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The AAPS Journal

, 22:7 | Cite as

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

  • Francesca CivoliEmail author
  • Aparna Kasinath
  • Xiao-Yan Cai
  • Meenu Wadhwa
  • Andrew Exley
  • Philip Oldfield
  • Safa Alvandkouhi
  • Gregor Schaffar
  • John Chappell
  • Ronald Bowsher
  • Viswanath Devanarayan
  • Joseph Marini
  • Shannon Rebarchak
  • Michael Anderson
  • Vera Koppenburg
  • Todd Lester
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Abstract

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.

Keywords

Immunogenicity Anti-drug antibodies ADA Biosimilar 

Notes

Acknowledgments

We greatly thank Joao Pedras-Vasconcelos and Haohang Yan at the Food and Drug Administration for their assistance with the review of this article and comments that helped significantly improve the manuscript.

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Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  • Francesca Civoli
    • 1
    Email author
  • Aparna Kasinath
    • 2
  • Xiao-Yan Cai
    • 3
  • Meenu Wadhwa
    • 4
  • Andrew Exley
    • 5
  • Philip Oldfield
    • 6
  • Safa Alvandkouhi
    • 7
  • Gregor Schaffar
    • 8
  • John Chappell
    • 9
  • Ronald Bowsher
    • 10
  • Viswanath Devanarayan
    • 11
  • Joseph Marini
    • 12
  • Shannon Rebarchak
    • 12
  • Michael Anderson
    • 13
  • Vera Koppenburg
    • 14
  • Todd Lester
    • 7
  1. 1.Coherus BioSciencesRedwood CityUSA
  2. 2.Syngene International LtdBangaloreIndia
  3. 3.Accurant Biotech, Inc.CranburyUSA
  4. 4.Medicines and Healthcare Products Regulatory Agency (MHRA)National Institute for Biological Standards and Control (NIBSC)HertfordshireUK
  5. 5.Regulatory Division, Medicines and Healthcare Products Regulatory Agency (MHRA)LondonUK
  6. 6.Philip Oldfield Bioanalytical ConsultingQuebecCanada
  7. 7.BioAgilytix LabsDurhamUSA
  8. 8.Hexal AG OberhachingGermany
  9. 9.Gyros Protein TechnologiesUppsalaSweden
  10. 10.B2S Life SciencesFranklinUSA
  11. 11.GlaxoSmithKlineCollegevilleUSA
  12. 12.Janssen Research & Development, LLCSpring HouseUSA
  13. 13.Immunologix LaboratoriesTampaUSA
  14. 14.Hexal AGHolzkirchenGermany

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