Practical Considerations for High Concentration Protein Formulations

Practical issues that arise for high concentration protein formulations can complicate manufacturing and affect injectability/device compatibility. High concentration protein formulations have an increased tendency for high solution viscosity, physical stability sensitivities (aggregation/particulation), and non-Newtonian solution behavior (shear thinning) due to high shear rates. Process unit operations can be negatively impacted by these factors, and it is critical to understand how they influence process performance. Device compatibility can be affected by changes in protein concentration and temperature that will impact product viscosity and injectability. Complete characterization of the solution physical properties (viscosity and shear thinning profile) as well as the stability profile must be understood to ensure efficient processing, delivery, and efficacy of the therapeutic product. If potential candidates with impeding viscosity values are not identified early in development, subsequent mitigation efforts to reduce viscosity likely pivot from a protein engineering approach to changes in formulation.