Innovative Analytical Characterization to Characterize Key Quality Attributes of Antibody-Drug Conjugates (ADCs)

The rapid evolution of biotherapeutics has brought forth a new era of complex drug modalities. Antibody-drug conjugates (ADCs) represent a rapidly advancing class that combines the targeting capabilities of monoclonal antibodies (mAbs) with the cytotoxic potential of small-molecule drugs by covalently attaching these drugs via chemically stable linkers to mAbs.
ADCs have an increased level of complexity as the heterogeneity of conjugation cumulates with the inherent microvariability of the biomolecule, compared to traditional drug modalities. As a result, these new modalities require innovative and advanced analytical methods to support process development, analytical characterization, formulation development, and to ensure product quality, safety, and efficacy.
Analytical characterization has evolved significantly during the CMC development of ADCs to effectively assess three key quality attributes: Drug-to-Antibody Ratio (DAR), Drug Load Distribution (DLD), and quantitation or evaluation of unconjugated mAb. We will explore state-of-the-art analytical strategies for the characterization of ADCs, with a focus on innovative techniques for determining these quality attributes. We will provide insights into various emerging technologies, discuss the most appropriate techniques for different molecules, and illustrate the pros and cons of each approach for assessing specific quality attributes, to inspire the adoption of innovative analytical methods that streamline development and facilitate the safe introduction of new drug modalities to the market.