As many biologic drugs patents fall into the public domain, the development of biosimilars shows a growing interest in the pharmaceutical sector. However, biosimilar such as all biomolecules are very complex to characterize and very sensitive to minor manufacturing conditions changes compared to generic small molecules. Therefore, certifying the comparability of biosimilar candidates to the reference product regarding the quality, safety and efficacy requires a large panel of methods.

Spectralys Biotech, through its expertise in FTIR spectroscopy combined with statistical tools provides rapid and reliable comparative analysis between batches of biosimilar candidates and the respective reference (originator). Our analyses allow to assess four types of critical quality attributes simultaneously in one single measurement: (I) the higher-order structure, (II) the glycosylation, (III) the total protein concentration and (IV) the quantity of other excipients (Tween, lipids,…).

We have already achieved multiple projects for companies developing biosimilars. The first critical quality attribute analysed is generally the secondary structure.

For instance, secondary structure prediction can be performed with an absolute error of 5.7% for α-helix and 6.7% for β-sheet[1]. Based on multivariate statistics, batch-to-batch comparison allow to detect structural changes as minor as 0.1% of α-helix or β-sheet content.

The first graph shows a comparison of 3 batches of a biosimilar candidate with 3 batches of the originator in terms of secondary structure. At least 5 FTIR spectra were recorded for each batch. No significant spectral difference is observed between the biosimilar batches and the originator batches. The high-order structure profiles and especially the secondary structure of the biosimilar candidate and the originator are thus identical.

Using other spectral regions, additional critical quality attributes can be assessed. In the second example concerning another biosimilar candidate, the spectral region associated with the glycosylation is analysed. In that case, three batches of the biosimilar and the originator do not cluster together revealing significant difference in the glycosylation pattern.

In conclusion, FTIR spectroscopy is thus a powerful tool for multiparametric comparative studies between biosimilar candidates and their reference products.

fig1 biosimilar

fig2 biosimilar

[1] E Goormaghtigh and all, 2006