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World Health Organization's Prequalification Program for medicines. V Conference of the PANDRH 17 – 19 November 2008 Buenos Aires, Argentina. Dr Lembit Rägo Coordinator Quality Assurance and Safety: Medicines Essential Medicines and Pharmaceutical Policies World Health Organization - PowerPoint PPT Presentation
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Department of Essential Medicines and Pharmaceutical Policies, Health Systems and Services
World Health Organization's Prequalification Program for
medicines
Dr Lembit RägoCoordinator
Quality Assurance and Safety: MedicinesEssential Medicines and Pharmaceutical Policies
World Health OrganizationGeneva, Switzerland
E-mail: [email protected]
V Conference of the PANDRH17 – 19 November 2008Buenos Aires, Argentina
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Department of Essential Medicines and Pharmaceutical Policies, Health Systems and Services
Is quality and safety of medicines still a big problem nowadays?
Panama case in 2006. It turned out the cause
of death of more than forty five persons was simple. The cough syrup and potentially other medicines produced in the governmental pharmaceutical factory were contaminated.
The death were caused by diethylene glycol (DEG) found in medicines. DEG is a chemical cousin of antifreeze and used widely by various industries. It is toxic to the kidneys and can cause deadly renal failure.
Pictures. 1. Waiting for answer. 2. A popular medicine in Panama that turned to be a killer. 3. Medicines traced down and removed from supply chain
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Department of Essential Medicines and Pharmaceutical Policies, Health Systems and Services
Viracept (nelfinavir) saga
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Department of Essential Medicines and Pharmaceutical Policies, Health Systems and Services
Heparin "saga" 2008 – many countries affected
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Department of Essential Medicines and Pharmaceutical Policies, Health Systems and Services
What is WHO doing to help the countries?
Normative functions
Capacity building
Prequalification
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Department of Essential Medicines and Pharmaceutical Policies, Health Systems and Services
Normative functions
Nomenclatures and classifications International Nonproprietary (generic) Names –
INNs Anatomical Therapeutic Chemical (ATC)
classification and Daily Defined Doses (DDD) International guidelines, standards and norms, mostly
in the area of quality assurance International Pharmacopoeia WHO GMP, interchangeability, fixed dose
combinations, variations, stability guidelines etc.
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Department of Essential Medicines and Pharmaceutical Policies, Health Systems and Services
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Department of Essential Medicines and Pharmaceutical Policies, Health Systems and Services
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Department of Essential Medicines and Pharmaceutical Policies, Health Systems and Services
New Specifications adopted by 41st WHO Expert Committee - examples
Abacavir oral solution Abacavir sulfate tablets Didanosine tablets Didanosine oral solution (adult formulation) Lamivudine oral solution Lamivudine tablets Stavudine capsules Zidovudine capsules Zidovudine IV injection Zidovudine oral solution Zidovudine and Lamivudine tablets Zidovudine, Lamivudine and Abacavir tablets
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Department of Essential Medicines and Pharmaceutical Policies, Health Systems and Services
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Department of Essential Medicines and Pharmaceutical Policies, Health Systems and Services
Prequalification of essential medicines
The UN prequalification program is an action plan for expanding
treatment access for patients with
HIV/AIDS
Tuberculosis
Malaria
… and includes also selected products for reproductive health
and Avian flu (oseltamivir)
by ensuring quality, efficacy and safety of medicines procured using
international organizations and funds (e.g. UNICEF, Global Fund,
UNITAID)
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Department of Essential Medicines and Pharmaceutical Policies, Health Systems and Services
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Department of Essential Medicines and Pharmaceutical Policies, Health Systems and Services
Why the prequalification is needed?
Risks • Sourcing of poor quality products or even counterfeit medicines
risk to patients, toxic reactions, treatment failure, resistance
bad quality (generic) products undermine public confidence Problems
• Millions of people living with HIV/AIDS, tuberculosis and malaria, have no or limited access to treatment
• Substandard and counterfeit products in different countries • Weak or absent QA systems of medicines supply chain• Lot of money invested in procurement
products with very different quality sourced
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Department of Essential Medicines and Pharmaceutical Policies, Health Systems and Services
Prequalification basic principles
Legitimate - General procedure and standards approved through WHO Expert Committee system involving all WHO Member States and WHO Governing bodies
Voluntary for participating manufacturers Widely discussed
• FIP Congress, Nice 2002 • Supported by International Conference of Drug Regulatory
Authorities (ICDRA) in 2002, 2004 and 2006 representing more than 100 national drug regulatory authorities;
Transparent (all information available on the web site http://mednet3.who.int/prequal/ )
Open to both innovators and multisource/generic manufacturers No cost for applicants as per today (in future fees considered) Capacity building important part of it
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Department of Essential Medicines and Pharmaceutical Policies, Health Systems and Services
Expected outcomes of prequalification
Public lists of products and manufacturing sites • Meeting international standards on quality, safety, and efficacy
Capacity building and harmonization• National Drug Regulatory Authorities (DRAs), manufacturers,
WHO treatment programs, NGOs, procurement organizations Ongoing quality monitoring
• Ongoing monitoring of prequalified products Facilitate access to treatment
• Through fair procurement mechanisms (e.g. tender, competition based on the same quality standards)
• WHO commitment to developing better access to quality medicines
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Department of Essential Medicines and Pharmaceutical Policies, Health Systems and Services
How prequalification is organized?
Role of WHO: Managing and organizing the project on behalf of the UN • provides technical and scientific support and guarantee that
international norms and standards are applied all through the process including assessment, inspection (GMP, GCP, GLP) and quality control
Partners: • UNICEF, UN Population Fund (UNFPA), UNAIDS and with the
support of the World Bank• Roll Back Malaria and Stop TB (Global Drug Facility); HIV/AIDS
Department Actors: Qualified assessors and inspectors from National DRAs of
ICH and non-ICH countries, and inspectorates belonging to PIC/S
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Department of Essential Medicines and Pharmaceutical Policies, Health Systems and Services
Assessment procedure- Product dossiers
Innovator products• Abridged procedure if approved by stringent authorities like EMEA and
US FDA• Assessment reports from Drug Regulatory Authorities (DRSs), WHO
Certificate of Pharmaceutical Product (CPP), batch certificate, update on changes
• Trusting scientific expertise of well-established DRAs Multisource products
• Full dossier with all data and information requested• Quality : information on starting materials and finished product
including API details, specifications, stability data, formulation, manufacturing method, packaging, labelling etc
• Efficacy and safety: Bio-equivalence study or clinical study report• US FDA tentative approvals for ARVs – recognition scientific assessment
based on information exchange (Confidentiality agreement between US FDA and WHO); the same approach apply for EU Art 58 and Canadian access procedure)
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Department of Essential Medicines and Pharmaceutical Policies, Health Systems and Services
Inspections and QA analysis
Inspections Manufacturing site (final product, packaging) Active pharmaceutical ingredient (API) Research laboratory or Contract Research Organization (CRO) Teamwork of inspectors
• WHO representative (qualified GMP inspector)• Inspector from well-established inspectorate (Pharmaceutical Inspection
Cooperation Scheme countries – PIC/S)• National inspector/s invited to be part of the team but have NO decision
making power (different GMP standards, potential conflict of interest)
Quality control analysis - upon need, but not always necessarily before prequalification and supply, increasingly as part of proactive follow-up
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Department of Essential Medicines and Pharmaceutical Policies, Health Systems and Services
Prequalification: the technical documents are WHO normative documents
The Expert Committee documents pass wide international consultation and are finally adopted by the Committee composed of outstanding international technical experts
In case WHO standards are "silent" other applicable standards such as ICH and national standards are used
New TRS No 943 with 41st Report from 2007 Updated PQ general procedure PQ of QC labs procedure
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Department of Essential Medicines and Pharmaceutical Policies, Health Systems and Services
Current status
Started with HIV/AIDS products in 2001 – malaria and TB products joined later
Prequalified products " Active" dossiers in pipeline • 171 HIV related medicines 65• 17 anti-tuberculosis medicines 25• 10 anti-malarial medicines 32• 184 115+
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Department of Essential Medicines and Pharmaceutical Policies, Health Systems and Services
Transparency: WHO Public Inspection Reports (WHOPIR) and WHO Public Assessment Reports (WHOPAR) on web
*WHOPAR – structure and amount of information the same as in European Public Assessment Report (EPAR)
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Department of Essential Medicines and Pharmaceutical Policies, Health Systems and Services
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Department of Essential Medicines and Pharmaceutical Policies, Health Systems and Services
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Department of Essential Medicines and Pharmaceutical Policies, Health Systems and Services
News example: latest 9 products listed
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Department of Essential Medicines and Pharmaceutical Policies, Health Systems and Services
Inspections 2005-2007
Inspections of finished products (FP) manufacturers in 2007 reaching 26
Active pharmaceutical ingredients (API) manufacturers in 2007 – 6
Contract Research Organizations (CRO) for BE studies in 2007 - 13
0
5
10
15
20
25
30
FP API CRO
2005
2006
2007
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Department of Essential Medicines and Pharmaceutical Policies, Health Systems and Services
Dossier assessment – number of assessment reports generated for different product groups
In 2007 total 511 assessment reports were generated
0
50
100
150
200
250
300
350
400
HIV TB Malaria
2005
2006
2007
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Department of Essential Medicines and Pharmaceutical Policies, Health Systems and Services
Publications 2005-2007
Prequalification of medicines. WHO Drug Information, 2005, 19:1.
WHO and its Prequalification Programme: an Overview. WHO Pharmaceuticals Newsletter, 2005, No. 2.
Dekker TG, van Zyl AJ, Gross O, Tasevska I, Stahl M, Rabouhans ML, Rägo L. Ongoing monitoring of antiretroviral products as part of WHO’s Prequalifi cation Programme. Journal of Generic Medicines, 2006, 3(2):96–105
Survey of the Quality of Antiretroviral Medicines Circulating in Selected African Countries, WHO/PSM/QSM/2007.9 (September 2007)
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Department of Essential Medicines and Pharmaceutical Policies, Health Systems and Services
Capacity building: Examples of trainings organized by in 2007Capacity building: Examples of trainings organized by in 2007
Workshop on Pharmaceutical Development with a Focus on Paediatric Medicines Cape Town, South Africa, 16 - 20 April 2007
Training Workshop on Dissolution, Pharmaceutical Product interchangeability and Biopharmaceuticals Classification System (BCS) Kiev, Ukraine, 25 - 27 June 2007
Pharmaceutical Quality, Good Manufacturing Practice and Bioequivalence with a Focus on TB products Jiaxing, China , 5 - 9 November 2007
Training Seminar for Quality Control Laboratories on Quality Assurance, Prequalification and Development of Standards Rabat, Morocco, 27 - 29 November 2007
Training Workshop on WHO Good Manufacturing Practices Dakar, Senegal, 11 - 14 December 2007
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Department of Essential Medicines and Pharmaceutical Policies, Health Systems and Services
Pharmaceutical Development with Focus on Paediatric formulationsPharmaceutical Development with Focus on Paediatric formulations
WHO/FIP/IUPHAR Training Workshop
Hyatt Regency Hotel
Sahar Airport Road
Andheri East, Mumbai, India
28 April 2008 – 2 May 2008
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Department of Essential Medicines and Pharmaceutical Policies, Health Systems and Services
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Department of Essential Medicines and Pharmaceutical Policies, Health Systems and Services
Participants of trainings organized and supported by WHO Medicines Prequalification Progarmme 2007
100
145
10200
QCLs Regulators Manufacturers Procurers
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Department of Essential Medicines and Pharmaceutical Policies, Health Systems and Services
Other specific regulatory pathways for products of public health needs
EU Article 58 US FDA tentative approvals linked to PEPFAR Canadian Access to medicines scheme
WHO cooperates with all the above mentioned Confidentiality agreement with US FDA in place and
working; CA with Health Canada in progress MoU (including confidentiality arrangements) under
developemnt with European Commission
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Department of Essential Medicines and Pharmaceutical Policies, Health Systems and Services
Summary Not so good news
Only limited number of products have met the required standards (especially malaria and TB products)
Takes time to get into compliance• Data to be generated, tests to be carried out …• GMP upgrade needed
Quality has its price Good news
Relatively large number of products and suppliers comply with the standards (mostly ARVs so far)
Many potential suppliers appreciating feedback and willing to improve Unique technical knowledge obtained about products, especially about
generic antiretrovirals and antimalarials Capacity building component appreciated a lot Working together – way to learn to recognize each others work and work for
reducing duplicative efforts
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Department of Essential Medicines and Pharmaceutical Policies, Health Systems and Services
Prequalification - a good engine to pull quality of medicines into international agenda
It challenges the still existing reality - "poor quality medicines for poor"
How best keep it going as huge unfinished agenda is ahead?