Development of Advanced Analytical Methods for the Characterization of Iron Carbohydrate Complex - Ferric Derisomaltose

开发表征碳水化合物铁复合物 - 麦芽糖铁的先进分析方法

• 批准号: 10491846
• 负责人: SARAH L MICHEL
• 金额: $ 30万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-20 至 2024-09-19
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10491846
• 关键词: Development; Advanced; Analytical; Methods; Characterization

PROJECT SUMMARY This proposal focuses on characterizing the recently approved iron nanoparticle drug, Monoferric (ferric dersiomaltose) to address key questions regarding the drug substance and drug product. Monoferric is utilized to treat iron deficiency anemia (IDA) for which cases are increasing world- wide. Monoferric belongs to a class of intravenous (IV) iron nanomedicines that are composed of a central iron oxy-hydroxy core with a carbohydrate shell. A clear advantage of Monoferric over earlier approved IV iron products is its slow iron release rate which allows for higher doses of the drug to be administered. This mitigates the need for multiple rounds of IV iron administration to patients. As such, Monoferric, is an appealing product for generic drug development. However, there are uncertainties regarding the composition of Monoferric’s drug substance and drug product and there is a need for novel analytical methods to characterize these complex molecules. In this proposal, we aim to determine the complex structure of Monoferric by characterizing the drug substance and the drug product with a focus on the iron core, the carbohydrate ligands, and the iron-ligand interactions. A multidisciplinary approach that utilizes a plethora of advanced and orthogonal analytical methods including LC-MS, LC-ICP-MS, DLS, SAXS, XAS, Mossbauer, XRPD, high-field multinuclei (7Li, 13C, 19F and 23Na) NMR diffusometry and relaxometry, and low- field wNMR will be taken. The data to be obtained will allow for regulatory scientists to connect the drug product attributes to safety, quality and performance data and aid in the development of generic products. The approach will be divided into five aims: (1) Develop and validate methods to analyze the iron core structure, (2) Develop and validate methods to characterize the ligands, including the carbohydrate structure and the interactions of the ligands with the iron core, (3) Assess the drug substance composition, (4) Obtain a full physico-chemical characterization of the drug product and (5) Analyze intrabatch and interbatch variabilities of Moniferric. The data to be obtained will contribute to the development of new generic products.

项目概要 该提案的重点是表征最近批准的铁纳米颗粒药物 Monoferric （皮麦芽糖铁）解决有关原料药和药品的关键问题。 Monoferric 用于治疗缺铁性贫血 (IDA)，该病的病例在世界范围内不断增加 Monoferric 属于一类静脉注射 (IV) 铁纳米药物，由以下成分组成。 具有碳水化合物壳的中心铁氧羟基核心，与 Monoferric 相比具有明显的优势。 早期批准的静脉铁剂产品的特点是其铁释放速率缓慢，允许更高剂量的铁剂 这减少了多轮静脉铁剂给药的需要。 因此，Monoferric 对于仿制药开发来说是一种有吸引力的产品。 Monoferric的原料药和药物成分存在不确定性 产品，并且需要新的分析方法来表征这些复杂分子。 在本提案中，我们的目标是通过表征 Monoferric 的复杂结构 药物物质和药物产品，重点是铁核、碳水化合物配体和 铁-配体相互作用是一种利用大量先进技术的多学科方法。 正交分析方法，包括 LC-MS、LC-ICP-MS、DLS、SAXS、XAS、Mossbauer、 XRPD、高场多核（7Li、13C、19F 和 23Na）NMR 扩散测定法和弛豫测定法以及低场 将采集现场 wNMR，获得的数据将允许监管科学家进行连接。 药品归因于安全性、质量和性能数据，并有助于开发 该方法将分为五个目标： (1) 开发和验证方法。 分析铁核结构，(2) 开发和验证配体表征方法， 包括碳水化合物结构以及配体与铁核的相互作用，(3) 评估药物成分，(4) 获得完整的理化特性 药品；(5) 分析 Moniferric 的批次内和批次间变量。 获得的成果将有助于新仿制药产品的开发。