UK drug discovery and development is increasingly being shaped through a complex interaction of research, policy and practice. However, our understanding of this innovation system is partially due to the dearth of systems-level empirical studies and to simplistic conceptual approaches. This study uses a Triple Helix systems approach to illustrate how a novel database of Research Excellence Framework 2014 impact case studies may be used both to advance empirical understanding of UK drug discovery and development and for theory development. The authors refine the Triple Helix system by identifying relationships between its three components (academia, government and industry) and various social actors. The paper also make two contributions to practice, concerning the relative unimportance for impact generation of geographical clusters relative to strategic alliances, network linkages and knowledge spillovers, and the strong bias towards national and Anglo-American academic--practitioner linkages with few or no links to emerging knowledge economies.