Chinese Journal of Magnetic Resonance ›› 2015, Vol. 32 ›› Issue (2): 342-353.doi: 10.11938/cjmr20150216

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Higher Order Structure Assessment of Biosimilars Based on the Correlation of NMR Spectral Fingerprints

XU Mei-feng,FANG Jun-jian,DONG Fang-ting,YAN Xian-zhong*   

  1. National Center of Biomedical Analysis, Beijing 100850
  • Received:2015-02-16 Revised:2015-05-08 Online:2015-06-05 Published:2015-06-05
  • About author:XU Mei-feng (1986-), female, born in Fujian, Master, her research focuses on liquid NMR, Tel: +86-10-66931443, Fax: +86-10-68246161, E-mail: xumeifeng103@126.com. *Corresponding author: YAN Xian-zhong, Tel: +86-10-66930305, E-mail:yanxz@proteomics.cn.
  • Supported by:

    The National Science and Technology Major Projects (2014ZX09304311-001, 2012ZX09301003-001-010).

Abstract:

A procedure based on the 1H NMR fingerprints of biologics was established for the assessment of higher order structure of biosimilar samples. The global correlation coefficients r and R2 of binned NMR spectra were used to quantify structural similarity between biosimilars and originators, and a local correlation analysis method was used to find out the specific regions that contribute to the structure differences. This method was applied to the quantitative
assessment of daptomycin, a lipopeptide antibiotic with a molecular weight of 1 620, by comparing the higher order structure of the biosimilar active pharmaceutical ingredient (API), its injection and originator injection Cubicin. The results showed that there were significant spectral differences among daptomycin samples, indicating structural differences between daptomycin originator and its biosimilars. Local correlation analysis further revealed the specific spectral regions that contributed to these differences. The method was also applied to a monoclonal antibody drug Trastuzumab, which is a large protein with a molecular weight of 145 423. 1H NMR spectra of the originator drug Herceptin and four lots of its biosimilar were recorded and binned for statistical analysis. The correlation coefficients r and R2 showed that Trastuzumab biosimilars seem to be highly similar to Herceptin. These results demonstrated that the combination of NMR fingerprints and statistical analysis is a powerful and robust technique in biosimilar quality control.

Key words: NMR fingerprint, biosimilar, similarity assessment, higher order structure

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