drug regulation and quality assurance 4874

8/3/2019 Drug Regulation and Quality Assurance 4874

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Drug regulation and quality

assurance:WHO normative functions in the

field of pharmaceuticals

Sabine Kopp, PhD

Quality Assurance and Safety: MedicinesDepartment of Medicines Policy and Standards


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Main points addressed

WHO role and function

WHO standard settingprocess

WHO international guidelines,standards and norms in thearea of quality assurance

WHO's operational strategies


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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 withMember 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 byMember 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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How does the WHO consultation processwork?

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, WorldBank, 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, nationalinstitutions and institutes ..

Regional and inter-regional groups (ICH)


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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 ratifiedby 19 states

1925 Brussels agreement (signed 1929)

League of Nations:international pharmacopoeia


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Quality Assurance in WHOHistorical 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 ofLeague of Nations

1948 First World Health Assemblyestablished ExpertCommittee on Unification of Pharmacopoeia


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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 partiesinvolved

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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WHOs global quality assuranceguidelines

Cover:

Production

Quality Control

Quality related regulatory guidelines

Inspection

Distribution

from manufacture to delivery to patient


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International Pharmacopoeia

current:4th edition! Supplement 1 in preparation

implementation:ready for use by Member States

Scope since 1975:

Model List of Essential Medicines and

Drugs recommended by WHO Specific diseaseprogrammes, e.g. Malaria, TB, HIV/AIDS


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WHOs strategy for quality control

Step-wise approach:

- Basic tests (identification) - Screening tests (TLC)

- The International Pharmacopoeia

- International chemical reference standards (ICRS)

- IR reference spectra


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WHOs global guidelines - quality control -

International specifications (Int.Ph., screening tests..)

WHO Model Certificate of Analysis(COA)

Considerations for requesting analysisof samples

Quality control laboratories:

Good practices for national control labs

List of equipment

External qc assessment scheme for labs


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External Quality Assessment Scheme for NationalDrug Quality Control Laboratories

Capacity building

Third phase

Series of 5 tests 42 participating laboratories, including WHO

Collaborating Centres

In all 6 WHO regions


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External Quality Assessment Scheme for NationalDrug Quality Control Laboratories

Phase 4 (06/2007 - 01/2009)

- 50 laboratories invited to participate.

- Studies: Titration

Water content by Karl-Fisher

Dissolution test

Determination of glucose by polarimetry

HPLC assay


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Participation in External Quality AssuranceScheme -> link with PQ Programme

Phase 3 (07/2004 - 06/2006)

11 of QC laboratories involved in prequalification procedure participated

Algeria, South Africa CENQAM, South Africa RIIP

Ghana, Kenya, Mali, Niger, Senegal, Tanzania, Uganda,

Zimbabwe 2 other African QC laboratories took part

Morocco, Tunisia

Phase 4 (06/2007 - 01/2009)

All 15 QC laboratories involved in prequalification procedure invited


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WHOs 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


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WHOs global guidelines -production (2)

New additional GMP texts:

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)


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WHO stability guidelines

Title: guidelines for stability testing of pharmaceuticalproducts containing well established drug substances inconventional dosage forms currently under revision !

->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


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WHO Stability guidelines second draftWhat's new?

Scope covers:

active pharmaceutical ingredients +pharmaceutical products

Marketed + new Transition period recommended for already

marketed actives and products

Additional advice given, e.g. model reportscurrently used in WHO Prequalification Programme


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WHO Stability guidelines second draftWhat's new? ctd -

Cross-reference to other guidelines, e.g. ICH texton photostability

List of WHO Member States' required long-term

stability conditions as per info received fromcountries, concept of classification of countries

according to climatic zones abandoned

-> preference to provide "real" conditions required

by national authorities


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WHOs guidance on interchangeability ofmedicines

WHO guideline onregistration requirementsto establishedinterchangeability for multisource pharmaceutical products (newlyrevised 2006)

Guidance on selection ofcomparator productsfor equivalenceassessment of interchangeable generic products(under revision)

Proposal to waive in vivo bioequivalencerequirements for theWHO model List of Essential Medicines (immediate release, soliddosage forms)

Guidelines for organizationsperforming in vivo bioequivalence

studies


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Related WHOs guidances

All guidelines for Prequalification of medicines,laboratories ..

Model Quality Assurance System for Assessment ofProcurement Agencies

Guideline for samplingof pharmaceuticals

Guidelines for registration of fixed-dose combinationmedicinal products

....


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WHOs operational strategies -2-

Work with interested parties and countries to combatcounterfeit and substandard drugs (IMPACT)

Assistance in establishing and evaluation of national andregional quality control laboratories

Training of drug regulatory staff (e.g. in registration ofHIV/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)

WHO ff t


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aim to improve access to quality medicines

Provide standards and norms in area of qualityassurance of medicines

Prequalification programme 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


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drug regulation and quality assurance 4874

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