Presentation on theme: "WHO and its activities in quality assurance of medicines Sabine Kopp, PhD Quality Assurance and Safety: Medicines Essential Drugs and Medicines Policy."— Presentation transcript:
WHO and its activities in quality assurance of medicines Sabine Kopp, PhD Quality Assurance and Safety: Medicines Essential Drugs and Medicines Policy World Health Organization
2 WHO - EDM SK 2003 n 1. What is WHO? n 2. How does WHO work and for whom? n 3. Details on WHO activities in the areas of quality assurance, including: ä - INN ä - Int. Ph. ä -GMP ä -Stability ä -pre-qualification project... n 4. Summary
3 WHO - EDM SK What is WHO? Some basic facts n 192 Member States n Two governing bodies: - World Health Assembly - Executive Board n WHO Secretariat: - HQ - six Regional Offices - WHO Expert Panels (e.g... on the International Pharmacopoeia and Pharmaceutical Preparations) Constitution 1946, in force since 7 April 1948 (World Health Day)
4 WHO - EDM SK How does WHO work and for whom? n WHO’s main functions: inter alia n - To act as the directing and coordinating authority on international health work n - To encourage technical cooperation for health with Member States
5 WHO - EDM SK > WHO responsibilities (inter alia) n To assist governments, upon request, in strengthening health services n To provide information, counsel and assist in the field of health n To stimulate eradication of epidemics, endemics and other diseases n To promote cooperation among scientific and professional groups which contribute to the enhancement of health n To promote international conventions and agreements in health matters n To promote and conduct research in the field of health n To develop, establish and promote international standards for food, biological and pharmaceutical products n
6 WHO - EDM SK 2003 Access gap - financing, delivery and other constraints still limit access to essential drugs n >1/3 of world’s population lacks regular access n 320 million in Africa have <50% n Problem worsens with economic pressures Percentage of populations and number of countries with regular access to essential drugs: 1 = <50% (43) 2 = 50-80% (64) 3 = 80-95% (30) 4 = >95% (41) 5 = No data available (1) Pharmaceutical gaps Source: WHO/DAP 1998
7 WHO - EDM SK 2003 What are the priorities for WHO’s medicines strategy? n Access to essential drugs ä for priority health problems (malaria, TB, childhood, HIV/AIDS) ä for poor and vulnerable populations n Quality and safety of all medicines ä creating and maintaining global guidelines and standards ä supporting effective drug regulation & quality assurance n Rational use of medicines ä by health professionals ä by households n National drug policies ä integrated in national health policies and systems ä emphasis on implementation and monitoring WHO medicine strategy
8 WHO - EDM SK 2003 WHO medicine strategy What guides and anchors WHO’s work in drugs and medicines policy? n Global norms, standards, guidelines, nomenclature ä Expert Committees and Expert Panels ä WHO Collaborating Centres n Essential drugs and national drug policies ä 1975 resolution introducing essential drugs concept ä Revised drug strategy (1986) and subsequent WHA resolutions n WHO medicines work today ä Governing bodies - Assembly, Executive Board, Regional Committees ä Meeting of Interested Parties - MIP ä --> changes as from 21 July 2003
9 WHO - EDM SK 2003 Challenges: past and present… n Past: ä Manufacture direct from API -> finished product ä Manufacture of API in sites close to or same as product ä Experience and long-standing knowledge of production, product and manufacture of parties involved ä Few intermediates in sales chain ä Usually stable trade and sales connections
10 WHO - EDM SK 2003 Challenges: past and present… n Present: ä Rationalization of drug production ä Contracting-out of many steps in manufacture ä Many intermediates in trade and sales chain ä Trade, shipping, long distances involved ä Increase of risks… ä Increase of requirements and documentation ä Increase of national control mechanisms
11 WHO - EDM SK 2003 Global challenges … n National vs international requirements n Number of requirements n Application and interpretation of requirements n Import vs export control on national level n Quality assurance systems applied n Knowledge of product by parties involved in manufacture n Cross-border promotion and sale n Free trade zones
12 WHO - EDM SK 2003 Global challenges… n Number of national and international inspections by same party n Number of inspections in same site by different parties n Applicability of new technologies in different settings n Contracts, agreements, MRAs….. n Risks of mistakes, accidents, human errors etc n Counterfeit drugs n …...
13 WHO - EDM SK 2003 National regulatory and inspection systems ä --> approx. 1/3 of WHO Member States have well developed regulatory systems, approx.. 1/3 have none n In developed countries ä well organized, controlling national market ä dossiers evaluation and inspections ä different approaches used, few MRA n In developing countries ä often difficulties of resources ä capacity? ä application of national and international guidelines… ä --> or non-existent ….
14 WHO - EDM SK 2003 Experience from WHO's pre-qualification project - example ARVs ä Inspections and dossiers evaluation can differ from country to country ä Small percentage of products and manufacturers participating in the project comply internationally ä Time needed from some manufacturers to get into compliance l data to be generated l GMP upgrade ä Quality Assurance at a price!
15 WHO - EDM SK 2003 WHO’s global guidelines and strategies n Requirements for drug registration and model legislation n Networking among and with regulatory authorities n International alerts n Counterfeit network n Global norms and standards in production, inspection, quality control, good storage practices and nomenclature (INN) …..
16 WHO - EDM SK 2003 WHO has a constitutional mandate to n "develop, establish and promote international standards with respect to biological, pharmaceutical and similar products” n (Article 2(u) of WHO's Constitution) --> Good Manufacturing Practices, stability guidelines, …… INN Programme …….
17 WHO - EDM SK 2003 WHO Procedure for the preparation of guidelines n Preliminary consultation and drafting n Draft guidelines n Circulation for comments n Revision process n n WHO Expert Committee n WHO Governing bodies n Recommendation to governments for implementation --> publication in Technical Reports
18 WHO - EDM SK 2003 WHO’s global guidelines and strategies - quality control - ä International specifications (Int.Ph., screening tests..) ä WHO Model Certificate of Analysis (COA) for use in trade and procurement ä Considerations for requesting analysis of drug samples ä Quality control laboratories good practices for national control labs list of equipment External qc assessment scheme for labs
19 WHO - EDM SK 2003 International Pharmacopoeia Historical overview 1874Discussion on Unification of terminology and composition of drugs 1902 First Conference organized by Belgian Government 1906Agreement on Unification of the Formulae of Potent Drugs ratified by 19 states 1925 Brussels agreement (signed 1929) League of Nations: “international pharmacopoeia”
20 WHO - EDM SK 2003 International Pharmacopoeia Historical overview 1937 First meeting (experts from B, DK, F, NL, CH, UK, USA) - League of Nations 1947 Interim Commission of WHO takes up health related work of League of Nations 1948 First World Health Assembly established Expert Committee on Unification of Pharmacopoeia
21 WHO - EDM SK 2003 International Pharmacopoeia Historical overview 1950 WHA approved publication of Pharmacopoeia Internationalis 1951 named: Expert Committee on International Pharmacopoeia 1959 named: Expert Committee on International Pharmacopoeia and Pharmaceutical Preparations --> to date
22 WHO - EDM SK 2003 International Pharmacopoeia current: Third edition implementation: “ready for use” by Member States Scope since 1975: Model List of Essential Drugs and Drugs recommended by WHO Specific disease programmes, e.g. Malaria, TB, HIV/AIDS
23 WHO - EDM SK 2003 WHO’s strategy for quality control Step-wise approach: - Basic tests (identification) - Screening tests (TLC) - International Pharmacopoeia + International reference materials (ICRS and IR reference spectra)
24 WHO - EDM SK 2003 IntPh and links to other WHO activities Establishment of monographs for antiretrovirals, HIV medicines - collaboration with other pharmacopoeias, including PDG, Ph.Eur. USP, JP, IP - collaboration with manufacturers - link with project on pre-qualification of suppliers for HIV drugs
25 WHO - EDM SK 2003 Type of monographs Drug substances Excipients Finished dosage forms General methods and requirements: oral sold dosage forms dissolution testing …
26 WHO - EDM SK 2003 INNs
27 WHO - EDM SK 2003 WHO’s global guidelines and strategies - distribution WHO Certification Scheme for Products Moving in International Commerce new scheme for pharmaceutical starting materials: - WHO model GMP certificate, when inspected - WHO model for self-assessment for manufacture of pharmaceutical starting materials n Good Distribution and Trading Practices for pharmaceutical starting materials n Good Storage Practices n Good Distribution Practices (in preparation)
28 WHO - EDM SK 2003 WHO’s global guidelines and strategies - production n Good Manufacturing Practices ….. n 1. Main principles for pharmaceutical products n 2. … for starting materials, including ä active pharmaceutical ingredients ä pharmaceutical excipients n 3. … for specific pharmaceutical products: ä Sterile pharmaceutical products ä Biological products ä Investigational pharmaceutical products for clinical trials in humans ä Herbal medicines ä Radiopharmaceuticals
29 WHO - EDM SK 2003 WHO’s global guidelines and strategies - inspection n Inspection of….. ä pharmaceutical manufacturers ä drug distribution channels (products) n Guidelines for pre-approval inspection n Quality systems requirements for national GMP inspectorates n Model GMP certificate n Model report for inspections
30 WHO - EDM SK 2003 WHO’s global guidelines and strategies - risk analysis n Application of risk analysis to production of pharmaceuticals, adopted in 2001
31 WHO - EDM SK 2003 WHO stability guidelines n Title: “guidelines for stability testing of pharmaceutical products containing well established drug substances in conventional dosage forms” n n -> stability testing of final drug products n -> well established (e.g. generics) n -> in conventional dosage forms (e.g. tablets)
32 WHO - EDM SK 2003 Developments in 2001 n 2001: new alternative being discussed to modify both ICH and WHO guidelines n for zone IV to: --> 30°C and 65% RH (then: 70%) n Consultative procedure: mailing of request to experts and discussion during informal consultation n Discussion and adoption during WHO Expert Committee on Specifications for Pharmaceutical Preparations held October 2001 in Geneva
33 WHO - EDM SK 2003 Long-term storage conditions modified n Zone I21°C45% RH n Zone II25°C60% RH n Zone III30°C35% RH n Zone IV30°C65 %RH l when special transportation and storage conditions were identified as being outside these criteria, additional study data supporting these conditions may need to be made available.
34 WHO - EDM SK 2003 Developments in …. n February 2002: ICH Data package for registration in climatic zones II and IV --> signed off by all 6 ICH partners as step 2 document n Consultative process in all three ICH regions by regulatory agencies n Comments and new drafts circulated in ICH Working Group n Discussed at ICH meeting February 2003 n now ICH document step 4
35 WHO - EDM SK 2003 Access to HIV/AIDS Drugs and Diagnostics of Assured Quality - pilot procurement project n Partners: ä WHO ä UNICEF ä UNAIDS ä UNFPA ä The World Bank (support) ä --> now expanded to anti-TB and antimalarial medicines
36 WHO - EDM SK 2003 Pilot Procurement, Quality and Sourcing Project Access to HIV/AIDS Drugs and Diagnostics of Assured Quality n Problems and deficiencies identified: ä General Problems identified with ARVs l Several substances and products not in pharmacopoeia l unacceptable chiral activity, stereo-isomerism l unacceptable impurities l lack of reference standards l no analytical methods and method validation l Regulatory authorities not following WHO recommendations for registration of products l Regulatory approval not based on thorough evaluation
37 WHO - EDM SK 2003 Pilot Procurement, Quality and Sourcing Project Access to HIV/AIDS Drugs and Diagnostics of Assured Quality n GMP deficiencies: ä Hormones, cytotoxics and ARVs in same area ä Qualification and validation lacking (premises, systems, equipment, processes) ä Cleaning validation ä No verification of air classification of areas for sterile product manufacturing ä Sampling and testing of APIs ä Loss in traceability of materials used in production
38 WHO - EDM SK 2003 WHO’s operational strategies n Assist countries to strengthen or establish national drug regulation n Study alternative ways of improving control and safe trade of starting materials and products n Promote the use of WHO norms and standards n Promote cooperation and harmonization among countries
39 WHO - EDM SK 2003 WHO’s operational strategies -2- Work with interested parties and countries to combat counterfeit and substandard drugs Establishing national and regional quality control laboratories Training of drug regulatory staff Development of “how to” manuals and tools
40 WHO - EDM SK 2003 Summary n WHO assists Member States in health related matters n WHO has inter alia a constitutional mandate to develop, establish and promote international standards n WHO issued a number of guidelines and norms in the area of quality assurance n Continuous dialogue and collaboration with with WHO Member States, regional and international harmonization efforts in drug regulation