“I think it is pretty clear that particulates in [the subvisible] range can be detected and appropriately quantified by various analytical techniques. Micro-Flow Imaging™ [among other technologies] can be used to characterize and quantitate these.” B.Cherney, PhD – US FDA. – (2011) 24th CASSS CMC Strategy Forum.
“… particle counting [using MFI™] may be the most sensitive technique available for the detection of aggregated protein.” – (2011) Journal of Pharmaceutical Sciences 100(2): 492-503.
“… [MFI™] is capable of detecting aggregated forms of protein that represent hundredths of a percent of the total protein in solution, making it far more sensitive than other aggregate detection techniques.” – (2011) Journal of Pharmaceutical Sciences 100(2): 492-503.
“Subvisible particle analysis using MFI™ can help present a more complete picture of the solution and in some cases also help identify the origins of the particles.” – (2011) Journal of Pharmaceutical Sciences DOI:10.1002/jps.22515.
“The [MFI™] results presented here clearly demonstrated that substantial information can be derived regarding the stability of protein formulations and their compatibility with storage containers by the use of techniques aimed at measuring particle size, concentration, and assessing their shapes.” – (2011) Journal of Pharmaceutical Sciences. DOI: 10.1002/jps.22515.
In comparison to Size Exclusion Chromatography (SEC) and Polyacrylamide Gel Electrophoresis methods… “Of all the analytical studies shown here, MFI™ is the only one sensitive enough to detect these larger particles because: 1) although micron-sized particles contain millions of proteins, they represent a trace amount of the total protein and would be nearly invisible by polyacrylamide gel electrophoresis; 2) the size of these particles would preclude them from entering the size exclusion chromatography column; and 3) in addition to protein, some of the particles could be resulting from non-protein materials such as silicone oil from the syringes.” – (2010) Retina 30: 887-892.
“Based on the accuracy and precision results with both PSs and a protein solution containing protein particles, the [MFI™] assay was considered qualified as method to count and monitor protein particle size and number in a high concentration IgG1 monoclonal antibody formulation. The [MFI™] assay showed sufficient accuracy and precision over extended time periods for its intended use as a characterization method to monitor protein particles [in the subvisible and visible size range].” – (2010) Journal of Pharmaceutical Sciences 99(8): 3343-3361.
