Abstract
A “generic” version of a biopharmaceutical may be introduced after patents and other exclusivity rights expire. However, the generic paradigm as it has developed for small molecules over the years cannot be used for biopharmaceuticals. In the European Union (EU) and the United States regulatory systems, the term “biosimilar” was coined for copies of brand-name, originator biopharmaceuticals. This chapter discusses the principles of biosimilar development and the regulatory frameworks that evolved both in the United States and the EU for the development, evaluation, and introduction of biosimilar drug products. In addition, this chapter considers the societal impact of biosimilar introduction together with key challenges and a future outlook.
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References
Autoriteit Consument & Markt (ACM) (2019) Sectoronderzoek TNF-alfaremmers. https://www.acm.nl/sites/default/files/documents/2019-09/sectoronderzoek-tnf-alfaremmers.pdf
Barbier L, Simoens S, Soontjens C, Claus B, Vulto AG, Huys I (2021) Off-Patent Biologicals and Biosimilars Tendering in Europe—A Proposal towards More Sustainable Practices. Pharmaceuticals 14: 499
Barbier L, Vulto AG (2021) Interchangeability of biosimilars: overcoming the final hurdles. Drugs 81(16):1897–1903. https://doi.org/10.1007/s40265-021-01629-4
Barbier L, Declerck P, Simoens S, Neven P, Vulto AG, Huys I (2019) The arrival of biosimilar monoclonal antibodies in oncology: clinical studies for trastuzumab biosimilars. Br J Cancer 121(3):199–210. https://doi.org/10.1038/s41416-019-0480-z
Barbier L, Vandenplas Y, Lacosta TB, Vulto AG (2021) Biosimilar interchangeability: regulatory & practical considerations. Biosimilar development. https://www.biosimilardevelopment.com/doc/biosimilar-interchangeability-regulatory-practical-considerations-0001
Barbier L, Mbuaki A, Simoens S, Declerck P, Vulto AG, Huys I (2022a) Regulatory information and guidance on Biosimilars and their use across Europe: a call for strengthened one voice messaging. Front Med 9:820755. https://doi.org/10.3389/fmed.2022.820755
Barbier L, Vandenplas Y, Boone N, Janknegt R, Vulto AG (2022b) How to select a best-value biological medicine? A practical model to support hospital pharmacists. Am J Health Syst Pharm 79:2001. https://doi.org/10.1093/ajhp/zxac235
Barcina Lacosta TB, Vulto AG, Turcu-Stiolica A, Huys I, Simoens S (2022) Qualitative analysis of the design and implementation of benefit-sharing programs for biologics across Europe. BioDrugs 36(2):217–229. https://doi.org/10.1007/s40259-022-00523-z
Boone HN, van der Kuy H, Scott M, Mairs J, Krämer I, Vulto A, Janknegt R (2013) How to select a biosimilar. Eur J Hosp Pharm 20:275–228. https://doi.org/10.1136/ejhpharm-2013-000370
Cardinal Health (2022a) New and upcoming biosimilar launches. https://www.cardinalhealth.com/content/dam/corp/web/documents/Report/cardinal-health-biosimilar-launches.pdf
Cardinal Health (2022b) Biosimilars report: the US journey and path ahead. https://www.cardinalhealth.com/content/dam/corp/web/documents/Report/cardinal-health-2022-biosimilars-report.pdf
Crommelin DJA, Storm G, Verrijk R, de Leede L, Jiskoot W, Hennink WE (2003) Shifting paradigms: biopharmaceuticals versus low molecular weight drugs. Int J Pharm 266:3–16. https://doi.org/10.1016/S0378-5173(03)00376-4
Declerck P, Rezk M (2017) The road from development to approval: evaluating the body of evidence to confirm biosimilarity. Rheumatology 56(suppl_4):iv4–iv13. https://doi.org/10.1093/rheumatology/kex279
Declerck P, Danesi R, Petersel D, Jacobs I (2017) The language of biosimilars: clarification, definitions and regulatory aspects. Drugs 77(6):671–677. https://doi.org/10.1007/s40265-017-0717-1
EMA (2014a) Guideline on similar biological medicinal products (CHMP/437/04 Rev 1). https://www.ema.europa.eu/en/similar-biological-medicinal-products
EMA (2014b) Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: quality issues (revision 1)
EMA (2015) Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: non-clinical and clinical issues. (EMEA/CHMP/BMWP/42832/2005 Rev1). https://www.ema.europa.eu/en/similar-biological-medicinal-products-containing-biotechnology-derived-proteins-active-substance-non
EMA (2017) Animated video for patients on biosimilars https://www.youtube.com/watch?v=zAt7vd3eiT8. Accessed Aug 2022
EMA (2019) From laboratory to patient: the journey of a medicine assesses by EMA. https://www.ema.europa.eu/en/documents/other/laboratory-patient-journey-centrally-authorised-medicine_en.pdf
EMA (2022) Multidisciplinary: biosimilar http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_000408.jsp&mid=WC0b01ac058002958c. Accessed Mar 2022
EMA and European Commission (2017). Biosimilars in the EU–information guide for healthcare professionals. https://www.ema.europa.eu/en/documents/leaflet/biosimilars-eu-information-guide-healthcare-professionals_en.pdf
EMA and HMA (2022) Statement on the scientific rationale supporting interchangeability of biosimilar medicines in the EU https://www.ema.europa.eu/en/documents/public-statement/statement-scientific-rationale-supporting-interchangeability-biosimilar-medicines-eu_en.pdf. Accessed Sept 2022
European Commission (2017) Questions and answers for patients–biosimilar medicines explained. https://ec.europa.eu/docsroom/documents/26643
European Commission (2020) Pharmaceutical strategy for Europe. https://eur-lex.europa.eu/legal-content/EN/TXT/HTML/?uri=CELEX:52020DC0761&from=NL
FDA (1996) Guidance document. Demonstration of comparability of human biological products, including therapeutic biotechnology-derived products. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/demonstration-comparability-human-biological-products-including-therapeutic-biotechnology-derived. Accessed Aug 2022
FDA (2016a) Clinical pharmacology data to support a demonstration of biosimilarity to a reference product. https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM397017.pdf. Accessed 18 Jan 2018
FDA (2016b) Labeling for biosimilar products guidance for industry. https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM493439.pdf. Accessed 18 Jan 2018
FDA (2017a) Considerations in demonstrating interchangeability with a reference product guidance for industry. https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM537135.pdf
FDA (2017b) Nonproprietary naming of biological products: guidance for industry. https://www.fda.gov/downloads/drugs/guidances/ucm459987.pdf. Accessed 18 Jan 2018
FDA (2021) Questions and answers on biosimilar development and the BPCI act guidance for industry. September 2021. https://www.fda.gov/media/119258/download. Accessed Nov 2022
FDA (2022) Biosimilar product information. https://www.fda.gov/drugs/biosimilars/biosimilar-product-information. Accessed 23 Sept 2022
FDA (2023) Biosimilar product information. https://www.fda.gov/drugs/biosimilars/biosimilar-product-information. Accessed 23 Sept 2023
GaBI (2023) Biosimilar development targets limited range of biologicals https://gabionline.net/reports/biosimilar-development-targets-limited-range-of-biologicals
IMS Institute for Healthcare Informatics (2016) The impact of biosimilar competition. https://ec.europa.eu/docsroom/documents/17325/attachments/1/translations/en/renditions/native
IQVIA (2018) The impact of biosimilar competition in Europe https://ec.europa.eu/docsroom/documents/31642/attachments/1/translations/en/renditions/native
IQVIA (2020a) Biosimilars in the United States 2020–2024. https://www.iqvia.com/insights/the-iqvia-institute/reports/biosimilars-in-the-united-states-2020-2024
IQVIA (2020b) The prospects for biosimilars of orphan drugs in Europe. https://www.iqvia.com/insights/the-iqvia-institute/reports/the-prospects-for-biosimilars-of-orphan-drugs-in-europe
IQVIA (2021) The impact of biosimilar competition in Europe. https://www.iqvia.com/library/white-papers/the-impact-of-biosimilar-competition-in-europe-2021
Kenett RS, Kenett DA (2008) Quality by design applications in biosimilar pharmaceutical products. Accred Qual Assur 13(12):681–690. https://doi.org/10.1007/s00769-008-0459-6
Kim S, Song J, Park S, Ham S, Paek K, Kang M, Chae Y, Seo H, Kim H, Flores M (2017) Drifts in ADCC-related quality attributes of Herceptin®: impact on development of a trastuzumab biosimilar. MAbs 9(4):704–714. https://doi.org/10.1080/19420862.2017.1305530
Kolbe AR, Kearsley A, Merchant L, Temkin E, Patel A, Xu J, Jessup A (2021) Physician understanding and willingness to prescribe biosimilars: findings from a US National Survey. BioDrugs 35:363–372
Kraemer I, Tredree R, Vulto A (2008) Points to consider in the evaluation of biopharmaceuticals. EJHP Pract 14:73–76
Kurki P, Barry S, Bourges I, Tsantili P, Wolff-Holz E (2021) Safety, immunogenicity and interchangeability of biosimilar monoclonal antibodies and fusion proteins: a regulatory perspective. Drugs 81(16):1881–1896. https://doi.org/10.1007/s40265-021-01601-2
Kurki P, Kang H, Ekman N, Knezevic I, Weise M, Wolff-Holz E (2022) Regulatory evaluation of biosimilars: refinement of principles based on the scientific evidence and clinical experience. BioDrugs 36(3):359–371. https://doi.org/10.1007/s40259-022-00533-x
MABEL (2022) The MABEL FUND—market analysis of biologics and biosimilars following loss of exclusivity. https://gbiomed.kuleuven.be/english/research/50000715/52577001/mabel/Keyinsights. Accessed 23 Sept 2022
MHRA (2021) Guidance on the licensing of biosimilar products. https://www.gov.uk/government/publications/guidance-on-the-licensing-of-biosimilar-products/guidance-on-the-licensing-of-biosimilar-products. Accessed Aug 2022
Niazi SK (2022a) The coming of age of biosimilars: a personal perspective. Biologics 2:107–127. https://doi.org/10.3390/biologics2020009
Niazi SK (2022b) Biosimilars: harmonizing the approval guidelines. Biologics 2(3):171–195. https://doi.org/10.3390/biologics2030014
Park JP, Jung B, Park HK, Shin D, Jung JA, Ghil J, Han J, Kim KA, Woollett GR (2022) Interchangeability for biologics is a legal distinction in the USA, not a clinical one. BioDrugs 36(4):431–443
Rathore AS, Stevenson JG, Chhabra H, Maharana C (2022) The global landscape on interchangeability of Biosimilars. Expert Opin Biol Ther 22(2):133–148. https://doi.org/10.1080/14712598.2021.1889511
Rojas-Chavarro L, de Mora F (2021) Extrapolation: experience gained from original biologics. Drug Discov Today 26(8):2003–2013. https://doi.org/10.1016/j.drudis.2021.05.006
Schiestl M, Stangler T, Torella C, Cepeljnik T, Toll H, Grau R (2011) Acceptable changes in quality attributes of glycosylated biopharmaceuticals. Nat Biotechnol 29:310–312. https://doi.org/10.1038/nbt.1839
Schiestl M, Ranganna G, Watson K, Jung B, Roth K, Capsius B, Trieb M, Bias P, Maréchal-Jamil J (2020) The path towards a tailored clinical biosimilar development. BioDrugs 34(3):297–306. https://doi.org/10.1007/s40259-020-00422-1
Schneider CK (2013) Biosimilars in rheumatology: the wind of change. Ann Rheum Dis 72(3):315–318. https://doi.org/10.1136/annrheumdis-2012-202941
Van de Wiele VL, Kesselheim AS, Sarpatwari A (2021) Barriers to US biosimilar market growth: lessons from biosimilar patent litigation. Health Aff (Millwood) 40:1198–1205. https://doi.org/10.1377/hlthaff.2020.02484
Vandenplas Y, Simoens S, Van Wilder P, Vulto AG, Huys I (2021) Off-patent biological and biosimilar medicines in Belgium: a market landscape analysis. Front Pharmacol 12:644187. https://doi.org/10.3389/fphar.2021.644187
Vezer B, Buzás Z, Sebeszta M, Zrubka Z (2016) Authorized manufacturing changes for therapeutic monoclonal antibodies (mAbs) in European public Assessment report (EPAR) documents. Curr Med Res Opin 32(5):829–834. https://doi.org/10.1185/03007995.2016.1145579
Vulto AG (2019) Delivering on the promise of biosimilars. BioDrugs 33(6):599–602. https://doi.org/10.1007/s40259-019-00388-9
Vulto AG, Barbier L (2022) When will American patients start benefitting from biosimilars? Mayo Clin Proc 97(6):1044–1047. https://doi.org/10.1016/j.mayocp.2022.04.013
Vulto AG, Jaquez O (2016) The process defines the product: what really matters in biosimilar design and production? Br J Rheumatol 56(4):iv14–iv29. https://doi.org/10.1093/rheumatology/kex278
Webster WJ, Wong WA, Woollet GR (2019) An efficient development paradigm for biosimilars. BioDrugs 33(6):603–611. https://doi.org/10.1007/s40259-019-00371-4
Weise M, Bielsky M-C, De Smet K, Ehmann F, Ekman N, Narayanan G, Heim H-K, Heinonen E, Ho K, Thorpe R, Vleminckx C, Wadhwa M, Schneider CK (2011) Biosimilars-why terminology matters. Nat Biotechnol 29(8):690–693. https://doi.org/10.1038/nbt.1936
Weise M, Kurki P, Wolff-Holz E, Bielsky MC, Schneider CK (2014) Biosimilars: the science of extrapolation. Blood 124(22):3191–3196. https://doi.org/10.1182/blood-2014-06-583617
WHO (2022) Guidelines on evaluation of biosimilars replacement of annex 2 of WHO technical report series, no. 977. https://cdn.who.int/media/docs/default-source/biologicals/bs-documents-(ecbs)/annex-3%2D%2D-who-guidelines-on-evaluation-of-biosimilars_22-apr-2022.pdf
Wolff-Holz E, Tiitso K, Vleminckx C, Weise M (2019) Evolution of the EU biosimilar framework: past and future. BioDrugs 33(6):621–634. https://doi.org/10.1007/s40259-019-00377-y
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Vulto, A.G., Barbier, L. (2024). Biosimilars: Principles, Regulatory Framework, and Societal Aspects. In: Crommelin, D.J.A., Sindelar, R.D., Meibohm, B. (eds) Pharmaceutical Biotechnology. Springer, Cham. https://doi.org/10.1007/978-3-031-30023-3_11
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