1 wh o technical briefing | september 2010 safe quality medicines
TRANSCRIPT
1 WHO Technical Briefing | September 2010
Safe quality medicines
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
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Main points addressed
WHO standard setting process WHO international guidelines,
standards and norms in the area of quality assurance
What's new ?
4 WHO Technical Briefing | September 2010
WHO does the work?
193 Member States Two governing bodies: - World Health Assembly
- Executive Board
WHO Secretariat: - Headquarters
- six Regional Offices and Country offices- WHO Expert Panels and Expert Committees(e.g... on the International Pharmacopoeia
and Pharmaceutical Preparations) Constitution 1946, in force since 7 April 1948(World Health Day)
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How to become a "WHO Expert"?
Official nomination process Upon proposal to WHO in consultation with:
Member State/national government (citizenship)+ WHO Regional Office (in accordance with
Member State) + WHO Headquarters
Period of maximum 4 years Possibility to renew
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What is the WHO Expert Committee?
Official Advisory Body to Director-General of WHO Governed though rules and procedures (Ref. WHO Manual) Participation in Expert Committee (EC) meetings:
Members ("Expert") selected from WHO Panel of Experts
Technical advisers Observers: - international organizations,
- NGOs, - professional associations…
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Outcome of the 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
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Examples of WHO Expert Committees ?
WHO Expert Committee on Specifications for Pharmaceutical Preparations
WHO Expert Committee on the Selection and Use of Essential Medicines
WHO Expert Committee on Drug Dependence WHO Expert Committee on Biological Standardization Joint FAO/WHO Expert Committee on Food Additives ….
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When does the WHO Expert Committee start development of a guideline/guidance?
Based on recommendations by :
World Health Assembly resolutions (e.g. WHA 20.34, GMP - Good manufacturing practices)
Executive Board resolutions (e.g. EB37.R9 delegating certain functions of INN Programme to DG based on advice from Experts)
International Conference of Drug Regulatory Authorities (e.g. 10th +11th ICDRA – FDC guidelines + Certification Scheme for pharmaceutical starting materials moving into international commerce)
Other WHO programmes and clusters (e.g. necessity for quality control specifications for specific medicines of major public health interest)
Expert Committee (e.g. revision of general methods included in The International Pharmacopoeia)
10 WHO Technical Briefing | September 2010
How does the WHO consultation process work?
Step 1. Preliminary consultation and drafting Step 2. Draft guidelines Step 3. Circulation for comments Step 4. Revision process .......... (back to step 2 and 3 as often as needed) WHO Expert Committee (EC) meeting
if guideline adopted, published in EC report as Annex -> WHO Governing bodies -> Recommendation to Member States for implementation
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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…)
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Why need for stringent standards for medicines?
"… drugs are a public good and not simply just another commodity: first for their high social value, and then because consumers and prescribers are unable to assess their quality, safety and efficacy" (Dr Gro Harlem Brundtland, former Director General of the World Health Organization)
medicines belong to one of the most regulated group of products
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Medicines Quality Assurance in WHO
Historical overview
1874 Discussion on Unification of terminology and composition of drugs 1902 First Conference organized by Belgian Government 1906 Agreement on Unification of the Formulae of Potent Drugs ratified
by 19 states 1925 Brussels agreement (signed 1929)
League of Nations: “international pharmacopoeia”
14 WHO Technical Briefing | September 2010
Medicines Quality Assurance in WHO
Historical overview (2)
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
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Quality of medicines remains a problem in many countries
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Challenges: past and present…
Past: Manufacture direct from API -> finished product Manufacture of API in sites close to or same as product Experience and long-standing knowledge of
production, product and manufacture of parties involved
Few intermediates in sales chain Usually stable trade and sales connections
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Challenges: past and present…
Present: Rationalization of drug production Contracting-out of many steps in manufacture Many intermediates in trade and sales chain Trade, shipping, long distances involved Increase of risks… Increase of requirements and documentation Increase of national control mechanisms
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Global challenges …
National vs international requirements Number of requirements Application and interpretation of requirements Import vs export control on national level Quality assurance systems applied Knowledge of product by parties involved in
manufacture Cross-border promotion and sale - Internet Free trade zones
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Global challenges…
Number of national and international inspections by same party
Number of inspections in same site by different parties Applicability of new technologies in different settings Contracts, agreements, eg Mutual Recognition Agreements Risks of mistakes, accidents, human errors etc Counterfeit drugs …...
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WHO’s global guidelines and strategies
Requirements for drug registration and model legislation
Networking among and with regulatory authorities International alerts Counterfeit network Global norms and international standards and
nomenclature
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INNs
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WHO’s medicines quality assurance guidelines
Cover: Development Production Quality Control Quality related regulatory guidelines Inspection Distribution from manufacture (and before) to delivery to
patient
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Adopted WHO guidance texts and guidelinesin medicines quality assurance (without PhInt)
Maintain to keep up to date:Total of :
56 CURRENT official WHO guidance texts and guidelines to date, including 7 (4 updates, 3 new, adopted 2009)
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Quality Control
http://www.who.int/medicines/areas/quality_safety/quality_assurance/control/
12 guidance documents and guidelines, including - Good laboratory practices + training materials- Guidelines for establishment of chemical reference standards- Model certificate of analysis- International Pharmacopoeia + Basic tests
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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 labsList of equipmentExternal qc assessment scheme for labs
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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
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External Quality Assessment Scheme for National Drug Quality Control Laboratories
Phase 5 (01/2010 - 12/2012)
- 60 laboratories participate- Studies: - Assay by titration: 1 April 2010 - Water content by Karl-Fischer: 1 September 2010 - Dissolution test: 1 February 2011 - Related substances by HPLC: 15 July 2011 - Related substances by TLC: 15 January 2012 - Assay by HPLC: 15 June 2012 - Dissolution test: 15 October 2012
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Distribution
http://www.who.int/medicines/areas/quality_safety/quality_assurance/distribution
More than 9 guidance documents and guidelines, e.g.: - Certification schemes (CPP and SMACS)- Quality system for Procurement- Good distribution practices for starting materials and finished
products- Good storage practices
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Production
- http://www.who.int/medicines/areas/quality_safety/quality_assurance/production/
18 guidance documents and guidelines, including: - Good Manufacturing Practices (GMP)
…..Consisting of 12 major "guideline" texts (regularly updated, new texts added as needs are identified)
- ….. Training materials (slides, video, GMP text)- Risk analysis (HACCP)
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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 Pharmaceutical excipients
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WHO’s global guidelines -production (2)
3. … for specific pharmaceutical products: Sterile pharmaceutical products Biological products (rev in progress) Investigational pharmaceutical products for clinical
trials in humans Herbal medicines Radiopharmaceuticals Blood establishments
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Inspection
http://www.who.int/medicines/areas/quality_safety/quality_assurance/inspections/en/index.html
6 guidance documents and guidelines
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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
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Quality related regulatory standards
http://www.who.int/medicines/areas/quality_safety/quality_assurance/regulatory_standards/
17 guidance documents and guidelines, including : - Stability testing requirements - Interchangeability of generic medicines- Fixed-dose combination- All prequalification procedures
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WHO’s guidance on interchangeability of medicines
WHO guideline on registration requirements to established interchangeability for multisource pharmaceutical products (revised in 2006)
Guidance on selection of comparator products for equivalence assessment of interchangeable generic products (under revision)
37 WHO Technical Briefing | September 2010
WHO’s guidance on interchangeability of medicines (2)
Proposal to waive in vivo bioequivalence requirements for the WHO model List of Essential Medicines (immediate release, solid dosage forms)
Guidelines for organizations performing in vivo bioequivalence studies
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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....
39 WHO Technical Briefing | September 2010
New WHO guidelines adopted during 45th Expert Committee held 18-22 October 2010
Good Pharmacy Practice (joint FIP/WHO, revised) Guidance for Pharmaceutical Microbiology
laboratories (new) Procedure for prequalification of laboratories
(revised) Preparing a Laboratory Information File (update) GMP: main principles (revised) GMP for blood establishments (jointly with ECBS) GMP for HVAC (revised)
40 WHO Technical Briefing | September 2010
New WHO guidelines adopted during 45th Expert Committee held 18-22 October 2010 (2)
GMP for sterile pharmaceutical products (revised) Guiding principles on transfer of technology (new) Guidelines for preparing a Site Master File (new) Model guidance for the storage and transport of
time- and temperature sensitive pharmaceutical products (new, jointly with ECBS)
Guidance on submission of documentation for prequalification of innovator FPPs approved by stringent regulatory authorities (new)
41 WHO Technical Briefing | September 2010
New WHO guidelines adopted during 45th Expert Committee held 18-22 October 2010 (3)
Procedure for prequalification of medicines (revised)
Guideline for submission of documentation for a multisource (generic) finished product (new)
Special guidance for artemisinin as a starting materials for production of antimalarials (subject to confirmation of impurity profile, new)
Definition of substandard medicines (new) Procedure for adoption of ICRS (revised)
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New Specifications adopted during 45th Expert Committee held 18-22 October 2010 (3)
27 new specifications and general texts, including :
Antiretrovirals Anti-TB medicines Antimalarials Anti-infectives Paediatrics
43 WHO Technical Briefing | September 2010
What is in the QA pipeline?
Guidelines/guidance :Paediatrics development (new)Development of generics (new)Risk analysis (update)Guideline on submission of
documentation for a multisource (generic) product – quality part (new)
44 WHO Technical Briefing | September 2010
What is in the QA pipeline? - 2 -
Guidelines/guidance:
Update of Comparator List Update of stability requirements in Member States Advice to NMRAs on Diethylene glycol intoxication Tools and framework for monitoring of market
situation
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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
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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
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As health professionals, in public and private sector, as an international community...we have a lot left to do
…all of us, together, things that do matter,in right time and in right order!
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WHO Medicines Quality Assurance website:
http://www.who.int/medicines/areas/quality_safety/quality_assurance