Domain ontologies that are created without reference to, or not based upon an upper ontology will undermine future ontology development both within and among domains. Applied ontologies based on sound design principles and theoretical foundations provide advantages compared to ontologies neglecting ontological analysis. In this paper we demonstrate the economic pay-offs of applying these principles to the development of ontology-driven systems. We focus on three topics: reuse of pre-existing resources, modularization of ontologies into separable and reusable components, and harmonization of ontologies and knowledge management systems and ex ante harmonization. We show, using cases from the medical and pharmaceutical domains, how rigorous and methodical use of an upper ontology built upon realist principles better enables parametric adaptation to future objects, cross-ontology interoperability, and accommodates objects of both scientific and social importance. More importantly, the application of those principles leads to a streamed-lined development process of ontologies and ontology-driven systems.