PROJECT SUMMARY The Critical Path Institute (C-Path) was established in 2005 as a public-private partnership with FDA under the auspices of the Agency’s Critical Path Initiative, with a mission to be a catalyst in the development of new approaches to advance medical innovation and regulatory science. This mission is realized by leading teams of stakeholders from industry, government, academia, and patient advocacy organizations that share data, knowledge, and expertise, resulting in sound, consensus-based regulatory science solutions and advances to address unmet needs in drug development. Developing such solutions and advances require C-Path competencies in data management and science, quantitative modeling and analytics, development of clinical outcome assessments (COAs) and biomarkers as well as knowledge of the appropriate regulatory pathways for the review and potential endorsement of such solutions. C-Path has established core competencies in these areas that allow our collaborations to achieve meaningful impact on unmet drug development needs. C-Path’s core competencies also function to further their respective fields (e.g., refine data management practices, develop new analytic and modeling techniques, develop specific COAs, or train future regulatory scientists) and to create a neutral collaborative environment for experts and stakeholders to address specific needs in drug development. Over the past 5 years, C-Path has launched new consortia and two extensive programs in rare and orphan diseases, as well as supporting the qualification of COAs, the fit-for-purpose endorsement of disease progression models and clinical trial simulation tools, the generation of new data standards and databases, the creation of a new data and analytics platform, and educational initiatives that advance regulatory science and model informed drug development. These accomplishments can decrease the time, resources, and number of patients needed to develop and approve medical products and thus de-risk and expedite the medical product development process. This proposal aims to maintain and expand on C- Path’s core competencies and continue to support the FDA to modernize drug development and potentially support future projects in real-world evidence/real-world data, artificial intelligence and machine learning, digital health technologies, and to establish new consortia in areas of critical unmet need. Altogether, these efforts support the FDA in its mission to promote public health and ensure the safety, efficacy, and efficiency of medical product development.