An Integrated, Physiologically Based, Multiscale Platform to Humanise Preclinical Assessment of Fetal Drug Exposure and Toxicity During Pregnancy

Pregnancy is a unique window during which the health and wellbeing of future generations are established. To maintain optimal maternal and fetal health, many women require at least one drug during pregnancy. For most drugs, the associated risks are poorly understood because the rodent and rabbit models used during drug development do not recapitulate human physiology. My research programme aims to transform the assessment of drug safety during pregnancy by developing a platform to generate human-pregnancy-relevant safety information early in development. I will deliver this through a transdisciplinary team supported by robust scientific collaborations. First, we will develop an open access pregnancy pharmacokinetics database to qualify maternofetal pharmacokinetic models for granular prediction of drug exposure across gestation. Second, we will develop a placenta-on-chip model to characterise drug disposition for pharmacokinetic model improvement and to investigate drug-induced perturbations. Lastly, integrated analysis of multi-omics data from placenta-on-chip will be used to uncover molecular signatures of drug- induced perturbations, which will form the basis for risk assessments. This work will underpin future addition of fetal organs-on-chip to the platform to characterise drug-induced perturbations in developing fetal organs. This programme will benefit from a comprehensive portfolio of stakeholders’ engagement for early input and policy influence.