Multi-Attribute Method (MAM) offers an ideal solution for development and release of safe and effective biotherapeutics

Significance of the Topic

Biotherapeutic development demands detailed and reliable characterization of product quality attributes to ensure patient safety and therapeutic efficacy. The Multi-Attribute Method (MAM) using LC-MS consolidates multiple analyses into a single workflow, offering higher sensitivity, reproducibility, and regulatory compliance than conventional assays.

Study Objectives and Overview

This case study describes the implementation of the Thermo Scientific MAM 2.0 workflow at Northeastern University’s Biopharmaceutical Analysis and Training Laboratory (BATL). It demonstrates how seamless method transfer between research and QC instruments accelerates process development and supports regulatory filings.

Methods and Instrumentation

• Sample Preparation: Standardized enzymatic digestions with optional automation to minimize manual variability.
• Mass Spectrometry Platforms: Orbitrap Exploris 240 for discovery and characterization; Orbitrap Exploris MX for routine QC.
• Data System: Chromeleon Chromatography Data System with integrated eWorkflow for acquisition, processing, pass/fail criteria, and reporting.
• Data Analysis Software: BioPharma Finder for peptide mapping, quantitation of post-translational modifications, and new peak detection.

Main Results and Discussion

• Achieved complete sequence coverage and high reproducibility in BSA digests across replicates.
• Quantified deamidation and glycoform levels with minimal variability, demonstrating robust QC performance.
• Validated direct method transfer between Orbitrap Exploris 240 and Exploris MX with consistent results.
• Enabled novice users to master the MAM workflow—from sample prep to data review—in a matter of weeks.

Benefits and Practical Applications

MAM reduces total analysis time and labor by combining multiple quality attribute assays into one LC-MS experiment. Its built-in compliance features and electronic signatures facilitate GMP documentation and regulatory submissions. Consistent workflows across R&D and QC streamline decision making and improve confidence in product quality.

Future Trends and Opportunities

Extension of MAM workflows to complex biotherapeutics such as antibody-drug conjugates and cell therapies is expected. Advances in automation, data analytics, and mass spectrometer sensitivity will enhance throughput and depth of characterization. Broader regulatory acceptance and standardized protocols will drive widespread industry adoption.

Conclusion

The Thermo Scientific MAM 2.0 solution provides an integrated, end-to-end LC-MS workflow that unites research, process development, and manufacturing QC. By combining advanced Orbitrap mass analyzers, seamless eWorkflows, and expert training, it accelerates biotherapeutic development and ensures robust monitoring of critical quality attributes throughout the product lifecycle.

Instrumentation Used

• Thermo Scientific Orbitrap Exploris 240 mass spectrometer
• Thermo Scientific Orbitrap Exploris MX mass detector
• Thermo Scientific Chromeleon Chromatography Data System
• Thermo Scientific BioPharma Finder software