Functioning of the common market of medicines within the Eurasian Economic Union is carried out in accordance with the Agreement on the Eurasian Economic Union of May 29, 2014, the Agreement on common principles and rules of circulation of medicines within the Eurasian Economic Union of December 23, 2014, as well as in accordance with acts of the Eurasian Economic Commission in the field of circulation of medicines.
The main legislative act regulating the registration of medicinal products in the territory of the EAEU Member States is the Decision of the Eurasian Economic Commission No. 78 of November 03, 2016 “On the rules of registration and expertise of medicinal products for human use”.
Registration of medicines under the unified rules of the Union becomes mandatory from January 2021. At the same time, all medicines registered under national procedures must be brought into compliance with the rules of the EAEU by the end of 2025. The Holder of the registration certificate (MAH) can be any legal entity, a resident or non-resident of an EAEU Member State.
The legislation defines several types of procedures for registering a medicinal product in the EAEU:
- Procedure for bringing the registration dossier to EAEU requirements;
- Registration by mutual recognition procedure (sequential procedure);
- Registration through a decentralized procedure (parallel procedure).
Despite similar terminology – registration procedures in the EAEU differ significantly from procedures in the European Union. Regardless of the procedure chosen, the competent authority of a member state is involved in the assessment of a medicinal product for the purpose of registration in a certain country. The competent authority evaluates the registration materials uploaded to the common electronic database and during the registration process has the right to ask questions (give comments) as well as to refuse to register a medicine in the member state.
Procedure for bringing the registration dossier in line with the EAEU requirements
This procedure makes it possible to obtain a registration certificate according to the EAEU requirements on the basis of previous national registration in one or more member states of the Union. This procedure is used to move from fragmented national registrations to a common certificate under the new rules. According to this procedure, registration dossiers of medicines registered before December 31, 2020 should be brought into compliance with the requirements of the Eurasian Economic Union before December 31, 2025.
The essence of the procedure is that the Applicant (Marketing Authorization Holder, MAH) of existing registration must submit a dossier corresponding to the format of the Union. The dossier is assessed and a registration certificate of EAEU is issued. The reference country for filing is chosen as the one in which the medicinal product is already registered.
When bringing the registration dossier in line with the EAEU requirements, the Applicant (MAH) may choose to submit an Application for registration only in those countries where the drug is already registered. In the future, the list of countries may be extended by the procedure of mutual recognition.
An important point is that before starting the procedure of bringing the registration dossier to EAEU requirements it is necessary to submit Applications for all required variations (changes). The registration dossier corresponding to the Union format should not contain any additional (new) data not included earlier. Changes can be made only upon the inquiry (comment, deficiency) of the regulatory authority.
File on this procedure shall be submitted in CTD format, according to the requirements and structure described in the Decision of the Council of the Eurasian Economic Commission No. 78 of November 3, 2016 “On Rules for Registration and Examination of Medicinal Products for Medical Use”. At the same time, Modules 1, 2 and 3 shall comply with the requirements to the format of the Common Technical Document (CTD) of the EAEU requirements, and Modules 4 and 5 may be presented without bringing them to the requirements.
The duration of the procedure should not exceed 100 calendar days, not including the clock stops required to respond to the comments (deficiencies). Also, according to the decision of the Commission, an unscheduled inspection may be carried out during the procedure, according to the Decision of the Council of the Eurasian Economic Commission of November 3, 2016 № 83 “On approval of the Rules of pharmaceutical inspections”.
As a result of this procedure, a registration certificate will be issued:
- for 5 years in the general case,
- or without expiry, if the drug was registered in 3 or more EAEU member states and was in circulation for at least 5 years.
Registration by mutual recognition procedure (sequential procedure)
This procedure implies consistent registration: at the beginning (first stage), a medicinal product is submitted for registration and receives a certificate in the first country (the reference state). Then, in the second stage, the product registration can be recognized in other EAEU member states.
Stage I: registration of the medicinal product in the reference country.
The Applicant (MAH) independently selects the EAEU Member State for registration according to the procedure approved by the Decision of the Council of the Eurasian Economic Commission of November 3, 2016, No. 78 “On the rules of registration and expertise of medicinal products for medical use”.
A full registration dossier is submitted for registration, according to the type of Application and the specifics of the medicinal product, in the format of the Common Technical Document (CTD), in 5 modules.
During the registration process, an inspection may be assigned.
The duration of the procedure should not exceed 210 calendar days, not including the clock stops required to respond to comments.
Stage II: Registration through the mutual recognition procedure in other countries.
The Applicant (MAH) chooses one or several countries of recognition. For mutual recognition, Module 1, as well as SmPC, instructions and labeling in the language of the recognizing member states should be submitted.
The duration of the procedure should not exceed 90 calendar days, not including the clock stops to respond to comments.
A consistent registration procedure allows the Applicant (MAH) to concentrate on the establishment of the registration in the reference country, then expand the list of countries through a fast-track recognition procedure.
Registration by the decentralized procedure (parallel procedure)
This procedure allows submitting a medicinal product for registration simultaneously in the several EAEU member states chosen by the Applicant.
The country to which the Application and the full registration dossier are submitted is hereinafter referred to as the “reference” country. The regulatory authority of this country is primarily responsible for the examination of the registration dossier, making a decision on approval or refusal of registration. Other countries, also selected by the Applicant, are referred to as “countries of recognition”.
The registration dossier is submitted to the reference country in full (Modules 1-5 of the EAEU CTD format), taking into account the type of medicine and the type of Application. For each selected country of recognition, the Applicant (MAH) additionally submits Module 1 with national documentation (instructions, layouts, brief description of product properties), according to the language requirements.
Requirements for the registration dossier: EAEU CTD format
When registering medicinal products according to the “Common” EAEU rules, a unified format of the registration dossier – the Common Technical Document (UTD) – applies. The structure and requirements are approved by the Decision of the Council of the Eurasian Economic Commission No. 78 of November 3, 2016 “On Rules for Registration and Examination of Medicines for Medical Use”.
The registration dossier in the CTD format consists of 5 Modules:
- Module 1: Administrative information;
- Module 2: Summary of the common technical document;
- Module 3: Quality;
- Module 4: Preclinical (non-clinical) research reports;
- Module 5: Clinical Trials Reports;
The EAEU CTD format is quite close to the CTD ICH format but has some significant differences.
The requirements to the format and structure (location of documents) are described in Appendix 4 to Decision No. 78, and a matrix of requirements for different types of Applications is also provided: original, reproduced (generic), hybrid, bio-analogical, vaccines (serums), homeopathic, herbal. The registration dossier is submitted to the regulatory authority through the Single Window in electronic form (eCTD). The requirements for the registration dossier are described in Appendix 5.
The Applicant (MAH) also submits national forms along with the file, namely:
- ND (the normative document: summary on the quality of the finished medicinal product), filled in accordance with the requirements of Annex 3 to Decision No. 78;
- suggested labeling, including full-color artworks of primary and secondary packaging, drawn up in accordance with the requirements of the Decision of the Council of the Eurasian Economic Commission No. 76 of November 3, 2016 “On approval of labeling requirements for medicinal products forhuman and veterinary use”;
- suggested instructions for use, drawn up in accordance with the requirements of the Decision of the Council of the Eurasian Economic Commission of November 3, 2016 № 88 “On approval of requirements for instructions for medical use of medicines and general characteristics of medicines for medical use”.
The registration dossier shall be submitted as follows:
- Application for registration: in paper and/or electronic form;
- the registration dossier in the format of the EAEU CTD:
- Module 1: in paper and electronic form;
- Modules 2-5: in electronic form (eCTD).
The following Module 1 parts are not required to be submitted in paper form: Risk Management Plan (RMP), Site Master File and Pharmacovigilance Master File.
Language requirements
The registration dossier in the EEU ETD format is submitted in Russian, or in English with the translation of the following parts into the Russian language:
Module 1: all, except sections:
- 1.6.3 GMP site inspection reports for the last 3 years;
- 1.10.1 Master file of the pharmacovigilance system: summary of the pharmacovigilance system should be translated into Russian;
- 1.10.3. Resume of the Risk Management Plan should be translated into Russian.
It is also necessary to provide a general description of a medicinal product, instructions for medical use and package layouts in the national language of each country.
Module 2: all sections should be translated or submitted in the Russian language;
Module 3: may be submitted in English, the following sections must be translated into Russian:
3.2.S.2.2 A description of the production process and its control;
3.2.S.2.5 Validation of the production process and/or its evaluation;
3.2.S.3.2 Excipients;
3.2.S.4.2 Analytical methods;
3.2.S.4.3 Validation of analytical methods;
3.2.S.4.5 Justification of the Specification;
3.2.S.7.1 Summary of stability tests and stability conclusion;
3.2.P.1 Description and composition of the medicinal product;
3.2.P.2.2.1 Pharmaceutical development;
3.2.P.2.2.2 Manufacturing surplus;
3.2.P.2.2.3 Physico-chemical and biological properties;
3.2.P.2.4 Packaging system (closures);
3.2.P.2.6 Compatibility;
3.2.P.3.3 Description of the production process and its control;
3.2.P.3.4 Control of critical stages and intermediate products;
3.2.P.3.5 Validation of the production process and/or its evaluation;
3.2.P.4.3 Validation of analytical methods;
3.2.P.4.4 Justification of Specification;
3.2.P.4.5 Human and animal origin ancillary substances;
3.2.R.4.6 New ancillary substances;
3.2.P.5.1 Specification;
3.2.P.5.2 Analytical methods;
3.2.P.5.3 Validation of analytical methods;
3.2.P.5.5 Characteristics of impurities;
3.2.R.5.6 Justification of Specifications;
3.2.R.7 Packaging and container closure system;
3.2.R.8.1 Summary of stability tests and stability conclusion;
3.2.R.8.2 Post-stability post-stability test program and stability study commitment;
3.2.A.2 Safety evaluation of foreign agents;
3.2.A.3 New auxiliary substances.
Module 4: allowed to submit in English;
Module 5: allowed to submit in English.
The registration certificate:
The validity period of a registration certificate for the first time registered medicinal product in the reference state is 5 years. After renewal, the registration certificate is issued without expiry.
A registration certificate shall consist of:
- The certificate itself;
- Normative Document (ND);
- Summary of Product’s Characteristics (SmPC);
- Instructions for use / Package insert / Leaflet;
- Package labeling artworks.
Changes and variations:
The Marketing Authorization Holder is responsible for keeping the registration certificate and registration dossier in compliance with the registered medicinal product. Application and relevant set of documents should be submitted to the competent authority for expert assessment and approval.
Description and classification of changes, documentation requirements and other aspects are approved by Annex 19 to Decision No. 78 of the Eurasian Economic Commission “On Rules for Registration and Examination of Medicines for Medical Use”. There are the following types of changes:
- type IA: a change that has minimal or no effect on the quality, safety and efficiency of a registered medicinal product;
- type IB: a change that does not fall within the definitions of changes to IA, type II and extension of registration;
- urgent safety restriction: an immediate change due to new information related to the safety of a medicinal product;
- type II: a change that may significantly affect the quality, safety or efficacy of a registered medicine;
- a change that requires new registration / extension of registration.
When several changes should be submitted simultaneously, separate Application (notification) and separate files are submitted. There are several exceptions, for example, insignificant identical changes of several type Ia medicines, related changes of type IB or type II are allowed to submit a single Application file.
Renewal of registration (confirmation of registration):
Renewal of registration is required to extend the validity of the registration certificate. The Marketing Authorization Holder submits Applications to all member states in which the product is registered.
An Application for renewal of registration should be submitted not earlier than 210 calendar days before the expiry date and not later than the expiry of the registration certificate. While the product is in the registration procedure, it may be imported and sold if it complies with the previously approved registration materials.
The Applicant (MAH) submits Applications for renewal of registration in all EAEU states where a medicinal product is registered. If the Application has not been submitted to any country, such a registration certificate will be canceled.
For renewal of registration it is required to submit:
- An Application form in hard and/or electronic, according to Annex 2 to Decision No. 78 of the Eurasian Economic Commission “On Rules for Registration and Examination of Medicines for Medical Use”;
- Modules 1 and 2 of the registration dossier in the EAEU CTD format.
Confirmation of registration (renewal of registration) shall be carried out on the basis of the revaluation of the benefit-risk ratio conducted by the competent authority of the reference state.
The period of renewal should not exceed 120 calendar days from the date of submission, not including the clock stops to respond to comments (up to 90 days).
After re-registration (confirmation of registration), the registration certificate is issued without an expiry date.
Cratia provides professional services of state registration (renewals, variations) of medicinal products in EAEU. We have an excellent knowledge of national legislation, necessary experience and resources.
To start cooperation or get advice, please contact us by phone: +38 068 064-78-31, +38 044 223-61-67, by e-mail: info@cratia.ua, or visit our office.