[Toward acceleration of drug development with proteomic and metabolomic biomarkers]

Biomarkers, reflecting disease states or predicting/assessing drug efficacy or adverse reactions, are expected to play pivotal roles in effective drug development and promoting proper usage of drugs. To accelerate biomarker identification and usage, administrative guidance can direct to design appropriate exploration, validation and utilization studies and show examination procedures. However, very limited number of guidance or its draft were released from Japanese, US and European regulatory authorities so far. From 2012, we have been conducting proteomic and metabolomic studies using blood and urine samples from human and rat, in order to establish draft guidance for sampling/storage of these biofluid and for extrapolation of biomarker candidates from animals in the non-clinical to humans in the clinical studies. The results are still partial and the rest of the analysis is ongoing. However, we developed sensitive proteomic system for urine and found large inter-sex differences in the proteomic profiles of rat. In addition, matrix-, sex- and generation-differences were also observed in the metabolite levels in human blood, some of which showed over 2-fold differences. We continue this regulatory science studies for contribution to accelerated novel biomarker findings and its usage by generation of the draft guidance.