Improve confidence and productivity on a MAM platform designed for QC

Significance of the Topic

Multi-attribute method (MAM) workflows are critical for quality control in biopharmaceutical manufacturing. They enable simultaneous monitoring of multiple product quality attributes (PQAs) and detection of unexpected variants, improving assurance of product consistency and safety.

Objectives and Overview of the Study

This application note describes Thermo Scientific™ MAM 2.0, an end-to-end QC platform. The goal is to demonstrate consistent quantitation of critical quality attributes (CQAs) and reliable new peak detection across multiple instruments, while ensuring compliance with regulations such as 21 CFR Part 11.

Methodology and Instrumentation

The workflow combines high-performance liquid chromatography with high-resolution mass spectrometry and integrated software control:

• Chromatographic separation using the Thermo Scientific™ Vanquish™ Flex or Horizon UHPLC system
• Mass detection with Orbitrap Exploris™ MX mass detector operating in full MS mode
• Data acquisition, processing and report generation via 21 CFR Part 11-ready Chromeleon™ CDS software

Main Results and Discussion

Reproducibility of NISTmAb N-glycosylation monitoring was assessed across ten technical replicates on separate Orbitrap Exploris MX units. Relative standard deviations for five glycoforms ranged from 2.3 % to 4.1 %, demonstrating instrument-to-instrument variation below 5 %. Consistent new peak detection confirmed the suitability of the platform for routine QC.

Benefits and Practical Applications

The MAM 2.0 workflow offers:

• Accurate and consistent CQA monitoring for batch release decisions
• Automated execution of sample analysis, reducing user intervention and error
• Direct transfer of methods from development to QC to minimize re-validation effort
• Compliance with data integrity regulations through Chromeleon CDS
• Dedicated support services for high uptime and rapid troubleshooting

Future Trends and Applications

Advancements may include integration of artificial intelligence for automated peak annotation, expansion of MAM to complex biotherapeutics beyond monoclonal antibodies, and real-time inline monitoring to accelerate process development and release testing.

Conclusion

Thermo Scientific MAM 2.0 delivers a robust, compliant, and reproducible QC solution for biopharmaceutical attribute monitoring. Its consistent performance across instruments and streamlined workflows help laboratories meet global regulatory requirements while improving operational efficiency.