Division of Monoclonal Antibody Products,Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Product, National Institutes for Food and Drug Control, Beijing 100050,China
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.
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