Erythropoietin (EPO) is known to aggregate under heat stress, which prevents storage of liquid compositions at ambient temperature. The key challenge of this study was to demonstrate that the application of the ArestatT tools can reduce significantly aggregation of EPO at an elevated temperature, compared with a marketed liquid formulation
A liquid EPO product was reformulated and the key parameters, such as pH, osmolality and the nature of the surfactant were kept unchanged in the new formulation. The critical change was the nature of the buffering species, which were selected to ensure minimal proton exchange between the protein molecule and excipients, and to minimise hydrophobic interactions. Incubation of the currently marketed EPO formulation at 40?C for 24 weeks resulted in considerable (>50%) high molecular weight species formation (HMWS, measured by size-exclusion chromatography). In contrast, the reformulated EPO, using the ArestatT alternative buffering species, showed virtually no aggregation following the same treatment.
The rate of aggregation of EPO (82 ?g/ml) at 40&deh;C in ArestatT formulation compared with the control.
