Key challenges that Analytical Chemists face when applying LC-MS to generate peptide maps and glycan profiles of biopharmaceuticals.
The role that Laboratory Automation plays in terms of reducing tedious and error-prone sample preparation steps that are necessary prior to characterizing biopharmaceuticals by LC-MS.
Leveraging the easy-to-use OneLab software suite and the OneLab Online Protocol Library to develop LC-MS sample preparation methods for biopharmaceuticals that can be automated on the Andrew+ Pipetting Robot.
Monoclonal antibodies and various protein molecules derived from antibodies are a very important branch of new drugs being developed in all therapy areas. Developability assessment is critical in establishing early that such molecules can advance successfully from discovery to development. This entails examination of multiple physicochemical properties, with LC-MS results arguably comprising the most significant readout. Typically, multiple protein sequences are subjected to a variety of stress conditions (high and low pH, oxidation, high temperature, etc.) to assess and identify sequence liabilities, that is amino acids that can undergo modifications (deamidation, cyclization, oxidation, disulfide bond scrambling), which may adversely affect biological activity or induce immunogenicity. This entails the generation and analysis of dozens of peptide maps, a tedious process prone to human error that is avoidable with automation.
Once one or two lead candidate sequences have been identified as having the least significant sequence liabilities, similar analyses are performed in support of cell culture and purification development and to assess stability in one or more formulations. LC-MS analyses of peptide maps and of glycosylation profiles are carried out. Again, automation can mitigate the tedium of manual sample processing and reduce human error. Finally, at the tail end of development, when a process has been finalized and material for animal studies and GMP material for human clinical studies is produced, automation is critical for the reproducibility of LC-MS analyses of peptide maps and glycan profiles that are used for the comprehensive and detailed characterization of drug product and to demonstrate process consistency.
