Flow imaging for particle characterization and quantification in biologicals: A perspective from the Japanese Biopharmaceutical Consortium.

Protein aggregates and particles in biologicals are considered impurities and critical quality attributes because they could elicit immunogenicity. An appropriate control strategy should be established to monitor and control them following their characterization. As aggregates and particles range in size from nanometer to millimeters, various analytical techniques are required to characterize aggregates and particles depending on their size, the scope of the analysis, and the development stage. To characterize protein aggregates and particles in the micron size range, light obscuration (LO), flow imaging (FI), and membrane microscopy are primarily used in the biopharmaceutical industry. LO is the preferred technique for quantifying subvisible particles as the internationally harmonized pharmacopoeia test. However, there have been several issues associated with LO for more than a decade, and FI has emerged as a promising technique to complement LO. This perspective paper discusses the efforts made by the Japanese Biopharmaceutical Consortium regarding FI to resolve issues related to LO and outlines the newly listed general information chapter of the Japanese Pharmacopoeia. Finally, the use of FI as well as future challenges for the generalization of FI are summarized from an industry perspective.