BIOT 228 |
| The degradation of therapeutic proteins due to inappropriate process or storage conditions is a major issue in biopharmaceuticals manufacturing both in terms of costs and safety. Today, we classically test the stability of a protein by time- and product-consuming accelerated degradation studies. While this type of experiments usually takes weeks, information about the stability of a protein in terms of aggregation can be obtained in few minutes by directly measuring the protein-protein self-interactions in solution. The magnitude of these interactions is captured in a thermodynamic parameter termed the second osmotic virial coefficient (B22). In this study, Self-Interaction Chromatography (SIC) was used to rapidly measure the level of B22 of purification process intermediates and drug substance formulations. This work shows that monoclonal antibodies or Fc-fusion proteins are less prone to aggregation when the formulation conditions induce strong repulsive self-interactions (B22 > 1.0*10-4 [mol ml/g2]). Industrial applications and case studies of this method will be presented. Miniaturization and high throughput format of the method will also be discussed. |
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Biophysical and Biomolecular Symposium: Protein Aggregation
3:00 PM-5:20 PM, Wednesday, August 22, 2007 BCEC -- 108, Oral
Division of Biochemical Technology |