An intercompany perspective on practical experiences of predicting, optimizing, and analyzing high concentration biologic therapeutic formulations

To understand solubility and viscosity, companies desire predictive tools, but experience indicates that these are not reliable and experimental strategies are best. Similarly, most companies prefer accelerated and stress stability studies to in-silico or biophysical-based prediction methods to assess aggregation. In addition, optimization of primary container closure and devices are pursued to mitigate challenges associated with high viscosity of the formulation. Formulation strategies including excipient selection and application of studies at low-concentration to high-concentration formulations are reported. Finally, analytical approaches to high-concentration formulations are presented. The survey suggests that although prediction of viscosity, solubility, and long-term stability is desirable, the outcome can be inconsistent and molecule dependent. Significant experimental studies are required to confirm robust product definition as modeling at low protein concentrations will not necessarily extrapolate to high-concentration formulations.