1. Access to paediatric ARV formulations Limitations due to regulations Experience from the field MSF

2. Limitations due to regulations Prequalification – disqualification Registration – marketing Patents Local distributors Price Lack of FDC due to lack of information (Pharmacokinetics, homogeneity – stability tests, bioequivalence,…) Other: Stiff regulation, poor stock management,…

3. Factors affecting access to paediatric ARV formulations Examples from the field

4. AZT: 100 mg caps, syrup Thailand –100 mg caps and syrup registered, not patent protected and generically produced (GPO Thailand) –On the field 100 mg caps often lacking (poor stock management, stiff regulations) Malawi –100 mg caps registered and patent protected –no price reduction offered for this formulation by originator

5. 3TC: tablet 150 mg, syrup Thailand –Syrup and tablet: registered, not patent protected and paediatric formulation (scored tablet, syrup) available generically. –Only syrup provided within National ARV program but children prefer tablets! Malawi –3TC 150 mg tablet Cipla (scored) temporarily dequalified, –no more scored formulation available (Ranbaxy and Glaxo are not scored). –We could be obliged to use non-qualified drugs

6. d4T 15, 20 mg and syrup Thailand –Syrup and tablet: registered, not patent protected and paediatric formulation available generically (Syrup, 15 and 20 mg caps) Malawi –15 mg is not marketed nor registered by local distributor –Storage syrup is problematic (no fridge, no electricity) –Opened capsules can only be stored for 1 day –Grandmothers?

7. ddI Thailand –Patent: Court case challenging breath of patent delaying production of generic version –CL not applied (political pressure) –Patent was revoked (out court agreement) –ddI 25, 50, 100 and 200 mg sachets now available (but SE, disclosure) –Scored tablets of 50, 125 and 200 mg produced soon –Enteric coated: originator applied for patent but not issued (yet), objection from generic producer (pending)

8. ddI (2) Malawi –Only 100 mg (generic) registered –25 and 50 mg not available –Generic 25, 50 and 100 mg are not WHO pre- qualified

9. NVP: syrup, 200 mg tablet Thailand –Patent for syrup formulation under investigation –Generic formulations = dry powder Malawi –Patent ?? (under study) –Generic syrup available in MSF setting (huge quantity) –Only Ranbaxy scored

10. EFV: syrup, 50 mg caps Thailand –50 mg was registered but not marketed (not distributed by local supplier) –syrup is not available –600 mg available, still poor availability of 50 mg caps., paediatricians are told to break 600 mg tabs.

11. EFV: syrup, 50 mg caps Thailand EFV 50 mg is a luxurious thing. We only have that formulation briefly. The company allow you to change the 200 mg cap to 50 mg cap, but not by mg-per- mg. Meaning that one 200 mg cap, you only can get two to three 50 mg cap. Recently, the MOPH gave us 600 mg cap. Go back to divide the capsule by yourself! Sometimes, I really feel emotional with these drug companies business!

12. Paediatric FDC (3TC/d4T/NVP) Thailand –is produced but not marketed yet (on the shelves, stability tests) –GPO drugs are not WHO-prequalified

13. Paediatric FDC eg.mini-vir Thailand

14. Paediatric FDC (3TC/d4T/NVP) Malawi –Not available –Expecting Cipla formulation

15. Adult FDC (3TC/d4T/NVP) Thailand –Registered, produced and marketed (GPO-vir, scored tablets) –Children (> 4 kg) get proportions of tablet, divided in quarters without NVP supplementation Malawi –Generic available but Ranbaxy's FDC temporarily dequalified –We could be obliged to continue dequalified drugs –Cipla: not scored and not WHO-prequalified

16. Common sense (guidelines)

17. LPV/r Thailand –Patent protected, very expensive –Only available through clinical trials –Can Thailand apply for the offered price reduction? –(cfr China: 8000USD versus 500)

18. Paediatric formulations are expensive

20. Conclusions Procurement and supply management at program level is very complicated Boost pre-qualification of paediatric formulations (matter of priorities) National authorities should fast-track registration –Context: lack of commercial interest Prices reductions should be offered in a systematic, simple way Countries should be encouraged to apply Doha. We need paediatric FDC urgently.

21. Conclusions We are asking manufacturers to develop appropriate formulations (chocolate) and to register and market them at cost or low price… and there is no market!!! We need also political commitment from UN (WHO, UNICEF), donors, national governments