What this document is
The Rules for Conducting Bioequivalence Studies of Medicinal Products within the Eurasian Economic Union were approved by Decision No. 85 of the Council of the Eurasian Economic Commission of 3 November 2016 and have applied since 6 May 2017. They were amended by Decisions No. 67 (2020), No. 22 (2023) and No. 30 (2024). The Rules are used when applications are filed to register medicines within the Union (clause 8); the cases in which a bioequivalence study is required are listed in clause 1: generic and hybrid medicines, changes to the registration dossier, combination products and others. Studies carried out outside the Union must comply with the Rules (clause 9).
What they apply to
- Solid oral dosage forms with immediate release — the main scope (clause 4).
- Other forms. Annex 9 covers topical corticosteroids, Annex 10 modified-release and transdermal forms, and Annexes 11–13 locally acting forms (clause 4 as amended in 2023); for the forms listed in clause 6 (including inhaled and liposomal products), other EAEU acts also apply.
- Chemical compounds only. The scope of the Rules is limited to comparing chemical compounds (clause 7).
Where to find what in the Rules
| Clause | What it covers |
|---|---|
| 2, 11 | The definition of bioequivalence: no significant difference in the rate and extent to which the active substance becomes available at the site of action at the same molar dose |
| 15 | The recommended (standard) design — a randomised two-period, two-sequence crossover study with a single dose; by the start of the second period the concentration in all participants must be below the limit of quantification, which usually takes five half-lives |
| 17, 31 | When patients may be used instead of healthy volunteers: where the risks for healthy people are unacceptable (clause 31); repeated dosing in patients — where a single dose is not tolerated by healthy volunteers and a single-dose study in patients is not possible (clause 17) |
| 18 | Choice of the reference product (as amended by Decision No. 30 of 2024) |
| 26 | The number of subjects is justified by a sample-size calculation; at least 12 are included in the analysis |
| 27 | Studies are conducted in healthy volunteers, except where the product poses an obvious threat to their health and such a study would be unethical |
| 28 | Inclusion and non-inclusion criteria are set out clearly in the protocol; age at least 18, body mass index where possible 18.5–30 kg/m² |
| 29 | Eligibility is confirmed by laboratory tests, history and a medical examination; sex does not matter, but the risk to women of childbearing potential is considered; alcoholism and drug addiction, including in the past, are non-inclusion criteria |
| 33 | Food intake (as amended by Decision No. 22 of 2023) |
| 71 | Re-analysis of samples is provided for in the protocol; under normal conditions re-analysis for pharmacokinetic reasons is not allowed |
| 76–77 | The criteria for excluding subjects are described in the protocol in advance |
| 89 | The statistical model of analysis is set in advance |
| 116, Annex 7 | The report: drawn up and signed by the investigator; it states the site, the responsible investigators, where and how long the study was conducted, certificates or conclusions from audits (if any) and information on compliance with ethical requirements (the composition of the independent ethics committee, data from the minutes of its meeting) |
| Annex 4 | Biowaiver under the Biopharmaceutics Classification System (as amended by Decision No. 30 of 2024) |
What the Rules do not contain
- Requirements for the licence, accreditation, premises and equipment of a site. We did not find them in the original or in the amendments. The subject is regulated by the legislation on licensing medical activity, Article 40 of the Law on the Circulation of Medicines and the EAEU GCP Rules.
- Rules on payments to participants, advertising of recruitment, insurance and confidentiality. Insurance and confidentiality are covered by Law No. 61-FZ (Art. 43, 44) and the EAEU GCP Rules; the principles for payments to participants are in the EAEU GCP Rules (clauses 3.1.8–3.1.9 and 4.8.10). Articles 38–44 of the Law contain no rules on the amount or procedure of payments — see “Regulatory framework”.
- General GCP requirements. The Bioequivalence Rules do not restate the GCP Rules but refer to them: for synopses of pilot studies (clause 13), for the study report (clause 116, Annex 7) and for studies in volunteers of locally applied medicines (Annex 13, clause 9). The GCP Rules apply to any study whose data are submitted to the authorities of the member states (Section I of the GCP Rules).
What this means for your project. The protocol must fit the Bioequivalence Rules, and the conduct of the study must fit the GCP Rules and the law. In practice there are five things to check in the protocol in advance: the sample-size calculation and the dropout allowance (at least 12 in the analysis), the inclusion and exclusion criteria, the possible reasons for re-analysing samples, the statistical model, and the structure of the report under Annex 7.
What next
You can estimate the number of volunteers in the calculator. If you are planning a study, send the protocol or synopsis: we will assess feasibility and prepare a proposal for the bioequivalence study.
Sources
- EEC Council Decision No. 85 of 3 November 2016 “On Approval of the Rules for Conducting Bioequivalence Studies of Medicinal Products within the Eurasian Economic Union”.
- Amendments: Decision No. 67 of 4 September 2020, Decision No. 22 of 15 February 2023, Decision No. 30 of 12 April 2024.
- The summary is based on the consolidated text of the Rules with the three amendments (No. 67, No. 22, No. 30); we found no other amendments as of 21 October 2026.
Questions and answers
Which medicines do the EAEU Bioequivalence Rules apply to?
The main scope is solid oral dosage forms with immediate release of the active substance (clause 4). For other forms there are separate annexes: Annex 9 for topical corticosteroids, Annex 10 for modified-release and transdermal forms, Annexes 11–13 for locally acting forms; for the forms listed in clause 6, other EAEU acts also apply. The Rules are limited to comparing chemical compounds (clause 7).
How many volunteers do the Rules require?
The number of subjects is justified by a sample-size calculation, and at least 12 subjects must be included in the analysis (clause 26). How many you need depends on the variability of your product: work it out in our calculator.
Who can take part in a bioequivalence study?
As a rule, healthy volunteers: studies are conducted in them except where the product poses an obvious threat to their health and such a study would be unethical (clause 27). The age is at least 18 and the body mass index is, where possible, 18.5–30 kg/m² (clause 28). The inclusion and non-inclusion criteria are set out clearly in the protocol.
Do the Rules contain requirements for a clinic’s licence and equipment?
We did not find in the text of the Rules (the original and three amendments) any requirements for the licence, accreditation, premises or equipment of the research site. Licence requirements follow from the law on licensing medical activity; requirements for the investigator, from Article 40 of Law No. 61-FZ; requirements for the site’s resources (staff, premises, equipment), from the EAEU GCP Rules. Current law provides no separate accreditation of medical organisations for clinical trials of medicines.
This material is for information only and is not legal advice. The rules are cited as of the date of the last update; check the current versions of the documents before making decisions.
See also
Calculator: how many volunteers a bioequivalence study needs
The calculator estimates how many volunteers a standard crossover bioequivalence study (2×2) needs in its analysis, from intra-subject variability, the expected T/R ratio, power and the 80–125 % limits. The output is the number in the analysis, the number to enrol with a dropout allowance, and a power curve.
Learn more
Regulatory framework: the rules for clinical trials and bioequivalence studies in Russia and the EAEU
Clinical trials in Russia are governed by Federal Law No. 61-FZ “On the Circulation of Medicines”, the Good Clinical Practice Rules and the Bioequivalence Rules of the Eurasian Economic Union (EAEU), and orders of the Ministry of Health. This page shows what each document contains and which open registers let you check a clinic.
Learn more
Bioequivalence studies in Moscow
A bioequivalence study shows that a generic medicine reaches the bloodstream in the same way as the reference medicine. Bessalar Clinic conducts such studies in healthy volunteers in its in-patient unit and processes samples on site.
Learn more