Multi-Attribute Method Analysis: Moving Toward The Mainstream For Biotherapeutic Development

By Scott Berger, Ph.D., Sr. Manager Biopharmaceutical Markets, Waters Corporation

The heterogeneity of biopharmaceuticals, both naturally occurring and the result of modifications such as oxidation, glycation, or deamidation, has created a need for robust monitoring tools that capture potential shifts in a drug product profile. Employing the Multi-Attribute Method (MAM) based on liquid chromatography-mass spectrometry (LC-MS) analysis of biotherapeutics represents a critical advancement in evaluating the increasing complexity of biotherapeutic molecules, as well as improving the product and process understanding underlying that complexity.

Often undertaken through LC-MS peptide mapping analysis, MAM offers operators more detailed insights into the specific attributes of a biotherapeutic protein. This can help drug developers achieve greater process and product understanding, as these assays enable a direct measurement of the critical quality attributes of a drug product when compared to traditional assays such as optical-based chromatography or electrophoresis, which measure the aggregate of these properties indirectly. Other levels of MAM analysis, either at the intact protein or subunit level, can also afford varying degrees of detailed understanding of the molecular features linked to a drug product’s various safety, stability, and efficacy measures.