Continuous Processing for Manufacturing of Antibody-Drug Conjugates (ADCs).

Area of Science:

• Biopharmaceutical Manufacturing
• Chemical Engineering
• Drug Delivery Systems

Background:

• Antibody-drug conjugates (ADCs) merge monoclonal antibodies (mAbs) with cytotoxic drugs for targeted therapy.
• Current ADC manufacturing faces challenges including inefficiency, waste, and control over drug-to-antibody ratio (DAR).

Purpose of the Study:

• To develop and evaluate a novel continuous conjugation process for ADCs.
• To improve manufacturing efficiency, reduce costs, and enhance safety in ADC production.

Main Methods:

• Utilized a coiled flow inverter reactor (CFIR) for continuous thiol-maleimide conjugation at mAb interchain cysteines.
• Screened process parameters for thiol reduction and conjugation.
• Optimized key parameters (mAb/drug concentration, duration, temperature) using Design of Experiments (DoE).

Main Results:

• The CFIR demonstrated 64.40% higher productivity than traditional batch conjugation.
• Achieved a 70% reduction in production costs.
• Produced ADCs with clinically relevant DAR and offered a safer manufacturing alternative.

Conclusions:

• Continuous processing with CFIR offers a more efficient, scalable, and sustainable platform for ADC manufacturing.
• This approach addresses key challenges in current ADC production, paving the way for improved biotherapeutic development.