Several compendial chapters (e.g. USP <788> and USP <787> refer to mandatory testing of particles below the visibility level of the unaided eye. rap.ID offers Light Obstruction, LO and Membrane Counting as well as Dynamic Imaging Analysis, Micro Flow Imaging, MFI for subvisible particles testing.
Especially for protein based formulations, the informational chapter USP <1788> recommends orthogonal techniques to gain additional information on the morphology and the chemical nature of the subvisible particles. Static imaging particle analysis directed raman microscopy, (SPE ls raman.ID) with wet-dispersion.AID and FlowCam are used to provide GMP compliant results. With these methods, it allows further qualitative and quantitative sample analysis. This ensures the chemical identification of proteinaceous particles and silicone droplets from extrinsic contamination is possible.
Raman spectroscopy on proteinaceous particles in situ, can provide you with valuable root cause analysis for agglomeration behavior and pathways of degeneration for your formulation development. The USP <1788> suggests use of orthogonal methods and categorization into extrinsic, intrinsic and inherent particles, becomes easily achievable and will be provided at the GMP level.
In the last 15 years, rap.ID supported numerous investigations revealing stability and root cause of protein aggregation: