Polystyrene and glass particles and pseudo protein particles were added to opalescent, viscous, and colored matrices to access sizing and counting effects of the methods. “The color, refractive index, and opalescence of actual product samples can provide erroneous data.” To study the effect of matrix irregularities on light obscuration and microflow digital imaging (MDI), Frommknecht used a number of artificial matrices and particle standards. “Ideal samples for detecting particles would consist of a clear, water-like fluid in which individual particles of high contrast and moderate buoyancy are effectively recognized,” said Tobias Frommknecht, formulation scientist, F. Subvisible particles can be quite heterogeneous and can come from a variety of sources, either externally from the production environment or from the protein itself. “In five years we will have a more diverse set of analytical tools as well as a much better understanding of what type of particles we need to control to minimize immunogenicity in the wide range of protein product types.” “These orthogonal technologies will be used to characterize SVPs in a sample, and to illustrate how to use the technology to develop protein formulations and decide which technology can better address regulatory concerns,” he continued. Functioning as a CRO, NorthStar Bio can characterize protein production samples using state-of-the-art microflow imaging, fluid imaging particle analysis, the Coulter principle, and other emerging technologies. Chou, NorthStar Bio is the first company created to better understand SVPs. In the last few years the regulatory agencies have been making a push for the industry to assess subvisible particles (SVPs) and their relevance to product quality, as well as to evaluate the technologies that can be used to measure them.”Īccording to Dr. “The quality of a protein pharmaceutical is defined by the analytical capability that is available. So we are missing the gap between what we can detect with SEC and light obscuration and what the human eye can see,” said Danny Chou, Ph.D., chief scientific officer, NorthStar Bio. “Despite its drawbacks, light obscuration is the current accepted method for monitoring of subvisible particulates during lot release. On the other extreme we look at particles visible to the naked eye that are 80–100 microns or larger. Today we have size exclusion chromatography (SEC) to look at the increase in the dimers, trimers, and oligomers of proteins. “Levels of protein aggregates have long been mentioned as a critical quality attribute and have potential clinical consequences. The challenges faced in measuring and characterizing these protein aggregates were discussed at the recent “PepTalk: The Protein Science Week” conference. Because protein product aggregates represent a potential risk factor for immunogenicity, industry and the FDA seek a method to accurately count and characterize these particles.
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