Stirred batch crystallization of a therapeutic antibody fragment

Recent advances in crystalline and amorphous particulate protein formulations for controlled delivery

“…Batch crystallization conditions are frequently explored using water vapor diffusion experiments with subsequent transfer to micro-batch and to large batch crystallization [29,30]. A two or more dimensional phase diagram can be produced narrowing down the optimal conditions for crystal growth (Fig.…”

Solid-state Protein Formulations

“…X-ray diffraction data clearly demonstrated distinct Bragg reflections when rhIFN was mixed in a 12:1 mol ratio of zinc acetate, confirming that crystals had been formed: this is depicted in Figure 3B and can be compared with the amorphous halo seen in the diffraction pattern of the native protein. In another study, Hebel et al demonstrated the successful crystallization of antibody fragments (FabC225) in a stirred tank [45]. For a more Solid-state protein formulations Review detailed treatment of the crystallization of bioactive proteins, the interested reader is directed to [35].…”

“…Those technologies have been reviewed elsewhere [36] and may be applied to formulate crystalline proteins. However, manufacturing issues such as batch-to-batch reproducibility and aseptic manufacture also need to be addressed to achieve large-scale production [35,45].…”

Current Trends and Advances in Bulk Crystallization and Freeze-Drying of Biopharmaceuticals

“…Hekmat and coworkers describe the successful transfer of vapor diffusion-based crystallization to agitated batch crystallization at milliliter scale using lysozyme as a model protein [19]. The same research group also describes a stirred-tank crystallization-based approach [53] towards successful scale-up of batch crystallization conditions using lysozyme, lipase [18], and therapeutic mAbs [17,52] as model proteins. Smejkal et al describe a maximum local energy dissipation-based scale-up approach for stirred crystallization using lysozyme and Canakinumab Fab-fragment as model proteins.…”

“…Crystallization happens to be a relatively mature industrial processing technique with several applications. Several studies describe successful purification and polishing of proteins such as aprotinin [42], mAbs [17,52], and lysozyme [19,24,25] by bulk crystallography approach. 4.…”