Demonstration of Functional Similarity of Proposed Biosimilar ABP 501 to AdalimumabReportar como inadecuado




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BioDrugs

, Volume 30, Issue 4, pp 339–351

First Online: 15 July 2016

Abstract

BackgroundDue to the complex molecular structure and proprietary manufacturing processes of monoclonal antibodies mAbs, differences in structure and function may be expected during development of biosimilar mAbs.
Important regulatory requirements for approval of biosimilar products involve comprehensive assessments of any potential differences between proposed biosimilars and reference mAbs, including differences in all known mechanisms of action, using sensitive and relevant methods.
Any identified structural differences should not result in differences in biofunctional or clinical activity.

ObjectiveA comprehensive assessment comparing the Amgen biosimilar candidate ABP 501 with FDA-licensed adalimumab adalimumab US and EU-authorized adalimumab adalimumab EU was conducted to demonstrate similarity in biofunctional activity.

MethodsThe functional similarity assessment included testing of binding kinetics to soluble tumor necrosis factor α TNFα and relative binding to transmembrane TNFα.
The neutralization of TNFα-induced caspase activation, TNFα- and lymphotoxin-α LTα-induced chemokine production, and cytotoxicity was also tested.
Binding to Fc-gamma receptors FcγRIa, FcγRIIa 131H, FcγRIIIa 158V and 158F, and neonatal Fc receptor FcRn was compared with the reference mAbs, as was antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity.

ResultsThe data demonstrate that ABP 501 is similar to both adalimumab US and adalimumab EU with respect to evaluated biofunctional activities.

ConclusionSimilarity in biofunctional activity is a critical component of the totality of evidence required for demonstration of biosimilarity.
The functional similarity demonstrated for ABP 501 comprehensively assesses the known mechanisms of action of adalimumab, supporting the conclusion that ABP 501, adalimumab US, and adalimumab EU are likely to be clinically similar.

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Fuente: https://link.springer.com/article/10.1007/s40259-016-0185-2



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