Zhiqiang An
Wenxin Luo
Ningshao Xia
Qinjian Zhao
1 State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen 361105, China;
2 School of Life Sciences, Xiamen University, Xiamen 361105, China;
3 Texas Therapeutics Institute, The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX 77054, USA
Funds: The authors acknowledge the funding supports from the National Natural Science Foundation of China (31670939, 81471934 and 31600748), and Fujian Provincial Science and Technology Projects & Natural Science Foundation (2014Y2004 & 2017J01066).
Received Date: 2017-04-30
Rev Recd Date:2017-06-29
Abstract
Abstract
Monoclonal antibody (mAb)-based therapeutics are playing an increasingly important role in the treatment or prevention of many important diseases such as cancers, autoimmune disorders, and infectious diseases. Multidomain mAbs are far more complex than small molecule drugs with intrinsic heterogeneities. The critical quality attributes of a given mAb, including structure, post-translational modifications, and functions at biomolecular and cellular levels, need to be defined and profiled in details during the developmental phases of a biologics. These critical quality attributes, outlined in this review, serve an important database for defining the drug properties during commercial production phase as well as post licensure life cycle management. Specially, the molecular characterization, functional assessment, and effector function analysis of mAbs, are reviewed with respect to the critical parameters and the methods used for obtaining them. The three groups of analytical methods are three essential and integral facets making up the whole analytical package for a mAb-based drug. Such a package is critically important for thelicensure andthepost-licensure lifecycle management of a therapeutic or prophylactic biologics. In addition, the basic principles on the evaluation of biosimilar mAbs were discussed briefly based on the recommendations by the World Health Organization.Keywords: monoclonal antibody,
molecular characterization,
ligand binding assay,
cell based assay,
heterogeneity,
functional assessment
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