Promises and partnership: FDA's Critical Path Initiative and its intersection with pharmacology: an ASPET 2011 annual meeting symposium

Abstract

The Critical Path Initiative (CPI) is a 2004 white paper of the US FDA, which fosters long-term strategies for incorporating 21st-century scientific advances into development, assessment, manufacture and use of medical products. Its ongoing implementation is paced by the outcome of numerous ad hoc, FDA-sponsored research projects and consortia in areas of major concern, some of which were discussed in this symposium. Of paramount importance is Tox21 program the aim of which is to identify novel predictive, cost-effective, mechanism-based investigational tools mainly of soft- and wet (in vitro)-ware nature firmly grounded in human biology for easily detecting xenobiotic-induced adverse reactions in humans and the environment. Additionally, the intelligent application of holistic approaches (e.g., systems biology and systems pharmacology) to the drug development process will also greatly help in predicting, avoiding and appropriately managing potential risks inherent in medical product use. Optimization of clinical investigations, another crucial objective of CPI, may be partly achieved by adopting targeted enrichment provisions (individual, pathophysiological, genomic (e.g., biomarkers)) for recruiting patients that would most likely respond to a treatment, as sought after. However, for regulatory purposes, drug development tools, such as biomarkers for demonstrating the value or the risk of a treatment, require an appropriate qualification that can be obtained following a recently released FDA guidance. In conclusion, a current major FDA commitment is the rejuvenation of drug ‘Critical Path’ platforms with the introduction of 21st-century best science tools and methods for rapidly turning ‘discoveries into medical miracles' for the benefit of people in need.

Keywords:

• Bioinformatics
• biomarker
• cheminformatics
• clinical trial enrichment
• critical path initiative
• drug development tool
• FDA
• patient report outcome
• predictive safety testing consortium
• qualification process
• safety assessment
• systems biology
• systems pharmacology
• Tox21

Acknowledgements

The author thanks H Holzgrefe and A Roach for patient reviewing and improving this text. Thanks are also extended to D Abernethy, AS Buckman, K Bruse, JM Guillon, H Kaplan, R Temple and P Zitoun for the time they dedicated to provide suggestions for the improvement of portions of this report. Particular thanks are extended to S Fitzpatrick, D Abernethy, J Woodcock and R Temple for generously providing their presentation material, in the absence of which this detailed report could not have been written. The author assumes full responsibility for the entire content of the report.