General characteristics of clinical trials for biosimilar drugs

Year 2021, , 89 - 94, 31.05.2021

Ahmet Akıcı Caner Vızdıklar

https://doi.org/10.5472/marumj.942752

Abstract

Biosimilar is a highly similar product to biological reference medicinal product. The development, licensing and clinical use of these
products differ from the implementations of conventional drugs shaped on the concept of equivalence in various aspects. Negative
attitudes about generic drugs, many of which are thought to be based on lack of knowledge, are still substantial. There is concern that
the problem may reach more serious dimensions in the use of biosimilars, which are known to be more complex compared to these.
Knowing the prominent critical aspects of the development process of the biosimilars may contribute to the solution of this problem
that causes significant difficulties in practice.
In all conventional and biological products, the innovative drug researches consist of the preclinical phase followed by the successive
phases I-IV. The first three phases are carried out before the license. The clinical trials required for licensing of generics are limited
by bioequivalence studies. However, in biosimilars, this process is more complex due to the nature of biological products. Adequate
quality, clinical efficacy and safety data are needed on the comparability basis of the reference products and their biosimilar. Phase
I and III are generally required for biosimilarity, although it may vary per product. Although, these phases are perceived as classical
phase studies, they differ considerably from those in the development process of reference drug in terms of design, purpose, content
and flexibility. Approaches that do not pay attention to these details sufficiently, can cause many problems such as the advantages
of biosimilars remain limited, risk management cannot be performed effectively, loss of trust, delay in product supplying, unfair
competition, etc. The general characteristics of clinical trials and the details of the subject specifically for biosimilars are mentioned
in this review article.

Keywords

Biosimilarity, Biological drug, Generic, Clinical trials

References

• İlaç ve Biyolojik Ürünlerin Klinik Araştırmaları Hakkında Yönetmelik (13.04.2013 Resmî Gazete Sayısı: 28617) [Regulation on Clinical Trials of Medicines and Biological Products (Turkish Legal Gazette No: 28617)] https://www. titck.gov.tr/mevzuat/ilac-ve-biyolojik-urunlerin-klinikarastirmalari- hakkinda-yonetmelik-271.220.18172740, Accessed: 13-12-2020
• Machin D, Day S, Green S. Textbook of Clinical Trials. 2 ed. West Sussex, England: John Wiley and Sons Ltd, 2006, ISBN: 13:978-0-470-01014-3.
• Kayaalp SO, (Ed). Klinik Farmakolojinin Esasları ve Temel Düzenlemeler [Principles and Basic Regulations of Clinical Pharmacology]. Updated 5th Edition, Ankara: Pelikan Yayıncılık, 2013. ISBN:978.605.5270-36-0.
• Akan H, İlbars H, Çetinkaya NÖ, (Eds), Klinik Araştırmalar Kitabı-2014 [Clinical Trials Book-2014]. Ankara: Bilimsel Tıp Yayınevi, ISBN:978.605.4488-48-3.
• Barbier L, Simoens S, Vulto AG, Huys I. European stakeholder learnings regarding biosimilars: Part i-improving biosimilar understanding and adoption. BioDrugs 2020;34:783-96. doi: 10.1007/s40259.020.00452-9.
• Cohen HP, McCabe D. The importance of countering biosimilar disparagement and misinformation. BioDrugs 2020;34:407-14. doi: 10.1007/s40259.020.00433-y.
• Halimi V, Daci A, Netkovska KA, Suturkova L, Babar Z, Grozdanova A. Clinical and regulatory concerns of biosimilars: A review of literature. Int J Environ Res Public Health 2020;17:5800. doi:10.3390/ijerph17165800.
• Toklu HZ, Dulger GA, Hidiroglu S, et al. Knowledge and attitudes of the pharmacists, prescribers and patients towards generic drug use in Istanbul – Turkey. Pharmacy Practice 2012;10:199-206.
• Oncu S, Bayram D, Aydin V, Isli F, et al. Knowledge, opinions, and attitudes of primary care physicians about generic drugs: a cross-sectional study. Fam Pract 2020; cmaa138. doi:10.1093/ fampra/cmaa138
• Turkish Ministry of Health, Turkish Medicines and Medical Devices Agency. “CTD Kılavuzu” [CTD Guide]. https://www. titck.gov.tr/mevzuat/ctd-kilavuzu-271.220.18172815 (Accessed 27-12-2020).
• Turkish Ministry of Health, Turkish Medicines and Medical Devices Agency. “Biyobenzer Tıbbi Ürünler Hakkında Kılavuz” Taslağı [Draft of “Guide on Biosimilar Medicinal Products”], 2017. (https://www.titck.gov.tr/mevzuat/biyobenzer-tibbiurunler- hakkinda-kilavuzu-taslagi-271.220.18173016 Accessed 27-12-2020.
• Al-Sabbagh A, Olech E, McClellan JE, Kirchhoff JF. Development of biosimilars. Semin Arthritis Rheum 2016;45(5 Suppl):S11-8.
• Çiçin İ. Biyobenzer İlaçlarda Klinik Çalışmalar ve Karşılaştırılabilirlik [Clinical Studies and Comparability in Biosimilar Drugs]. In: Biyoteknolojik İlaçlar [Biotechnological Drugs]. 2nd Edition. Araştırmacı İlaç Firmaları Derneği. İstanbul:Saner Basım Hizm. San. Tic. Ltd. Şti, 2020. ISBN:978- 625-400-344-8.
• European Medicines Agency (EMA). Biosimilar guidelines. https://www.ema.europa.eu/en/human-regulatory/researchdevelopment/ scientific-guidelines/multidisciplinary/ multidisciplinary-biosimilar Accessed 27-12-2020.
• European Medicines Agency (EMA). Guideline on similar biological medicinal products. (CHMP/437/04 Rev 1). https:// www.ema.europa.eu/documents/scientific-guideline/guidelinesimilar- biological-medicinal-products-rev1_en.pdf. Accessed 27-12-2020.
• European Medicines Agency (EMA). Information guide for patients: What I need to know about biosimilar medicines, Information guide for healthcare professionals: Biosimilars in the EU, and animated video on biosimilars in the EU. https://www.ema.europa.eu/en/human-regulatory/overview/ biosimilar-medicines. Accessed 13-12-2020.
• Wolff-Holz E, Tiitso K, Vleminckx C, Weise M. Evolution of the EU biosimilar framework: past and future. BioDrugs 2019;33:621-34. doi: 10.1007/s40259.019.00377-y.
• Crommelin DJA, Shah VP, Klebovich I, et al. The similarity question for biologicals and non-biological complex drugs. Eur J Pharm Sci 2015;76:10-7. doi: 10.1016/j.ejps.2015.04.010.
• Ishii-Watabe A, Takashi Kuwabara T. Biosimilarity assessment of biosimilar therapeutic monoclonal antibodies. Drug Metab Pharmacokinet 2019;34:64-70. doi: 10.1016/j. dmpk.2018.11.004.