(39c) The Impact of Modeling in Drug Product and Process Development

In most large pharmaceutical companies, the commercial drug product and process development cycle begins in earnest after the first dose has been administered to humans and ends when the manufacturing process has been developed, scaled up, and transferred to the intended manufacturing site. Before First Human Dose (FHD), the goal of development is to get the Active Pharmaceutical Ingredient (API) into the blood stream of a healthy volunteer. After successful FHD, the goals change, and a commercially viable manufacturing process must be identified to reliably produce large quantities of stable drug product at a reasonable cost. The input to the development engine is the API, usually as a white crystalline powder. The output is knowledge: a recipe for robust manufacturing of tablets, capsules, or other drug products. Formulation scientists and process engineers who develop this recipe must reduce the enormous design space of possible materials and unit operations into a single recommended path forward. It is in these decisions that a judicious use of modeling and scientific planning can frequently reap significant rewards.  In this work, a review of relevant modeling approaches is provided. Those areas of significant impact as well as areas of significant need are highlighted.