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Implementing LC-MS Based Multi-Attribute Method (MAM) for Monoclonal Antibody Characterization

PROVEN INTELLIGENCE ACCELERATING NEXT-GENERATION THERAPIES

Implementing LC-MS Based Multi-Attribute Method (MAM) for Monoclonal Antibody Characterization

LC-MS Multi-Attribute Method (MAM) for Viral Vector Product Characterization

CELL & GENE | RNA | BIOLOGICS

Proven Intelligence Accelerating Next-Generation Therapies.

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Executive Summary

The Multi-Attribute Method (MAM) is a liquid chromatography-mass spectrometry (LC-MS) based analytical platform that monitors multiple product quality attributes within a single assay. For viral vector-based therapies, particularly those expressing therapeutic proteins like monoclonal antibodies, MAM provides a high-resolution view of product identity, purity, and post-translational modifications. This consolidated approach streamlines characterization, accelerates process development, and strengthens regulatory submissions by replacing multiple conventional assays with one information-rich method.

Frequently Asked Questions

    What is a Multi-Attribute Method (MAM)?

    MAM is a mass spectrometry-based analytical workflow used for the characterization and quality control of therapeutic proteins. It involves digesting the protein into peptides, separating them via liquid chromatography, and analyzing them by high-resolution mass spectrometry to simultaneously monitor a predefined list of product attributes, including sequence variants, glycosylation, oxidation, and deamidation.

    How does MAM apply to AAV or Adenovirus vector characterization?

    For viral vectors, MAM can be applied in two primary ways. First, it can characterize the viral capsid proteins themselves, confirming identity and identifying post-translational modifications that could impact transduction efficiency or immunogenicity. Second, it can characterize the therapeutic protein payload (e.g., a monoclonal antibody) expressed from the vector’s transgene, as demonstrated in platforms designed for in vivo protein production.

    Can MAM replace multiple conventional release assays?

    Yes, a key objective of implementing MAM is to replace several traditional, single-attribute methods such as ion-exchange chromatography (IEX), capillary electrophoresis (CE), and peptide mapping. A well-validated MAM assay can provide equivalent or superior data for multiple quality attributes, creating significant efficiencies in GxP quality control environments.

    What are the primary outputs of a MAM analysis?

    The platform provides targeted monitoring of predefined quality attributes against established acceptance criteria. It also enables “new peak detection,” which can identify unexpected modifications or impurities that might arise during manufacturing, offering a powerful tool for process monitoring and comparability assessments.

The Challenge of Characterizing Complex Protein Products

Viral vector platforms, including Adeno-Associated Virus (AAV) and Adenovirus (AdV), are increasingly engineered to produce complex therapeutic proteins directly in vivo. This approach requires analytical methods that can comprehensively characterize not only the delivery vehicle but also the resulting protein product. Traditional analytical strategies often rely on a collection of separate assays, each designed to measure a single attribute, leading to extended timelines and a fragmented view of product quality.

A consolidated analytical strategy accelerates development without compromising product understanding. The ability to monitor dozens of attributes from a single sample injection provides a more holistic profile of the biologic.

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A Consolidated Approach with LC-MS MAM

The Multi-Attribute Method leverages high-resolution mass spectrometry to provide a detailed molecular profile from a single analysis. By creating a targeted method for known quality attributes, the platform moves beyond simple characterization into a quantitative quality control tool. This method is uniquely suited for the complex products generated by next-generation therapies.

This platform supports:

  • Simultaneous monitoring of post-translational modifications (PTMs).

  • Confirmation of protein sequence and detection of variants.

  • Quantification of product-related impurities.

  • Direct comparison between manufacturing lots or process changes.

Application to Viral Vector Payloads and Capsids

The strategic value of MAM extends directly to viral vector programs. For platforms designed to achieve sustained expression of a therapeutic protein, such as an antibody, confirming the fidelity of that protein is a primary analytical objective. The scientific precedent for using AAV to deliver antibody-encoding genes for protection against respiratory pathogens [PMID: 23720583] highlights the need for methods that can characterize the resulting antibody’s structure and integrity. MAM provides the resolution to confirm that the in vivo expressed antibody matches the intended design.

Similarly, for adenovirus-based vaccines designed to express specific antigens and elicit a T-cell response [PMID: 18788905], MAM can be used during process development to ensure the identity and quality of the viral proteins that are fundamental to the vector’s function.

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Franklin Biolabs’ GxP-Compliant MAM Platform

Within our >100,000 sq ft facility, we have established a GxP-compliant MAM platform specifically to support viral vector and complex biologic programs. Our approach integrates robust analytics early in the development cycle, providing the data integrity required for confident decision-making. This analytical rigor is a component of our ability to help programs achieve their IND milestones within an 18-24 month timeline. This capability is built upon a scientific foundation that has contributed to a 100% successful IND rate for associated programs since 2019, with the Franklin Biolabs brand itself launching in 2024 to expand these services to the broader industry.

For more information on our full suite of analytical services, please visit our parent Vector | CMC | Analytics Services page.

Technical Visualization: The Multi-Attribute Method (MAM) Workflow

Scientific Process Diagram

This content is for informational purposes. For guidance specific to your therapeutic program, please contact our team for a consultation.

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