1. Selection of malaria treatments & diagnostics Presentation by Rémy Prohom RBM Partnership Secretariat, Malaria Medicines & Supplies Services Anglophone PSM Workshop, Nairobi Kenya, 20-24February 2006

2. Treatments Selection of malaria treatments & diagnostics

3. Artemisin-based combination therapies have proven to be the most effective. ISSUE: API of artemisinin cannot be produced yet by synthesis ACTs manufacturing rely then on agricultural raw material production

4. Joint tender WHO-UNICEF to manufacturers of ACTs Long Term Agreement to ensure low and stable price with selected manufacturers WHO-UNICEF-IAPSO can order Coartem@ at cost price for public health sector Partners advocacy to strengthen production and bring more manufacturers in the loop Practical solutions

5. Combination therapies recommended by WHO WHO Technical Consultation on “Antimalarial Combination Therapy” – April 2001 Artesunate + amodiaquine Artemether/Lumefantrine Artesunate + SP Artesunate + mefloquine FDC ACTs Response to increasing resistance

6. Artemether/Lumefantrine Treatment of acute uncomplicated malaria due to Plasmodium falciparum or mixed infections including P. falciparum in areas with significant multidrug resistance.

7. Model Model Description Units box Unit Price Coartem® (30X24) Artemether 20 mg + Lumefantrine 120 mg, tablets (6x4) treatment for patients over 35 kg 30$2.4 Coartem® (30X18) Artemether 20 mg + Lumefantrine 120 mg, tablets (6x3) treatment for patients from 25 to 34 kg 30$1.9 Coartem® (30X12) Artemether 20 mg + Lumefantrine 120 mg, tablets (6x2) treatment for patients from 15 to 24 kg 30$1.4 Coartem® (30X6) Artemether 20 mg +Lumefantrine 120 mg, tablets (6) treatment for patients from 5 to 14 kg. 30$0.9 Artemether/Lumefantrine Novartis Pharma AG

8. Treatment of acute uncomplicated malaria due to Plasmodium falciparum or mixed infections including P. falciparum in areas with significant drug resistance to Chloroquine or Sulfadoxine-Pyrimethamine. Artesunate+Amodiaquine

9. 3 Manufacturers currently selected: –CIPLA –IPCA –SANOFI AVENTIS Artesunate+Amodiaquine

10. Average prices for AS+AQ: 3+3$0.50 6+6$0.85 12+12$1.51 Artesunate+Amodiaquine

11. CIPLA ModelModel Description units/ box Falcimon kitArtesunate 50 mg+Amodiaquine 153mg (base) tablets (3+3) in co-blister, combined treatment for children from 1 to 7 years old (10-20 kg), individually packed. 1 Falcimon kitArtesunate 50 mg+Amodiaquine 153mg (base) tablets (6+6) in co-blister, combined treatment for children from 7 to 13 years old (21-40 kg), individually packed. 1 Falcimon kitArtesunate 50 mg+Amodiaquine 153mg (base) tablets (12+12) in co-blister, combined treatment for patients over 13 years old (over 40kg), individually packed. 1 Artesunate+Amodiaquine

12. IPCA PHARMACEUTICALS Model Description units/ box Artesunate 50 mg+Amodiaquine 153mg (base) tablets (3+3) in co-blister, combined treatment for children from 1 to 7 years old (10-20 kg) 10 and 100 Artesunate 50 mg+Amodiaquine 153mg (base) tablets (6+6) in co-blister, combined treatment for children from 7 to 13 years old (21-40 kg) 10 and 100 Artesunate 50 mg+Amodiaquine 153mg (base) tablets (12+12) in co-blister, combined treatment for patients over 13 years old (over 40kg) 10 and 100 Artesunate+Amodiaquine

13. ModelModel Descriptionunits/box Arsucam®Artesunate 50 mg+Amodiaquine 153mg (base) tablets (3+3) in co-blister, combined treatment for children from 1 to 6 years old (10-20 kg) 25 Arsucam®Artesunate 50 mg+Amodiaquine 153mg (base) tablets (6+6) in co-blister, combined treatment for children from 7 to 13 years old (21-40 kg) 25 Arsucam® adult Artesunate 50 mg+Amodiaquine 153mg (base) tablets (12+12) in co-blister, combined treatment for patients over 13 years old (over 40kg) 25 Artesunate+Amodiaquine SANOFI-AVENTIS

14. Treatment of acute uncomplicated malaria due to Plasmodium falciparum in areas where resistance to Sulfadoxine- Pyrimethamine is low (i.e. where the 28-day cure exceeds 80%). Artesunate+ Sulfadoxine/Pyrimethamine

15. ModelModel Descriptionunits/box Unit price Artecospe for children Artesunate 50mg + Sulfadoxine/Pyrimethamine 500/25mg tablets (6+2) in co-blister, combined treatment for paediatric patients from 5 months to 13 years old (or under 40 kg), individually packed. 1$0.79 Artecospe for adults Artesunate 100mg + Sulfadoxine/Pyrimethamine 500/25mg tablets (6+3) in co-blister, combined treatment for patients over 14 years old and body weight over 40kg, individually packed. 1$1.41 Artesunate+ Sulfadoxine/Pyrimethamine GUILIN

16. Until now both independent drug WHO GMP approved were purchased separately and given together to the patient; A co-blister formulation has just been GMP approved and is available on the market, but at a much higher price. Artesunate+Mefloquine

17. Lead time delivery Address a request to the manufacturer (or procurement agent) for each and every order for any ACT and get a written answer on the delivery time for your specific order. Lead time may vary depending of many factors (production site, quantities, packaging, volume and destination) and therefore should be planned much ahead.

18. Remember about ACTs… Short shelf life (24 months) Increased costs Longer lead time for deliveries Challenging implementation

19. Rapid Diagnostic Tests Selection of malaria treatments & diagnostics

20. Considerations for choosing an RDT include: Plasmodium species to be detected (P. falciparum only, or panspecific) Shelf -life and temperature stability in intended conditions of storage and use Ease of use, including format of the test (e.g. cassette, dipstick, card) Requirement for post-treatment testing of patients Cost (including transport, training, and quality control) Sensitivity Good quality assurance processes after purchase are likely to be of greater importance. Choice of RDTs

21. Quality assurance Quality assurance system to sustain the reliability of RDTs Transport & stock Monitoring & temperature control Manufacturer Good manufacturing practices/control Laboratory Nat/Regional Batch control District/remote areas sensitivity check Final user Training & supervision

22. Procurement issues Real-time temperature stability data on the product, and accelerated data on the purchased lot Evidence of successful operational use, or good quality field data on the product Long-term viability of manufacturer (to ensure continuity of supply) Evidence of Good Manufacturing Practice /ISO certification (ISO13485:2003 is specific for quality management systems for medical devices) …/…

23. Procurement issues Availability of product support Provision of sample products for assessment and testing for ease of use Agreement for replacement of products which fail agreed quality control procedures (see above) Box sizes appropriate to the rate of use of tests in the intended area, to minimize storage time in poor conditions and reduce the need to split boxes.

24. How to contact us… Malaria Medicines & Supply Services (MMSS) Roll Back Malaria Partnership Secretariat Website: http://rbm.who.int/mmss/http://rbm.who.int/mmss/ Mr Remy Prohom Technical Officer ACTs and RDTs related issues Tel: +41 (0)22 791 2679 E-mail: prohomr@who.intprohomr@who.int