WHO’s Normative Work in the Field of Pharmaceuticals - introduction

1. WHO’s Normative Work in the Field of Pharmaceuticals - introduction November 2003 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

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

3. To assess QUALITY, SAFETY and EFFICACY norms and standards are needed • New innovative medicines (NCE or NDA) • QUALITY, SAFETY; EFFICACY • Multisource or generic medicine • QUALITY, and proof of being therapeutically interchangeable

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

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

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

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

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

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

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

11. Drug Regulatory Support • Marketing Authorization of Pharmaceutical Products with Special Reference to Multisource (Generic) Products • A Manual for a Drug Regulatory Authority • Prevention of counterfeit drugs • guideline published • raising awareness • information sharing • cooperation between DRAs and other authorities needed

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

13. Drug Safety • Promoting pharamcovigilance ---Series of technical guidelines • Safety Monitoring- Guidelines for setting up a Pharmacovigilance Centre • The Importance of Pharmacovigilance • Guidelines for Safety monitoring in Communities • Guidelines to improve reporting by physicians • Guidelines on Crisis Management • Guidelines on Monitoring herbal medicines

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

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

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

17. QSM’s other activities • HIV / AIDS, TB and Antimalarial Drugs Pre-qualification Expected outcomes are: • Operational Quality Manual for Procurement of Pharmaceuticals • Pre-qualification of suppliers and individual AIDS-related pharmaceutical products • Model Quality Assurance System for Procurement of Pharmaceuticals

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