Ensuring Access to Antimalarial Drugs

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Antimalarial Medicines Current Status in Africa
Dr Clive Ondari Medicines Policy and Standard
Department WHO/HQ

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Access framework
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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

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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.

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Failure rates () Content (2003)
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Failure Rates () Dissolution (2003)
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Malaria distribution and reported case of
resistance or treatment failure
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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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Selection Artemisinin-based Combination
Therapies (ACTs)

• Artemether/lumefantrine

• Artesunate amodiaquine

ACTs

• Artesunate SP

• Artesunate mefloquine

• Amodiaquine SP

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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
AFRICA 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
AFRICA Côte d'Ivoire, Gabon, Mozambique, Sudan (N), Sao Tomé Principe, Zanzibar AL 2nd
AFRICA Mozambique, Sudan (N), South Africa (Mpumalanga) AS SP 1st
ASIA Cambodia, Myanmar, Thailand AS MQ 1st
ASIA Bangladesh, Bhutan, Laos, Saudi Arabia AL 1st
ASIA Indonesia AS AQ 1st
ASIA Afghanistan, India (5 Provinces), Iran, Somalia, Tajikistan, Yemen AS SP 1st
ASIA Viet Nam DP 1st
ASIA Papua New Guinea AS SP 2nd
ASIA Philippines, Iran AL 2nd
SOUTH AMERICA Ecuador, Peru AS SP 1st
SOUTH AMERICA Bolivia, Peru, Venezuela AS MQ 1st
SOUTH AMERICA 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 ...

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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 (letterfiles)
• 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

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Cost implications of moving to ACTs
Average cost per adult treatment (US) (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