Transcript Ensuring Access to Antimalarial Drugs

Antimalarial Medicines:
Current Status in Africa
Dr Clive Ondari
Medicines Policy and Standard Department
WHO/HQ
Access framework
Rational
Sustainable
Selection & Use
financing
ACCESS
Affordable
prices
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Reliable
health and
supply systems
Scope of the presentation
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Situation analysis on antimalarials in Africa
WHO recommendations on combination antimalarials (ACTs)
Characteristics of ACTs (from a regulatory angle)
Process of regulation of antimalarials
Conclusions
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Situation analysis: the challenges
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Quality of antimalarial drugs has been declining.
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The efficacy of (affordable) antimalarial drugs has been
declining (drug resistance) and high cost of
replacement options.
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60-90% of the population seek initial treatment from
non- public sector, i.e. street vendors, kiosks.
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Supply of drugs is often inefficient and unreliable.
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Failure rates (%) – Content (2003)
100
80
Chloroquine Syrup
60
Chloroquine Tablets
40
Sulphadoxine/Pyrimetha
mine Tablets
20
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Failure Rates (%) – Dissolution (2003)
80
60
40
20
Chloroquine Tablet s
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SP Tablet s
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Percent Failure (%)
100
Malaria distribution and reported case of resistance or treatment failure
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Factors leading to development of resistance
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Lack of guidelines/poor drug treatment policies
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Irrational prescribing
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Irrational drug use
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Drug concentration “tail” – poor formulations
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Liberalized, uncontrolled drug market leading to poor
quality products circulating in international and
domestic markets
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Selection: Artemisinin-based Combination
Therapies (ACTs)
FDC
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Artemether/lumefantrine
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Artesunate + amodiaquine
ACTs
MDT
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Artesunate + SP
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Artesunate + mefloquine
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Amodiaquine + SP
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Continent
AFRICA
ASIA
SOUTH
AMERICA
Countries
Line
Burundi, Cameroon, Côte d'Ivoire, Democratic Republic of Congo, Gabon, Ghana,
Guinea, Liberia, Madagascar, Mali, Senegal, Sao Tomé & Principe, Sierra Leone,
Sudan (S), Zanzibar
AS + AQ
1st
Angola, Benin, Burkina Faso, Central African Republic, Comoros, Ethiopia,
Gambia, Guinea Bissau, Kenya, Namibia, Niger, Nigeria, Rwanda, Uganda, S.
Africa, Tanzania, Tchad, Togo, Zambia
AL
1st
Côte d'Ivoire, Gabon, Mozambique, Sudan (N), Sao Tomé & Principe, Zanzibar
AL
2nd
Mozambique, Sudan (N), South Africa (Mpumalanga)
AS + SP
1st
Cambodia, Myanmar, Thailand
AS + MQ
1st
Bangladesh, Bhutan, Laos, Saudi Arabia
AL
1st
Indonesia
AS + AQ
1st
Afghanistan, India (5 Provinces), Iran, Somalia, Tajikistan, Yemen
AS + SP
1st
Viet Nam
DP
1st
Papua New Guinea
AS + SP
2nd
Philippines, Iran
AL
2nd
Ecuador, Peru
AS + SP
1st
Bolivia, Peru, Venezuela
AS + MQ
1st
Brazil, Guyana, Suriname
AL
1st
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Drug
ACTs are not typical “generic” products
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Usually generic drugs “well established” …
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Most ACTs do not have quality standards
For most ACTs reference standards not readily available
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ACTs are relatively new, or very new drugs
Limited information available in public domain
Reference standards available only for those that have
pharmacopoeial monographs
Difficulties of proving “interchangeability”
Regulators have limited experience with this group of
drugs ...
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WHO Pre-qualification of ACT Products
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Processes of Pre-qualification of manufacturers (of
artemisinin-based combination antimalarial drug
products)
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Preparatory Phase
• Drafting of specifications and guidelines (products and
product files)
• Publication of Expression of Interest (EOI) - IHT and
WWW
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Documentation Review Phase
• Receiving of EOI (letter+files)
• Screening, assessing, and reviewing dossiers  Report
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Plant Inspection (GMP compliance) Phase
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Reporting Phase
• Team of inspectors appointed by QSM/EDM
• Inspections carried out jointly with respective DRA
• Results in a “white” list of products and manufacturers
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Average cost per adult treatment (US$)
(2002)
Cost implications of moving to ACTs
6
5
4
3
2
1
0
CQ
SP
AS/AQ
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AS/SP
AT/LM AS/MF
Regulation of Medicines at National Level:
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Drug Registration
Manufacturing (enforcing GMP standards)
Drug Distribution (scheduling: POM, PM, OTC/General Sales)
Information and Promotion Control
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Registration:
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Safety
Efficacy
Quality
Affordability (pricing)
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Who may apply for registration
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Manufacturer
Representative of a manufacturer (in the country of origin) –
power of attorney required
An agent of a manufacturer (within the country) – power of
attorney required
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Data required for approval of application
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Chemical data (both active substance and formulating
ingredients)
Pharmaceutical Data of the Product
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Complete formula of the product (including specifications)
Manufacturing Processes (including validation data)
Analytical and quality specifications of the finished product
Method of analysis and assay of active ingredient in the
finished product
Product stability profile
Clinical data (safety and efficacy)
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Clinical Data
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Innovator product s
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full documentation of preclinical and clinical safety and
efficacy according to ICH guidelines
all claims on the SmPC have to be substantiated
Multi-source products
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Bio-equivalance demonistrated
Direct evidence in support of safety and efficacy
SMPC = summary of product characteristics
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Conclusions
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In order to improve and sustain access to good quality,
effective antimalarials in malaria-endemic countries, it will
be necessary to intensify work to:
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Develop and/or expand capacity for effective pharmaceutical
regulation and control
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Strengthen the capacity and efficiency of drug supply systems
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Evolve more effective and efficient drug-financing arrangements
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Ensure that antimalarial medicines are used in a rational manner
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