Innovative solution for higher-order structure assessment of biopharmaceuticals combining spectroscopy with machine learning and statistical methods

Description:
The market for new modalities of biopharmaceutical, such as therapeutic antibodies and nucleic acid drugs, has been dramatically expanding over the past decade. Similarly, the development and manufacture of biosimilars are accelerating. The efficacy of biopharmaceuticals is linked to the higher-order structures (HOS) driven by covalent and non-covalent bond formation. The HOS can be affected by various stimuli during the manufacturing process, possibly resulting in the formation of various structural impurities derived from native substances leading to reduced drug efficacy. While biopharmaceuticals are a successful modality, it is crucial to understand and manage the unique nature of HOS.
Spectroscopy, including circular dichroism (CD) is a powerful tool for the rapid, non-destructive acquisition of biopharmaceuticals HOS knowledge. The international council for harmonization: ICH-Q6B guideline recommends CD spectroscopy as one of the methods for the physicochemical characterization of biopharmaceuticals, and the application of CD to biopharmaceuticals is accelerating. Fourier transform infrared (FTIR), Raman, Fluorescence, and UV/Vis spectroscopy are also known to be useful for protein characterization.
Innovative HOS evaluation of each process from R&D to production is possible by combining spectral data with machine learning and statistical methods. Furthermore, the importance of orthogonal assessment, which combines multiple spectroscopic methods with different principles, is increasing.
In this study, we report an innovative solution for the structural analysis of therapeutic antibodies using a new structure estimation algorithm, a spectral similarity evaluation methodology, and using multiple spectroscopic instruments.

Speaker: Forrest Kohl - JASCO
Dr. Forrest Kohl is an Application Scientist at JASCO specializing in electronic spectroscopy such as circular dichroism.