Multi-Attribute Method Analysis: Avoiding Potential Traps During Assay Development And Deployment

By Scott Berger, Ph.D., Waters Corporation

Multi-Attribute Method (MAM) analysis using liquid chromatography – mass spectrometry (LC-MS) has emerged as a valuable tool for drug discovery, development, process monitoring and quality control. By affording operators greater insights into the critical quality attributes (CQAs) of a biotherapeutic protein, MAM LC-MS can help improve a drug’s safety profile and optimize its commercial viability over time. By measuring the product variation directly as specific levels of targeted product attributes, process science teams can achieve an unprecedented amount of process knowledge and control.

Despite the advantages conferred by MAM LC-MS analysis for process monitoring and quality control (QC), many bioprocess organizations are reluctant to incorporate these technologies into existing laboratory workflows. This is largely due to the perception that both running the LC-MS, as well as performing MAM analysis, require a depth of expertise that necessitates additional, highly trained personnel and a burdensome amount of work to integrate within existing monitoring paradigms. Additionally, the perceived costs of deploying these assays, as well as concerns surrounding regulatory compliance, robustness, and reproducibility have likewise served to hinder their adoption. Recent advances in the technology and automation supporting MAM LC-MS have mitigated or even eliminated the issues surrounding the complexity of these systems, facilitating robust, reliable, and automated data acquisition and processing even for novice MS users.