Medicines for children in developing countries: from challenges to specifications

1. Atieno Ojoo Technical Specialist, Pharmaceuticals UNICEF Supply Division, Copenhagen, Denmark Medicines for children in developing countries: from challenges to specifications WHO PreQ; EU generic manufacturers meeting 261109, Copenhagen, Denmark

2. Presentation outline EU generic manufacturers meeting 261109, Copenhagen, Denmark

3. Causes of death in under 5s World Health Statistics 2007 http://www.who.int/child_adolescent_health/data/child/en/index.html EU generic manufacturers meeting 261109, Copenhagen, Denmark

4. Some success stories 2006 U5M <10 million (9.7m in 2006) 2007 1st WHO paediatric EML 1st Paediatric ARV FDCs 2008 1st Paediatric ACT antimalarial FDC U5M <8.8 million 2009 2nd Paediatric ACT Antimalarial FDC BUT Its not yet time to celebrate ! EU generic manufacturers meeting 261109, Copenhagen, Denmark

5. Health worker challenges • Weight & height measurements often not taken • Busy clinics • No weight and height measuring devices • No suitable dose measuring & administration devices • What is a teaspoonful? Any spoon? • No spacers for MD Inhalers (Cost issue) • Reconstitution of powders for oral suspension/liquid • Challenge if bottles not marked • Water supply challenges • no cold storage • Repackaging • No clean bottles - patients have to bring own bottles, • no measuring/counting devices • no labels EU generic manufacturers meeting 261109, Copenhagen, Denmark

6. Solutions? EU generic manufacturers meeting 261109, Copenhagen, Denmark

7. Current solution: ½, ¼, 1/8 tablets EU generic manufacturers meeting 261109, Copenhagen, Denmark

8. Patient/caregiver challenges • Palatability-Child refuses to take medicine • Too much liquid volume per dose • Child vomits, not sure how much to re-administer • No storage space for bulky liquids • Also significant if caregiver has to carry and walk long distances • Difficult to follow Instructions • Mix with apple or apple-grape juice or applesauce or yoghurt • Open capsule and sprinkle contents over a spoonful of applesauce, or yoghurt, consume immediately • Crush tablets and mix with condensed milk prior to administration • Break tablets into 8 equal pieces (How?) • Dissolve tablet water, then administer by dropper, oral syringe (not provided) or drink directly • To be swallowed whole- not to be chewed EU generic manufacturers meeting 261109, Copenhagen, Denmark

9. Challenges for HIV+ children Adult Child: too many bottles EU generic manufacturers meeting 261109, Copenhagen, Denmark

10. No cold storage • Quote“ two years ago, I was involved in a study…….in children and adolescents. One of the subjects, a 5 year old boy, had to commute daily accompanied by either of his parents to the hospital to take the drug, which was a suspension that needed to be stored in a refrigerator. The family did not have a refrigerator and did not have electricity connection either, so we could not even donate a refrigerator as there was provision for this” EU generic manufacturers meeting 261109, Copenhagen, Denmark

11. WHO-UNICEF joint plan • Work on a global project to make paediatric medicines a priority • Add missing essential formulations to the Model list in 2009; advise on doses • Develop EML for children (2007-8) • Update treatment guidelines (2007-9) • Develop paediatric prescribing information – a formulary • Develop effective methods for provision of information at the point of care • Collaborate with regulatory authorities to encourage appropriate drug development and approval processes in all regulatory authorities • Develop quality standards for paediatric medicines • Public development support for missing essential medicines for children • Advocate for the development of paediatric medicines by the industry • Develop a system for enhancing safety monitoring of medicines in children • Provide guidance on procurement and supply of paediatric medicines EU generic manufacturers meeting 261109, Copenhagen, Denmark

12. Ideal paediatric medicine • Route of administration: Oral most frequently used • Dosage form? SODF** Liquids? • Sufficient bioavailability • Dose uniformity • Non toxic excipients • Acceptable organoleptic properties: Taste • Dosing aids • Ease of administration for both parent and child • Clear product information/instructions • Cost effective • Does not require cold storage • Minimum steps of manipulation before use • **Chewable, fast melts, effervescent, granules, sprinkles, soluble tablets,, sublingual, etc EU generic manufacturers meeting 261109, Copenhagen, Denmark

13. We need the support of manufacturers • Solid oral dosage forms that can me made into liquid at the time of use • Dispersible tablets, effervescents, solubles • Reduce requirements for additional water • Fast melts, sublingual, lollipops • Reduce requirements for cold storage • Course of therapy individual patient packs • No bulk packs for repacking • Provide information on sources and prices of paediatric medicineshttp://www.unicef.org/supply/index_47129.html. EU generic manufacturers meeting 261109, Copenhagen, Denmark

14. Coated particles in tablet form for preparing suspension Courtesy of J. Breitkreutz EU generic manufacturers meeting 261109, Copenhagen, Denmark

15. Example of win-win strategies • Reduced input costs for solid formulations Vs liquid formulations • Most Solid dose manufacture technology already exists • Reduced need for excipients, less safety concerns • Reduced complexity • Going green/reducing carbon foot prints while meeting developing country end user needs • Drug product with no cold storage requirements • Reduced freight loads-reduced cost • No need to transport water around the world! EU generic manufacturers meeting 261109, Copenhagen, Denmark

16. Thank you EU generic manufacturers meeting 261109, Copenhagen, Denmark