ChBE Seminar Series: Adil Mohammad, Division of Product Quality Research, U.S. FDA
Title: Development of a Continuous Crystallization Process for Carbamazepine and Monitoring Using Process Analytical Technology Tools
Speaker: Adil Mohammad, Staff Fellow, Division of Product Quality Research, U.S. Food and Drug Administration, CDER
Batch manufacturing of pharmaceuticals processes materials step-by-step until completion and is still the dominant mode of manufacturing unlike other industries. FDA is taking proactive steps to facilitate innovation and modernization of pharmaceutical development and manufacturing to improve manufacturing efficiency, robustness, and assurance of drug quality. CDER’s emerging technology program therefore promotes continuous manufacturing (CM) as innovative tool to support this cause. One important step in the drug substance manufacturing is crystallization, which is the final purification and isolation step. Crystallization can have significant impact on the physiochemical properties of drug substance such as particle size, shape, purity and polymorphism. With Agency and industry trying to implement and adopt CM, research efforts on continuous crystallization have increased significantly in the past few years. This presentation discuss a case study on the risk factors involved in setting up continuous crystallization system of a model compound, carbamazepine (CBZ). A lab-scale, automated two-stage mixed suspension mixed product removal (MSMPR) platform for CBZ was engineered and set up to monitor crystallization process. The system was integrated with online process analytical technology (PAT) tools such as Raman spectroscopy (to monitor the polymorph and CBZ concentration) and focused beam reflectance microscopy (FBRM, to monitor particle size). The MSMPR system was also designed with feedback/feedforward controls to achieve constant levels in crystallizers, a centralized automation program coded in LabVIEW. The performance, process dynamics and control of the continuous crystallization process capable of detecting changes will be discussed. The overall goal of this research is to generate in-house data and knowledge pool for the Agency which help and facilitate regulatory assessment and approvals of drug substance and drug products related to CM technology.