ADC Payloader-Linker CMC Process Development Strategy

With expanding ADC pipelines and more complex conjugate designs, payload-linker CMC strategy can be a key driver of IND-to-NDA success. As novel modalities continues to develop rapidly, innovative and AI-enabled responsive linkers, highly toxic payloads with low immunogenicity, and site-specific glycoconjugation techniques are receiving increasing attention. In this webinar, Dr. Zheng Wei will share a practical payload-linker CMC development strategy across four areas: guidance and interpretation, route design and principles for regulatory starting material (RSM) selection, stage-appropriate quality control (QC) strategy, and separation/purification process optimization.

The session highlights how payload-linker CMC planning differs between clinical supply and commercial registration, and what drives route definition and RSM designation, using an IND vs NDA case to illustrate stage-appropriate route planning. It also explains how QC expectations shift from release testing/characterization to CQA-linked specifications, with optimization considerations mapped to a typical process flow

Key takeaways

• Key guideline statements referenced for payload-linker CMC, and scientifically justified adjustments under technical constraints
• Route definition and RSM designation strategy for registration planning across clinical and commercial stages
• Stage-appropriate QC strategy from release testing and characterization to CQA-linked specifications, with impurity-control considerations
• Optimization considerations across purification, crystallization, lyophilization, ultrafiltration, and nanofiltration