Abstract
The ever-increasing cost of healthcare together with our improved understanding of biotech therapeutic drugs has fueled the rise of biosimilars. A step towards achieving the successful development of a biosimilar is to establish analytical similarity with the innovator drug. This is necessary so as to avail the significant reduction in clinical data required for achieving regulatory approval. A key concern is the limited understanding of how the different quality attributes (QA) affect its safety and efficacy profile. India has successfully demonstrated its ability to make affordable, high-quality pharmaceutical products for the world, particularly the small molecule generics. This fact is validated by the trend that the share of Indian made pharmaceutical products in the US market has been constantly increasing and is presently more than 30%. The question is if India can successfully replicate its success, in manufacturing complex biotherapeutic products. This chapter explores India’s journey in the field of biosimilar manufacturing with an emphasis on the regulatory aspect. Followed by a concise overview of the evolution of global regulatory guidelines, the Indian framework has been discussed in detail. Major changes introduced in the latest guidelines for similar biologics (2016) have been highlighted. Insight into the key developments related to clinical experiences and thereby addition of more sophisticated platforms to the analytical armory in the past decade for characterization of biosimilars has been given. Two recently published case studies on analytical platform approach used to establish similarity for microbial (GCSF) and mammalian product (Rituximab), in the Indian marketplace, using an array of advanced, orthogonal, high-resolution analytical methods, have been discussed. Finally, the importance post-approval pharmacovigilance as a feedback mechanism to update and improve existing regulatory framework has been outlined.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Beck A, Diemer H, Ayoub D, Debaene F, Wagner-Rousset E, Carapito C, Van Dorsselaer A, Sanglier-Cianférani S. Analytical characterization of biosimilar antibodies and Fc-fusion proteins. Trends Anal Chem. 2013;48:81–95. https://doi.org/10.1016/j.trac.2013.02.014.
Bennett CL, Chen B, Wyatt MD, Schulz RM, Georgantopoulos P, Kessler S, Qureshi ZP, Lu ZK, Love BL, Noxon V, Bian J, Ray P, Ablin RJ, Hruskesky WJ, Hermanson T, Raisch DW, Bobolts L, Armitage M, Hrushesky WJ, Macdougall IC, Sartor O, Armitage JO. Regulatory and clinical considerations for biosimilar oncology drugs. Lancet Oncol. 2014;15(13):e594–605. https://doi.org/10.1016/S1470-2045(14)70365-1.
Berkowitz SA. Biosimilar drug product development. Boca Raton: CRC Press; 2017. p. 15–82. https://doi.org/10.1201/9781315119878-3.
Biosimilar Development. Global biosimilars follow-on-biologics market 2016 industry demand insight profile and research to 2020. 2016.
Biosimilars in Global Markets CPhI China. 2017. Available at http://www.cphi.com/china/visit/news-and-updates/biosimilars-global-markets.
Brennan Z. India’s CDSCO warns against using Roche’s Avastin as eye treatment, regulatory affairs professional society. 2016. Available at http://206.79.211.135/Regulatory-Focus/News/2016/01/21/23941/India’s-CDSCO-Warns-Against-Using-Roche’s-Avastin-as-Eye- Treatment/#.
Bui LA, Hurst S, Finch GL, Ingram B, Jacobs IA, Kirchhoff CF, Ng CK, Ryan AM. Key considerations in the preclinical development of biosimilars. Drug discovery today. 2015; 20:3–15. http://dx.doi.org/10.1016/j.drudis.2015.03.011.
Carlsson G, Ahlin A, Dahllof G, Elinder G, Henter J-I, Palmblad J. Efficacy and safety of two different rG-CSF preparations in the treatment of patients with severe congenital neutropenia. Br J Haematol. 2004;126(1):127–32. https://doi.org/10.1111/j.1365-2141.2004.05008.x.
Christl L. FDA’s Overview of the regulatory guidance for the development and approval of biosimilar products in the US. 2016. Available at http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/UCM431118.pdf.
DBT and CDSCO. Guidelines on similar biologics 2016 guidelines on similar biologics: regulatory requirements for markeng authorizaon in India. 2016.
Declerck PJ. Biologicals and biosimilars: a review of the science and its implications. GaBI J. 2012;1(1):13–6. https://doi.org/10.5639/gabij.2012.0101.005.
Domestic Biologicals Cost Less in India. Generics and Biosimilars Initiative Journal. 2016. Available at http://www.gabionline.net/Biosimilars/Research/Domestic-biologicals-cost-less-in-India. Accessed 21 June 2017.
European Medicines Agency. Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: quality issues. 2006. pp. 1–8. doi: https://doi.org/10.1136/bmj.333.7574.873-a.
European Medicines Agency. Guideline on non-clinical and clinical development of similar biological medicinal products containing recombinant human insulin and insulin analogues. EMEA. 2015;44:1–7.
FDA. Scientific considerations in demonstrating biosimilarity to a reference product guidance for industry scientific considerations in demonstrating biosimilarity to a reference product. Guidance for industry (February). 2015.
Flores-Ortiz LF, Campos-García VR, Perdomo-Abúndez FC, Pérez NO, Medina-Rivero E. Physicochemical properties of rituximab. J Liq Chromatogr Relat Technol. 2014;37(10):1438–52. https://doi.org/10.1080/10826076.2013.794738.
GaBI Journal Editor. Patent expiry dates for best-selling biologicals. GaBI J. 2015;4(4):178–9. https://doi.org/10.5639/gabij.2015.0404.040.
George B. Changes in regulatory requirements for biosimilar development in India. 2016. Available at https://www.biosimilardevelopment.com/doc/changes-in-regulatory-requirements-for-biosimilar-development-in-india-0001.
Hernandez MP, Lopez-Moralez CA, Ramirez-Ibanez ND, Pina-Laura N, Perez NO, Molina-Perez A, Revilla-Beltri J, Flores-Ortiz LF, Medina-Rivero E. Assessment of physicochemical properties of rituximab related to its immunomodulatory activity. J Immunol Res. 2015;2015:910763. https://doi.org/10.1155/2015/910763.
Holzmann J, Hausberger A, Rupprechter A, Toll H. Top-down MS for rapid methionine oxidation site assignment in filgrastim. Anal Bioanal Chem. 2013;405(21):6667–74. https://doi.org/10.1007/s00216-013-7138-0.
ICH Guidelines. Specifications: test procedures and acceptance critreia for biotechnological/biological products Q6B (March). 2000. pp. 1–20.
ICH Guidelines. Comparability of biotechnological/biological products subject to changes in their manufacturing process Q5E (March). 2013. pp. 1–20.
Indian Biosimilars Market May Reach $40 bn by 2030. The Economic Times. 2016. Available at http://economictimes.indiatimes.com/industry/healthcare/biotech/pharmaceuticals/indian-biosimilars-market-may-reach-40-bn-by-2030-report/articleshow/54717517.cms.
James S. Biosimilars market size is projected to reach $41.7 billion, demand in various end-use industries till 2024: Grand View Research, Inc; 2016. Available at https://globenewswire.com/news-release/2016/07/19/857002/0/en/Biosimilars-Market-Size-Is-Projected-To-Reach-41-7-Billion-Demand-In-Various-End-use-Industries-Till-2024-Grand-View-Research-Inc.html.
Joshi VS, Kumar V, Rathore AS. ‘Role of organic modifier and gradient shape in rp-hplc separation: analysis of gcsf variants. J Chromatogr Sci. 2015;53(3):417–23. https://doi.org/10.1093/chromsci/bmu222.
Kanase SJ, Gavhane YN, Khandekar A, Gurav AS, Yadav AV. Biosimilar: an overview. Int J Pharm Sci Res. 2013;4(6):2132–44. https://doi.org/10.13040/IJPSR.0975-8232.4(6).2132-44.
Kashyap V. Highlights of proposed biosimilar guidelines, LexOrbis. 2016. Available at https://www.lexorbis.com/highlights-of-proposed-biosimilar-guidelines-2016/. Accessed 21 June 2017.
Konangi S, Raviteja MN, Vishal GN. Comparison of global regulatory approvals for biosimilar products. Int J PharmTech Res. 2013;5(3):924–35.
Konara CS, Barnard RT, Hine D, Siegel E, Ferro V. The tortoise and the hare: evolving regulatory landscapes for biosimilars. Trends Biotechnol. 2016;34(1):70–83. https://doi.org/10.1016/j.tibtech.2015.10.009.
Kumar R, Singh J. ‘Biosimilar drugs: current status. J Appl Basic Med Res. 2014;4(2):63–5. https://doi.org/10.4103/2229-516x.136774.
Lo C. Going global: India’s big biosimilar move - Pharmaceutical Technology. 2016.
Malhotra H, Krishnan A, Mody R. Global regulatory landscape of biosimilars: emerging and established market perspectives. Biosimilars. 2015;2015:19–32. https://doi.org/10.2147/BS.S44052.
Mordor Intelligence. Global biosimilar market|industry report|outlook|analysis|size and forecast. 2017.
Nagarjunareddy D, Brahmaiah B. Regulatory requirements of “similar biologics” for marketing authorization in India. Int J Drug Regul Aff. 2017;51:20–4. https://doi.org/10.22270/ijdra.v5i1.193.
Nupur N, Singh SK, Narula G, Rathore AS. Assessing analytical comparability of biosimilars: GCSF as a case study. J Chromatogr B Analyt Technol Biomed Life Sci. 2016;1032:165–71. https://doi.org/10.1016/j.jchromb.2016.05.027.
Nupur N, Dash R, Chhabra N, Rathore A. Assessing analytical comparability of biosimilars: rituximab as a case study. MAbs. 2017;10(1):143–58.
Partnerships Driving Similar Biologics Development in India. Generics and Biosimilars Initiative Journal. 2016. Available at http://www.gabionline.net/Biosimilars/Research/Partnerships-driving-similar-biologics-development-in-India. Accessed 21 June 2017.
Patel D. Patients report eye inflammation, Intas recalls its drug. The Indian Express. 2017. Available at https://www.pressreader.com/india/the-indian-express/20170403/282063391812417. Accessed 18 June 2017.
Philippidis A. The top 15 best-selling drugs of 2016|the lists|GEN, Genetic Engineering and Biotechnology News. 2017. Available at http://www.genengnews.com/the-lists/the-top-15-best-selling-drugs-of-2016/77900868. Accessed 21 June 2017.
Rao R. Indian companies gearing up to solve the biosimilars puzzle|Business Standard News. 2016.
Rathore AS. Follow-on protein products: scientific issues, developments and challenges. Trends Biotechnol. 2009;27(12):698–705. https://doi.org/10.1016/j.tibtech.2009.09.004.
Schellekens H, Jiskoot W. Eprex-associated pure red cell aplasia and leachates. Nat Biotechnol. 2006;24(6):613–4.
Schellekens H, Moors E. Clinical comparability and European biosimilar regulations. Nat Biotechnol. 2010;28(1):28–31. https://doi.org/10.1038/nbt0110-28.
Shaw KM. Biotechnology: helping India innovate for the future. Employment News, February. 2016. p. 1.
Shuster M, Farmer-Koppenol P. A Comparison of US and EU biosimilars regimes. Fenmick and West LLP; 2013. pp. 3–4.
Similar Biologics Approved and Marketed in India. Generics and Biosimilars Initiative Journal. 2012. Available at http://www.gabionline.net/Biosimilars/General/Similar-biologics-approved-and-marketed-in-India. Accessed 21 June 2017.
Similar Biologics Approved and Marketed in India. Gernerics and Biosimilars Initiative. 2016. Available at http://www.gabionline.net/Biosimilars/General/Similar-biologics-approved-and-marketed-in-India. Accessed 18 June 2017.
Singh Sekhon Vikrant Saluja B, Singh Sekhon B. Biosimilars: an overview. Biosimilars. 2011;1:1–11. https://doi.org/10.2147/BS.S16120.
Skrlin A, Radic I, Vuletic M, Schwinke D, Runac D, Kusalic T, Paskvan I, Krsic M, Bratos M, Marinc S. Comparison of the physicochemical properties of a biosimilar filgrastim with those of reference filgrastim. Biologicals. 2010;38(5):557–66. https://doi.org/10.1016/j.biologicals.2010.05.002.
Swamilingiah G. Insight: the biopharmaceuticals ecosystem in India and opportunities for European Collaboration, European Business and Technology Centre. 2014. Available at http://ebtc.eu/index.php/communication/ebtc-news/195-biotechnology-news/367-insight-the-biopharmaceuticals-ecosystem-in-india-and-opportunities-for-european-collaboration. Accessed 17 June 2017.
Tank Chintankumar J, Borkhataria Chetan H, Baria Ashok H, Patel Rakesh P, Tamizharasi S, Sureja DK, Patel SD, Parmar GR. Formulation and evaluation of aceclofenac loaded maltodextrin based proniosome. Int J ChemTech Res. 2009;1(3):567–73. https://doi.org/10.1056/NEJM197302222880814.
Unnikrishnan C. Biosimilar market to cross 40 billion in India by 2030 - BW Businessworld. 2016. Available at http://businessworld.in/article/Biosimilar-Market-To-Cross-40-Billion-In-India-By-2030/06-10-2016-106686/.
US Department of Health and Human Services. Clinical pharmacology data to support a demonstration of biosimilarity to a reference product. Guidance for Industry, (December). 2016. pp. 1–18.
Welch AR. Health Canada’s unique approach to biosimilar regulation. 2016.
WHO. Guidelines on evaluation of monoclonal antibodies as similar biotherapeutic products (SBPs). World Health Organization (October). 2016. pp. 17–21.
Acknowledgements
This work was funded by the DBT Centre of Excellence for Biopharmaceutical Technology grant under Department of Biotechnology, Government of India (BT/COE/34/SP15097/2015).
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 American Association of Pharmaceutical Scientists
About this chapter
Cite this chapter
Rathore, A.S., Joshi, S., Bhargava, A., Nupur, N. (2018). Development and Commercialization of Biosimilars in India: Current Regulatory and Clinical Experience. In: Gutka, H., Yang, H., Kakar, S. (eds) Biosimilars. AAPS Advances in the Pharmaceutical Sciences Series, vol 34. Springer, Cham. https://doi.org/10.1007/978-3-319-99680-6_24
Download citation
DOI: https://doi.org/10.1007/978-3-319-99680-6_24
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-99679-0
Online ISBN: 978-3-319-99680-6
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)