(355f) Crystallization Scale-up with Process Analytical Technologies – Ensuring Success From the R&D Lab to the Manufacturing Plant

Crystallization is one of the most common separation and purification techniques in the fine chemical and bio-pharmaceutical industries. Once considered an art, crystallization has developed into a sophisticated science rooted in understanding and control of particle nucleation, growth, agglomeration, and breakage. A crystallization process must take into account the complex interaction of particles with control parameters and process equipment. Often the crux of crystallization process development is the scale-up from the lab to manufacturing plant. Problems such as batch-to-batch inconsistencies in the crystals size distribution and the crystal purity profile can have a significant impact on product quality and downstream process unit operations including filtration, drying, milling, and product formulation. With the advent of process analytical technology such as FBRM, PVM, FTIR, and Raman one can quickly measure solution and particle phase behavior in-situ without pulling samples. This paper reviews the simple application of in-situ process analytical tools to avoid problems by understanding, optimizing, and controlling a crystallization process throughout scale up.