Liu Y Diana, Cadang Lance, Bol Karenna, Pan Xiao, Tschudi Katherine, Jazayri Mansour, Camperi Julien, Michels David, Stults John, Harris Reed J, Yang Feng
Pharma Technical Development, Genentech/Roche, South San Francisco, CA 94080, USA.
Bioengineering (Basel). 2022 Nov 3;9(11):641. doi: 10.3390/bioengineering9110641.
Heterogeneity of therapeutic Monoclonal antibody (mAb) drugs are due to protein variants generated during the manufacturing process. These protein variants can be critical quality attributes (CQAs) depending on their potential impact on drug safety and/or efficacy. To identify CQAs and ensure the drug product qualities, a thorough characterization is required but challenging due to the complex structure of biotherapeutics. Past characterization studies for basic and acidic variants revealed that full characterizations were limited to the basic charge variants, while the quantitative measurements of acidic variants left gaps. Consequently, the characterization and quantitation of acidic variants are more challenging. A case study of a therapeutic mAb1 accounted for two-thirds of the enriched acidic variants in the initial characterization study. This led to additional investigations, closing the quantification gaps of mAb1 acidic variants. This work demonstrates that a well-designed study with the right choices of analytical methods can play a key role in characterization studies. Thus, the updated strategies for more complete antibody charge variant characterization are recommended.
治疗性单克隆抗体（mAb）药物的异质性是由生产过程中产生的蛋白质变体所致。这些蛋白质变体可能是关键质量属性（CQA），具体取决于它们对药物安全性和/或疗效的潜在影响。为了识别关键质量属性并确保药品质量，需要进行全面的表征，但由于生物治疗药物结构复杂，这具有挑战性。过去对碱性和酸性变体的表征研究表明，全面表征仅限于碱性电荷变体，而酸性变体的定量测量存在差距。因此，酸性变体的表征和定量更具挑战性。一项针对治疗性单克隆抗体1的案例研究在初始表征研究中占富集酸性变体的三分之二。这导致了进一步的研究，填补了单克隆抗体1酸性变体的定量空白。这项工作表明，精心设计的研究以及正确选择分析方法在表征研究中可以发挥关键作用。因此，建议采用更新的策略以更全面地表征抗体电荷变体。
