The trends in time, cost and success rate metrics for the R&D of new biopharmaceuticals indicate that the current paradigm is unsustainable. While there are factors both upstream and downstream on the R&D continuum that have given rise to the productivity shortfall, the most fundamental limitations remain entrenched within the process of development itself. The Tufts Center for the Study of Drug Development (Tufts CSDD) has undertaken several projects in recent years that have surveyed the biopharmaceutical and service provider industry, examined the extant literature, and analyzed data from publicly available and commercial databases to identify consensus problems and to propose solutions, or at least the starting points, for moving from challenge to change.