Manufacturers strive to avoid even small differences in the molecules that make up a biotherapeutic. In a monoclonal antibody, for instance, one post-translational modification could change the efficacy and safety. With the multi-attribute method (MAM), scientists can use mass spectrometry to characterize the structure and modifications in such biotherapeutics.
“With MAM, you get more information than with some conventional methods, like released-glycan analysis,” said Casey Snodgrass, market segment leader, pharmaceutical biotechnology, Hamilton Company. For example, released-glycan analysis doesn’t provide specific information on the location of modified residues, but MAM provides that in detail.
In bioprocessing, MAM improves quality control. “Being able to monitor modifications in detail and seeing heterogeneity—what percentage of molecules are modified in a batch—can be used to assess the quality of a biotherapeutic,” Snodgrass explained.
To make MAM easier to use, Hamilton developed in-tip sample-preparation workflows using their liquid-handling robots. Here, the reactions take place in specialized pipette tips. “In a partnership with IMCS, we added a size-exclusion step on the robot, and we’re now automating MAM sample prep with good results,” Snodgrass said. “One major benefit of MAM is the ability to detect new peaks from batch to batch,” Snodgrass added. “If you detect a new peak, it could indicate that there was an unexpected modification, which could mean that there is a problem with the biotherapeutic batch.”
With a sample taken from a bioprocessing line, Hamilton’s automated MAM sample preparation workflow can be used to process the material for downstream analysis. “This replaces some conventional methods, like released-glycan analysis, and improves the data,” Snodgrass said. “Plus, automating the sample prep provides more reproducible results from run to run.”
The future looks promising for putting MAM in bioprocessing facilities. As Snodgrass noted, “MAM is being adopted by regulatory agencies.” So, with growing regulatory support and robust methodology, more MAM surely lies ahead in bioprocessing.