Transcript Wish list for Paediatric formulations Young Children

Wish list for design of Paediatric formulations
Young Children
• Syrups reserve for < 10-15kg
– No need refrigeration
– Stability data for longstorage times, at high temps and high
humidity
– Small volumes
– Package storage info for 28-35 days
– According to:
• 2-3kg bands in younger children (can be 5kg in older kids)
– Provide dose administrator with packaging:
• ? Re-usable syringe
• ? Use bottle-tops;? Teaspoons – less exact
– Taste dependent on culture, but aim to cover bad tastes
– If possible not glass bottles!!
– If possible think of alternatives to syrups
• sachets; granulates; dispersable tablets
Wish list for Paediatric formulations
Older Children
• Solid formulations >10-15kg
– Crushable tablets may be cheapest;
• granulates; dispersable tablets might be better
– Same issues storage, packaging 28-35 days; 5kg bands;
taste;
– Use of smaller adult tablets for single drugs, and scored
tablets
Single Drug priorities
• Scaling down dose of and scoring adult tablets:
– Only need chemistry (but may need expensive stability
data) if you have comparable PK data across ages;
probably don’t need bio-equivalence data for
regulatory:
• 3TC; ZDV; D4T; ABC; NVP; EFV
• Already have for NFV tablets
• Ask companies to re-look at formulations used
during the development process
• New scaled down tablets of drugs not yet available
for children:
– TDF lower dose tablets e.g. re-use 75mg tablet and/or
score tablets
FDCs - Principles
• If need different ratios of drugs compared to adult
FDC, will need separate bio-equivalence studies to
be done:
– In healthy adults (generally not in children)
– Cross-over studies with standard single drugs
– (for FDA, need to be US approved single drugs)
• Some drugs cannot be put together clinically or
chemically?:
– ZDV/3TC/TDF – always need ZDV bid and TDF od
– Tablets or Powders
– PIs hard to combine with anything except themselves !!
(Soft gels/liquids hard to combine with other drugs)
• Packaging needs attention
• Stability and dissolution data will be needed
Pre – FDCs
Co-packaging of single drugs
• Attention to packaging – must be OK for all
the drugs – or else need to go back and do
12 month stability studies
• Possibilities egs:
– ZDV, 3TC, EFV
– ddI, 3TC, EFV
2-drugs FDC priorities
• Those already available for adults and PK
data available for children:
– d4T/3TC
– ZDC/3TC
– 3TC/ABC
• Full data not yet available for children:
– FTC/TDF
(nb these are within the same companies)
3-drugs FDC priorities
• Immediate: Those already available for
adults:
– d4T/3TC/NVP
– ZDC/3TC/NVP
– ZDV/3TC/ABC
• FTC/TNF/EFV (planned for adults; plan for
children at the same time)
(nb ? IPR as across 2 companies)
Learn from other areas – Anti-TB
and Antimalarial drugs
• Do paediatric PK studies using adult formulations
(registered) where there are no PK in children:
– Show that there is a need for scored and smaller tablets
– Then use private-public partnership to develop
paediatric formulation (granulates for FDCs for
malaria)
– Need to advocate for PK paediatric studies in the field
on the target population!
Recommendations and Ways
Forward I
• Advocacy (press releases, statements, etc) about
need for treatment and paediatric formulations for
children (WHO, UNICEF, MSF, other stakeholders)
• WHO convenes a meeting to bring national and
other relevant regulators (wide representation
from relevant areas) together to agree minimum
drug product specific criteria acceptable for
paediatric single drugs and FDCs
Recommendations and Ways Forward
II
• Expression of interest from organisations who will buy
drugs (UNICEF, Global Fund, PEPFAR, Clinton, Gates)
(Need estimates of numbers)
– Advocacy for alternative systems for drug development eg
PPPs (models are MMV; GATB; FIND; GAVI; DNDI) –
who?? ? GATES ?UNICEF; Rockefeller; TDR)
– Further engage Pharmaceutical companies
• WHO 3 X 5 estimates of numbers of children needing
and will be on treatment over specific time-frames
Recommendations and Ways
Forward III
• Make EOI for paediatric formulations a priority HIV/AIDS department at WHO (3x5)
• Capacity development for companies to fulfil
dossiers for pre-qualification (WHO EDM)
• Strengthen National Regulatory authorities to enable
fast-tracking through pre-qualificiation (EDM)
• Based on drug priorities, approach and start dialogue
with relevant companies (everyone, WHO 3X5)