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

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

doi:10.3390/nano8010025

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

Nanomaterials (Basel). 2018 Jan 5;8(1):25. doi: 10.3390/nano8010025.

Authors

Dajun Sun¹, Rodney Rouse², Vikram Patel³, Yong Wu⁴, Jiwen Zheng⁵, Alokita Karmakar⁶, Anil K Patri⁷, Priyanka Chitranshi⁸, David Keire⁹, Jia Ma¹⁰, Wenlei Jiang¹¹

Affiliations

¹ Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA. dajun.sun@fda.hhs.gov.
² Division of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA. rodney.rouse@fda.hhs.gov.
³ Division of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA. vikram.patel@fda.hhs.gov.
⁴ Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA. yong.wu@fda.hhs.gov.
⁵ Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA. jiwen.zheng@fda.hhs.gov.
⁶ National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, USA. Alokita.Karmakar@fda.hhs.gov.
⁷ National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, USA. anil.patri@fda.hhs.gov.
⁸ Division of Pharmaceutical Analysis, Office of Testing and Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Saint Louis, MO 63110, USA. Priyanka.chitranshi@fda.hhs.gov.
⁹ Division of Pharmaceutical Analysis, Office of Testing and Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Saint Louis, MO 63110, USA. david.keire@fda.hhs.gov.
¹⁰ Bindley Bioscience Center, Purdue University, West Lafayette, IN 47907, USA. ma420@purdue.edu.
¹¹ Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA. wenlei.jiang@fda.hhs.gov.

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.

Keywords: Ferrlecit; bioequivalence; generic drugs; parenteral iron; sodium ferric gluconate complex.