Technical Summary

Excipents are chemicals added to medicines to improve their quality. 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 microlitre) including dry blood spot methods and estimates of excipient exposures based on only 2-4 samples per baby. Hypothesis 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.|Hypothesis 2: small volume blood samples can be used to generate models of systemic excipient exposure. Our consortium comprises researchers from Estonia, France and the UK with extensive experience in all aspects of the study. We will develop a platform of techniques to assess excipient exposure including: a 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. This work will lead to recommendations for the European Medicines Agency and other stakeholders about assessment of excipient exposure and underpin future work to relate exposures to outcomes.|

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