Aggregation In Antibody-Drug Conjugates: Causes And Mitigation

Advancing antibody-drug conjugate (ADC) candidates to clinical trials, full-scale GMP manufacturing, and eventual commercialization is often a slow and complex process. Unlike traditional monoclonal antibodies (mAbs), ADCs present unique challenges due to their intricate structure, which complicates the definition, optimization, and assurance of critical quality attributes (CQAs). One of the most significant hurdles in ADC development is protein aggregation—the clustering of ADC molecules—which can severely impact the drug’s stability, efficacy, and safety. This aggregation typically arises from conformational and/or colloidal instability. Conformational instability may lead to globally or partially unfolded molecular states, or near-native states, while colloidal instability results from self-interactions among these various molecular forms.

Addressing these challenges early in development is crucial to ensuring a successful path to commercialization. Explore how experts who understand the complexities of ADCs can help you navigate the path from development to delivery with confidence.