Process analysis of end-to-end continuous pharmaceutical manufacturing using PharmaPy

As pharmaceutical manufacturing is transitioning from traditional batch to continuous manufacturing (CM), there is a lack of tools for CM design and development, which can integrate drug substance and drug product unit operations for overall evaluation. Recently, a Python-based PharmaPy framework was proposed to advance the design, simulation, and analysis of continuous pharmaceutical processes. However, the initial library of models only addressed upstream drug substance processing. In this work, new capabilities, including drug product unit operations such as feeder, blender, and tablet press, have been added to the PharmaPy framework, enabling end-to-end study and optimizing the effects of material properties and process conditions on solid oral dosage products. The platform supports computational efficiency and model accuracy by allowing the development of different mechanistic and semi-mechanistic models. Sensitivity analysis is performed on the integrated end-to-end simulator to identify critical input variables influencing product quality and control strategies. The analysis lowers the complexity of the model by ranking significant input variables. Finally, feasibility studies are conducted on extracted influential input variables to characterize the process design space and achieve desirable output. The enhanced PharmaPy package can now support decision-making from early research and development stages through manufacturing.