Etanercept (trade name Enbrel) is a recombinant protein made by fusing the TNF-receptor and the constant region of the IgG1 antibody. It is a large biopharmaceutical with a molecular weight of 150 kDa that, similar to Humira, Simponi and Remicade, inhibits tumor necrosis factor alpha (TNFα). TNFα is central to the inflammatory response and plays a major role in inflammatory/ autoimmune diseases such as arthritis, plaque psoriasis and ankylosing spondylitis. Etanercept is therefore used to treat certain inflammatory diseases.

Biosimilar Characterization Considerations

The guidelines state that characterization of Etanercept 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. Disulfide bridges (particularly in the TNFα region)
  2. C-terminal Lysine
  3. N-linked glycosylation (in particular galctosylation, fucosylation and sialylation levels and site occupancy)
  4. O-linked glycosylation (sialylation levels and site occupancy)
  5. Deamidation
  6. Oxidation