Non-Destructive Analysis of Subvisible Particles with Mie-Scattering-Based Light Sheet Technology: System...

Area of Science:

• Pharmaceutical Manufacturing
• Analytical Chemistry
• Biotechnology

Background:

• Subvisible particles (SbVPs) are critical quality attributes for injectable and ophthalmic solutions.
• Current testing methods (light obstruction, microscopic count) are destructive and sample-intensive.
• A need exists for non-destructive methods to analyze SbVPs in final drug product containers.

Purpose of the Study:

• To develop and validate a non-destructive analyzer for subvisible particles (SbVPs) in pharmaceutical drug product (DP) containers.
• To enable direct analysis of SbVPs within intact DP containers, preserving sample integrity.
• To improve the efficiency and reduce waste in pharmaceutical quality control testing.

Main Methods:

• Development of a non-destructive SbVP analyzer integrating a light-sheet microscope.
• Utilized custom sample housings to minimize optical aberrations from container curvature.
• Applied Mie scattering theory with refractive indices to model particle scattering events and estimate size.
• Quantified particle concentration based on scattering events and light sheet volume.

Main Results:

• The analyzer successfully detected SbVPs directly in intact ISO 2R and 6R vials.
• Capable of sorting detected SbVPs into standard size bins (≥ 2 µm, ≥ 5 µm, ≥ 10 µm, ≥ 25 µm).
• Reliably quantified SbVP concentrations from 4.6e2 to 5.0e5 particles/mL with ±15% error (90% confidence interval).

Conclusions:

• The developed analyzer offers a non-destructive solution for SbVP analysis in pharmaceutical drug products.
• Enables direct, in-situ analysis of critical quality attributes without sample destruction.
• Provides accurate particle sizing and quantification, enhancing pharmaceutical quality control processes.