Monitoring the Critical Quality Attributes of Antibody Drug Conjugates (ADCs) as Part of Biosimilar Development: Case Studies of Ado-Trastuzumab Emtansine

摘要

The recent commercial success of FDA approved antibody drug conjugates (ADCs) validates the ADCs as a therapeutic approach and it prompts great interests in developing their biosimilar candidates. On account of the increasing level of ADC sample complexity that comes from the heterogeneity of the conjugation, it is crucial to implement efficient, routine and robust analytical capabilities to characterize the heterogeneity of drug-linker content and other PTM modification sites as well as to demonstrate lot-to-lot consistency or product stability. In this study, we present a LC/MS accurate mass screening method for monitoring multiple critical quality attributes of ADCs across innovator and its biosimilar candidates at peptide level. The establishment of these assays is crucial to ensure biosimilar ADCs comparability.