Physicochemical and biological similarity assessment of LBAL, a biosimilar to adalimumab reference product (Humira®)

Abstract

LBAL was developed as an adalimumab (Humira®) biosimilar using Chinese hamster ovary cell lines. Comparable quality, safety, and efficacy between a biosimilar and its reference product should be ensured for regulatory approval. Here, we present the results of a comprehensive physicochemical and biological characterization between LBAL and Humira®. As physicochemical attributes, primary and higher-order structure, N-glycan profile, and disulfide linkage were investigated. Biological attributes were evaluated by target/receptor binding analysis and in vitro/ex vivo cell-based assays, which are linked to mechanisms of action. As a result, LBAL had the identical amino acid sequence, similar post-translational modifications and N-/C-terminal variants, and comparable primary, secondary, and tertiary structures and disulfide linkage profile. However, some differences in N-glycan profiles were observed. Biological activities, including tumor necrosis factor (TNF) binding, TNF-neutralization, apoptosis, Fc receptor binding, and complementdependent cytotoxicity, were largely consistent. Despite a slightly lower antibody-dependent cellular cytotoxicity activity in LBAL, this difference was not significant under physiological conditions. As indicated, this extensive analytical characterization and functional comparison assessment showed that LBAL was similar to Humira®, with minor differences of no clinical relevance. Taken together, our comparative assessment of physicochemical and biological attributes demonstrated that LBAL is structurally and functionally very similar to Humira®, supporting the biosimilarity of clinical efficacy and safety.

Human Endogenous Retroviruses: Friends and Foes in Urology Clinics

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“…The unwanted activation of HERVs can be induced by inflammation, endocrine imbalance, exogenous viral infections, chemical exposures, and other environmental conditions [4,[22][23][24]. Understanding the way HERVs function for human biology and clinical status supports the development of efficient therapeutic tools for treating various human illnesses [25][26][27][28][29][30].…”

Mannose-6-phosphate glycan for lysosomal targeting: various applications from enzyme replacement therapy to lysosome-targeting chimeras

“…However, Myozyme was replaced with a new brand name, Lumizyme, because scale-up changed the glycan profile; therefore, the resulting product was considered different from the previous Myozyme. Glycan profiles are considered critical for quality control because glycans play essential roles in hydrophilic structures, clinical efficacy, in vivo half-life, and immunogenicity (Duivelshof et al 2019 ; Kwon et al 2021 ). Therefore, regulatory authorities require that biosimilars have a glycan profile similar to that of the original product.…”