Micro-flow imaging: flow microscopy applied to sub-visible particulate analysis in protein formulations.

The need to monitor, measure, and control sub-visible proteinaceous particulates in biopharmaceutical formulations has been emphasized in recent publications and commentaries. Some of these particulates can be highly transparent, fragile, and unstable. In addition, for much of the size range of concern, no practical measurement method with adequate sensitivity and repeatability has been available.

Quantification and characterization of subvisible proteinaceous particles in opalescent mAb formulations using micro-flow imaging.

Micro-flow imaging (MFI) has been shown to be more sensitive than light obscuration (LO) methods for measuring subvisible proteinaceous particles in protein formulations. Given the potential challenges in detecting particulates in opalescent mAb formulations, the accuracy of MFI to size and count particles in opalescent solutions was investigated and compared to LO and membrane microscopy methods. Proteinaceous monoclonal antibody (mAb) particles, generated either by chemical denaturation or agitation stress, polystyrene and glass particles were used as model systems for measurements in opalescent mAb solutions.

Quantitation of protein particles in parenteral solutions using micro-flow imaging.

The U.S. and European Pharmacopeias require subvisible (> or =10 and > or =25 microm) and visible particulate testing of therapeutics to ensure their safety and suitability for clinical use.