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Light Obscuration Measurements of Highly Viscous Solutions: Sample Pressurization Overcomes Underestimation of Subvisible Particle Counts

ABSTRACT

Light obscuration (LO) is the current standard technique for subvisible particle analysis in the quality control of parenterally administered drugs, including therapeutic proteins. Some of those, however, exhibit high viscosities due to high protein concentrations, which can lead to false results by LO measurements. In this study, we show that elevated sample viscosities, from about 9 cP, lead to an underestimation of subvisible particle concentrations, which is easily overlooked when considering reported data alone. We evaluated a solution to this problem, which is the application of sample pressurization during analysis. The results show that this is an elegant way to restore the reliability of LO analysis of highly viscous products without the necessity of additional sample preparation.

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ACKNOWLEDGMENTS

The authors thank Coriolis Pharma (Martinsried, Germany) for the organizational and financial support, Sarah Zölls for her help regarding project initiation and Partikelmess- und Analysesysteme GmbH (Rutesheim, Germany) for providing the PAMAS SBSS light obscuration system and supporting the analytical work.

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Correspondence to Andrea Hawe.

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Weinbuch, D., Jiskoot, W. & Hawe, A. Light Obscuration Measurements of Highly Viscous Solutions: Sample Pressurization Overcomes Underestimation of Subvisible Particle Counts. AAPS J 16, 1128–1131 (2014). https://doi.org/10.1208/s12248-014-9629-0

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  • DOI: https://doi.org/10.1208/s12248-014-9629-0

KEY WORDS

  • high viscosity
  • light obscuration
  • protein formulation
  • subvisible particles