(596f) Challenges in Process Development of Antibody Drug Conjugates (ADCs)

Antibody drug conjugates (ADCs) are a class of biopharmaceutical drugs in which a cytotoxic agent is chemically linked to an antibody that recognizes a tumor-associated antigen. The basic strategy is to combine target selectivity of antibodies with the potent cytotoxic molecules, with a goal of generating drugs that are highly efficacious and also safe.

Pfizer Biotherapeutics Pharmaceutical Sciences is responsible for developing scalable manufacturing processes for Pfizer’s portfolio of ADCs. Process development group is engaged in initially receiving the technology from discovery groups/external collaborators and developing the technology further for preparation of these ADCs from small scale (several grams) to large scale (hundreds of grams to kilograms). Pfizer’s early stage ADCs utilize several conjugation chemistries via cysteines, lysines or glutamines on the antibody as well as several different linkers and payloads. Each ADC molecule, even of the same type of conjugation chemistry, poses unique challenges for process and analytical development groups in the development and implementation of preparative and analytical technologies.

This presentation highlights conjugation and purification development of ADCs to illustrate Pfizer’s development paradigm. In the process development arena the approach to maintain acceptable yields while maintaining quality attributes will be discussed. Our emphasis on thorough characterization of the final product will be discussed as well as consistency across multiple batches.