Project summaryReliable manufacturing of products capable of consistent performance requires the understanding of complexinteracting phenomena occurring at different scales from the molecular to the macro scale. Moreover, effectiveand reliable manufacturing requires understanding how the sequential steps used to make the product interactwith one another and contribute to the performance of the finished product. This can be a daunting task, sincethe manufacturing process can be affected by the properties of multiple raw materials and their blends, as wellas environmental variables and human error and consist of a number of interacting processing steps. Thus,manufacturing processes are rarely optimized, and often lack robustness and are prone to unexpected failures.At present, these problems in the pharmaceutical industry are addressed largely ad hoc, relying heavily onheuristics. Fortunately, the industry as well as the Food and Drug Administration (FDA) have recognized theneed for modernizing pharmaceutical manufacturing and the FDA has launched an initiative for enhancingprocess understanding through Quality by Design (QbD) and Process Analytical Technology (PAT) tools. Themajor goals of these efforts include the development of scientific mechanistic understanding of a wide range ofprocesses; harmonization of processes and equipment; development of technologies to perform onlinemeasurements of critical material properties during processing; performance of real-time control andoptimization; minimization of the need for empirical experimentation and evaluation of process design space.Predictive models are extremely useful tools for achieving these goals. A predictive model can be used todesign, trouble shoot, and optimize a process, and assess and mitigate risks associated with different types ofperturbations, whether due to changes in material properties, process variability, or human error. Modeling ofthe tablet manufacturing process requires a comprehensive understanding of the physical phenomenaunderlying the correlation between the properties of the starting particulates and the mechanical characteristicsof the end product. This proposal will focus on developing this framework. In particular the following tasks havebeen identified: (a) to develop flowsheet modeling tools for continuous pharmaceutical manufacturing of solidbased drug products; (b) to develop and integrate within the overall framework the sensitivity analysis toolsrequired to perform systematic risk assessment and failure mode analysis needed to determine the robustnessof a process. In this phase we will also demonstrate the use of the flowsheet simulation tools in thedevelopment of efficient control strategies; and (c) to validate the models and analysis tools using theexperimental facility and the data in our pilot plant and from our industrial partners.The ultimate target is to deliver to FDA a generic modeling tool that can be used to simulate, monitor, controland optimize pharmaceutical manufacturing processes for solid based drug products. We propose a closecollaboration with the agency so that the developed tools meet their expectations and maximize their usability.
|Effective start/end date||9/10/14 → 8/31/17|
- Food and Drug Administration (FDA)