Excipients facilitate formulation design and perform a wide range of functions to obtain desired properties for the finished drug product. Sporadic reports indicate that some may be toxic for neonates and lead to significant morbidity or death. However, there is insufficient information about the risks generated by excipient exposure because systematic surveys have not been done and studies on babies have not been ethical in the past. Recent advances allow determination of excipient levels in very small blood volumes (50 microliter) including dry blood spot methods and estimates of excipient exposure based on only 2 – 4 samples per baby. We have set up the European Study of Neonatal Excipient Exposure to meet the needs for data. We will address the following hypotheses: 1) information about exposures across the EU will promote reduction of neonatal exposure to excipients by highlighting opportunities for product substitution and priorities for reformulation; 2) small volume blood samples can be used to generate models of systemic excipient exposure. A platform of techniques is currently under development to assess excipient exposure including: a pan-European questionnaire and point prevalence study of neonatal excipient exposure; systematic reviews of relevant literature; dried blood spot assays for high impact excipients; a cohort study to construct population excipient kinetic models (EK, analogous to active drug pharmacokinetics or PK) for high impact excipients.

We will liaise strongly with the European Paediatric Formulations Initiative.

A mixed-methods approach will provide data from multiple perspectives. The survey and systematic review is underway and planning for the clinical study is well advanced. This work will lead to recommendations for the European Medicines Agency and other stakeholders about assessment of excipient exposure underpin future work to relate exposures to outcomes and provide proof-of-concept for a platform that provides systematic information about excipients.

Teaching Goals:

• the description of the aims of the project
• the risks of using excipients containing drugs in neonates
• the consequences of excipient exposure to neonates
• the role of pharmacists in formulating better medicines for neonates

Learning objectives:

After the presentation the participant should:

• understand the necessity to study the effects of excipients in neonates
• join and contribute to ESNEE project
• develop means/actions to safer formulating, compounding, and administration of medicines for neonates