Systematic retrofitting methodology for pharmaceutical drug purification processes

• A method for retrofitting pharmaceutical drug purification processes is proposed.
• The method includes a decision-tree diagram to support creation of the process models.
• Path-flow decomposition plays an essential role in modeling pharmaceutical batch processes.
• The methodology is applied to an industrial case study to prove its effectiveness.
• Quality requirements of pharmaceutics need to be well reflected in the optimization problem.

A systematic retrofitting methodology supported by real data implementation was developed to facilitate the optimization of pharmaceutical drug purification processes. The methodology consists of five tasks: (I) understand the plant through measurements, (II) create a process model, (III) adapt the model for optimization, (IV) optimize the process model, and (V) interpret the outcome of the task. A novelty of this methodology is the use of path-flow decomposition as a tool to provide a visual representation of the process, thus facilitating its understanding and the creation of the process model. Furthermore, a decision-tree diagram furnishes detailed and specific support during the creation of the process model, in particular for a dissolution–filtration–crystallization process. Identification of constraints and optimization variables ensure the applicability of the methodology to pharmaceutics. Incorporation of measured process data improves the reliability of the methodology, making it applicable in real case studies. The methodology was applied to an industrial case study.