Straight through to breakthrough Thermo Scientific MAM 2.0 Workflow

Significance of Topic

Biopharmaceutical products require precise and efficient analytical methods to ensure safety, efficacy and consistent quality. The multi-attribute method (MAM) leverages high-resolution peptide mapping by LC-MS to monitor multiple critical quality attributes (CQAs) in a single run, aligning with Quality by Design principles and satisfying stringent regulatory expectations.

Study Objectives and Overview

This article introduces Thermo Scientific™ MAM 2.0, an end-to-end workflow designed to accelerate biotherapeutic development and streamline QC. Objectives include comprehensive CQA characterization, sensitive new peak detection, robust method transfer from R&D to QC and global data sharing.

Methodology and Instrumentation

• Peptide-mapping MAM strategy using high-resolution Orbitrap LC-MS to quantify modifications such as oxidation, deamidation, glycosylation variants and aggregation.
• Single-run analysis of multiple attributes to replace traditional profile-based assays.
• Advanced data processing with composite scoring and intelligent peak integration to achieve high specificity and sensitivity.

Used Instrumentation

• Thermo Scientific™ Orbitrap Exploris™ 240 Mass Spectrometer coupled to Vanquish™ Flex or Horizon UHPLC system for development.
• Orbitrap Exploris™ MX Mass Detector paired with Vanquish Flex or Horizon UHPLC for QC environments.
• Thermo Scientific™ Ardia™ platform for data aggregation, secure sharing and dynamic versioning.
• Chromeleon™ Chromatography Data System and BioPharma Finder™ software for compliance-ready data management and in-depth attribute analysis.

Key Results and Discussion

• Demonstrated reproducibility with relative standard deviations below 10% for low-abundance modifications and below 5% for N-glycosylation profiling across ten replicates.
• Cross-platform consistency between Exploris 240 and Exploris MX instruments, maintaining mass accuracy within 3 ppm over six weeks.
• Reduction in total assay count by consolidating multiple chromatographic and electrophoretic tests into one LC-MS run.
• Reliable new peak detection with minimized false positives and negatives, speeding decision making.

Benefits and Practical Applications

• Increased throughput by simultaneous analysis of multiple CQAs.
• Enhanced sensitivity to detect trace impurities and post-translational modifications.
• Improved data integrity and compliance via a unified enterprise data system supporting 21 CFR Part 11 requirements.
• Regulatory acceptance by agencies such as the US FDA validates MAM as a preferred analytical approach in biopharma.

Future Trends and Opportunities

• Application of MAM workflows to emerging modalities such as gene and cell therapies.
• Integration with AI-driven analytics for real-time process monitoring and predictive quality control.
• Expansion of automated and cloud-based informatics to support global labs and continuous manufacturing environments.

Conclusion

Thermo Scientific MAM 2.0 provides a scalable, robust LC-MS solution that bridges discovery and QC, enabling faster development cycles, high-confidence CQA monitoring and streamlined regulatory compliance. Implementation of this unified platform positions biopharmaceutical organizations to accelerate innovation and consistently deliver safe, effective therapies.