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Current Drug Delivery

Editor-in-Chief

ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

Mini-Review Article

Influence of Nano-Particulate Impurities and β-glucans on the Stability of Protein-Based Formulations

In Press, (this is not the final "Version of Record"). Available online 30 January, 2024
Author(s): Soumya Ranjan Satapathy, Rudra Narayan Sahoo and Amit Kumar Nayak*
Published on: 30 January, 2024

DOI: 10.2174/0115672018290111240119115306

Price: $95

Abstract

Pharmaceutical grade sugars manufactured under Current Good Manufacturing Practice (cGMP) and complied with International Pharmaceutical Excipients Council (IPEC) quality standards, also contain a significant amount of nano-particulate impurities (NPIs). This review will focus on the origin of NPIs, the mechanism of their interference with Dynamic light scattering (DLS) and endotoxin tests, filtration technology to effectively reduce the NPIs, methodologies for analytical quantification of NPIs, guidance for setting the limits of threshold concentration and the overall impact of NPIs on the therapeutic activity, performance, stability of biopharmaceuticals and protein-based formulations. NPIs with an average particle size of 100 to 200 nm are present in sugars and are a combination of various chemicals such as dextrans (with the presence of β-glucans), ash, inorganic metal salts, aromatic colorants, etc. These NPIs primarily originate from raw materials and cannot be removed during the sugar refinement process. While it is commonly believed that filtering the final formulation with a 0.22 μ sterilizing grade filter removes all microbes and particles, it is important to note that NPIs cannot be filtered using this standard sterile filtration technology. Exceeding the threshold limit of NPIs can have detrimental effects on formulations containing proteins, monoclonal Antibodies (mAbs), nucleic acids, and other biopharmaceuticals. NPIs and β-glucans have a critical impact on the functionality and therapeutic activity of biomolecules and if present below the threshold limit of reaction, stability and shelf-life of biologics formulation will be greatly improved and the risk of immunogenic reactions must be significantly decreased.

Keywords: Protein stability, Nano-particulate impurities, Pathogen-associated molecular patterns, Nano-particle tracking analysis, Dynamic light scattering


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