title: Biosimilar structural comparability assessment by NMR: from small proteins to monoclonal antibodies.
abstract: Biosimilar drug products must have a demonstrated similarity with respect to the reference product's molecules in order to ensure both the effectiveness of the drug and the patients' safety. In this paper the fusion framework of a highly sensitive NMR fingerprinting approach for conformational changes and mathematically-based biosimilarity metrics is introduced. The final goal is to translate the complex spectral information into biosimilarity scores, which are then used to estimate the degree of similarity between the biosimilar and the reference product. The proposed method was successfully applied to a small protein, i.e., filgrastim (neutropenia treatment), which is the first biosimilar approved in the United States, and a relatively large protein, i.e., monoclonal antibody rituximab (lymphoma treatment). This innovative approach introduces a new level of sensitivity to structural changes that are induced by, e.g., a small pH shift or other changes in the protein formulation.
authors: Protein Biophysics and Bioinformatics Department, Sandoz Biopharmaceuticals, Kolodvorska 27, SI-1234 Mengeš Slovenia.
authors: Boštjan
authors: B
authors: Japelj
authors: Slovenian NMR Centre, National Institute of Chemistry, Hajdrihova 19, SI-1000 Ljubljana, Slovenia.|EN-FIST Centre of Excellence, Trg Osvobodilne fronte 13, SI-1001, Ljubljana, Slovenia.
authors: Gregor
authors: G
authors: Ilc
authors: Protein Biophysics and Bioinformatics Department, Sandoz Biopharmaceuticals, Kolodvorska 27, SI-1234 Mengeš Slovenia.
authors: Jaka
authors: J
authors: Marušič
authors: Protein Biophysics and Bioinformatics Department, Sandoz Biopharmaceuticals, Kolodvorska 27, SI-1234 Mengeš Slovenia.
authors: Jure
authors: J
authors: Senčar
authors: Protein Biophysics and Bioinformatics Department, Sandoz Biopharmaceuticals, Kolodvorska 27, SI-1234 Mengeš Slovenia.
authors: Drago
authors: D
authors: Kuzman
authors: Slovenian NMR Centre, National Institute of Chemistry, Hajdrihova 19, SI-1000 Ljubljana, Slovenia.|EN-FIST Centre of Excellence, Trg Osvobodilne fronte 13, SI-1001, Ljubljana, Slovenia.|Faculty of Chemistry and Chemical Technology University of Ljubljana, Večna pot 113, SI-1000 Ljubljana, Slovenia.
authors: Janez
authors: J
authors: Plavec
mesh_terms: D059451:Biosimilar Pharmaceuticals / Q000737:chemistry*; D000069585:Filgrastim / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D000069283:Rituximab / Q000737:chemistry*
chemical_list: D059451:Biosimilar Pharmaceuticals; D000069283:Rituximab; D000069585:Filgrastim