BIOT 13 |
| The purpose of this study was to develop a high concentration rhuMAb VEGF formulation for subcutaneous (SC) delivery. A stability study was designed with 100mg/ml rhuMAb VEGF, based on rhuMAb VEGF's unique reversible self-association. The extent of self-association depends on pH, protein concentration and ionic strength. Formulations were tested over a narrow pH range to minimize aggregation. Protein stability in these formulations was evaluated at 2-8°C and –20°C storage by Size Exclusion HPLC and Ion Exchange HPLC. Due to concern of potential hydrolysis of sucrose under the lower pH conditions, a boronate affinity HPLC method was utilized to evaluate glycation on stability samples. The study shows that lower pH can help to minimize the amount of aggregate at a rhuMAb VEGF concentration of 100mg/ml. As expected, sugars helped in freeze/thaw stability and storage at –20°C. There are significant differences in aggregate content between sucrose-containing and trehalose -containing liquid formulations stored at 2-8°C, and the differences are not due to glycation.
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Biophysical and Biomolecular Symposium: Protein Stability
8:00 AM-11:10 AM, Sunday, August 19, 2007 BCEC -- 107 A/B, Oral
Division of Biochemical Technology |