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

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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.