(596d) Process Development and Scale-up of an ADC Conjugation Process

Antibody-drug conjugates (ADCs) are a class of pharmaceuticals that use an antibody to selectively deliver a cytotoxic drug to cancer cells. Critical quality attributes (CQAs) are controlled by means of the input quality of antibody and small molecule drug/linker components as well as execution of the conjugation within defined process parameter ranges. Fairly minor changes in ADC process parameters may have the potential to result in changes to the drug substance CQAs. Furthermore, the limitations of in-process sampling may not offer immediate detection nor the potential for corrective action. Thus, in-depth understanding of the conjugation process, determination of scale-dependent parameters, and operating knowledge of manufacturing equipment are essential elements necessary to develop a control strategy. This presentation will provide an overview of the experiences learned from a successful scale-up campaign.