Variability of intended copies for etanercept (Enbrel®): Data on multiple batches of seven products

Abstract

Fusion protein and monoclonal antibody-based tumor necrosis factor (TNF) inhibitors represent established treatment options for a range of inflammatory diseases. Regulatory authorities have outlined the structural characterization and clinical assessments necessary to establish biosimilarity of a new biotherapeutic product with the innovator biologic drug. Biologic products that would not meet the minimum World Health Organization's standard for evaluation of similar biotherapeutic products are available in some countries; in some cases relevant data to assess biosimilarity and appropriate regulatory approval pathways are lacking. Batches of seven intended copy (IC) products for etanercept (Enbrel®) were subjected to a subset of test methods used in the routine release and heightened characterization of Enbrel®, to determine key attributes of identity, quality, purity, strength, and activity. While a number of quality attributes of the IC lots tested met the release specifications for Enbrel®, none fell within these limits across all methods performed, and there were no IC lots that satisfied the criteria typically applied by the innovator to support comparability with Enbrel®. Although the consequences of these differences are largely unknown, the potential for unanticipated clinical outcomes should not be overlooked.

Review of biologics, biosimilars, and intended copies in rheumatology, and current practice in Iraq

“…Due to the proximity with Iran, these products may be accessible to some Iraqi patients. According to an analytical assessment of Altebrel, several attributes were not comparable to those of the originator: peptide sequence, distribution of charged species, and posttranslational modifications 52. Although the clinical impact of these differences is unknown, Altebrel should not be considered an etanercept biosimilar, and patients should not be switched between the two products.…”

Biosimilars in oncology and inflammatory diseases: current and future considerations for clinicians in Latin America

“…60 Furthermore, a recent analytical assessment of seven intended copies of etanercept (among them Etanar® and Infinitam®) found that, although each copy exhibited a degree of similarity to the originator in structure and binding activity, a number of significant structural and biochemical differences were apparent. 61 None of the seven products met release-specification criteria typically applied to originator etanercept across all test assays. The study’s authors noted that the potential for unanticipated clinical consequences resulting from such differences should not be overlooked.…”

“…The study’s authors noted that the potential for unanticipated clinical consequences resulting from such differences should not be overlooked. 61 …”

Anticorps monoclonaux biosimilaires

“…Cette approche également connue sous le nom de cartographie peptidique a aujourd'hui presque totalement remplacé les méthodes anciennes de séquençage des protéines, longues, fastidieuses et coûteuses, comme la dégradation d'Edman. Ainsi, des cartes peptidiques ont été réalisées pour deux AcM ou une protéine de fusion de référence et leurs biosimilaires (rituximab [12,13], adalimumab [14] et étanercept [15]). Dans ces études de comparabilité, la séquence d'acides aminés a été validée pour les biosimilaires du rituximab et de l'adalimumab, avec une couverture de séquence très proche ou égale à 100 %.…”