284173 Feed-Forward Dynamic Control of an API Crystallization Enabled Through PAT

Tuesday, October 30, 2012: 2:10 PM
Crawford West (Westin )
Shane T. Grosser, Chemical Process Development and Commercialization, Merck & Co., Inc., Rahway, NJ, George Zhou, Analytical Development and Commercialization, Merck & Co., Inc., Rahway, NJ and Paul Fernandez, Chemical Process Development and Commerciliazation, Merck & Co., Inc., Rahway, NJ

The work presented here focuses on the development and at-scale implementation of a process for the final crystallization of and API that simultaneously provides operational flexibility and sufficient process robustness inline with QbD filing strategies. Additionally, much of the process centers on the use of PAT methodologies for both rapid and robust process development, and at-scale cycle time optimization. Particular challenges of this process stem from variability in the incoming solution composition and it's impact on crystallization performance including the strong dependence of final API PSD on the optimal seed temperature. To accommodate solution variability, we have developed a mechanism by which the optimal seed temperature is determined in real-time using dynamic feed-forward process control, facilitated through NIR spectroscopy. Additionally, we will discuss the use of FTIR spectroscopy in the lab-scale development of the feed-forward control model including the automated collection of solubility data crucial to accurate seed temperature prediction. Lastly, a brief discussion of the at-scale implementation and performance of the process will also be discussed.

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See more of this Session: PAT for Crystallization Development and Manufacturing
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