Variability in Flow-Imaging Microscopy Measurements and Considerations for Biopharmaceutical Development.

ABSTRACT

Flow-imaging microscopy is widely used in the biopharmaceutical industry to characterize populations of subvisible (1-100 µm) particles due to high sensitivity and the ability to discriminate different particle morphologies. The present work provides a comprehensive assessment of the capabilities of flow-imaging microscopy by exploring the impacts of a variety of factors on the observed variability of these measurements. A novel graphical presentation is proposed to facilitate both determination of expected levels and detection of potential atypical results. Data collected across different products and container-closure systems illustrate that a substantial amount of historical experience is typically required to adequately define the expected levels of subvisible particles for any specific system. It is also shown, however, that an appropriate level of control can be demonstrated without the need to pool large numbers of containers or perform replicate measurements.