Developing a medium combination to attain similar glycosylation profile to originator by DoE and cluster analysis method

Scientific Reports

Zhihui Shao¹  Zhanqing Wang²  Yingfeng Huang³  Xun Zou⁴  Jian Xu⁵  Yaling Shen⁵ 

[1] CAS Key Laboratory of Synthetic Biology, CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, China;Process Development Department, Dragon Sail Pharmaceutical, Shanghai, China;R&D Laboratories, Dragonboat Biopharmaceutical, Shanghai, China;Shanghai Sanjin Bioscience and Technology, Shanghai, China;State Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Center for Biomanufacturing Technology, East China University of Science and Technology, 200237, Shanghai, China;

DOI  :  10.1038/s41598-021-86447-0

来源: Springer

【 摘 要 】

Glycosylation is critical for monoclonal antibody production because of its impact on pharmacokinetics and pharmacodynamics. Modulation of glycan profile is frequently needed in biosimilar development. However, glycosylation profile is not a single value like that of cell culture titer, hence making it challenging for the Design of Experiment (DoE) methodology to be directly applied. In this study, a Her2-binding antibody was developed as a biosimilar to Herceptin. Cluster analysis was introduced to demonstrate the similarity of glycan profiles between the samples and the reference with specific value—distance. The glycosylation was subsequently optimized with the DoE method. Basal medium and feed medium were found to be the significant factors to the glycosylation pattern. Moreover, a combination of medium and feed strategy was developed to attain the most similar glycoprotein molecule to that of the originator biologic drug. This study may provide an additional option to evaluate multivariable factors and assess biosimilarity and/or comparability in monoclonal antibody production.

【 授权许可】

CC BY