Automated, High-Throughput Infrared Spectroscopy for Secondary Structure Analysis of Protein Biopharmaceuticals

Protein higher order structure (HOS) is an important product quality attribute that governs the structure-function characteristics, safety, and efficacy of therapeutic proteins. Infrared (IR) spectroscopy has long been recognized as a powerful biophysical tool in determining protein secondary struct...

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Bibliographic Details
Published in:Journal of pharmaceutical sciences 2020-10, Vol.109 (10), p.3223-3230
Main Authors: Liu, Lucy L., Wang, Libo, Zonderman, Jeffrey, Rouse, Jason C., Kim, Hai-Young
Format: Article
Language:English
Subjects:
Automated mid-infrared spectroscopy
Comparability/biosimilarity
Microfluidic modulation spectroscopy
Protein secondary structure
Therapeutic monoclonal antibody
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Summary:Protein higher order structure (HOS) is an important product quality attribute that governs the structure-function characteristics, safety, and efficacy of therapeutic proteins. Infrared (IR) spectroscopy has long been recognized as a powerful biophysical tool in determining protein secondary structure and monitoring the dynamic structural changes. Such biophysics analyses help establish process and product knowledge, understand the impact of upstream (cell culture) and downstream (purification) process conditions, create stable formulations, monitor product stability, and assess product comparability when process improvements are implemented (or establish biosimilarity to originator products). This paper provides an overview of a novel automated mid-IR spectroscopic technique called microfluidic modulation spectroscopy (MMS) for the characterization of protein secondary structure. The study demonstrates that MMS secondary structure analysis of therapeutic monoclonal antibodies (mAb) is comparable with a conventional Fourier transform infrared (FTIR) method. More importantly the study shows MMS exhibits higher sensitivity and repeatability for low concentration samples over FTIR, as well as provides automated operation and superior robustness with simplified data analysis, increasing the utility of the instrument in determination of mAb secondary structure. Therefore, we propose that the MMS method can be widely applied in characterization and comparability/biosimilarity studies for biopharmaceutical process and product development.
ISSN:0022-3549
1520-6017
DOI:10.1016/j.xphs.2020.07.030