anatomical Therapeutic Chemical (ATC) classification and Defined Daily Dose (DDD) ä WHO Collaborating Centre for Drug Statistics and Methodology ä Used by countries to measure drug consumption data l to follow trends in drug utilization l to audit use against guidelines l to use in pharmacovigilance studies l to assess the access to drugs

17. 17 WHO - EDM Meeting with FDA, Mar. 2002 QSMs other activities n HIV / AIDS, TB and Antimalarial Drugs Pre- qualification Expected outcomes are: ä Operational Quality Manual for Procurement of Pharmaceuticals ä Pre-qualification of suppliers and individual AIDS-related pharmaceutical products ä Model Quality Assurance System for Procurement of Pharmaceuticals

18. 18 WHO - EDM Meeting with FDA, Mar. 2002 Future Challenges n Normative work not sexy for donors n WHO alone can not change the World - ä more than ever good cooperation rather than duplication and competition needed n Dreams - Global Alliance for Quality of Pharmaceuticals? ä Participants may include: UN organizations, DRAs, pharmacopoeias, development institutions, international professional societies, and NGOs ä Coordinate the efforts of the participants in the field of quality assurance of pharmaceuticals ä Offer, where feasible, through joint or coordinated efforts, technical expertise, training and/or financial support to countries