Foreign clinical trial acceptance in the EAEU differs from FDA and EMA. Three conditions of Decision No. 78 decide it
Regulatory teams that have previously worked with the FDA or EMA typically include a dedicated stage in their dossier preparation plan: an ethnic sensitivity analysis of the drug and, if necessary, a bridging study based on ICH E5(R1) logic. For the EAEU market, this rationale works only partially. An assessor who receives Module 5 of the marketing authorization dossier applies three formal conditions from paragraph 36 of Decision No. 78 of the Eurasian Economic Commission (EEC) Council dated 3 November 2016. A scientific assessment of population similarity plays no part in these conditions.
If none of these conditions are met, the applicant must conduct at least one clinical trial within the territory of the Union. An analysis of ethnic factors does not waive this obligation and is not mentioned anywhere in the text of Decision No. 78. Let us break down what exactly an assessor checks, where formal criteria end and scientific argumentation begins, and what to do about it in practice.
Module 5 in the Structure of the Common Technical Document
A marketing authorization dossier under Decision No. 78 is compiled in the Common Technical Document (CTD) format and consists of five modules. Module 1 contains administrative information and is specific to each member state, whereas Modules 2 through 5 are common to all Union states. This is confirmed by Annex No. 1 to the Rules, as well as by methodological guidance from the Scientific Centre for Expert Evaluation of Medicinal Products under the Ministry of Health of the Russian Federation, which prepares clarifications for applicants regarding dossier structure.
Table 1: The Five Modules of the EAEU Common Technical Document
| Module | Contents |
|---|---|
| Module 1 | Administrative information: application forms, draft package leaflet, mock-ups of packaging, information about the applicant and manufacturer |
| Module 2 | Summaries and overviews of quality, non-clinical, and clinical data |
| Module 3 | Quality: chemical, pharmaceutical, and biological data on the active substance and finished product |
| Module 4 | Non-clinical study reports: pharmacology, toxicology, and pharmacokinetics in laboratory animals |
| Module 5 | Clinical study reports: pharmacokinetics, efficacy, safety, and post-authorization data in humans |
Module 5 is divided into seven subsections, listed in section 5 of Annex No. 1 to Decision No. 78.
Table 2: Subsections of Clinical Study Reports (Section 5.3 of Annex No. 1)
| Subsection | Contents |
|---|---|
| 5.3.1 | Biopharmaceutic study reports (bioavailability, bioequivalence) |
| 5.3.2 | Reports of pharmacokinetic studies using human biomaterials |
| 5.3.3 | Human pharmacokinetic study reports |
| 5.3.4 | Human pharmacodynamic study reports |
| 5.3.5 | Reports of efficacy and safety studies |
| 5.3.6 | Reports of post-marketing experience |
| 5.3.7 | Case report forms and individual patient listings |
It is these reports that the assessor examines against the criteria of paragraph 36, discussed next.
Where the Expectation of Ethnic Sensitivity Comes From
International practice for compiling registration dossiers relies heavily on the evaluation of ethnic factors. The ICH E5(R1) guideline describes how the pharmacokinetics and pharmacodynamics of a drug can vary across different populations and introduces the concept of a complete clinical data package that can be extrapolated to a new region once insensitivity to such factors is established. A separate guideline, ICH E17, applies to multi-regional trials, while the statistical framework for assessing the consistency of results across regions was proposed by Jun Shao and Shein-Chung Chow in a 2002 paper in the journal Statistics in Medicine.
This methodology works in jurisdictions that have officially adopted it: the US, the European Union, Japan, and other countries in the ICH region. Russian and Eurasian consultants frequently transpose this logic onto the EAEU by analogy, since it is well documented in the international literature and sounds convincing. The problem is that the terms «ethnic factors» and «bridging study» are entirely absent from the text of Decision No. 78 and the Rules for Registration and Examination of Medicinal Products it approved. An assessor at the expert organization evaluates the formal conditions of paragraph 36. Scientific population comparability plays no part in that evaluation.
Three Conditions of Paragraph 36 — The First, Formal Gate
Paragraph 36 of Decision No. 78 permits the assessor to consider clinical study reports included in Module 5 if one of three conditions is met.
The first condition: the clinical trials were conducted in EAEU member states before 1 January 2016, or were still ongoing as of that date with patient recruitment already completed.
The second condition: the trials were conducted, wholly or in part, in countries of the ICH region before 1 January 2016, and the medicinal product was authorized in those specific countries on the basis of these trials.
The third condition concerns trials initiated after 1 January 2016: they must comply with the legal acts of the Union, and at least one of them must be conducted, wholly or in part, within the territory of the EAEU.
If none of these conditions is met, the applicant has two options. The applicant may, at its own discretion and subject to agreement with the competent authority, conduct at least one clinical trial within the territory of the Union. Alternatively, the competent authority may order an unscheduled inspection of one of the clinical sites where the trial took place, and the registration decision will then depend on the outcome of that inspection. For orphan medicinal products, paragraph 36 does not apply at all: this is a dedicated exemption explicitly stated in the text.
Table 3: Common Perceptions vs. What the Assessor Actually Evaluates
| Common Perception (US / EU Experience) | Actual Criterion Under Paragraph 36 of Decision No. 78 |
|---|---|
| Analysis of the ethnic sensitivity of the drug | Date and location of the trial: before or after 1 January 2016, within the Union or in ICH countries |
| Bridging study following ICH E5(R1) logic | At least one trial within the territory of the Union if none of the three conditions is met |
| Shao-Chow consistency index as grounds for accepting the data | Inspection of the clinical site as an alternative to an additional trial |
| Identical requirements for all drug categories | A dedicated exemption for orphan medicinal products |
GCP, GLP, and the Declaration of Helsinki — The Second, Substantive Gate
Paragraph 35 of Decision No. 78 adds a substantive requirement on top of the date and location conditions: non-clinical studies conducted outside the EAEU are considered by the assessor provided they were planned, conducted, and reported in accordance with Good Laboratory Practice (GLP) rules equivalent to, or stricter than, Union requirements. Clinical trials must meet the same Good Clinical Practice (GCP) standard, with an explicit reference to the principles of the World Medical Association Declaration of Helsinki.
This is the second, substantive gate. The date and location of the trial open the door for the data to be considered at all, while GCP and GLP compliance determines whether the dossier passes the assessment on its merits. An applicant may formally satisfy one of the three conditions of paragraph 36; however, if it cannot demonstrate the equivalence of the trial conduct standards, the assessor is entitled to conclude that the data are insufficient already at the quality-review stage.
When a Clinical Site Inspection Is Inevitable
Paragraph 38 of Decision No. 78 lists the circumstances under which the competent authority orders an unscheduled GCP inspection of a clinical trial.
The list is extensive. In practice, assessors most often rely on a handful of trigger groups:
absence of independent ethics committee approval, or irregularities in obtaining informed consent;
ambiguities in the trial’s administrative structure: unclear sponsor, CRO, or data-ownership roles;
substantial protocol amendments not reflected in the final study report;
exclusion of individual patients’ data from the statistical analysis without justification;
inconsistent or implausible results compared with other trials of the same drug;
the trial was conducted in a region where clinical trial standards are lower than those of the Union.
An inspection does not replace an ethnic sensitivity analysis. It is a separate tool for verifying data integrity. The competent authority applies it based on its own risk assessment, without relying on formulas from the international statistical literature. The procedure for conducting such inspections is set out in EEC Council Decision No. 83 of the same date, 3 November 2016.
Multi-Regional Clinical Trials as the Safest Route
Federal Law No. 61-FZ explicitly recognizes international multi-center clinical trials as a distinct category, on par with national and post-authorization trials. This aligns directly with the third condition of paragraph 36 of Decision No. 78: if at least one trial site operates within the territory of the Union while the remaining sites are located abroad, the data pass the formal gate automatically, without any additional trials and without the inspection risk associated with purely foreign sites.
The ICH E17 guideline describes how to plan such trials from the outset, including endpoint selection and sample-size allocation across regions. For teams designing a clinical development programme for several markets at once, including an EAEU site in the global protocol at the planning stage costs less than a subsequent bridging study or a foreign-site inspection after the dossier has already been submitted.
Recommended Action Plan
Verify the dates and sites of trials already conducted. Compare the Module 5 protocols against the three conditions of paragraph 36: establish when and where the last patient’s last visit actually took place, and confirm whether the drug was authorized in an ICH country on the basis of these specific data.
Compile evidence of GCP and GLP equivalence. For each foreign site, obtain a document or a justified statement confirming that the trial was conducted to a standard equal to or higher than the Union’s requirements, including explicit adherence to the Declaration of Helsinki.
Assess the risk of an unscheduled inspection under paragraph 38. If the dossier contains any of the risk factors (protocol amendments, excluded patients, contradictory results), prepare the explanation in advance, before the assessor’s request.
Consider adding an EAEU site to a new protocol at the planning stage, if the drug is still in development. This satisfies the third condition of paragraph 36 without a separate bridging study later on.
Do not spend resources on an ethnic sensitivity analysis as though it were a formal EAEU requirement. Use that methodology for the scientific justification of the dossier. It is not needed for clearing the assessor’s formal gate: these are two different levels of argumentation.
The three conditions of paragraph 36 do not replace the scientific side of dossier preparation. They determine whether foreign clinical data will be considered at all, before the assessor begins evaluating their content on the merits. Regulatory teams are better served by clearing this formal gate first, and reserving ICH E5(R1) methodology and Shao-Chow statistics for the substantive argumentation within Module 5, where they work best.
Regulatory Framework:
1. EEC Council Decision No. 78 of 03.11.2016 «On the Rules for Registration and Examination of Medicinal Products for Human Use» (Paragraphs 35, 36, 38; Annex No. 1, Sections 1 and 5 — structure of the registration dossier and of Module 5)
2. EEC Council Decision No. 83 of 03.11.2016 «On Approval of the Rules for Conducting Pharmaceutical Inspections»
3. Federal Law No. 61-FZ of 12.04.2010 «On the Circulation of Medicines» (Article 38)
4. ICH Guideline E5(R1) «Ethnic Factors in the Acceptability of Foreign Clinical Data»
5. ICH Guideline E17 «General Principles for Planning and Design of Multi-Regional Clinical Trials»