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Current Pharmaceutical Biotechnology

Author(s): Zahir S. Akhunzada*, Mario Hubert, Erinc Sahin and James Pratt

DOI: 10.2174/1389201020666190214100840

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Separation, Characterization and Discriminant Analysis of Subvisible Particles in Biologics Formulations

Page: [232 - 244] Pages: 13

  • * (Excluding Mailing and Handling)

Abstract

Background: The presence of subvisible particles (SVPs) in parenteral formulations of biologics is a major challenge in the development of therapeutic protein formulations. Distinction between proteinaceous and non-proteinaceous SVPs is vital in monitoring formulation stability.

Methods: The current compendial method based on light obscuration (LO) has limitations in the analysis of translucent/low refractive index particles. A number of attempts have been made to develop an unambiguous method to characterize SVPs, albeit with limited success.

Results: Herein, we describe a robust method that characterizes and distinguishes both potentially proteinaceous and non-proteinaceous SVPs in protein formulations using Microflow imaging (MFI) in conjunction with the MVAS software (MFI View Analysis Suite), developed by ProteinSimple. The method utilizes two Intensity parameters and a morphological filter that successfully distinguishes proteinaceous SVPs from non-proteinaceous SVPs and mixed aggregates.

Conclusion: The MFI generated raw data of a protein sample is processed through Lumetics LINK software that applies an in-house developed filter to separate proteinaceous from the rest of the particulates.

Keywords: Protein aggregation, proteinaceous particles, non-proteinaceous particles, subvisible particles, MFI, MVAS, lumetics link, discriminant analysis.

Graphical Abstract

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