286640 Apply PAT-Enabled Platform to Realize the QbD Control Strategy for Crystallization Processes

Tuesday, October 30, 2012: 1:45 PM
Crawford West (Westin )
George Zhou1, Aaron Moment2, Shane T. Grosser3, Paul Fernandez2, Luke Schenck4 and John Higgins5, (1)Analytical Development and Commercialization, Merck & Co., Inc., Rahway, NJ, (2)Chemical Process Development and Commerciliazation, Merck & Co., Inc., Rahway, NJ, (3)Chemical Process Development and Commercialization, Merck & Co., Inc., Rahway, NJ, (4)Chemical Process Development and Commercialization, Merck & Co, Inc., Rahway, NJ, (5)Process Analytical Technologies, Merck and Company, Inc., West Point, PA

 It is critical to achieve the desired crystal form for an active pharmaceutical ingredient (API) because polymorphic behavior may affect its chemical stability, solubility, morphology, density and bioavailability.  The automated API platform enabled by process analytical technologies (PAT) provides the flexibility for crystallization process development.  It can significantly enhance our capability to explore the design space of crystallization processes and improve the ability in maintaining the crystallization performance under different or unexpected scenarios of disturbances and scale-up variations.  In this presentation, this enhancement of capability will be illustrated through several case studies.  For example, risk assessment and corresponding DoE studies on crystallization and PSD indicate that the final PSD of a high volume API strongly depends on the seeding-point temperature which in turn relies on the solution composition.  Therefore, by successfully utilizing this PAT-enabled automated API platform to map out the solubility for a through-process stream across the multi-dimensional solvent composition space as a function of temperature, control space of the crystallization process can be defined  It has enabled a QbD control strategy which incorporates the accurate measurement of batch composition in real-time for a robust process that reduces cycle time, and increases yield and productivity as well as realizes QbD benefits - greater process stability, process portability, and process flexibility.

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See more of this Session: PAT for Crystallization Development and Manufacturing
See more of this Group/Topical: Separations Division