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

Area of Science:

• Biopharmaceutical analysis
• Particle characterization
• Metrology

Background:

• Accurate measurement of sub-micrometer particles in biotherapeutics is critical for product quality and safety.
• Existing methods face challenges in characterizing polydisperse particle populations, especially those below 1 micrometer.

Purpose of the Study:

• To assess measurement variability in characterizing sub-micrometer polydisperse particle dispersions.
• To evaluate the performance of various particle-counting instruments across different laboratories.
• To provide guidance for developing polydisperse reference materials for biotherapeutic particle analysis.

Main Methods:

• An interlaboratory comparison study involving 20 laboratories (industry, academia, government).
• Characterization of a sub-micrometer polydisperse particle dispersion using poly(methyl methacrylate) (PMMA) and silica beads.
• Analysis of data organized by instrument class to compare intralaboratory and interlaboratory performance.

Main Results:

• High interlaboratory variability was observed, with coefficients of variation ranging from 13% to 189%.
• Intralaboratory variability accounted for approximately 37% of interlaboratory variability within instrument classes.
• Discrepancies noted in size range coverage and particle sub-population counts; however, mean distributions indicated instrument class size coverage.

Conclusions:

• Significant variability exists in the measurement of sub-micrometer polydisperse particles across different laboratories and instruments.
• Polydisperse samples can effectively assess the performance of particle measurement instrument setups.
• The study highlights the need for improved standardization and the development of polydisperse reference materials for biotherapeutic particle characterization.