Background/Purpose: A biosimilar is a biopharmaceutical product that is highly similar to an already licensed one in terms of quality, safety, and efficacy. We (Samsung Bioepis) have been developing a biosimilar of Humira^® (adalimumab), designated as SB5. To demonstrate its biosimilarity in quality to Humira^®, we performed a comprehensive characterization in terms of structure, heterogeneity in size and charge, and biological properties following the ICH, FDA, and EMA guidelines.

Methods: We analyzed all available lots of SB5 and more than 70 US- or EU-sourced lots of Humira^®, using state-of-the-art methods whenever desirable, and compared the two sets of data. The structural properties comprised primary and higher-order structures and N-glycosylation. The physicochemical characteristics were categorized into liquid chromatographic patterns and electrophoretic pattern concerning size and charge heterogeneity. The biological properties were examined by in vitro functional assays.

Results: Amino acid sequence and modification were demonstrated by peptide mapping analysis using mass spectrometry, which resulted in the identity in amino acid sequence and the identical site of N-glycosylation between SB5 and Humira^®. All N-glycan species were also identical to each other. To testify 3-dimension structural similarity, the butterfly plots of hydrogen/deuterium exchange (HDX) was conducted and showed that SB5 and Humira^®are highly similar in terms of solvent accessibility. These results demonstrated a high degree of structural similarity.

The %contents of High Molecular Weights (%HMWs) were determined by size-exclusion HPLC (SE-HPLC) and were shown to be highly similar between SB5 and Humira^®. The %contents of Low Molecular Weights (%LMWs) were determined by capillary-electrophoresis sodium dodecyl sulfate, with reduced samples and non-reduced samples (CE-SDS-R, and CE-SDS-NR, respectively). Non-glycosylated heavy chain (NGHC) by CE-SDS-R was the impurity that the amounts are not highly similar between SB5 and Humira^®; however, the difference is not considered to be significant clinically.

The charge heterogeneity was investigated not only for the %contents of the variants, by cation-exchange HPLC (CEX-HPLC) and imaged capillary isoelectric focusing (icIEF) but also for the structural identities. The variants were found to contain identical structures, and although the %contents showed difference but it will not considered to be significant clinically based on the result of clinical study.

With regard to TNF-α binding and neutralization, which are the primary modes of action of adalimumab, SB5 was similar to Humira^®. The levels of apoptosis, another Fab-related function, and all the Fc-related functions analyzed, including Fc receptor binding, antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) were found similar between SB5 and Humira^®.

Conclusion: A comprehensive set of physicochemical and biological characterizations has demonstrated that SB5 is highly similar to Humira^® in product quality.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/biosimilarity-between-humira-and-the-biosimilar-candidate-sb5-in-product-quality/