Factors Governing the Accuracy of Subvisible Particle Counting Methods

Abstract A number of new techniques for subvisible particle characterization in biotechnological products have emerged in the last decade. Although the pharmaceutical community is actively using them, the current knowledge about the analytical performance of some of these tools is still inadequate to support their routine use in the development of biopharmaceuticals (especially in the case of submicron methods). With the aim of increasing this knowledge and our understanding of the most prominent techniques for subvisible particle characterization, this study reports the results of a systematic evaluation of their accuracy. Our results showed a marked overcounting effect especially for low concentrated samples and particles fragile in nature. Furthermore, we established the relative sample size distribution as the most important contributor to an instrument’s performance in accuracy counting. The smaller the representation of a particle size within a solution, the more difficulty the instruments had in providing an accurate count. These findings correlate with a recent study examining the principal factors influencing the precision of the subvisible particle measurements. A more thorough understanding of the capabilities of the different particle characterization methods provided here will help guide the application of these methods and the interpretation of results in subvisible particle characterization studies.