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

2. EU generic manufacturers meeting 261109, Copenhagen, Denmark
Presentation outline
Safety, efficacy and quality of medicines is a prerequisite before looking for appropriate formulations-UNICEF technical requirements for pharmaceutical products
Without access and affordability, any medicine will not reach the intended beneficiary- Medicines do not work in those who do not take them
UNICEF
EU generic manufacturers meeting , Copenhagen, Denmark

3. EU generic manufacturers meeting 261109, Copenhagen, Denmark
Causes of death in under 5s
World Health Statistics 2007
UNICEF
EU generic manufacturers meeting , 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 !
UNICEF
EU generic manufacturers meeting , 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
No standard methods for extemporaneous preparations
Reformulating existing (adult) formulations
In house manufacture, lack of critical ingredients
Quality concerns
UNICEF
EU generic manufacturers meeting , Copenhagen, Denmark

6. EU generic manufacturers meeting 261109, Copenhagen, Denmark
Solutions?
Splitting tabs or dividing caps powder
1/8 of Frusemide 40mg=5mg. How?
Challenge if tablet is coated, not scored
UNICEF
EU generic manufacturers meeting , Copenhagen, Denmark

7. Current solution: ½, ¼, 1/8 tablets
UNICEF
EU generic manufacturers meeting , 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
School going children-scheduling of when to give medicines?
UNICEF
EU generic manufacturers meeting , Copenhagen, Denmark

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

10. EU generic manufacturers meeting 261109, Copenhagen, Denmark
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”
UNICEF
EU generic manufacturers meeting , Copenhagen, Denmark

11. EU generic manufacturers meeting 261109, Copenhagen, Denmark
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
UNICEF
EU generic manufacturers meeting , 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
If scored
Must break easily without use of additional devices
Validated for equal distribution of actives within each split portion
Stability of split tablets- portions that have to be stored for use later
UNICEF
EU generic manufacturers meeting , 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 medicines
Suitable formulations needed for
Anti-infectives
Micronutrients, vitamins & minerals
Antiepileptics
Cardiovascular medicines
ACT antimalarials
HIV & TB Medicines
UNICEF
EU generic manufacturers meeting , Copenhagen, Denmark

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

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