Assessing Analytical Similarity of Proposed Amgen Biosimilar ABP 501 to Adalimumab

Abstract

BackgroundABP 501 is being developed as a biosimilar to adalimumab. Comprehensive comparative analytical characterization studies have been conducted and completed.ObjectiveThe objective of this study was to assess analytical similarity between ABP 501 and two adalimumab reference products (RPs), licensed by the United States Food and Drug Administration (adalimumab [US]) and authorized by the European Union (adalimumab [EU]), using state-of-the-art analytical methods.MethodsComprehensive analytical characterization incorporating orthogonal analytical techniques was used to compare products. Physicochemical property comparisons comprised the primary structure related to amino acid sequence and post-translational modifications including glycans; higher-order structure; primary biological properties mediated by target and receptor binding; product-related substances and impurities; host-cell impurities; general properties of the finished drug product, including strength and formulation; subvisible and submicron particles and aggregates; and forced thermal degradation.ResultsABP 501 had the same amino acid sequence and similar post-translational modification profiles compared with adalimumab RPs. Primary structure, higher-order structure, and biological activities were similar for the three products. Product-related size and charge variants and aggregate and particle levels were also similar. ABP 501 had very low residual host-cell protein and DNA. The finished ABP 501 drug product has the same strength with regard to protein concentration and fill volume as adalimumab RPs. ABP 501 and the RPs had a similar stability profile both in normal storage and thermal stress conditions.ConclusionBased on the comprehensive analytical similarity assessment, ABP 501 was found to be similar to adalimumab with respect to physicochemical and biological properties.

Clinical similarity of the biosimilar ABP 501 compared with adalimumab after single transition: long-term results from a randomized controlled, double-blind, 52-week, phase III trial in patients with moderate-to-severe plaque psoriasis

“…Comprehensive analytical assessment of ABP 501 compared with adalimumab has shown that the two molecules are highly similar in physicochemical properties and biological activity . Additionally, a phase I single‐dose study conducted in healthy adults has demonstrated pharmacokinetic equivalence of ABP 501 to adalimumab .…”

“…TNF‐α) important in the immunopathogenesis of moderate‐to‐severe psoriasis, are safe and effective . Analytical and functional evaluations have demonstrated that ABP 501 and adalimumab are highly similar in their structural and functional properties, as well as biological activity . A phase I, single‐dose study of ABP 501 in healthy adults demonstrated similar pharmacokinetics to that of adalimumab .…”

Heterologous recombinant expression of non-originator NISTmAb

“…Currently, the “goalpost” for analytical similarity is defined by the historical performance of the originator’s process and process changes/improvements via characterization of multiple commercial drug product lots to form an analytical target profile (ATP) 22,23,30,32 . The RM 8671 ATP is that of a single homogenized batch.…”

“…The ATP may include analytical characterization (e.g., primary structure, size variants, charge variants, glycosylation and other PTMs), biophysical characterization (HOS, colloidal stability, conformational stability), as well as biological characterization (e.g., in vitro binding studies, potency assays) 22,23 . The subset of analytical measurements we used to characterize the non-originator materials in this study demonstrated moderate differences.…”

Novel chemical degradation pathways of proteins mediated by tryptophan oxidation: tryptophan side chain fragmentation

“…Trp side chain cleavage), which was subsequently confirmed to proceed under exposure to ambient light . Forced degradation (including thermal forced degradation) has also become an important tool for biosimilar analysis . However, certain limitations of forced degradation studies of proteins must also be acknowledged.…”