Denosumab (trade name Prolia) is a human IgG2 monoclonal antibody with the primary function of stopping the development of cells which specifically break-down bone. Due to this function, it is approved for the treatment of osteoporosis, bone loss, bone metastases, and giant cell tumor of bone.

Biosimilar Characterization Considerations

The guidelines state that characterization of Denosumab products should include determination of physicochemical and structural properties, purity, impurities and quantity in line with ICH Topic Q6B:

Structural Characterization

Physicochemical Characterization

Product Specific Technical Considerations

Particular attention should be paid to the Post Translational Modifications (PTMs) including:

  1. Levels of Pyroglutamination of the light and heavy chains
  2. Disulfide bridges
  3. Heavy chain C-terminal Lysine
  4. Glycosylation (in particular galctosylation and fucosylation levels)
  5. Deamidation
  6. Oxidation