抗体药物偶联物即adc类药物的生物分析.pdf

Bioanalysis of antibody–drug conjugates 总结与评论专员 章登吉 Bioanalytical challenges from ADC  multicomponent structure(Mixtures)  inherently heterogeneous  dynamic nature  Therefore, multiple analytes are utilized to determine PK and fate of ADCs in vivo Analytes commonly assessed for ADC *DAR: Drug to Antibody Ratio Linker and linker-small molecule should also be considered based on your case. assessed for ADC PK/TK Assay strategies  Platforms commonly used for ADC:  Ligand binding assay: ELISA or other methods  LC-MS/MS Assay format: Intact ADC: Target human tumor antigen or anti-drug Ab as capturing reagents Total mAb: Target human tumor antigen as capturing reagents usually PK/TK Assay validation for ADC General Bioanalytical guidelines for bioanalysis can be used for ADC PK/TK Assays:  生物样品定量分析方法验证指导原则(2015版药典）  Guidance for Industry: Bioanalytical Method Validation(FDA,2013)  Guideline on bioanalytical method validation (EMA,2011) Validation parameters  Standard curve  LLOQ/ULOQ  Accuracy and Precision  Selectivity  Specificity  Dilution linearity  Parallelism  Stability  Although there are no specific guidelines for validating LBA- or LC-MS/MS-based PK/TK assays for ADC, there is strong scientific rationale to use the general guidelines therapeutic protein and small molecule assay validation as much as possible. Example: TK assays(EIA methods) for one ADC perfo 180000 系列1 160000 140000 系列2