Micro-flow imaging: flow microscopy applied to sub-visible particulate analysis in protein formulations

Area of Science:

• Biopharmaceutical analysis
• Particulate matter characterization
• Analytical chemistry

Background:

• Sub-visible proteinaceous particulates are critical quality attributes in biopharmaceutical formulations.
• Existing methods lack sensitivity and repeatability for transparent, fragile protein particles.
• Distinguishing protein particles from other contaminants (silicone oil, air bubbles) is challenging.

Purpose of the Study:

• To address the need for accurate measurement of sub-visible protein particulates.
• To evaluate analytical methods for characterizing these particles in complex formulations.
• To identify a method capable of independent analysis of protein particle populations.

Main Methods:

• Utilizing micro-flow imaging (MFI) technology.
• Assessing MFI's sensitivity for transparent and fragile protein particles.
• Evaluating MFI's capability to differentiate protein particles from other contaminants.

Main Results:

• Micro-flow imaging demonstrates high sensitivity in detecting transparent protein particles.
• MFI provides a unique capability to independently analyze protein particle populations.
• The method effectively distinguishes protein particles amidst silicone micro-droplets, air bubbles, and contaminants.

Conclusions:

• Micro-flow imaging is a suitable analytical method for sub-visible protein particulate monitoring.
• MFI overcomes limitations of traditional methods in biopharmaceutical formulation analysis.
• This technique enhances the ability to control critical quality attributes in biopharmaceuticals.