Variability in Flow-Imaging Microscopy Measurements and Considerations for Biopharmaceutical Development.
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.
Global Statistical Sciences, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285.
Adam P
AP
Rauk
Global Statistical Sciences, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285.
Kristi L
KL
Griffiths
Biopharmaceutical Research and Development, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285.
Melody D
MD
Gossage
Biopharmaceutical Research and Development, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285. Electronic address: weiss_william_f_iv@lilly.com.
William F
WF
Weiss
D001702:Biopharmaceutics / Q000379:methods* / Q000592:standards*; D002626:Chemistry, Pharmaceutical / Q000379:methods / Q000592:standards; D004349:Drug Packaging / Q000379:methods / Q000592:standards*; D008853:Microscopy / Q000592:standards; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000032:analysis / Q000592:standards*; D015203:Reproducibility of Results
D004364:Pharmaceutical Preparations
biotechnology; particle size; physical stability; protein aggregation; protein formulation