An Interlaboratory Comparison on the Characterization of a Sub-micrometer Polydisperse Particle Dispersion.

The measurement of polydisperse protein aggregates and particles in biotherapeutics remains a challenge, especially for particles with diameters of ≈ 1 µm and below (sub-micrometer). This paper describes an interlaboratory comparison with the goal of assessing the measurement variability for the characterization of a sub-micrometer polydisperse particle dispersion composed of five sub-populations of poly(methyl methacrylate) (PMMA) and silica beads. The study included 20 participating laboratories from industry, academia, and government, and a variety of state-of-the-art particle-counting instruments. The received datasets were organized by instrument class to enable comparison of intralaboratory and interlaboratory performance. The main findings included high variability between datasets from different laboratories, with coefficients of variation from 13 % to 189 %. Intralaboratory variability was, on average, 37 % of the interlaboratory variability for an instrument class and particle sub-population. Drop-offs at either end of the size range and poor agreement on maximum counts of particle sub-populations were noted. The mean distributions from an instrument class, however, showed the size-coverage range for that class. The study shows that a polydisperse sample can be used to assess performance capabilities of an instrument set-up (including hardware, software, and user settings) and provides guidance for the development of polydisperse reference materials.

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Copyright © 2021. Published by Elsevier Inc.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: N. Do is an employee of Spectradyne LLC, which manufactures and sells microfluidic resistive pulse sensing-based instrumentation for particle quantification. D. Grier is a founder of Spheryx, Inc., the company that manufactures the xSight instrument that was used for part of the NYU study. J. Hadley was employed at Malvern Panalytical, which develops and sells the Archimedes and LM10, LM14, LM20, NS300, and NS500 instruments used in this study. C. Probst was employed by Luminex Corporation, the manufacturer of the Amnis® CellStream® and FlowSight® that were used in this study. During this study J. Tatarkiewicz was employed by MANTA Instruments, Inc. which since then was acquired by HORIBA Scientific, Inc. The measurements were done using ViewSizer 3000 instrument. Alpha Nano Tech LLC is a Contract Research Organization; it has actual contracts with Particle Metrix Inc., as well as with other instruments vendors, and provides services for the companies on request. In general, Alpha Nano Tech LLC has contracts with Particle Metrix and special terms on acquiring instruments. Alpha Nano Tech provides services on variety of instruments/techniques, including those which compete with each other. Spheryx Inc. sells the Holographic Characterization Instrument (xSight and xCell8) used in this publication. We also hold the patents associated to this technology. Yokogawa Fluid Imaging Technologies, Inc. develops and sells the FlowCam® Nano flow imaging microscope used in this study. All other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.