Immunogenicity Assessment of Biosimilars: A Multidisciplinary Perspective

Chamberlain, Paul; Kurki, Pekka

doi:10.1007/978-3-319-99680-6_19

Cited by 4 publications

(4 citation statements)

References 108 publications

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“…Some 173 switch trials have almost universally shown biosimilars to be equally safe and efficacious as originators 20,21 . The argument of immunogenicity has been spelled out in detail, and there is now positive evidence that biosimilars bear no additional risks to immune response than originators 22,23 . Responsible health care professionals like doctors and pharmacists who work in a solidarity‐based healthcare system cannot deny the nation the immense advantages and savings brought about by biosimilars.…”

Section: Outlook and Recommendationsmentioning

confidence: 99%

“…20,21 The argument of immunogenicity has been spelled out in detail, and there is now positive evidence that biosimilars bear no additional risks to immune response than originators. 22,23 Responsible health care professionals like doctors and pharmacists who work in a solidarity-based healthcare system cannot deny the nation the immense advantages and savings brought about by biosimilars. Refusal to improve healthcare sustainability with biosimilars is actually a sign of distrust in the drug regulatory system as a whole.…”

Section: Outlook and Recommendationsmentioning

confidence: 99%

See 1 more Smart Citation

Biologicals and Biosimilars in Hematology: The Case of Rituximab

Vulto

2019

HemaSphere

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Section: Outlook and Recommendationsmentioning

confidence: 99%

Section: Outlook and Recommendationsmentioning

confidence: 99%

Biologicals and Biosimilars in Hematology: The Case of Rituximab

Vulto

2019

HemaSphere

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“…While there are no definitive examples of mechanistically proven, large complex-mediated immunogenicity to a therapeutic, strong correlative data exist. Adalimumab and infliximab both bind trimeric TNFα and form complexes of 4,000 kDa and 14,000 kDa, respectively; both are immunogenic in clinical studies, while etanercept does not form large complexes and is relatively non-immunogenic ( 37 , 38 ). Multi-specific therapeutics can further enhance this complex forming ability since there are multiple targets.…”

Section: Introductionmentioning

confidence: 99%

Immunogenicity Risk Assessment for Multi-specific Therapeutics

Kroenke

Milton

Kumar

et al. 2021

AAPS J

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The objective of this manuscript is to provide the reader with a hypothetical case study to present an immunogenicity risk assessment for a multi-specific therapeutic as part of Investigational New Drug (IND) application. In order to provide context for the bioanalytical strategies used to support the multi-specific therapeutic presented herein, the introduction focuses on known immunogenicity risk factors. The subsequent hypothetical case study applies these principles to a specific example HC-12, based loosely on anti-TNFα and anti-IL-17A bispecific molecules previously in development, structured as an example immunogenicity risk assessment for submission to health authorities. The risk of higher incidence and safety impact of anti-drug antibodies (ADA) due to large protein complexes is explored in the context of multi-specificity and multi-valency of the therapeutic in combination with the oligomeric forms of the targets.

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“…Biosimilarity assessment is based on stepwise assessments of analytical, non-clinical, and clinical characteristics, with detailed physicochemical and functional evidence of similarity obtained before the initiation of the clinical program (3,4,35,36). A key requirement in the development of biosimilars is the demonstration of similar immunogenicity in a comparative (head-tohead) clinical study, as per United States Food and Drug Administration (FDA) and European Medicines Agency (EMA) Guidelines (1)(2)(3)34). These guidance documents outline general principles for handling the scientific challenges related Views should not be misconstrued as representing those of the MHRA or the EMA to demonstrating biosimilarity between a proposed biological product and a reference product.…”

Section: Introductionmentioning

confidence: 99%

Recommendations for the Development and Validation of Immunogenicity Assays in Support of Biosimilar Programs

Civoli

Kasinath

Cai³

et al. 2019

AAPS J

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For biosimilar drug development programs, it is essential to demonstrate that there are no clinically significant differences between the proposed biosimilar therapeutic (biosimilar) and its reference product (originator). Based on a stepwise comprehensive comparability exercise, the biosimilar must demonstrate similarity to the originator in physicochemical characteristics, biological activity, pharmacokinetics, efficacy, and safety, including immunogenicity. The goal of the immunogenicity assessment is to evaluate potential differences between the proposed biosimilar product and the originator product in the incidence and severity of human immune responses. Establishing that there are no clinically meaningful differences in the immune response between the products is a key element in the demonstration of biosimilarity. An issue of practical, regulatory, and financial importance is to establish whether a two-assay (based on the biosimilar and originator respectively) or a one-assay approach (based on the biosimilar) is optimal for the comparative immunogenicity assessment. This paper recommends the use of a single, biosimilar-based assay for assessing immunogenic similarity in support of biosimilar drug development. The development and validation of an ADA assay used for a biosimilar program should include all the assessments recommended for an innovator program (10-16, 29). In addition, specific parameters also need to be evaluated, to gain confidence that the assay can detect antibodies against both the biosimilar and the originator. Specifically, the biosimilar and the originator should be compared in antigenic equivalence, to assess the ability of the biosimilar and the originator to bind in a similar manner to the positive control(s), as well as in the confirmatory assay and drug tolerance experiments. Practical guidance for the development and validation of anti-drug antibody (ADA) assays to assess immunogenicity of a biosimilar in comparison to the originator, using the one-assay approach, are described herein.

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Immunogenicity Assessment of Biosimilars: A Multidisciplinary Perspective

Cited by 4 publications

References 108 publications

Biologicals and Biosimilars in Hematology: The Case of Rituximab

Biologicals and Biosimilars in Hematology: The Case of Rituximab

Immunogenicity Risk Assessment for Multi-specific Therapeutics

Recommendations for the Development and Validation of Immunogenicity Assays in Support of Biosimilar Programs

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