SPaeDD-UK: Smart Paediatric Drug Development - UK  Accelerating paediatric formulation development

An open innovation R&D project -

The ambition of the Consortium was to establish an industry standard framework and suite of tools to develop safe and efficacious paediatric dosage forms.  The output and agreed tools are detailed below with links to any relevant peer-reviewed publications:

• Taste evaluation

An existing tool that was further developed as part of WS1 activities was a Brief Access Taste Aversion (BATA) test that was verified as part of the activities within the consortium.  The tool essentially allows the mapping of taste from a rat scale (IC) to a human scale (EC) with respect to bitterness.  A key correlation is the concentration of the API at which the reduction of licks is decreased by half to give an IC50 vs EC50 correlation.  For further information, please click here.

• Prediction of human exposure in children

A series of paediatric biorelevant media and dissolution conditions have been developed which describe differences in the gastrointestinal environment between children and adults. These differences have been shown to translate into alterations in the solubility of APIs and dissolution rates of formulations. In addition, a methodology by which the age-appropriate biorelevant solubility of APIs and the age-appropriate dissolution profiles of formulations are incorporated into adult and paediatric PBPK models to predict pharmacokinetics has also been developed.  For further information, please click here

• Taste Masking and technology platforms for paediatric medicines

A technology review was performed to develop a database of taste masking approaches and their properties. A review of the published literature, patent landscape, intellectual property databases, supplier product portfolios, and internal industry experience was performed and a database of the information developed.The technologies or approaches were broadly categorised according to their design or formulation concept.  In order to enable the taste masking technology review, a generic Quality Target Product Profile (QTPP) for paediatrics which was developed by the consortium based on industrial and regulatory expectations. This is summarised here and puts forward suggested key critical quality attributes and other key considerations for any paediatric product being considered for development.

• Acceptability testing

A tool developed as part of the literature research performed as part of WS4 activities was an algorithm that shows where evidence is available to demonstrate acceptability of a range of formulations over different paediatric age ranges. This can be used as a basis for selecting the size and volume of particular dosage forms for paediatric usage based on age during product development.  For further information, please click here

An additional tool developed as part of the research activities in WS4 was a pragmatic, reliable acceptability assessment questionnaire from a field based ‘ACCEPT’ study. The tool recommended is the 5-point hedonic scale (see below) with a mean hedonic score of ≤3 (neutral or positive face) and <60% of participants responding “no” to the question, “Did you think the medicine tasted OK?” together with a simple check that the child took the medicine as intended and did not spit out or vomit the dose.  For further information, please click here

This project focussed on creating a development pathway comprising a tool box of testing methodologies (in-vitro, in-vivo and in-silico techniques) for predicting taste, drug release and human exposure in paediatric patients.  The project was co-funded by Innovate UK, the UK's innovation agency.

These tools could be used to help select the most appropriate formulations to support the development and commercialisation of paediatric pharmaceutical products. It is anticipated that the outputs of the project will be leveraged to provide a commercially available service to appropriately evaluate and help accelerate development of paediatric dosage forms.