General characteristics of clinical trials for biosimilar drugs
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.
___
- 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.