Figure 4: Similarity between biosimilar (BF) and originator filgrastim (OF) spectra in the pH 3.0, 4.0 and 4.4 formulation.

(a) PCA scores showing the high similarity of the biosimilar filgrastim batches to the reference batches. Coloured groups (yellow, red, blue) represent different formulations. (b) Pairwise ¹H and ¹⁵N weighted chemical-shift correlation coefficients between the originator and biosimilar filgrastim batches in pH 4.0 and pH 3.0 formulation. The yellow rectangle shows the scaled r value for US and EU originator, the green rectangles shows the comparison between OF and BF in the pH 4.0 formulation, the cyan rectangles comparison between the 3 BF batches and blue comparison between the three replicates of the same sample. The grey rectangles shows the scaled r values for comparison between pH 4.0 and 3.0 formulations. (c) Normalized Euclidean distance metrics for ¹H and ¹⁵N weighted chemical-shift shifts in pH 4.0, pH 4.4 and pH 3.0 formulation. The normalized distances are shown as circles with a scaled diameter and colour in the upper triangular matrix, whereas the corresponding values shown as numbers are mirrored through the diagonal to the lower triangular matrix. (d) Hierarchical clustering of the ¹H and ¹⁵N chemical shifts.