(322f) Continuous Crystallization Using Mixed Suspension Mixed Product Removal (MSMPR) Crystallizers and Oscillatory Baffled Crystallizers (OBC)

Emerging technologies, such as continuous manufacturing (CM), have been trending in the pharmaceutical industry in the past few years^1-2. Continuous crystallization is an important step to achieve an end-to-end CM process. Currently, there are two popular approaches for continuous crystallization processes: sequential mixed suspension mixed product removal (MSMPR) crystallizers³, and plug-flow oscillatory baffled crystallizer (OBC)⁴. Combined with our experience in developing continuous crystallization processes, we will discuss our understanding and lessons learned regarding the two systems from the perspective of risk assessment, process dynamics, implementation of PAT tools/methods, and the related control strategies. *This presentation only reflects the views of the authors and should not be construed to represent FDA’s views or policies

References:

1. Lee, S. L.; O’Connor, T. F.; Yang, X.; Cruz, C. N.; Chatterjee, S.; Madurawe, R. D.; Moore, C. M. V.; Yu, L. X.; Woodcock, J., Modernizing Pharmaceutical Manufacturing: from Batch to Continuous Production. J Pharm Innov 2015, 1-9.
2. Adamo, A.; Beingessner, R. L.; Behnam, M.; Chen, J.; Jamison, T. F.; Jensen, K. F.; Monbaliu, J.-C. M.; Myerson, A. S.; Revalor, E. M.; Snead, D. R., On-demand continuous-flow production of pharmaceuticals in a compact, reconfigurable system. Science 2016, 352 (6281), 61-67.
3. Acevedo, D.; Peña, R.; Yang, Y.; Barton, A.; Firth, P.; Nagy, Z. K., Evaluation of mixed suspension mixed product removal crystallization processes coupled with a continuous filtration system. Chemical Engineering and Processing: Process Intensification 2016, 108, 212-219.
4. Lawson, S.; Steele, G.; Shering, P.; Zhao, L.; Laird, I.; Ni, X. W., Continuous Crystallization of Pharmaceuticals Using a Continuous Oscillatory Baffled Crystallizer. Org. Proc. Res. Devel. 2009, 13, 1357-1363.