Transcript Drug regulation and quality assurance: WHO normative functions in the field of pharmaceuticals Technical Briefing Seminar 20 September 2005 Sabine Kopp, PhD presented by Marie Rabouhans Quality Assurance.

Drug regulation and quality
assurance:
WHO normative functions in the
field of pharmaceuticals
Technical Briefing Seminar
20 September 2005
Sabine Kopp, PhD
presented by Marie Rabouhans
Quality Assurance and Safety: Medicines
Department of Medicines Policy and Standards
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Main points addressed
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WHO role and function
WHO standard setting
process
WHO international guidelines,
standards and norms in the
area of quality assurance
WHO's operational strategies
WHO does the work?
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192 Member States
Two governing bodies:
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WHO Secretariat:
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- World Health Assembly
- Executive Board
- 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)
How to become a "WHO Expert"?
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Official nomination process
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Upon proposal to WHO in consultation with:
 Member State/national government (citizenship)+
 WHO Regional Office (in accordance with
Member State) +
 WHO Headquarters
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Period of maximum 4 years
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Possibility to renew
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What is the WHO Expert Committee?
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Official Advisory Body to Director-General of WHO
Governed though rules and procedures (Ref. WHO Manual)
Participation in Expert Committee (EC) meetings:
 Voting 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?
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Report of the WHO Expert Committee:
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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
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WHO technical guidance
Examples of WHO Expert Committees ?
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WHO Expert Committee on Specifications for
Pharmaceutical Preparations
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WHO Expert Committee on the Selection and Use of
Essential Medicines
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WHO Expert Committee on Drug Dependence
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WHO Expert Committee on Biological Standardization
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Joint FAO/WHO Expert Committee on Food Additives
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….
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How does the WHO consultation process
work?
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Step 1. Preliminary consultation and drafting
Step 2. Draft guidelines
Step 3. Circulation for comments
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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
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-> Recommendation to Member States for implementation
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WHO Partners
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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-IGPAWSMI, 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…)
Quality Assurance in WHO
Historical overview
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1874
1902
1906
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1925
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Discussion on Unification of terminology and composition of drugs
First Conference organized by Belgian Government
Agreement on Unification of the Formulae of Potent Drugs ratified
by 19 states
Brussels agreement (signed 1929)
League of Nations:
“international pharmacopoeia”
Quality Assurance in WHO
Historical overview - 2 -
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1937 First meeting (experts from B, DK, F, NL, CH, UK, USA) League of Nations
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1947 Interim Commission of WHO takes up health related work of
League of Nations
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1948 First World Health Assembly established Expert
Committee on Unification of Pharmacopoeia
Challenges: past and present…
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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
Challenges: past and present…
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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
Global challenges …
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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
Free trade zones
Global challenges…
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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
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Contracts, agreements, eg Mutual Recognition Agreements
Risks of mistakes, accidents, human errors etc
Counterfeit drugs
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…...
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Experience with WHO pre-qualification project
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Major problems with quality of medicines used in
HIV/AIDS, TB Malaria treatment, experience in past years
of project:
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> 70% of manufacturing sites did not pass in first
inspection and > 80% of more than 400 dossiers
evaluated do not meet requirements
Can lead to: treatment failure; development of resistance;
avoidable deaths + wasted resources
WHO’s global guidelines and strategies
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Requirements for drug registration and model
legislation
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Networking among and with regulatory authorities
International alerts
Counterfeit network
Global norms and standards and nomenclature (INN)
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INNs
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WHO’s global quality assurance
guidelines
Cover:
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Production
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Quality Control
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Quality related regulatory guidelines
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Inspection
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Distribution
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 from manufacture to delivery to patient
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International Pharmacopoeia
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current: Third edition
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implementation: “ready for use” by Member States
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Scope since 1975:
 Model List of Essential Drugs and
 Drugs recommended by WHO Specific disease
programmes, e.g. Malaria, TB, HIV/AIDS
WHO’s strategy for quality control
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Step-wise approach:
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- Basic tests (identification)
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- Screening tests (TLC)
- International Pharmacopoeia
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+ International chemical reference materials:
- ICRS and
- IR reference spectra
Links to other partners and programmes
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Establishment of specifications for antiretrovirals,
HIV medicines
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- Collaboration with other pharmacopoeias,
including PDG, Ph.Eur. USP, JP, IP, ChPh
- Collaboration with manufacturers
- Collaboration with suppliers (also agencies)
for HIV drugs
WHO’s global guidelines - quality control -
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International specifications (Int.Ph., screening
tests..)
WHO Model Certificate of Analysis (COA) for use in
trade and procurement
Considerations for requesting analysis of drug
samples
Quality control laboratories
 Good practices for national control labs
 List of equipment
 External qc assessment scheme for labs
External Quality Assessment Scheme for National Drug
Quality Control Laboratories
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Capacity building
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Third phase
Series of 5 tests
42 participating laboratories, including WHO
Collaborating Centres
In all 6 WHO regions
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WHO’s global guidelines - distribution
 WHO
Certification Scheme for Products Moving in
International Commerce
 SMACS new scheme for pharmaceutical starting
materials: - model certificate, when inspected by national authority
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- WHO model for self-assessment for manufacture of
pharmaceutical starting materials
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Good Distribution and Trading Practices for
pharmaceutical starting materials (GTDP)
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Good Distribution Practices (GDP) (for products in prep.)
Good Storage Practices (GSP)
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WHO’s global guidelines - production
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Good Manufacturing Practices (GMP) …..
1. Main principles for pharmaceutical products
2. … for starting materials, including
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3. … for specific pharmaceutical products:
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active pharmaceutical ingredients
pharmaceutical excipients
Sterile pharmaceutical products
Biological products
Investigational pharmaceutical products for clinical trials in humans
Herbal medicines
Radiopharmaceuticals
WHO’s global guidelines - inspection
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Inspection of…..
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pharmaceutical manufacturers
drug distribution channels (products)
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Guidelines for pre-approval inspection
Quality systems requirements for national GMP
inspectorates
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Model GMP certificate
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Model report for inspections
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WHO’s global guidelines and strategies -
risk analysis
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Application of risk analysis to production of
pharmaceuticals, adopted in 2001
WHO stability guidelines
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Title: “guidelines for stability testing of pharmaceutical
products containing well established drug substances in
conventional dosage forms”
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-> stability testing of final drug products
-> well established (e.g. generics)
-> in conventional dosage forms (e.g. tablets)
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--> close collaboration with
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ICH group Q1, ASEAN and other regional harmonization
groups
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WHO’s guidance on interchangeability of
medicines
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WHO guideline on registration requirements to
established interchangeability for multisource
pharmaceutical products (1996 under revision)
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Guidance on selection of comparator products for
equivalence assessment of interchangeable generic
products (under revision)
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WHO’s operational strategies
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Assist Member States to strengthen or establish
national drug regulation (upon request)
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Study alternative ways of improving control and safe
trade of starting materials and products
Promote cooperation and harmonization among
countries (e.g. ICDRA)
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Collaborate with regional and inter-regional regulatory
harmonization efforts (in all 6 WHO regions)
WHO’s operational strategies -2
Work with interested parties and countries to combat
counterfeit and substandard drugs (International
Convention?)
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Assistance in establishing and evaluation of national and
regional quality control laboratories
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Training of drug regulatory staff (e.g. in registration of
HIV/AIDS medicines)
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Development of “how to” manuals and tools
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Responding to national and international requests in area
of quality assurance for medicines (e.g. for Gobal Fund)
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WHO efforts
 aim to improve access to quality medicines
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Provide standards and norms in area of quality
assurance of medicines
Pre-qualification project for UN procurement
Provide assistance in regulatory area
Promote logical order of actions:
 Priority setting (ABC first … )
 Capacity building
 Collaboration and co-operation
http://www.who.int/medicines