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Biosimilar Higher Order Structure Testing and Analysis

OVERVIEW
Testing, analysis and validation of the
higher order structures (HOS) of biosimilars is critical to the development of products that adhere to patient safety principles. SARomics Biostructures offers a multidisciplinary approach that provides the best possible comparability assessment and analysis at atomic resolution - by combining NMR spectroscopy with X-ray crystallography, we can provide both global structural information and detailed atomic position analysis, which will detect any differences in the structure of the samples.

Our biosimilars testing and analysis services are based on recent revolutionary advances in NMR spectroscopy that have made it possible without expensive isotope labeling to acquire a unique fingerprint representation of the 3D conformation of large, complex molecules like biologics. By directly matching the NMR fingerprint of a given protein to its high-resolution 3D structure, e.g. determined by X-ray crystallography, or to a fingerprint of another protein batch or a biosimilar, we can rapidly assess and analyze comparability and show that the molecules, for example a biosimilar and its originator, or different batches or alternative preparations of the same biologic, have identical higher order structure.


For the nuclear magnetic resonance (NMR) experiments we have access to a number of ultra high-filed instruments. Please see the NMR technology page and the NMR services page for details on the NMR experiments.

Oxford 900 pumped magnet, Bruker Avance III HD spectrometer
Oxford 800 pumped magnet, Bruker Avance III HD spectrometer
Oxford 800 magnet, Bruker Avance III HD spectrometer
Varian INOVA 600#1 NMR-spectrometer

Biosimilars testing, validation and analysis

Any changes in the higher order structure of biosimilars potentially caused by changes or alterations in the manufacturing process may severely worsen their quality, and are likely to affect its safety, efficacy, and pharmacokinetic properties. For this reason, regulatory agencies demand detailed assurance of comparability of biosimilars’ structures at atomic level to ensure that they are not affected by manufacturing, storage and delivery.

Commonly used analysis methods, which evaluate and analyze global properties of samples such as thermostability, chromatographic and spectroscopic parameters, do not provide the necessary detailed information on the three-dimensional structure. Only NMR spectroscopy and X-ray crystallography allow detailed analysis of the higher order structures at atomic level.