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

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.

Comparative Evaluation of U.S. Brand and Generic Intravenous Sodium Ferric Gluconate Complex in Sucrose Injection: In Vitro Cellular Uptake

“…Commercially available lots of Ferrlecit ® and generic SFG compliant with FDA-approved specifications were purchased from a retail pharmacy. These products were fully characterized and the generic SFG has similar particle size distribution, iron core, composition of carbohydrate shell, and other physicochemical properties as the reference drug Ferrlecit ® [ 34 ]. In this study, the iron uptake comparison between Ferrlecit ® and the generic SFG was performed in three different human macrophage cell lines: THP-1, HL60, and U937.…”

Reflections on FDA Draft Guidance for Products Containing Nanomaterials: Is the Abbreviated New Drug Application (ANDA) a Suitable Pathway for Nanomedicines?

“…The FDA should revisit its suggestion that comparative physicochemical testing is sufficient to support generic approvals of drug products containing nanomaterials, given that the mechanisms of action by which these products impact biological targets within the body are not fully understood. The FDA presumes that comparable structural features will ensure compatible tissue distribution, when instead a totality-of-evidence approach that includes biological, preclinical, and clinical data evaluated in a stepwise manner is more appropriate for the complexity of these products (16,17). However, the requested factors outlined by the FDA, namely: & understanding of the mechanism by which the physicochemical properties of the material impact its biological effects (e.g., effect of particle size on pharmacokinetic parameters) and & understanding the in vivo release mechanism based on the material physicochemical properties are not met for numerous iron carbohydrates.…”

“…The CQAs for such products cannot be properly defined, and therefore it is not possible to design informative comparative physicochemical assessments. In a seeming acknowledgement of this challenge, FDA initiated a clinical study comparing the safety and efficacy of brand and generic intravenous sodium ferric gluconate complexes, after it had already approved the generic version based on physicochemical testing, the results of which are still pending (16,18). It will be interesting to see how it will compare to the results of a pilot study, which evaluated the physicochemical profiles of the brand and generic versions, and saw both similarities and differences in the range of methods used (16).…”

Impact of Weak Organic Acids on Precipitation of Poly(acrylic acid) Stabilized Silver Nanoparticles; an Electrochemical Approach

“…OWADAYS, synthesis of metal nanoparticles is generating a lot of research work because of their utilization in fields of catalysis, [1][2][3] biomedicine, [4,5] optics [6] and electronics. [7,8] Most of the applications are due to the fact that metal particles in the nanometre size have drastically different properties compared to the same bulk material.…”

“…Hydrodinamic CVs of the prepared nano-ink, w(PAA-AgNP) = 3.46 %, obtained by adding 150 μL of nanosilver in a 10 mL BR buffer solution pH = 6.00. Curve denoted 1 depicts specimen at the end of the nanosilver synthesis; CVs represent AgNPs precipitated with weak organic acids: oxalic (2), citric (3), ascorbic (4), acetic(5), succinic(6). Measurement set up was the same as inFigure 1.…”