How to respond to assessor requests when registering medicines in the EAEU, and when the response period is extended up to 180 working days
Under the Rules for Registration and Regulatory Review of Medicines for Medical Use (hereinafter the Rules), approved by Decision No. 78 of the Council of the Eurasian Economic Commission (EEC) of 3 November 2016, the applicant’s total time to respond to requests during registration of a medicinal product in the Eurasian Economic Union (EAEU) does not exceed 180 working days. A single request has no more than 90 working days from the day it is received. On the applicant’s justification, this period may be extended by the authorized body or expert organization of the reference state, that is, the EAEU member state that prepares the expert report on the product.
A critical comment from an assessor means that the dossier data do not confirm the quality or efficacy of the product, or that the benefit-risk balance is unacceptable, and this makes registration impossible. A minor comment describes a deviation from the requirements of Union acts that cannot lead to a risk of harm to human health from taking the product. For example, if the Summary of Product Characteristics (SmPC) or the package leaflet does not meet the requirements of EEC Council Decision No. 88 of 3 November 2016 (requirements for the package leaflet and the SmPC), a comment on this is minor provided that the deviation cannot lead to a risk of harm to health.
Who sends a request and what can be requested in it
In Russia, a request for missing materials is sent by the expert institution (the federal state budgetary institution that conducts the regulatory review of medicines) to the applicant’s personal account in the Unified State Health Information System. The head of the institution or an authorized person signs the request with a qualified electronic signature (QES), under Federal Law No. 61-FZ of 12 April 2010 «On the Circulation of Medicines». An assessor is not entitled to request materials from the applicant directly. A separate request to clarify information in the dossier documents during the check is sent by the Russian Ministry of Health, named in Federal Law No. 61-FZ as the authorized federal executive body.
In Union procedures, the authorized body or expert organization of the reference state may send a request in writing or electronically. They request missing information, explanations or clarification of dossier documents and data, and may propose changing the SmPC, the package leaflet, packaging mock-ups, the normative document on quality or other dossier documents. After the first request, further requests are permitted only on additional questions that concern information from the applicant’s response to the preceding request.
In the decentralized procedure, the reference state forms the request on the basis of questions from the states of recognition, that is, the member states where the product is registered taking the reference state’s expert report into account. The states of recognition send their requests no later than 30 working days after receiving the preliminary assessment report, and the reference state sends the applicant a single request within 20 working days after receiving the last of them. In the mutual recognition procedure, a state of recognition may also send a request, and the applicant responds to it within no more than 90 working days. If the documents requested by a state of recognition are not submitted on time, review and registration in that state are terminated.
If the reference state decides to conduct an unscheduled pharmaceutical inspection, it sends the applicant a request to arrange the inspection, stating the reasons and citing acts of Union bodies. The response to this request is given within the same time limits as the response to an assessor’s request: up to 90 working days with a possible extension, and no more than 180 working days in total for responses. A valid document on the manufacturing site’s compliance with the Union’s Good Manufacturing Practice (GMP) is part of the dossier at filing. If it cannot be provided, the applicant submits instead the documents and information listed in the Rules, and on that basis the reference state decides whether to conduct an unscheduled inspection within the time limit of the registration procedures.
Response period and extension in Russia and in the Union
| Parameter | Russia, Federal Law No. 61-FZ | EAEU, the Rules |
|---|---|---|
| Response period for a request | No more than 90 working days | No more than 90 working days |
| From which day the period runs | From the day the expert institution received electronic notification that the applicant received the request | From the day the request is received: it is considered received after 1 working day from the date it is sent, and in the decentralized procedure after 1 calendar day |
| Extension | Not provided for a request from the expert institution, except for a copy of the conclusion or certificate of compliance with the Union’s GMP: up to 180 working days are allowed for it | On the applicant’s justification; the decision is made by the authorized body or expert organization of the reference state |
| Limit for responses to requests | Not specified for a request from the expert institution | The total time to respond to requests is no more than 180 working days |
| Response time within the procedure time limit | Not counted when calculating the review time limit | Not included in the time limit for regulatory review and registration |
| Response period missed | For a request from the expert institution, the provisions on such a request do not name a consequence; for a request from the Russian Ministry of Health, failure to respond is grounds for refusing to arrange the reviews | Review and registration are terminated, and the applicant is notified within 14 working days; failure to submit the requested documents on time is among the grounds for refusing registration |
In the decentralized procedure, the procedure for sending requests and submitting responses is set by the legislation of the member states, and the authorized body of the reference state may extend the period. The Rules do not specify the point in time by which the applicant submits the justification for an extension.
In other procedures, the response period for a request also does not exceed 90 working days. This is how it is written for variations to the dossier and for confirmation of registration, and extension is not mentioned in these procedures. In dossier alignment with Union requirements, 90 working days are allowed for a response, and the total time to respond to requests does not exceed 180 working days.
How to sort out a comment before starting work
To respond to an assessor’s comment, one of three things is needed: correct a document, show data that is already in the dossier, or carry out laboratory testing.
Developers, manufacturers and registration holders must comply with Union acts and be guided by the approaches set out in the decisions and recommendations of the EEC. If, in developing the product, in studies, manufacturing, pharmacovigilance or document preparation, the applicant has chosen an approach that differs from these recommendations, it must submit a justification that the chosen approach is acceptable in terms of ensuring the quality, efficacy and safety of the product, and this justification is evaluated during the regulatory review.
| Subject of the comment | Union act |
|---|---|
| SmPC, package leaflet, packaging mock-ups | EEC Council Decision No. 88 (requirements for the package leaflet and the SmPC) |
| Bioequivalence studies | EEC Council Decision No. 85 (rules for conducting bioequivalence studies) |
| Biological medicines | EEC Council Decision No. 89 (rules for conducting studies of biological medicines) |
| Quality and quality control methods | EEC Board Decision No. 100 (Union Pharmacopoeia) |
For comments on bioequivalence studies, the decision on an unscheduled inspection of their results is made on the basis of an overall evaluation of the factors listed in the Rules. For comments on quality, the regulatory review includes laboratory testing for compliance with the normative document on quality and for reproducibility of the declared methods.
Samples, reagents and laboratory testing
For laboratory testing at the expert organization, the applicant submits samples of the product, reference standards of active pharmaceutical ingredients and related impurities, specific reagents and other materials, as agreed with that organization. The quantity of these materials is agreed with the expert organization and calculated for no more than a threefold analysis under the normative document on quality or other specifications from the dossier. The time for handing over the materials is agreed with the authorized body or expert organization and is not included in the overall time limit for regulatory review and registration.
Samples, reagents and materials are not required if testing at the expert organization is impossible because the materials are difficult to obtain, the conditions for their transport and storage cannot be met, or special equipment is not available. They are also not required for other reasons, by decision of the authorized body or expert organization, in cases of force majeure or circumstances beyond the parties’ control. Materials that are difficult to obtain include, among others, materials of orphan, advanced therapy, radiopharmaceutical, narcotic and psychotropic medicinal products, and of products for treating high-cost nosologies, because of their high cost. In such cases, laboratory testing is carried out in the manufacturer’s quality control laboratory or in a contract laboratory used by the manufacturer, in the presence of representatives of the expert organization. If this is not possible, then, as agreed with the authorized body or expert organization, the quality review is carried out on the basis of the manufacturer’s analysis reports, including by audio or video link.
Before an application is filed, the authorized bodies and expert organizations of the member states may, at the applicant’s request, hold scientific and pre-registration consultations, including on the need to submit samples, reference standards, specific reagents and consumables for the laboratory quality review. In Russia, scientific advice is provided by the Russian Ministry of Health with the involvement of subordinate federal state budgetary institutions that do not take part in organizing the quality review (under Federal Law No. 61-FZ).
Preparing and submitting the response
A response to a request is submitted with a new version of the electronic registration dossier. The submission version (sequence) number consists of four Arabic numerals and is given together with an application for variations and/or in response to a request; for the initial submission of the dossier, «0000» is given.
It is convenient to present a response as a table: the assessor’s question, the applicant’s position, a reference to the data in the dossier, and a list of amended documents. A further request is permitted on information from this response, so before filing, the applicant cross-checks the accompanying documents against the modules already submitted.
What happens after the response is submitted
In the decentralized procedure, the regulatory review resumes after the responses to requests are submitted. The final expert report includes an evaluation of the explanations, documents and information submitted in response to the request. The authorized body of the reference state makes the decision on the results of the review within no more than 10 working days from the day the report is signed. If the decision is positive, it issues the registration certificate within no more than 10 working days.
The authorized body of the reference state refuses registration if the benefit-risk balance is unfavorable, the efficacy or quality of the product is not confirmed, the quality control methods are not reproducible, the applicant has submitted inaccurate information, the inspection has not confirmed compliance with the Union’s good pharmaceutical practices, or the requested documents were not submitted on time. The applicant is notified of a refusal within 10 working days from the day of the decision.
What to do
Identify the procedure, the type of request and the deadline. Establish under which procedure and by whom the request was sent: the expert institution or the Russian Ministry of Health, the reference state or a state of recognition, and whether it concerns an inspection. Note the day the request was received and write down the end of the 90 working days. The total time to respond to requests does not exceed 180 working days.
Sort the comments by category and by how each will be closed. Use the definitions in the Rules to separate critical comments from minor ones. Then determine for each comment what is needed to respond: a corrected document, data that is already in the dossier, or laboratory testing. Assign a person responsible for each comment.
Decide on an extension while the first 90 working days are running. If the longest action does not fit into 90 working days, submit a justification for extending the period. The Rules do not state the moment for submitting the justification. The authorized body or expert organization decides on the extension, and the outcome is not guaranteed.
Agree on samples, reagents and the place of testing. If laboratory testing is needed to respond to a comment, request the list of samples, reference standards of impurities and consumables, and agree on the quantity within a threefold analysis and on the handover time. If the materials cannot be handed over, propose testing in the manufacturer’s laboratory in the presence of assessors, or a quality review based on the manufacturer’s analysis reports.
Answer each comment with data and a reference to the Union act. For each question, give the position, the data from the dossier, a reference to the Union act and a list of amended documents. If you depart from an EEC recommendation, attach a justification of the acceptability of the chosen approach. Before filing, cross-check the accompanying documents against the modules already submitted, because a further request is permitted on information from your response.
Regulatory framework:
1. Decision of the EEC Council No. 78 of 3 November 2016 «On the Rules for Registration and Regulatory Review of Medicines for Medical Use» (as amended on 26 November 2025)
2. Federal Law No. 61-FZ of 12 April 2010 «On the Circulation of Medicines» (as amended on 4 August 2026, with amendments and additions taking effect on 1 September 2026)
3. Decision of the EEC Council No. 85 of 3 November 2016 «On Approval of the Rules for Conducting Bioequivalence Studies of Medicinal Products within the Eurasian Economic Union» (as amended on 12 April 2024)
4. Decision of the EEC Council No. 88 of 3 November 2016 «On Approval of the Requirements for the Instructions for Medical Use of a Medicinal Product and the Summary of Product Characteristics of a Medicinal Product for Medical Use» (as amended on 21 February 2025)
5. Decision of the EEC Council No. 89 of 3 November 2016 «On Approval of the Rules for Conducting Studies of Biological Medicines of the Eurasian Economic Union» (as amended on 22 January 2025)
6. Decision of the EEC Board No. 100 of 11 August 2020 «On the Pharmacopoeia of the Eurasian Economic Union» (as amended on 25 June 2024)