Characterization and comparability of stress-induced oxidation and deamidation on vulnerable sites of etanercept products.

•An etanercept biosimilar, TuNEX® was compared to the innovator drug, Enbrel®, in terms of stress-induced oxidation and deamidation as well as bioactivity by LC–MS/UV method and bioactivity assay.•The profiles of intrinsic and stress-induced oxidation on methionine (M) and deamidation on asparagine (N) as well as stress-induced bioactivity of the two etanercept products were similar regardless of a two-amino acid residue variance in the heavy chain (Fc).•Oxidative stress increased the oxidation from an intrinsic low level to a high or moderate level for all M residues. Alkali stress only increased the deamidation level of N404 to a moderate level while the rest fifteen N residues were not affected.•The bioactivity was not altered by oxidative stress but was reduced by the alkaline stress for both etanercept products.