Measuring Subvisible Particles in Protein Formulations Using a Modified Light Obscuration Sensor with Improved...

Area of Science:

• Biopharmaceutical Analysis
• Particle Characterization
• Analytical Chemistry

Background:

• Light obscuration (LO) is the standard for subvisible particle analysis in biopharmaceuticals.
• Current LO technology struggles with detecting small (<2 μm) and translucent protein particles.
• Existing methods can produce artifacts, affecting measurement accuracy, particularly at low concentrations.

Purpose of the Study:

• To evaluate a modified light obscuration sensor with a novel width-based measurement mode.
• To assess the sensor's performance in detecting small and translucent subvisible particles.
• To compare the new method against standard LO and flow imaging microscopy.

Main Methods:

• A modified light obscuration sensor was developed, focusing on signal width (length) instead of amplitude (height).
• Experimental evaluations were conducted using various particle types and concentrations.
• Performance was benchmarked against standard light obscuration and flow imaging microscopy.

Main Results:

• The novel width-based detection mode significantly improved the detection of subvisible particles smaller than 2 μm.
• Artifacts were reduced, especially for low concentrations of translucent protein particles.
• Higher counting accuracy was achieved compared to both standard LO and flow imaging microscopy.

Conclusions:

• The modified light obscuration sensor offers enhanced capabilities for subvisible particle analysis in biopharmaceuticals.
• This new approach provides improved accuracy and reliability for detecting challenging particle types.
• The width-based measurement mode represents a significant advancement over traditional LO techniques.