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KMID : 1142220230180010015
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Regulatory Research on Food, Drug & Cosmetic
2023 Volume.18 No. 1 p.15 ~ p.23
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Analysis of Charge Variants of Monoclonal Antibody in the Stress-test Condition Using CEX-HPLC
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Son Ae-Ra
Park Mi-Sun
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Abstract
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Monoclonal antibody (mAb) drugs are widely applied to the treatment of infectious diseases and immune diseases as well as cancer because of their specificity and high efficacy and are rapidly occupying the global biotherapeutics market. The quality and biological activity of mAb drugs can be sensitively affected by charge heterogeneity which is caused by unexpected protein modification including glycosylation, oxidation, and deamidation. In particular, an increase in charge variants of mAb drugs that can occur depending on the manufacturing process, pH, and temperature changes during storage and distribution, can affect the efficacy and stability of drugs. To investigate the effect of stress-test conditions on the charge variants of mAb drugs, we performed a quantitative evaluation of decomposition patterns and physicochemical changes of mAb under harsh temperature or pH conditions. Samples artificially stressed by harsh temperature and pH were measured using CEX-HPLC, which is infliximab concentrated solution?charge variants analysis method in European Pharmacopoeia. As a result, a significant change was not observed in the ratio of the main peak and each charge variants peak according to the temperature change (4~40oC). On the other hand, under severe conditions with both temperature and pH change, the significant decrease of the main % peak area of mAb was accelerated as the stress-test time elapsed, especially at 40°C. In addition, the low pH condition (2-4) significantly affected the change in the ratio of the charge variants compared to the high pH (8-9). Therefore, it is proposed to evaluate charge variants according to pH changes during the manufacturing process of mAb drugs and to monitor changes in charge variants for potentially harsh conditions during storage and transportation. In this study, we demonstrated that charge heterogeneity is highly sensitive to pH-stressed conditions, suggesting that quantitative evaluation of charge variants of mAb during the manufacturing process and storage can provide one of the good indicators for stability. These results also contribute to the efficient quality control during the life-cycle of mAb drugs as reference data.
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KEYWORD
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Monoclonal antibody drug, Charge variants, Stress-test, Stability, Quality control
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