Abstract
Recent years have brought major shifts in the way that drug manufacturers are approaching the design and development of novel therapeutics with multifunctional drugs taking center stage. These complex modalities include antibody-drug conjugates, antibody-oligonucleotide conjugates, peptide conjugates, and other engineered modalities that combine large and small molecule components within a single therapeutic system.
Bioanalysis, like therapeutic modalities, has traditionally been divided into two distinct categories: small molecule methods, predominantly based on LC-MS, and large molecule methods that are largely comprised of immunoassays. However, as the boundaries between small and large molecule therapeutics become increasingly difficult to segregate, so have the methods used to support them. As such, providing bioanalytical support for complex modalities cannot be approached using small versus large molecule thinking but instead require a combination of ligand-binding assays, LC-MS, hybrid immunocapture methods, immunogenicity assessments, and complementary characterization methods.
This presentation and discussion will explore how bioanalytical strategies must evolve from platform-based testing toward integrated, question-led approaches. Using complex therapeutics as examples, we will examine analyte identification, reference material verification, sample stability, platform selection, method validation, and the interpretation of multiple PK species.
The future of bioanalysis will not be defined by choosing between LC-MS and immunoassays, but by knowing how to take a comprehensive approach to generate a coherent picture of drug exposure, disposition, and biological activity by selecting and integrating the appropriate technologies to answer the scientific questions at hand.
