Subvisible particles (SVPs) are a significant quality attribute of injectable therapeutic proteins (TPs) that must be regulated due to potential medication product quality hazards. The existing compendial methods for analyzing SVPs for lot release give particle size and count information. On the other hand, chemical identification of specific particles is necessary for root-cause analysis. Researchers provide Morphologically-Directed Raman Spectroscopy (MDRS) for TP SVP characterization. For technique development, the following particles were used: (1) polystyrene microspheres, a traditional industry standard; (2) photolithographic (SU-8); and (3) ethylene tetrafluoroethylene (ETFE) particles, candidate reference materials created by NIST. In the study, MDRS created high-resolution images (> 90%) for ETFE particles spanning in size from 19 to 100 m, covering the majority of the SVP range, and produced morphological data equivalent to flow imaging microscopy. The method was used to analyze particles generated in stressed TPs, and Raman spectroscopy was used to identify individual particles chemically. MDRS may compare proteinaceous particles’ shape and transparency properties to those of reference materials. According to the findings, MDRS might be used to supplement the current TP’s SVP analysis system and product quality characterization workflow throughout the development and commercial lifecycle.
The work developed a new analytical approach for monitoring SVPs in TPs and characterizing proteinaceous particles in stressed mAb drug products using Morphologically-Directed Raman Spectroscopy. The purpose was to broaden TP SVP analysis methods for product quality characterization, which would influence public health. MDRS offered particle morphology and size distribution data comparable to FIM’s current orthogonal approach in analyzing monodisperse and polydisperse particles.
Related Content: Single Nanodiamond Sensors For In-Situ EPR Spectroscopy