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

2. Department of Medicines Policy and Standards 2 Access framework Rational Selection & Use Reliable health and supply systems Affordable prices Sustainable financing ACCESS

3. Department of Medicines Policy and Standards 3 Scope of the presentation n Situation analysis on antimalarials in Africa n WHO recommendations on combination antimalarials (ACTs) n Characteristics of ACTs (from a regulatory angle) n Process of regulation of antimalarials n Conclusions

4. Department of Medicines Policy and Standards 4 Situation analysis: the challenges n Quality of antimalarial drugs has been declining. n The efficacy of (affordable) antimalarial drugs has been declining (drug resistance) and high cost of replacement options. n 60-90% of the population seek initial treatment from non- public sector, i.e. street vendors, kiosks. n Supply of drugs is often inefficient and unreliable.

5. Department of Medicines Policy and Standards 5 Failure rates (%) – Content (2003)

6. Department of Medicines Policy and Standards 6 Failure Rates (%) – Dissolution (2003)

7. Department of Medicines Policy and Standards 7 Malaria distribution and reported case of resistance or treatment failure

8. Department of Medicines Policy and Standards 8 Factors leading to development of resistance n Lack of guidelines/poor drug treatment policies n Irrational prescribing n Irrational drug use n Drug concentration “tail” – poor formulations n Liberalized, uncontrolled drug market leading to poor quality products circulating in international and domestic markets

9. Department of Medicines Policy and Standards 9 n Artesunate + amodiaquine Artemether/lumefantrine n Artesunate + SP n Artesunate + mefloquine FDC ACTs n Amodiaquine + SP Selection: Artemisinin-based Combination Therapies (ACTs) MDT

10. Department of Medicines Policy and Standards 10 ContinentCountriesDrugLine 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 + AQ1st Angola, Benin, Burkina Faso, Central African Republic, Comoros, Ethiopia, Gambia, Guinea Bissau, Kenya, Namibia, Niger, Nigeria, Rwanda, Uganda, S. Africa, Tanzania, Tchad, Togo, Zambia AL1st Côte d'Ivoire, Gabon, Mozambique, Sudan (N), Sao Tomé & Principe, Zanzibar AL2nd Mozambique, Sudan (N), South Africa (Mpumalanga) AS + SP1st ASIA Cambodia, Myanmar, Thailand AS + MQ1st Bangladesh, Bhutan, Laos, Saudi Arabia AL1st Indonesia AS + AQ1st Afghanistan, India (5 Provinces), Iran, Somalia, Tajikistan, Yemen AS + SP1st Viet Nam DP1st Papua New Guinea AS + SP2nd Philippines, Iran AL2nd SOUTH AMERICA Ecuador, Peru AS + SP1st Bolivia, Peru, Venezuela AS + MQ1st Brazil, Guyana, Suriname AL1st

11. Department of Medicines Policy and Standards 11 ACTs are not typical “generic” products n Usually generic drugs “well established” … ä ACTs are relatively new, or very new drugs ä Limited information available in public domain n Most ACTs do not have quality standards n For most ACTs reference standards not readily available ä Reference standards available only for those that have pharmacopoeial monographs n Difficulties of proving “interchangeability” n Regulators have limited experience with this group of drugs...

12. Department of Medicines Policy and Standards 12 WHO Pre-qualification of ACT Products n Processes of Pre-qualification of manufacturers (of artemisinin-based combination antimalarial drug products) ä Preparatory Phase Drafting of specifications and guidelines (products and product files) Publication of Expression of Interest (EOI) - IHT and WWW ä Documentation Review Phase Receiving of EOI (letter+files) Screening, assessing, and reviewing dossiers  Report ä Plant Inspection (GMP compliance) Phase Team of inspectors appointed by QSM/EDM Inspections carried out jointly with respective DRA ä Reporting Phase Results in a “white” list of products and manufacturers

13. Department of Medicines Policy and Standards 13 Cost implications of moving to ACTs Average cost per adult treatment (US$) (2002)

14. Department of Medicines Policy and Standards 14 Regulation of Medicines at National Level: n Drug Registration n Manufacturing (enforcing GMP standards) n Drug Distribution (scheduling: POM, PM, OTC/General Sales) n Information and Promotion Control

15. Department of Medicines Policy and Standards 15 Registration: n Safety n Efficacy n Quality n Affordability (pricing)

16. Department of Medicines Policy and Standards 16 Who may apply for registration n Manufacturer n Representative of a manufacturer (in the country of origin) – power of attorney required n An agent of a manufacturer (within the country) – power of attorney required

17. Department of Medicines Policy and Standards 17 Data required for approval of application n Chemical data (both active substance and formulating ingredients) n Pharmaceutical Data of the Product ä Complete formula of the product (including specifications) ä Manufacturing Processes (including validation data) ä Analytical and quality specifications of the finished product ä Method of analysis and assay of active ingredient in the finished product ä Product stability profile n Clinical data (safety and efficacy)

18. Department of Medicines Policy and Standards 18 Clinical Data n Innovator product s ä full documentation of preclinical and clinical safety and efficacy according to ICH guidelines ä all claims on the SmPC have to be substantiated n Multi-source products ä Bio-equivalance demonistrated ä Direct evidence in support of safety and efficacy SMPC = summary of product characteristics

19. Department of Medicines Policy and Standards 19 Conclusions n In order to improve and sustain access to good quality, effective antimalarials in malaria-endemic countries, it will be necessary to intensify work to: ä Develop and/or expand capacity for effective pharmaceutical regulation and control ä Strengthen the capacity and efficiency of drug supply systems ä Evolve more effective and efficient drug-financing arrangements ä Ensure that antimalarial medicines are used in a rational manner