Type of Posting: General Chapter Prospectus
Posting Date : 26-Apr-2024
Input Deadline 26-May-2024
Expert Committee: General Chapters-Dosage Form
Suggested audience: Suppliers and manufactures of drug substances, drug products, regulatory agencies; contract manufacturing and testing organizations.
Estimated proposal PF: Pharmacopeial Forum 51(5)
Background and objectives:
Iron colloidal products are formulations containing nanomaterials or nanocolloidal complexes for intravenous (IV) therapy for the treatment of Iron deficiency and Iron deficiency anemia. These products consist of particles with a polynuclear Fe (III)-oxyhydroxide and a carbohydrate shell. The carbohydrate not only stabilizes the polymeric iron complex but also the fate of whole product in the body (PK, PD, safety, and tolerance). There are several products in the market with a variety of carbohydrate shells, which include gluconate, sucrose, dextran, carboxy maltose, isomaltoside, and polyglucose sorbitol. Due to the proprietary nature of the manufacturing process and the use of a different carbohydrate shell, these complex formulations show important differences in their physical characteristics and in-vivo performance. Therefore, the therapeutic bioequivalence of an equivalent generic product cannot be established using the normal generic approach. Several orthogonal physical characterization methods must be utilized to completely understand the innovator product, which must be identical to the developed generic alternate formulation to produce a safe and effective profile.
The purpose of this proposed chapter is to provide information and guidance regarding how to determine various physicochemical properties of iron complexes, including particle size and morphology, viscosity, colloidal nature, molecular weight, surface charge, chemical nature of the carbohydrate shell, total iron content, and labile iron content. The analytical techniques utilized include, dynamic light scattering (DLS), scanning transmission electron microscopy (STEM), atomic force microscopy (AFM), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), size exclusion chromatography (SEC), inductively coupled plasma mass spectrometry (ICP-MS), energy-dispersive X-ray (EDX), transmission electron microscopy/nano beam electron diffraction (TEM/NBED), nuclear magnetic resonance (NMR), X-ray absorption near-edge structure (XANES), thermal gravimetric analysis (TGA), differential scanning calorimetry (DSC), polarography and others.
Description of scope and application: The proposed chapter is intended to provide guidance for the characterization of various iron colloidal formulations, and use of the various physicochemical characterization methods and a discussion of these orthogonal methods and their applicability and acceptance.
Preliminary outline:
- Introduction
- Background.
- Complexity of the Iron-colloidal formulations due to the use of various carbohydrate shells
- Toxicity associated with excessive release of Iron due to formulation complexities.
- Physicochemical characterization of Iron colloidal formulations
- Whole particle
- Iron assay.
- Carbohydrate assay
- Molecular weight distribution
- Labile iron
- Particle size distribution
- Iron core
- Iron core size and morphology.
- Crystallinity
- Iron environment
- Fe3+ to Fe2+ reduction potential and Fe (II) content
- Magnetic properties
- Carbohydrate shell
- Carbohydrate composition
- Surface charge
- Characterization of polysaccharides
- Whole particle
- Considerations on the variability of the characterization methods
- Method validation
- Orthogonal techniques
- Comparative characterization of multiple batches
- Sample preparation and data analysis.
- Discussion
- Glossary
- References
USP is requesting early input from stakeholders on this proposal of a new General Chapter, <1155> Iron Colloidal Formulations – Characterization Methods, which is planned to be published for comments in the Pharmacopeial Forum.
Anticipated implementation timing: Routine (six months after USP-NF publication)
Contact: prabhakar.gruddanti@usp.org