NIBRT research publish high impact paper in Nature Protocols

NIBRT research has made a great start to the new year with the recent publication of a high-impact paper in the prestigious journal Nature Protocols titled “Comprehensive Multi-Attribute Method Workflow for Biotherapeutic Characterization and Current Good Manufacturing Practices Testing”.

Authored by NIBRT Characterization and Comparability Laboratory scientists Dr. Silvia Millán-Martín, Dr. Craig Jakes, Dr. Sara Carillo and Prof. Jonathan Bones, and co-authored by MAM consortium leaders Dr. Da Ren and Dr. Rich Rogers, the paper guides scientists in the implementation and deployment of MAM workflow.

Over the last decade, biotherapeutics have become more and more complex in their structure, fostering the need for state-of-the-art analytical workflows to address these advances, and overcome the limitations posed by conventional methods, such as lack of sensitivity and the need to use multiple techniques orthogonally. The multi-attribute method (MAM) is an emerging analytical approach which is gaining substantial attention within the biopharmaceutical industry as the method of choice to meet Quality by Design (QbD) principle requirements for improving product and process understanding during development and manufacturing of biotherapeutics and biosimilars, ensuring product quality, safety and efficacy.

The main advantage of MAM is its ability to monitor numerous critical quality attributes (CQAs) at the amino acid level of the biopharmaceutical product simultaneously and directly, such as identity testing based on primary sequence verification, detection and quantitation of post-translational modifications and impurities, making it a more informative, streamlined and productive workflow for biopharmaceutical analysis than conventional chromatographic and electrophoretic assays. MAM relies on proteolytic digestion of the sample, followed by a high-resolution LC-MS analysis in two phases. Firstly, a discovery study to determine CQAs for monitoring followed by the creation of a targeted workbook for high-resolution retention time plus accurate mass analysis. The second aspect of MAM is new peak detection using differential analysis of the data to determine the presence, absence or change of any species that might be affect the activity or stability of the biotherapeutic.

Accordingly, there is a need for standardization of the protocol, where all the workflow steps from sample preparation, LC-MS analysis and data processing are well established and meticulously described to help the scientific community for its implementation. Method transferability between labs would also benefit from the availability of a well-established MAM protocol, a resource that was not yet available to the community.

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