In the development of biotherapeutics, a thorough understanding of a molecule’s product quality attributes (PQAs), and their effect on various structure-function relationships and long-term stability, is essential for ensuring the safety and efficacy of the product. At present, numerous routine chromatographic and electrophoretic assays are used to characterize and monitor individual PQAs. However, execution of multiple routine methods for batch release, stability time-points, and process/formulation development support becomes time and resource intensive, and often provides an indirect measure of biologically relevant PQAs. Introduced in 2015, the multi-attribute method (MAM), based on LC-MS peptide mapping and automation principles, provides simultaneous and site-specific detection, identification, quantitation, and quality control (monitoring) of PQAs.
A dedicated Pfizer team has been regularly employing MAM on an in-house MAM platform to support biotherapeutic process and product development. In parallel, this team has continually explored and implemented improvements in the Pfizer MAM platform, including sample preparation and data processing automation, to move toward the next generation of MAM. Recently, a pre-commercial demo model of the new Thermo Scientific Orbitrap Exploris MX mass detector was evaluated in-house by the Pfizer MAM team. Here, the results of the evaluation and an assessment of the Orbitrap Exploris MX mass detector’s suitability as a next generation MAM instrument are presented.
- Pfizer MAM platform milestones for characterization and routine monitoring
- Automation of sample handling and data processing and reporting
- Evaluation and optimization of the Orbitrap Exploris MX mass detector for MAM