Micro-flow imaging (MFI)

particle_characterization

Micro-flow imaging (MFI) is a well-established and frequently-used technique for sizing, quantifying, visualizing and, in certain cases, identifying (sub-) visible particles.

In MFI (officially called flow imaging microscopy (FIM) or dynamic imaging analysis (DIA)), bright-field images are captured in successive frames as a continuous sample stream passes through a flow-cell positioned in the field of view of a microscopic system. The digital images of the particles present in the sample are processed by image morphology analysis software that allows their quantification in size and count.

Coriolis operates several systems from different suppliers, such as Micro-flow imaging devices from ProteinSimple and FlowCam systems from Fluid Imaging Technology. These instruments typically cover a size range from about 1 to 400 µm, while the upper particle concentration limit is typically higher than that of light obscuration systems. Besides enumerating the subvisible particles present in the sample, flow imaging microscopy provides information about particle morphology for particles larger than about 3-4 µm. This capability marks an inherent advantage of MFI over many other particle characterization techniques, as it may allow identification of substances commonly present in biopharmaceuticals, such as silicone oil droplets.

MFI has become an established technique for subvisible particle analysis, though no monograph/specifications in the pharmacopoeias exist so far. The instructional chapter USP<1787> mentions MFI as a possible orthogonal technique for subvisible particle analysis in addition to light obscuration. Even though MFI is also a light-based technique, it is typically superior to light obscuration in the detection of particles with a refractive index close to that of the surrounding formulation.

MFI is primarily used as a research tool, but has gained in importance, for example, during trouble shooting to further characterize or identify subvisible particles detected by light obscuration. The identification of silicone oil-like droplets in prefilled syringes or double-chamber cartridges is a major application of the technique. At Coriolis, MFI can be offered in full GMP compliance for, e.g., lot release testing.

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D.J. Houde, A.S. Berkowitz, eds., Biophysical Characterization of Proteins in Developing Biopharmaceuticals, 1st ed., Newnes, 2014

S. Zölls, R. Tantipolphan, M. Wiggenhorn, G. Winter, W. Jiskoot, W. Friess, A. Hawe, Particles in therapeutic protein formulations, Part 1: overview of analytical methods., J. Pharm. Sci. 101 [2012] 914–35. doi:10.1002/jps.23001.

Weinbuch D, Zölls S, Wiggenhorn M, et al. Micro-flow imaging and resonant mass measurement [archimedes] - complementary methods to quantitatively differentiate protein particles and silicone oil droplets. J Pharm Sci. 2013;102(7:2152-2165. doi:10.1002/jps.23552)

Zölls et al. 2012, Particles in therapeutic protein formulations, Part 1: overview of analytical methods

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