Antimalarial Medicines: Current Status in Africa Dr Clive Ondari Medicines Policy and Standard Department WHO/HQ
Antimalarial Medicines: Current Status in Africa
Dr Clive Ondari
Medicines Policy and Standard DepartmentWHO/HQ
Department of Medicines Policy and Standards
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Access framework
RationalSelection & Use
Reliablehealth and
supply systemsAffordable
prices
Sustainable
financing
ACCESS
Department of Medicines Policy and Standards
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Scope of the presentation
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
Department of Medicines Policy and Standards
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Situation analysis: the challenges
Quality of antimalarial drugs has been declining.
The efficacy of (affordable) antimalarial drugs has been declining (drug resistance) and high cost of replacement options.
60-90% of the population seek initial treatment from non- public sector, i.e. street vendors, kiosks.
Supply of drugs is often inefficient and unreliable.
Department of Medicines Policy and Standards
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Failure rates (%) – Content (2003)
0
20
40
60
80
100
Gabon
Ghana M
ali
Kenya
Moz
ambiq
ue
Zimba
bwe
Sudan
Chloroquine Syrup
Chloroquine Tablets
Sulphadoxine/Pyrimethamine Tablets
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0
20
40
60
80
100
Perc
en
t F
ail
ure
(%
)
Chloroquine Tablets SP Tablets
Failure Rates (%) – Dissolution (2003)
Department of Medicines Policy and Standards
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Malaria distribution and reported case of resistance or treatment failure
Department of Medicines Policy and Standards
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Factors leading to development of resistance
Lack of guidelines/poor drug treatment policies
Irrational prescribing
Irrational drug use
Drug concentration “tail” – poor formulations
Liberalized, uncontrolled drug market leading to poor quality products circulating in international and domestic markets
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Artesunate + amodiaquine
• Artemether/lumefantrine
Artesunate + SP
Artesunate + mefloquine
FDC
ACTs
Amodiaquine + SP
Selection: Artemisinin-based Combination Therapies (ACTs)
MDT
Department of Medicines Policy and Standards
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Continent Countries Drug Line
AFRICA 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
ASIA 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
SOUTHAMERICA
Ecuador, Peru AS + SP 1st
Bolivia, Peru, Venezuela AS + MQ 1st
Brazil, Guyana, Suriname AL 1st
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ACTs are not typical “generic” products
Usually generic drugs “well established” … ACTs are relatively new, or very new drugs Limited information available in public domain
Most ACTs do not have quality standards For most ACTs reference standards not readily available
Reference standards available only for those that have pharmacopoeial monographs
Difficulties of proving “interchangeability” Regulators have limited experience with this group of
drugs ...
Department of Medicines Policy and Standards
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WHO Pre-qualification of ACT Products Processes of Pre-qualification of manufacturers (of
artemisinin-based combination antimalarial drug products) Preparatory Phase
• Drafting of specifications and guidelines (products and product files)
• Publication of Expression of Interest (EOI) - IHT and WWW Documentation Review Phase
• Receiving of EOI (letter+files)• Screening, assessing, and reviewing dossiers Report
Plant Inspection (GMP compliance) Phase• Team of inspectors appointed by QSM/EDM• Inspections carried out jointly with respective DRA
Reporting Phase• Results in a “white” list of products and manufacturers
Department of Medicines Policy and Standards
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Cost implications of moving to ACTs
0
1
2
3
4
5
6
CQ SP AS/AQ AS/SP AT/LM AS/MF
Ave
rag
e co
st p
er a
du
lt t
reat
men
t (U
S$)
(2002)
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Regulation of Medicines at National Level:
Drug Registration Manufacturing (enforcing GMP standards) Drug Distribution (scheduling: POM, PM, OTC/General Sales) Information and Promotion Control
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Registration:
Safety Efficacy Quality Affordability (pricing)
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Who may apply for registration
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
Chemical data (both active substance and formulating ingredients)
Pharmaceutical Data of the Product 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
Innovator product s 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 Bio-equivalance demonistrated Direct evidence in support of safety and efficacy
SMPC = summary of product characteristics
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Conclusions
In order to improve and sustain access to good quality, effective antimalarials in malaria-endemic countries, it will be necessary to intensify work to:
Develop and/or expand capacity for effective pharmaceutical regulation and control
Strengthen the capacity and efficiency of drug supply systems
Evolve more effective and efficient drug-financing arrangements
Ensure that antimalarial medicines are used in a rational manner