Development of bio-based production process : process synthesis, design and simulation

In this work, an end to end bio-pharmaceutical production process of the API lovastatin is developed through a systematic process synthesis and design approach, and then simulated. The developed simulation is intended to be used as benchmark process model as it captures the generic process dynamics of a bio-pharmaceutical process, and as such it is well-suited to use as a test problem to evaluate different processing scenarios in continuous and semi continuous fermentation processes. Bio-pharmaceutical manufacturing is a highly regulated field, where the regulations together with economics dictate that the process for production of an active pharmaceutical ingredient (API), which is generally synthesized in lab scale for clinical trials, must be quickly scaled up to full scale manufacturing once approval of the drug is granted. Due to strict time constraints dictated by patent expiry, nowadays interest is shifted on process development and integration rather than conceive new purification strategies, which results to be time consuming and may require long and costly trial and error stage before purification is optimized. As such the development of a robust benchmark purification strategy relying on few unit operations represents a new challenge . In this work the author proposes a benchmark process model so designed that the process can be operated as an end to end model or as a separate downstream process, alongside the process can be used to develop strategies for control of continuous manufacturing processes which are becoming increasingly attractive.

La seguente tesi ha come oggetto di studio lo sviluppo di un processo di "benchmark" per applicazioni in campo bio-farmaceutico. Il progetto è diviso in tre parti.I primi tre capitoli trattano la sintesi e il design del processo di "upstream", la parte centrale riguarda la sintesi del processo di "downstream", ovvero quel tratto del processo dedicato al recupero e purifica della molecola farmaceutica scelta come caso di studio; mentre l'ultima sezione si concentra sulla simulazione in anello aperto dell'intero processo.