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

Area of Science:

• Biopharmaceutical analysis
• Analytical chemistry
• Microscopy techniques

Background:

• Flow-imaging microscopy (FIM) is crucial for characterizing subvisible particles (1-100 μm) in biopharmaceuticals.
• FIM offers high sensitivity and particle morphology discrimination.
• Understanding FIM measurement variability is essential for reliable biopharmaceutical quality control.

Purpose of the Study:

• To comprehensively assess the capabilities of flow-imaging microscopy.
• To explore the impact of various factors on measurement variability.
• To propose a novel graphical method for analyzing FIM data.

Main Methods:

• Investigated the impact of different factors on FIM measurement variability.
• Collected data across diverse products and container-closure systems.
• Developed a novel graphical presentation for expected and atypical results.

Main Results:

• Substantial historical data is often needed to define expected subvisible particle levels for specific systems.
• The proposed graphical method aids in determining expected levels and detecting atypical results.
• Demonstrated that adequate control can be shown without extensive container pooling or replicate measurements.

Conclusions:

• Flow-imaging microscopy is a powerful tool for subvisible particle characterization in the biopharmaceutical industry.
• The developed graphical approach enhances the interpretation of FIM data and variability assessment.
• Efficient control demonstration is achievable with optimized FIM data analysis strategies.