The principles for assessing therapeutic equivalence based on bioequivalence studies as accepted in Russia are significantly different from those adopted abroad, in particular with respect to drugs with narrow therapeutic indices (NTI). Certification of these drugs based on bioequivalence studies with commonly recognized limits is unacceptable in practice because drugs in this concentration range can cause serious adverse side effects and be more dangerous than the reference drug. The situation becomes especially critical when the reference drug is replaced by a generic. This circumstance creates the need to develop stricter regulations for NTI drugs. This article analyzes possible approaches to planning bioequivalence investigations for NTI drugs as adopted by leading world regulatory institutions in order to harmonize them with bioequivalence studies of NTI drugs in the Russian Federation. General recommendations for planning bioequivalence studies of NTI drugs were formulated based on the analysis.
Similar content being viewed by others
References
V. G. Kukes and D. Berry (eds.), Therapeutic Drug Monitoring: A Tool of Personalized Medicine [in Russian], International Association of Clinical Pharmacologists and Pharmacists Press, Moscow (2013).
Guidance on Bioavailability and Bioequivalence Studies for Orally Administered Drug Products – General Considerations, US Food and Drug Administration [internet]; [cited Jul. 20, 2016]; http://www.fda.gov/ohrms/dockets/ac/03/briefing/3995B1_07_GFI-BioAvail-BioEquiv.pdf
Immediate Release Solid Oral Dosage Forms. Scale-Up and Postapproval Changes: Chemistry, Manufacturing, and Controls, In Vitro Dissolution Testing, and In Vivo Bioequivalence Documentation, US Food and Drug Administration [internet]; [cited Jul. 20, 2016]; http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm-070636.pdf
Draft Guidance on Warfarin Sodium, US Food and Drug Administration [internet]; [cited Jul. 20, 2016]; http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM201283.pdf
Draft Guidance on Dabigatran Etexilate Mesylate, US Food and Drug Administration [internet]; [cited Jul. 20, 2016]; http://www.fda.gov/downloads/Drugs/GuidanceCompliance-RegulatoryInformation/Guidances/UCM308030.pdf
Investigation of Bioequivalence (CPMP / EWP / QWP / 1401 /98 Rev. 1), European Medicines Agency [internet]; [cited Jul. 20, 2016]; http://www.ema.europa.eu/docs/en_GB/document_library/contacts/not_yet_available.pdf
Comparative Bioavailability Standards: Formulations Used for Systemic Effects, Health Canada [internet]; [cited Jul. 20, 2016]; http://www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/guide-ld/bio/gd_standards_ld_normeseng.php
Guideline for Bioequivalence Studies for Formulation Changes of Oral Solid Dosage Forms, Pharmaceutical and Food Safety Bureau [internet]; [cited Jul. 20, 2016]; http://www.nihs.go.jp/drug/be-guide(e)/form/GL-E_120229_shohou.pdf
Bioequivalence Study Rules for Drugs of the Eurasian Economic Union (version 2 dated Feb. 20, 2015) [internet]; [cited Jul. 20, 2016]; http://www.eurasiancommission.org/ru/act/texnreg/deptexreg/konsultComitet/Documents/%D0%9F%D1%80%D0%B0%D0%B2%D0%B8%D0%BB%D0%B0%20%D0%91%D0%AD%D0%98%20%D0%B8%D1%82%D0%BE%D0%B3%2020.02.2015%20%D0%BD%D0%B0%20%D1%81%D0%B0%D0%B9%D1%82.pdf
A. N. Mironov (ed.), Handbook for Drug Evaluation [in Russian], Vol. 1, Grif I K, Moscow (2013), pp. 174 – 215.
D. P. Romodanovskii, T. V. Eremenkova, M. A. Dranitsyna, et al., Vedom. NTsESMP, 4, 5 – 10 (2015).
A. S. Smirnov, A. Shnaider, M. Yu. Frolov, and V. I. Petrov, Khim.-farm. Zh., 48(5), 3 – 10 (2014); Pharm. Chem. J., 48(5), 303 – 309 (2014).
Author information
Authors and Affiliations
Additional information
Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 50, No. 12, pp. 42 – 45, December, 2016.
Rights and permissions
About this article
Cite this article
Romodanovskii, D.P., Goryachev, D.V., Olefir, Y.V. et al. Planning Bioequivalence Studies of Drugs with Narrow Therapeutic Indices. Pharm Chem J 50, 814–816 (2017). https://doi.org/10.1007/s11094-017-1538-y
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11094-017-1538-y