Challenges And Solutions In Lyophilization Development For Antibody-Drug Conjugates (ADCs)

By Gregory Sacha, Ph.D.

Antibody-drug conjugates (ADCs) provide highly targeted delivery of therapeutics to specific cancer cells. Due to the inherent instability of the antibody component, which can aggregate and fall out of solution, approximately 90% of commercially available ADCs are manufactured as lyophilized powders to enhance stability and extend shelf-life.

However, the nature of ADCs—containing both biologic and small molecule components—presents unique challenges for lyophilization. The temperature and pressure parameters for the three basic steps of freeze-drying (cooling, primary drying, and secondary drying) must be individually optimized for each unique ADC to ensure the final product meets its pre-defined safety, efficacy, quality, and stability parameters.

A robust development approach begins with thermal characterization, utilizing differential scanning calorimetry (DSC) and freeze-dry microscopy (FDM) to identify critical parameters like the glass transition temperature, eutectic melting temperature, and the product's failure point. Understand the technical depth required for successful ADC lyophilization development.