drug regulation and quality assurance: who normative functions in the field of pharmaceuticals...
TRANSCRIPT
Drug regulation and quality assurance:
WHO normative functions in the field of pharmaceuticals
Technical Briefing Seminar Technical Briefing Seminar
19 September 200619 September 2006
Sabine Kopp, PhD Quality Assurance and Safety: Medicines
Department of Medicines Policy and Standards
TBS 2005
TBS 20062
Main points addressed
WHO role and function WHO standard setting
process WHO international guidelines,
standards and norms in the area of quality assurance
WHO's operational strategies
TBS 20063
WHO does the work?
192 Member States Two governing bodies: - World Health Assembly
- Executive Board
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)
TBS 20064
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
TBS 20065
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:
Voting members ("Expert") selected from WHO Panel of Experts
Technical advisers Observers: - international organizations,
- NGOs, - professional associations…
TBS 20066
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
TBS 20067
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 ….
TBS 20068
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
TBS 20069
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…)
TBS 200610
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”
TBS 200611
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
TBS 200612
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
TBS 200613
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
TBS 200614
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 Free trade zones
TBS 200615
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 …...
TBS 200616
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 standards and nomenclature (INN)
…..
TBS 200617
INNs
TBS 200618
WHO’s global quality assurance guidelines
Cover:
Production Quality Control Quality related regulatory guidelines Inspection Distribution from manufacture to delivery to patient
TBS 200619
The International Pharmacopoeia
current: Third edition - > 4th edition in preparation
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
TBS 200620
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
TBS 200621
Links to other partners and programmes
Establishment of specifications for antiretrovirals, HIV/AIDS medicines
- Collaboration with other pharmacopoeias, including PDG, Ph.Eur., USP, JP, IP, ChPh
- Collaboration with manufacturers - Collaboration with suppliers (also agencies)
for HIV drugs
TBS 200622
WHO’s global guidelines - quality control -
International specifications (Int.Ph., 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
TBS 200623
External Quality Assessment Scheme for National Drug Quality Control Laboratories
Capacity building
Third phase Series of 5 tests 42 participating laboratories, including WHO
Collaborating Centres In all 6 WHO regions
TBS 200624
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
- WHO model for self-assessment for manufacture of pharmaceutical starting materials
Good Distribution and Trading Practices for pharmaceutical starting materials (GTDP)
Good Distribution Practices (GDP) (for products) Good Storage Practices (GSP)
TBS 200625
WHO’s global guidelines -production
Good Manufacturing Practices (GMP) ….. 1. Main principles for pharmaceutical products 2. … for starting materials, including
active pharmaceutical ingredients pharmaceutical excipients
3. … for specific pharmaceutical products: Sterile pharmaceutical products Biological products Investigational pharmaceutical products for clinical trials in humans Herbal medicines Radiopharmaceuticals
TBS 200626
WHO’s global guidelines -production (2)
New additional GMP texts (adopted in 2004+2005):
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
3. … for specific pharmaceutical products:+++ Herbal medicines (revised)
TBS 200627
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
TBS 200628
WHO’s global guidelines and strategies - risk analysis
Application of risk analysis to production of pharmaceuticals (adopted in 2001)
TBS 200629
WHO stability guidelines
Title: “guidelines for stability testing of pharmaceutical products containing well established drug substances in conventional dosage forms”
-> stability testing of final drug products -> well established (e.g. generics) -> in conventional dosage forms (e.g. tablets)
--> close collaboration with
ICH group Q1, ASEAN and regional harmonization groups
TBS 200630
WHO’s guidance on interchangeability of medicines
WHO guideline on registration requirements to established interchangeability for multisource pharmaceutical products (newly revised 2006)
Guidance on selection of comparator products for equivalence assessment of interchangeable generic products (under revision)
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
TBS 200631
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....
TBS 200632
WHO’s operational strategies
Assist Member States to strengthen or establish national drug regulation (upon request)
Study alternative ways of improving control and safe trade of starting materials and products
Promote cooperation and harmonization among countries (e.g. ICDRA)
Collaborate with regional and inter-regional regulatory harmonization efforts (in all 6 WHO regions)
TBS 200633
WHO’s operational strategies -2-
Work with interested parties and countries to combat counterfeit and substandard drugs (IMPACT)
Assistance in establishing and evaluation of national and regional quality control laboratories
Training of drug regulatory staff (e.g. in registration of HIV/AIDS medicines)
Development of “how to” manuals and tools Responding to national and international requests in area
of quality assurance for medicines (e.g. for Global Fund)
TBS 200634
aim to improve access to quality medicines
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
WHO efforts
TBS 200635
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!
WHO Medicines Quality Assurance website:
http://www.who.int/medicines/areas/quality_safety/quality_assurance