Evaluation of Higher Order Structure of Biologics at Atomic Resolution using NMR

The need for high-resolution techniques is regarded as being urgent for Higher Order Structure (HOS:secondary, tertiary and quaternary structure) comparability and similarity assessment. Recently, new developments in acquisition and data analysis have emerged to establish NMR as a powerful tool for HOS characterization of intact molecules at natural abundance.

The application of 1D and 2D NMR of the intact molecule at isotope natural abundance to routine analyses (characterization for comparability/similarity) will be presented. Fast 1D fingerprinting methods will give a quick answer if a batch is comparable to another or to the reference material. To identify changes at the amino acid level, 2D NMR methods are required. Results obtained from three real case studies will be discussed: a nanobody (40 kDa molecule in simple buffer) and two recombinant mAbs in a complex buffer (142 kDa and 177 kDa, respectively).

There is no single solution to the problem of evaluation of HOS. Techniques typically used for HOS characterization (CD, HDX-MS, fluorescence, FT-IR, thermal analysis by NanoDSC) measure different aspects of structure, either directly and indirectly. NMR offers superior resolution, sensitivity, and characterization of multiple structural aspects with a single experiment.

• How NMR provides a solution to the need for Atomic Resolution in HOS characterization;
• How NMR can be applied to intact molecules at natural abundance, with acquisition times reasonable for routine analysis;
• How NMR is a high precision analytical technique and produces data that is the ideal input for robust statistical tools required for HOS evaluation;

This webinar will be of interest to those involved in the development and manufacturing of biologics and biosimilars, especially in their analysis, testing and quality control - analytical R&D, QC, QA scientist and leaders seeking to enhance and optimize their analytical capabilities with cutting-edge, information-rich technology. Also relevant for academics developing analytical methods for the study of therapeutic drugs and those working in close collaboration with the biopharmaceutical industry.