Abstract
Biologic products have revolutionized the management of many rheumatic diseases, but access to these products might be limited by their relatively high costs. The US Biologics Price Competition and Innovation Act of 2009, which is contained within the Patient Protection and Affordable Care Act, established an abbreviated pathway for licensure by the FDA of biologic products that are demonstrated to be biosimilar to or interchangeable with FDA-licensed biologic products, termed reference products. This law allows for the approval of biosimilar biologic products, which are expected to increase access to treatment for patients, and ensuring the implementation of this Act is a high priority for the FDA. In this Perspectives article we describe the considerations for approval of proposed biosimilar products, including those to treat rheumatological conditions, by describing the FDA's rigorous approach to assessment of biosimilarity.
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References
US Food and Drug Administration. Guidance for industry — scientific considerations in demonstrating biosimilarity to a reference product. FDA http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM291128.pdf (2015).
US Food and Drug Administration. Guidance for industry — quality considerations in demonstrating biosimilarity to a reference protein product. FDA http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM291134.pdf (2015).
Woodcock, J. et al. The FDA's assessment of follow-on protein products: a historical perspective. Nat. Rev. Drug Discov. 6, 437–442 (2007).
FDA Center for Drug Evaluation and Research. List of licensed biological products with (1) reference product exclusivity and (2) biosimilarity or interchangeability evaluations to date. FDA http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/Biosimilars/UCM439049.pdf (2016).
US Food and Drug Administration. Guidance for industry: clinical pharmacology data to support a demonstration of biosimilarity to a reference product. DRAFT GUIDANCE. FDA http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM397017.pdf (2014).
Jefferis, R. Isotype and glycoform selection for antibody therapeutics. Arch. Biochem. Biophys. 526, 159–166 (2012).
Jefferis, R. Recombinant antibody therapeutics: the impact of glycosylation on mechanisms of action. Trends Pharmacol. Sci. 30, 356–362 (2009).
Hodoniczky, J., Zheng, Y. Z. & James, D. C. Control of recombinant monoclonal antibody effector functions by Fc N-glycan remodeling in vitro. Biotechnol. Prog. 21, 1644–1652 (2005).
Boyd, P. N., Lines, A. C. & Patel, A. K. The effect of the removal of sialic acid, galactose and total carbohydrate on the functional activity of Campath-1H. Mol. Immunol. 32, 1311–1318 (1995).
Shinkawa, T. et al. The absence of fucose but not the presence of galactose or bisecting N-acetylglucosamine of human IgG1 complex-type oligosaccharides shows the critical role of enhancing antibody-dependent cellular cytotoxicity. J. Biol. Chem. 278, 3466–3473 (2003).
Shields, R. L. et al. Lack of fucose on human IgG1 N-linked oligosaccharide improves binding to human Fcgamma RIII and antibody-dependent cellular toxicity. J. Biol. Chem. 277, 26733–26740 (2002).
Ferrara, C. et al. Unique carbohydrate-carbohydrate interactions are required for high affinity binding between FcgammaRIII and antibodies lacking core fucose. Proc. Natl Acad. Sci. USA 108, 12669–12674 (2011).
Peipp, M. et al. Antibody fucosylation differentially impacts cytotoxicity mediated by NK and PMN effector cells. Blood 112, 2390–2399 (2008).
Ferrara, C., Stuart, F., Sondermann, P., Brunker, P. & Umana, P. The carbohydrate at FcgammaRIIIa Asn-162. An element required for high affinity binding to non-fucosylated IgG glycoforms. J. Biol. Chem. 281, 5032–5036 (2006).
Smith, K. G. & Clatworthy, M. R. FcgammaRIIB in autoimmunity and infection: evolutionary and therapeutic implications. Nat. Rev. Immunol. 10, 328–343 (2010).
Herter, S. et al. Glycoengineering of therapeutic antibodies enhances monocyte/macrophage-mediated phagocytosis and cytotoxicity. J. Immunol. 192, 2252–2260 (2014).
Lin, C. W. et al. A common glycan structure on immunoglobulin G for enhancement of effector functions. Proc. Natl Acad. Sci. USA 112, 10611–10616 (2015).
Thomann, M., Reckermann, K., Reusch, D., Prasser, J. & Tejada, M. L. Fc-galactosylation modulates antibody-dependent cellular cytotoxicity of therapeutic antibodies. Mol. Immunol. 73, 69–75 (2016).
Pace, D. et al. Characterizing the effect of multiple Fc glycan attributes on the effector functions and FcgammaRIIIa receptor binding activity of an IgG1 antibody. Biotechnol. Prog. 32, 1181–1192 (2016).
Putnam, W. S., Prabhu, S., Zheng, Y., Subramanyam, M. & Wang, Y. M. Pharmacokinetic, pharmacodynamic and immunogenicity comparability assessment strategies for monoclonal antibodies. Trends Biotechnol. 28, 509–516 (2010).
Wright, A. & Morrison, S. L. Effect of C2-associated carbohydrate structure on Ig effector function: studies with chimeric mouse-human IgG1 antibodies in glycosylation mutants of Chinese hamster ovary cells. J. Immunol. 160, 3393–3402 (1998).
Yu, M. et al. Production, characterization, and pharmacokinetic properties of antibodies with N-linked mannose-5 glycans. MAbs 4, 475–487 (2012).
Keck, R. et al. Characterization of a complex glycoprotein whose variable metabolic clearance in humans is dependent on terminal N-acetylglucosamine content. Biologicals 36, 49–60 (2008).
Jones, A. J. et al. Selective clearance of glycoforms of a complex glycoprotein pharmaceutical caused by terminal N-acetylglucosamine is similar in humans and cynomolgus monkeys. Glycobiology 17, 529–540 (2007).
Raju, T. S. & Jordan, R. E. Galactosylation variations in marketed therapeutic antibodies. MAbs 4, 385–391 (2012).
Raju, T. S., Briggs, J. B., Borge, S. M. & Jones, A. J. Species-specific variation in glycosylation of IgG: evidence for the species-specific sialylation and branch-specific galactosylation and importance for engineering recombinant glycoprotein therapeutics. Glycobiology 10, 477–486 (2000).
Gomord, V. et al. Plant-specific glycosylation patterns in the context of therapeutic protein production. Plant Biotechnol. J. 8, 564–587 (2010).
US Food and Drug Administration. 2015 Meeting Materials, Oncologic Drugs Advisory Committee. FDA http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/ucm426351.htm (2015).
US Food and Drug Administration. Drugs@FDA Zarxio. FDA http://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/125553Orig1s000TOC.cfm (2015).
Felson, D. T. et al. American College of Rheumatology. Preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum. 38, 727–735 (1995).
Demin, I., Hamren, B., Luttringer, O., Pillai, G. & Jung, T. Longitudinal model-based meta-analysis in rheumatoid arthritis: an application toward model-based drug development. Clin. Pharmacol. Ther. 92, 352–359 (2012).
US Food and Drug Administration. Guidance for industry — biosimilars: questions and answers regarding implementation of the Biologics Price Competition and Innovation Act of 2009. FDA http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM273001.pdf (2015).
Acknowledgements
The authors thank S. Yim, B. Chowdhury, S. Kozlowski, K. Clouse, S. Lim, J. Weiner, L. Zhang, D. Abernethy and L. Christl for critical review of the manuscript. This article reflects the views of the authors and should not be construed to represent FDA's views or policies.
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Nikolov, N., Shapiro, M. An FDA perspective on the assessment of proposed biosimilar therapeutic proteins in rheumatology. Nat Rev Rheumatol 13, 123–128 (2017). https://doi.org/10.1038/nrrheum.2016.204
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DOI: https://doi.org/10.1038/nrrheum.2016.204
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