Case Studies and Publications

Run effective comparability programs

Analysis of tertiary structure. Spectra normalized for protein concentration by simultaneous absorbance measurements. Chirascan™ Q100, n=3

Determine innovator HOS characteristics

CD analysis of tertiary structure in a highly absorbing chiral formulation buffer suggested differences in tryptophan region of Fab fragments from different innovator lots.

Tier 2 quality range test applied, +/-2SD acceptance criteria
Office of Biostatistics and Office of Biotechnology Products, CDER/FDA. Weighted spectral difference method: Dinh, Nikita et al. Anal. Biochem. 464 (2014): 60-62

Objective, quantifiable evaluation of differences and similarities

Differences in tertiary structure of innovator lots from different geographical regions were statistically significant.

Subsequent comparison between biosimilar and innovator confirmed statistical significance of minor differences seen in tertiary structure (data not shown).

Monitor change under stressed conditions
(forced degradation)

Analysis of tertiary structure. Spectra normalized for protein concentration by simultaneous absorbance measurements.
Chirascan™ Q100, n=6

Monitor change under stressed conditions (forced degradation)

High sensitivity CD analysis of IgG1 samples subjected to a range of degradation conditions revealed minor differences in tertiary structure when compared to a control sample.

Weighted spectral difference method: Dinh, Nikita et al. Anal. Biochem. 464 (2014): 60-62

Quantifiable assessment of changes in tertiary structure

Statistical analysis enabled objective confirmation of spectral results. Degradation conditions have affected local environment of aromatic side chains (no changes were detected in secondary structure – results not shown).

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Selected recent publications

Miao et al. 2017. “Physicochemical and Biological Characterization of the Proposed Biosimilar Tocilizumab.” BioMed Research International 2017 (March). Hindawi: 1–13.

Vorob’ev et al. 2017. “Physicochemical Properties, Toxicity, and Specific Activity of a Follitropin Alpha Biosimilar.” Pharmaceutical Chemistry Journal 50 (11). Springer US: 753–60.