The Bethesda Hospitals' Emergency Preparedness Partnership identified a need to design training systems for hospital emergency management scenarios. As part of this partnership, the National Library of Medicine was challenged to develop an engaging, learner-centered simulation to specifically address hospital procedures for highly infectious diseases (HIDs) for multiple healthcare roles. A cognitive task analysis was used to collect the rich psychomotor, procedural, and cognitive data necessary for the design of a serious game for handling HIDs. Based on that data, a proof of concept prototype was developed in Second Life. That success has led to continued development. In this paper, we discuss the use of a novel Agile ISD process used to develop a new prototype using Unity 3d as the platform. An agile process was explicitly followed for this project to accommodate the limited budget that had abundant project visions. It was anticipated at the outset that the project would likely require continuous project re-scoping and refinement of product requirements that would need to be addressed smartly and efficiently. Furthermore, questions about fidelity in terms of visual representation as well as instructional integrity would still need to be addressed simultaneously. The project was conducted within a flexible contract environment that accommodated the anticipated re-scoping and refining during development. An overarching vision statement helped keep the product development moving forward with evolving requirements. The agile sprint process was invaluable for iterative reviews throughout the development process which afforded changes and redirection. However, usability testing revealed a significant change that was not noted as part of the iterative review process. This paper will briefly describe the Agile ISD process, show how it was applied to develop medical training on doffing personal protective equipment, share lessons learned, and briefly discuss flexible contract environments.