Charge heterogeneity is a critical quality attribute for therapeutic biologics including antibody-drug conjugates (ADCs). Developing an ion exchange chromatography (IEX) or an imaged capillary isoelectric focusing (icIEF) method for ADCs with high drug-to-antibody ratio (DAR) is challenging because of the increased hydrophobicity from the payload-linker, DAR heterogeneity, and payload-linker instability. A sub-optimal method can be poorly stability-indicating due to the inability to discern contributions from charge and size variants conjugated with different number of drugs/payloads. Systematic strategy and guidance on charge variant method development is highly desired for high DAR ADCs with various complex structures.

中文翻译：

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高 DAR ADC 电荷变体的成像毛细管等电聚焦方法开发


电荷异质性是治疗性生物制剂（包括抗体-药物偶联物 （ADC））的关键质量属性。为具有高药物抗体比 （DAR） 的 ADC 开发离子交换色谱 （IEX） 或成像毛细管等电聚焦 （icIEF） 方法具有挑战性，因为有效载荷接头的疏水性增加、DAR 异质性和有效载荷接头不稳定性。由于无法辨别与不同数量的药物/有效载荷偶联的电荷和大小变体的贡献，次优方法的稳定性指示可能很差。对于具有各种复杂结构的高 DAR ADC，非常需要关于电荷异构体方法开发的系统策略和指导。