(42am) Crystallization Process Development of a Chemically Modified Small Protein

Crystallization of proteins has been proven as a processing step for protein purification in addition to the conventional application of Protein structure analysis. Crystallization increases the advantage provided to the formulation for solid crystalline protein compared to protein in solution. A crystalline drug substance for a chemically modified small protein process was developed to encompass the two advantages of crystallization - stability and purity.  The challenges encountered during the development were due to the high solubility of the molecule, shear sensitivity, and lack of a representative scale down model. Through cross functional collaboration, an adequate scale down model was developed that led to crystallization process conditions and investigation into multiple factors found to affect crystal morphology, kinetics, and yield. Use of PAT tools for reaction monitoring such as FBRM and PVM aided in process understanding and in setting of scale-up parameters. In conclusion, a crystallization process has the potential to be included in downstream processing as a low cost and high efficiency step.