Tracking the Behavior of Monoclonal Antibody Product Quality Attributes Using a Multi-Attribute Method Workflow

The multi-attribute
method (MAM) is a liquid chromatography–mass
spectrometry based method that is used to directly characterize and
monitor many product quality attributes and impurities on biotherapeutics,
most commonly at the peptide level. It utilizes high-resolution accurate
mass spectral data which are analyzed in an automated fashion. MAM
is a promising approach that is intended to replace or supplement
several conventional assays with a single LC-MS analysis and can be
implemented in a Current Good Manufacturing Practice environment.
MAM provides accurate site-specific quantitation information on targeted
attributes and the nontargeted new peak detection function allows
to detect new peaks as impurities, modifications, or sequence variants
when comparing to a reference sample. The high resolution MAM workflow
was applied here for three independent case studies. First, to monitor
the behavior of monoclonal antibody product quality attributes over
the course of a 12-day cell culture experiment providing an insight
into the behavior and dynamics of product attributes throughout the
process. Second, the workflow was applied to test the purity and identity
of a product through analysis of samples spiked with host cell proteins.
Third, through the comparison of a drug product and a biosimilar with
known sequence variants. The three case studies presented here, clearly
demonstrate the robustness and accuracy of the MAM workflow that implies
suitability for deployment in the regulated environment.