Development of an Integrated Mathematical Model for Comparative Characterization of Complex Molecule

复杂分子比较表征综合数学模型的开发

• 批准号: 8882897
• 负责人: Marcus Laird Forrest
• 金额: $ 60万
• 依托单位: UNIVERSITY OF KANSAS LAWRENCE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-10 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8882897
• 关键词: Development; Integrated; Mathematical; Model; Comparative

Summary The overall goal of this proposal is to develop integrated mathematical algorithms to assess the similarity of analytical characterization data comparing multiple batches of two different complex molecules. First, multiple batches of a biopolymer-drug conjugate (hyaluronic acid-cisplatin) and a pharmaceutically relevant glycoprotein (IgG1-Fc) will be prepared. For the IgG1-Fc molecules, we utilize technology to produce six different, well- defined glycoforms, which can be characterized individually and then mixed together in different ratios resulting in varying levels of binding activity to various Fc receptors for subsequent analytical comparability testing. Second, the biological, chemical and physical properties of both complex molecules will be monitored using a wide range of analytical technologies, including during accelerated stability testing to elucidate correlations between physicochemical changes and biological activity. Third, we will then employ a combination of currently available data visualization tools used our laboratories, along with novel mathematical algorithms to be developed in this proposal, to integrate the structural and biological data to provide an overall assessment of their critical quality attributes (CQAs). Finally, the ability of the mathematical algorithm(s) to assess the overall similarity of multiple lots of each complex biopharmaceutical will be validated using appropriate positive and negative controls, and therefore, provide an overall assessment of analytical comparability.

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