Application of Microflow Digital Imaging in Sub-visible Particle Detection of Monoclonal Antibodies / 中国药学杂志

ABSTRACT

OBJECTIVE: To explore the application value of microflow digital imaging (MDI) in sub-visible particle detection of monoclonal antibodies(mAbs). METHODS: Polystyrene latex particles were adopted as standard particles to evaluate the stability and accuracy of MDI, then MDI was used to detect the quantities and compositions of sub-visible particles with diameters of ≥10 μm and ≥25 μm in two groups of mAbs. One group containing three mAbs from different companies against EGFR was selected to show the compositional difference of sub-visible particles. Another group was set to evaluate the impact of storage conditions on stability of sub-visible particles in mAb against TNF-α. The storage conditions included 4℃, 37℃ and exposure under light of 6 000 lx. RESULTS: Using polystyrene latex particles, MDI method showed acceptable stability and accuracy. The analysis showed that the numbers of sub-visible particles in mAbs from Company 1 and Company 2 were comparable, but their main compositions were non-protein and protein particles separately. The number of sub-visible particles in mAb from Company 3 was much higher than that of Company 1 and Company 2 and the sub-visible particles included both non-protein and protein particles, indicating differed strategies should be adopted to control sub-visible particles. It was also found that the selected antibody against TNF-α was much more unstable when stored at 37℃ or exposed under light of 6 000 lx as the quantities of protein particles were increased dramatically, which suggested the obvious impact of storage conditions on stability of protein in mAbs. CONCLUSION: MDI can provide not only diameters and the quantities of sub-visible particles, but also morphological information and tell the nature of the particles. These functions are powerful tools for sub-visible particle control and quality evaluation of mAbs.