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

Curr Pharm Biotechnol. 2019;20(3):232-244. doi: 10.2174/1389201020666190214100840.

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

MeSH terms

  • Biological Products / analysis*
  • Biological Products / chemistry*
  • Discriminant Analysis
  • Particle Size*
  • Protein Aggregates* / physiology

Substances

  • Biological Products
  • Protein Aggregates