Rich Rogers discusses his vision of what the future may hold for the multi-attribute method (MAM) in the biopharmaceutical industry

Importance of the Topic

The multi-attribute method (MAM) represents a transformative analytical approach in biopharmaceutical development and quality control. By combining peptide mapping with high-resolution mass spectrometry and new peak detection, MAM enables comprehensive monitoring of critical quality attributes (CQAs) in biologics. This depth of molecular insight supports a Quality by Design (QbD) framework, driving enhanced process understanding, tighter manufacturing control, and potential consolidation of multiple traditional release assays into a single workflow.

Objectives and Overview of the Article

This case study interview with Rich Rogers, president of the MAM Consortium, outlines the origins, regulatory milestones, and strategic aims of MAM adoption. It reviews how the industry consortium formed, defines the core components of MAM, and highlights the collective effort to gain regulatory acceptance and streamline implementation in quality control laboratories.

Methodology and Instrumentation

• Attribute Analytics: Targeted LC-MS analysis monitors predefined post-translational modifications, degradations, and impurities.
• High-Resolution Accurate Mass Spectrometry: Instruments such as the Thermo Scientific Q Exactive Plus provide high sensitivity and mass accuracy for intact and fragmented peptides, enabling precise identification of product variants.
• New Peak Detection (NPD): Differential analysis highlights unexpected or emerging peaks by comparing test samples with reference standards, offering a route to replace conventional purity assays.

Key Results and Discussion

The article recounts the first FDA acceptance of MAM data in 2019, marking a major regulatory success. It describes robust MAM workflows: initial full characterization of the molecule, setting up a targeted list of product quality attributes (PQAs), routine monitoring via LC-MS/MS, and application of NPD to flag new modifications. Collaborative efforts within the MAM Consortium have clarified terminology, standardized best practices, and addressed challenges around system suitability, data robustness, and software upgrades.

Benefits and Practical Applications

• Improved Process Understanding—Quantitative tracking of CQAs throughout development accelerates troubleshooting and process optimization.
• Consolidation of Assays—MAM has the potential to replace multiple traditional release tests (glycan analysis, charge variants, host cell protein assays) with a single mass spectrometry workflow.
• Regulatory Confidence—Early dialogue and collective data submission to agencies pave the way for MAM acceptance as a release method.

Future Trends and Opportunities

• Automation—End-to-end workflows from bioreactor sampling through automated digestion to LC-MS analysis and report generation will drive throughput and consistency.
• Software Templates—Prebuilt target lists for common antibody modification hotspots will speed method development and transfer across laboratories.
• Enhanced NPD Capabilities—Integration of MS2 data capture for new peak confirmation will strengthen the regulatory case and support expert review processes.

Conclusion

MAM stands poised to revolutionize biopharmaceutical analytics by unifying multiple quality assays into a single, mass spectrometry–based platform. Its adoption relies on strong collaborations among industry, vendors, and regulators to establish robust workflows, standardized software solutions, and effective system suitability testing. As automation and advanced data analytics mature, MAM will further accelerate biologics development and streamline product release.

Reference

Rich Rogers. Development of a quantitative mass spectrometry multi-attribute method for characterization, quality control testing and disposition of biologics. 2015. FDA acceptance noted in 2019.