Learnings from the External Implementation of Liquid Chromatography – Mass Spectrometry Analytical Methods for the Bioanalysis of Antibody Oligonucleotide Conjugates
Senior Scientist Eli Lilly and Company Indianapolis, Indiana
The recent rise in antibody oligonucleotide conjugates (AOC) across the pharmaceutical industry necessitates the development of multiple liquid chromatographic-mass spectrometry (LC-MS) analytical methods for quantifying total antibody, antibody associated siRNA and total siRNA in regulated bioanalytical laboratories for both non-clinical and human matrices. This demand challenges sponsor bioanalytical oversight teams to explore and utilize bioanalytical labs equipped with high-resolution mass spectrometry and LC-MS expertise needed for successful AOC method development. Additionally, providing necessary resources such as capture antibody, stable label internal standards, analyte concentrations to meet Cmax needs of the sponsor programs, and sourcing CSF matrices from appropriate vendors is critical. Furthermore, bioanalytical lab timelines for delivering analytical methods for non-clinical and clinical sample analysis have increased compared to small molecule and other large molecule modalities, such as peptides and siRNA, due to the increased number of LC-MS methods required per sample. Case studies in overcoming these challenges and how they have shaped sponsor expectations for an AOC across multiple regulated bioanalytical labs will be presented to demonstrate how to maintain consistent timelines and robust analytical methods.
