Comparative Evaluation of U.S. Brand and Generic Intravenous Sodium Ferric Gluconate Complex in Sucrose Injection: Physicochemical Characterization.

Dajun Sun,David Keire,Jia Ma,Rodney Rouse,Anil Patri,Yong Wu,Jiwen Zheng,Alokita Karmakar,Wenlei Jiang,Priyanka Chitranshi,Vikram Patel

doi:10.3390/nano8010025

Abstract

The objective of this study was to evaluate physicochemical equivalence between brand (i.e., Ferrlecit) and generic sodium ferric gluconate (SFG) in sucrose injection by conducting a series of comparative in vitro characterizations using advanced analytical techniques. The elemental iron and carbon content, thermal properties, viscosity, particle size, zeta potential, sedimentation coefficient, and molecular weight were determined. There was no noticeable difference between brand and generic SFG in sucrose injection for the above physical parameters evaluated, except for the sedimentation coefficient determined by sedimentation velocity analytical ultracentrifugation (SV-AUC) and molecular weight by asymmetric field flow fractionation-multi-angle light scattering (AFFF-MALS). In addition, brand and generic SFG complex products showed comparable molecular weight distributions when determined by gel permeation chromatography (GPC). The observed minor differences between brand and generic SFG, such as sedimentation coefficient, do not impact their biological activities in separate studies of in vitro cellular uptake and rat biodistribution. Coupled with the ongoing clinical study comparing the labile iron level in healthy volunteers, the FDA-funded post-market studies intended to illustrate comprehensive surveillance efforts ensuring safety and efficacy profiles of generic SFG complex in sucrose injection, and also to shed new light on the approval standards on generic parenteral iron colloidal products.

Highlights

Among iron’s many critical roles in metabolic processes, the most essential function is in the synthesis of hemoglobin to meet the need for oxygen transport
We present inductively coupled plasma-mass spectrometry (ICP-MS), total organic carbon (TOC) measurement, thermogravimetric analysis (TGA), viscosity measurement, cryo-transmission electron microscopy (TEM), atomic force microscopy (AFM), sedimentation velocity analytical ultracentrifugation (SV-AUC), gel permeation chromatography (GPC) and asymmetric field-flow fractionation (AFFF)
Iron and organic carbon of Ferrlecit and the generic sodium ferric gluconate (SFG) were measured by ICP-MS and nondispersive infrared (NDIR), respectively

Summary

Introduction

Among iron’s many critical roles in metabolic processes, the most essential function is in the synthesis of hemoglobin to meet the need for oxygen transport. As of May 2017, innovator iron-carbohydrate complex drug products on the U.S market include INFed (iron dextran), Dexferrum (iron dextran), Ferrlecit (sodium ferric gluconate (SFG) complex), Venofer (iron sucrose), Feraheme (ferumoxytol), and Ferinject (ferric carboxymaltose). These iron colloidal nanoparticle products differ in the composition of their carbohydrate shells, iron core sizes and hydrodynamic radii. In humans these drugs are distributed and cleared from the bloodstream through a similar process that involves phagocytosis in the reticuloendothelial system (RES) [1]. The mechanism of action of these iron colloidal drugs involves uptake by cellular lysosomes in which iron ions are released from the colloidal nanoparticles and become part of the intracellular labile iron pool for use in biological processes [2]

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