Safe quality medicines

1. Safe quality medicines

2. Medicines quality assurance: WHO normative functions in the field of pharmaceuticals Sabine Kopp, PhD Quality Assurance and Safety: Medicines Department of Medicines Policy and Standards

3. Main points addressed • WHO international guidelines, standards and norms in the area of medicines quality assurance • WHO's anti-counterfeiting activities and IMPACT

4. WHO Expert Committee • Report of the WHO Expert Committee: • Summarizes discussion • Gives recommendations to WHO + Member States • Includes newly adopted guidelines; • Is presented to WHO Governing Bodies for final comments, endorsement and implementation by Member States •  constitutes WHO technical guidance

5. WHO Partners • National and regional authorities • International organizations (UNAIDS, UNFPA, UNICEF, World Bank, WIPO, WTO, WCO, etc) • International professional and other associations, NGOs (including consumer associations, MSF, industry: IFPMA-IGPA- WSMI, FIP, WMA, etc) • WHO Expert Panels (official nomination process) • Specialists from all areas, regulatory, university, industry……… • WHO Collaborating Centres (official nomination process) • Pharmacopoeia Commissions and Secretariats, national institutions and institutes .. • Regional and inter-regional groups (ICH…)

6. WHO’s medicines quality assurance guidelines Cover: • Production • Quality Control • Quality related regulatory guidelines • Inspection • Distribution •  from manufacture to delivery to patient

7. WHO’s global guidelines - quality control - • International specifications (Ph. Int., screening tests..) • WHO Model Certificate of Analysis (COA) • Considerations for requesting analysis of samples • Quality control laboratories: • Good practices for national control labs • List of laboratory equipment • External qc assessment scheme for labs

8. International PharmacopoeiaPh.Int. • current: 4th edition! Supplement 1, no 2 in prep. • implementation: “ready for use” by Member States • Scope since 1975: • Model List of Essential Medicines and • Drugs recommended by WHO Specific disease programmes, e.g. Malaria, TB, HIV/AIDS, medicines for children

10. WHO’s strategy for quality control • Step-wise approach: • - Basic tests (identification) • - Screening tests (TLC) • - The International Pharmacopoeia • + International chemical reference standards (ICRS) • + IR reference spectra  1. Suppl.

11. External Quality Assessment Scheme for National Drug Quality Control Laboratories • Phase 4 (06/2007 - 05/2009) - 50 laboratories participate - Studies: • Titration • Water content by Karl-Fisher • Dissolution test • Determination of glucose by polarimetry • HPLC assay

12. WHO’s global guidelines - distribution • WHO Certification Scheme for Pharmaceutical Products Moving in International Commerce • SMACS new scheme for pharmaceutical starting materials: • - Model certificate, when inspected by national authority • - Model for self-assessment for manufacture of pharmaceutical starting materials

13. WHO’s global guidelines – distribution (2) • Good Distribution and Trading Practices for pharmaceutical starting materials (GTDP) • Good Distribution Practices (GDP) (for products) (newly revised) • Good Storage Practices (GSP)

14. WHO’s global guidelines - production • Good Manufacturing Practices (GMP) ….. • 1. Main principles for pharmaceutical products • Requirement for the sampling of starting materials (amendment) • Water for pharmaceutical use • Heating, ventilation and air-conditioning (HVAC) systems • Validation • 2. … for starting materials, including • Active pharmaceutical ingredients (newly revised) • Pharmaceutical excipients

15. WHO’s global guidelines - production (2) • 3. … for specific pharmaceutical products: • Sterile pharmaceutical products (revised) • Biological products (rev in progress) • Investigational pharmaceutical products for clinical trials in humans • Herbal medicines Herbal medicines (revised) • Radiopharmaceuticals

16. WHO’s global guidelines - inspection • Inspection of….. • pharmaceutical manufacturers • drug distribution channels (products) • Guidelines for pre-approval inspection • Quality systems requirements for national GMP inspectorates • Model GMP certificate • Model report for inspections

17. WHO’s global guidelines and strategies - risk analysis • Application of risk analysis to production of pharmaceuticals (adopted in 2001)

18. WHO stability guidelinesnewly revised ! • Scope now covers: active pharmaceutical ingredients + finished pharmaceutical products • Marketed + new • ++ List of WHO Member States' required long-term stability conditions as per info received from countries, "real" conditions required by national authorities --> close collaboration with ICH group Q1, ASEAN, GCC and other regional harmonization groups

19. WHO’s guidance on interchangeability of medicines • WHO guideline onregistration requirements to established interchangeability for multisource pharmaceutical products (revised in 2006) • Guidance on selection ofcomparator productsfor equivalence assessment of interchangeable generic products(under revision)

20. WHO’s guidance on interchangeability of medicines (2) • Proposal to waive in vivo bioequivalencerequirements for the WHO model List of Essential Medicines (immediate release, solid dosage forms) • Guidelines for organizations performing in vivo bioequivalence studies

21. Related WHO’s guidances … • All guidelines for Prequalification of medicines, laboratories ….. • Model Quality Assurance System for Assessment of Procurement Agencies • Guideline for sampling of pharmaceuticals • Guidelines for registration of fixed-dose combination medicinal products • ....

22. 44th WHO Expert Committee on Specifications for Pharmaceutical Preparations Texts for inclusion in The International Pharmacopoeia • Medicines for HIV and related conditions: • — lopinavir • — tenofovir disoproxil fumarate • — efavirenz (revised text) • — indinavir capsules • — saquinavir tablets • — tenofovir tablets • — lopinavir and ritonavir tablets

23. 44th WHO Expert Committee on Specifications for Pharmaceutical Preparations • Antimalarial medicines • — artesunate • — amodiaquine tablets • — artesunate tablets • — quinine bisulfate tablets • — quinine sulfate tablets (revised text) • Antituberculosis drugs • — amikacin (revised text) • — amikacin sulfate (revised text) • — kanamycin monosulfate • — kanamycin acid sulfate • — amikacin injection

24. 44th WHO Expert Committee on Specifications for Pharmaceutical Preparations • Other medicines • — oxytocin • — mebendazole (revised text) • — oseltamivir phosphate (revised text) • — oxytocin injection • Radiopharmaceuticals • - final texts for the 18 individual and • - 2 general monographs

25. Global quality assurance guidelines adopted in 44th Expert Committee • Update of good distribution practices for pharmaceutical products (based on recommendation from IMPACT working group) • Update of good practices for quality control laboratories • Guideline for the preparation of a contract research organization master file (CROMF) • Guideline on requalification of prequalification dossiers • Updates and revisions of GMP texts, e.g. • for actives pharmaceutical ingredients • for sterile pharmaceutical products • for products containing hazardous materials

26. Advantages of WHO's Expert Committee standard-setting process • 1. Guidelines and specifications validated internationally, through an independent scientific process, adoption by members of WHO Expert Advisory Panels • 2. Collaboration with standard-setting organizations and parties, including regional and national pharmacopoeias • 3. Networking and close collaboration with WHO Member States, Drug Regulatory Authorities, national medicines quality control laboratories

27. Advantages of WHO's Expert Committee standard-setting process (2) • 4. Links with other WHO activities • 5. Reality check: Input from manufacturers (including international associations of research, generic and self-medication associations) around the world • 6. Consideration of costs, e.g. keeping need for reference standards at a minimum • 7. Service FREE FOR USE by all Member States

28. Problem: Counterfeiting medicines is a major public health concern

29. What is the problem? • Counterfeiting medicines is a lucrative "business" and seems emerging, affecting both developing and developed countries • The real magnitude of the problem is unknown: • Existing data not comprehensive • All parties concerned reluctant to make data AVAILABLE or REPORT

30. Is there a health risk ? • Under treatment or non-treatment • Public health risk: ineffective medicines • Intoxication: harmful ingredients • No quality assurance • Adverse reactions not monitored: an effective product recall not possible • Erosion of public confidence in medical care and health systems • Waste of money • ….

31. WHO’s work in combating counterfeit medicines: Three strategies • Providing tools, international norms, standards and guidelines to assist that drugs circulating in national and international commerce are safe, efficacious and of good quality • Providing support to Member States to build national regulatory capacity • Developing global activities to combat counterfeit medicines

33. IMPACT's conceptual framework • IMPACT: a voluntary coalition of partners with purpose of coordinating international activities aimed at combating counterfeit medical products • IMPACT partners reflect fact that combating counterfeiting of medical products cannot be successfully achieved by health sector alone but requires coordinated effort and effective collaboration among health sector, enforcement, border control, justice (all at different administrative levels), as well as health professionals, manufacturers, importers, distributors, media, patients/consumers

34. IMPACT's conceptual framework • IMPACT led by WHO to keep focus on public health implications of counterfeiting rather than on IPR-related aspects • IMPACT output include recommendations, policy advice, and reference and training materials that reflect consensus reached among IMPACT partners

35. Who is/should be in IMPACT ? European Commission All 193 WHO Member States and major international partners, such as:

36. How does IMPACT work? • Secretariat: WHO • 5 working groups, focusing on areas where weaknesses were identified and action is required at national and international level: • legislative and regulatory infrastructure • regulatory implementation • enforcement • technology • communication

37. Issues arising during past 12 months • Concerns that fight against counterfeit medicines may have negative impact on generics • Use of counterfeit argument for limiting free trade / competition / parallel trade • Use of term "counterfeit medicinal product" in patent disputes • Concerns from some parties that technical measures would be too costly, e.g. for OTC and Generics

38. Future … until WHA 2010 + … • New programme in EMP – ACM • Continuation of WHO involvement in IMPACT as Chair and Secretariat • Fund-raising and staffing for ACM and IMPACT related activities • Communication with WHO Member States to prepare the WHA 2010

39. Conclusions • Fighting counterfeit medicines • Working together with all parties concerned, nationally and internationally, is the key!

40. WHO Medicines Quality Assurance and IMPACT websites: http://www.who.int/impact http://www.who.int/medicines/areas/quality_safety/quality_assurance