Setpoint Determination Method for Pharmaceutical Continuous Manufacturing: Proactive-RTD-based Approach *

Pasindu Herath Pathirannahalage, Ayumu Nabetani, Shota Kato, Kanta Sato, Keita Yaginuma, Shuichi Tanabe, Manabu Kano

Abstract: The pharmaceutical industry is facing a transition from batch manufacturing to continuous manufacturing in order to overcome the inefficiencies of batch manufacturing. However, quality assurance of in-process materials during pharmaceutical continuous manufacturing remains an arduous task. Product quality of pharmaceuticals is assured by sustaining critical material attributes (CMAs) within a region known as the design space (DS). This study proposes a method to determine the setpoints of CMAs within the DS for a manufacturing line of more than two processes, each with multiple CMAs. The proposed method is based on the distribution of time that in-process materials remain in each process. We conducted control simulations with three different process time constants and compared the performance of four methods: our proposed method and three other methods. The results demonstrated that our method excels in sustaining the CMAs within the DS.