Advances in biopharmaceutical sub-visible analysis through submicron IR (O-PTIR) micro-spectroscopy

Particulates are a significant concern in pharmaceuticals due to their potential immunogenic effects and influence on drug safety and efficacy. Characterization has advanced from visible to sub-visible particles, primarily focusing on counting, sizing, and morphology. Although chemical identification is crucial for root-cause analysis, current methods face limitations. Raman microscopy is hindered by autofluorescence and slow measurements, while traditional vibrational techniques struggle with particles under 20 µm. Optical Photothermal Infrared (O-PTIR) spectroscopy emerges as a sensitive alternative, offering high spatial resolution, no autofluorescence, and minimal sample damage, making it ideal for detailed analysis of sub-visible particulates in drug products.