A plant-wide dynamic model of a continuous pharmaceutical process

The pharmaceutical industry has historically benefited from high profit margins for their products, and over the years limited efforts have been made to change the main manufacturing concept from batch into continuous. However, over the last decade, as a result of an increased demand for more efficient and cost-effective processes, interest has grown in the application of continuous manufacturing to address economical and technical issues in the pharmaceutical field. This option is becoming more viable particularly with the implementation of new process analytical technology (PAT). In this paper, we present a plant-wide mathematical model inspired by a recently developed continuous pharmaceutical pilot plant. This model is first used to simulate a basecase which shows typical limitations in achieving simultaneously high productivity and quality. The main critical quality attribute considered is the purity of the final product. To alleviate the basecase limitations and improve the pilot plant performance, the effects of several design parameters are investigated and the most critical are identified. In addition, alternative start-up scenarios To whom correspondence should be addressed 1 are considered to improve the transient performance of the pilot plant, particularly time to steady state. The environmental footprint of the pilot plant is evaluated and shown to be low. Keywords Continuous pharmaceutical manufacturing, Plant-wide dynamic model, Computer aided process design, Start-up, Recycling.