Evaluation of structural characteristics of therapeutic antibodies by Multi-attribute method

Description:
Therapeutic monoclonal antibodies (mAbs) undergo many modifications, including deamidation, isomerization, oxidation and glycosylation, during the manufacturing process and storage. Some modifications are linked to the biological activities, pharmacokinetics, and structural stability of mAbs. To ensure product quality of mAbs, it is important to establish a control strategy ensuring that the structural properties, of which the change has potential impacts on efficacy or safety, are within an appropriate limit, range or distribution. To date, evaluation methods for the chemical structural characteristics of mAbs using several chromatographic techniques have been successfully established. However, most of these conventional methods, including reversed-phase liquid chromatography, ion exchange chromatography and hydrophobic interaction chromatography, usually only indirectly evaluate the limited characteristics of mAbs, and therefore, complicated and time-consuming multiple tests are required to perform a comprehensive structural characterization of mAbs. Currently, the integration of these tests is one of the challenges in the biopharmaceutical industry. A quantitative analytical method called Multi-attribute method (MAM) based on a peptide mapping technique using liquid chromatography/high resolution mass spectrometry is attracting attention as an alternative to conventional methods. MAM can provide detailed qualitative and quantitative information about multiple structural aspects and process and product-related impurities in only a single run. Recently, several MAM systems have been provided by mass spectrometer and software vendors, and they are gradually gaining popularity in regulatory authorities as well as industry. This presentation will describe major modifications of mAbs and our research and the issues of MAM analysis.

Speaker: Noritaka Hashii - Division of Biological Chemistry and Biologicals, National Institute of Health Sciences
Noritaka Hashii is the section chief of Division of Biological Chemistry and Biologicals, National Institute of Health Sciences (NIHS), Japan.
He received his bachelor’s, master’s and PhD degrees in pharmacy from Josai University in 1998, 2000 and 2003, respectively.
He also worked at NIHS as a postdoc from 2003. Since 2005, he has been working at NIHS as a researcher.
His research interests include the regulatory science of biopharmaceuticals, especially the evaluation of structural characterization of glycoproteins by liquid chromatography/mass spectrometry.