The Multi-Attribute Method (MAM) as a Biologics Lifecycle Backbone

The Multi-Attribute Method (MAM) is a comprehensive approach designed to streamline quality control across the lifespan of a biologic product. Rather than relying on a single instrument or assay, MAM employs a council of various instruments, each specialized in detecting specific product quality attributes. These attributes can include selected critical quality attributes, deamidation, oxidation, site-specific glycoforms, sequence variants, and other product-related features.

The MAM framework consists of two primary movements: a broad characterization phase and a monitoring phase. During the characterization phase, a product-specific peptide library is assembled using a peptide-mapping LC-HRMS workflow. This library serves as the foundation for the monitoring phase, where the relative abundance of selected attributes is tracked batch after batch.

MAM's unique strength lies in its new peak detection capability. This feature uses a threshold-based comparison to identify any unexpected peptide-level features, flagging them for further review. This proactive approach allows for the detection of unexpected changes while the process is still in development, rather than after the process has been locked in place. This can be particularly valuable in situations where the attribute that ultimately matters may not have been predicted earlier in the process.

When a biologic product undergoes changes, such as shifting from a perfusion process to a fed-batch process or moving to a second manufacturing site, MAM can provide continuous evidence of the product's quality attributes. This continuity can strengthen the comparability package, making it less of an emergency to build and present to regulators. Instead of piecing together scattered legacy assays, MAM allows for a seamless continuation of data, providing a more robust defense of comparability.