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 261109, Copenhagen, Denmark

Presentation outline

UNICEF

EU generic manufacturers meeting 261109, Copenhagen, Denmark

Causes of death in under 5s

10 3 3
injuries

3 8

AIDS measles malaria

26

11

others diarrhoeal diseases pneumonia other neonatal causes

17 19
UNICEF

neonatal severe infections

World Health Statistics 2007

http://www.who.int/child_adolescent_health/data/child/en/index.html EU generic manufacturers meeting 261109, Copenhagen, Denmark

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 261109, Copenhagen, Denmark

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
UNICEF EU generic manufacturers meeting 261109, Copenhagen, Denmark

Solutions?

UNICEF

EU generic manufacturers meeting 261109, Copenhagen, Denmark

Current solution: , , 1/8 tablets

UNICEF

EU generic manufacturers meeting 261109, Copenhagen, Denmark

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

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?)

Difficult to follow Instructions

Dissolve tablet water, then administer by dropper, oral syringe (not provided) or drink directly

To be swallowed whole- not to be chewed

UNICEF EU generic manufacturers meeting 261109, Copenhagen, Denmark

Challenges for HIV+ children

Child: too many bottles
Adult

UNICEF

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 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 261109, Copenhagen, Denmark

Ideal paediatric medicine

1. Route of administration: Oral most frequently used 2. Dosage form? SODF** Liquids?
1. 2. 3. 4. 5. Sufficient bioavailability Dose uniformity Non toxic excipients Acceptable organoleptic properties: Taste Dosing aids

3. Ease of administration for both parent and child 4. Clear product information/instructions 5. Cost effective 6. Does not require cold storage 7. Minimum steps of manipulation before use ** Chewable, fast melts, effervescent, granules, sprinkles, soluble tablets,,
sublingual, etc
UNICEF EU generic manufacturers meeting 261109, Copenhagen, Denmark

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

http://www.unicef.org/supply/index_47129.html.
UNICEF EU generic manufacturers meeting 261109, Copenhagen, Denmark

Coated particles in tablet form for preparing suspension

Courtesy of J. Breitkreutz
UNICEF EU generic manufacturers meeting 261109, Copenhagen, Denmark

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 261109, Copenhagen, Denmark

Thank you

UNICEF

EU generic manufacturers meeting 261109, Copenhagen, Denmark