The Eurasian Economic Union (EAEU) regulates all stages of the circulation of medicines, including their development, preclinical studies, clinical trials, industrial production, pharmacy manufacturing, sale, storage, transportation, medical use, return to the manufacturer or supplier and destruction.
Moreover, regulation is carried out at several levels, namely:
1. At the level of the EAEU legislation. The EAEU rules are uniform for all member states, and are aimed at harmonization (similar regulation) or unification (determination of identical rules) of the laws of the member states in the field of drug circulation;
2. At the level of legislation of each of the Member States [1]. Such issues, which are not unified or harmonized at the EAEU level, can be regulated differently in each of the member states.
The list of issues that are regulated at the national or supranational levels is determined by the Agreement on Uniform Principles and Rules for the Circulation of Medicines within the framework of the Eurasian Economic Union of 23.12.2014.
At the supranational level, issues aimed at creating a unified market for the EAEU medicines are regulated. A single market means that medicines that meet the standards of good pharmaceutical practices (laboratory, manufacturing, clinical, pharmacovigilance, etc.) and registered in accordance with the unified rules of registration and examination are freely moving within the EAEU.
The main regulatory authority of the EAEU in the field of drug circulation is the Eurasian Economic Commission (EEC) [2].
Issues that are not within the competence of the EAEU bodies are resolved at the level of legislation of the member states. Each state has its own body responsible for regulating the circulation of medicines (as a rule, such functions are performed by the ministry of health of the respective state).
| PROCESSES REGULATED ON THE NATIONAL LEVEL |
PROCESSES REGULATED ON THE SUPRANATIONAL LEVEL |
| - development (including harmonization of Pharmacopoeia) |
- issuing permits for preclinical and Clinical trials of drugs |
| - preclinical and clinical studies |
- pricing |
| - quality control |
- retail and pharmacy manufacturing |
| - registration |
- government procurement of medicines and other procedures related drug reimbursement system |
| - distribution of medicines |
-drug advertising |
| -production |
|
Registration and examination of medicines in the EAEU
When registering medicines, the compliance of medicines with the requirements of safety, effectiveness and quality is checked.
The procedure for drug registration is defined both at the level of national legislation of each of the member states and at the level of the EAEU legislation (unified Rules for the registration and examination of medicines for medical use [3]).
Drug registration according to uniformed rules allows ensuring access of medicines to the market of the entire EAEU. Based on the results of registration, drugs are included in special national registers or the Unified Register of Registered Medicines of the EAEU [4].
In order to harmonize the pharmaceutical markets of the EAEU Member States, a transitional period has been established that provides for the smooth replacement of national regulation with unified regulation.
| Time period |
Process should be implemented |
| Before 31.12.2020 |
Applicants were entitled to choose registration either according to the unified Rules of the EAEU for registration and examination of medicines for medical use, or in accordance with the laws of the Member State.
Moreover, drugs registered under the laws of the Member State are allowed to be circulated only in the territory of the respective state.
|
| Before 31.12.2025 |
Medicines registered in accordance with the national laws of the Member States should be brought into line with the uniformed requirements of the EAEU. |
| From 01.01.2020 |
The validity of registration certificates for medicines issued in accordance with the national laws of the Member States shall be terminated. Accordingly, the circulation of medicines that have not passed the registration procedure or bring 8 in line with the requirements of the EAEU is also stopped. |
The EAEU Unified Rules provide for two procedures for the registration of medicines:
• mutual recognition procedure;
• decentralized procedure.
As part of the mutual recognition procedure, the drug is first registered in one of the EAEU Member States (the so-called reference state), and in this state receives a registration certificate. After that, the drug is registered in other member states of the EAEU (the so-called recognition states), but by the shortened procedure, also with the receipt of a registration certificate in the recognition state.
The difference between the decentralized procedure is that the registration dossier is evaluated simultaneously in the reference state and the state of recognition. This reduces the overall registration period in several states.
As for the mutual recognition procedure, the EAEU member states have committed to mutually recognize the results of preclinical, clinical and other studies of drugs, the results of production inspections, preclinical, clinical studies of drugs, pharmacovigilance systems for compliance with the rules of good pharmaceutical practices, as well as the requirements approved by the Eurasian Economic Commission [5].
When registering and examining medicines according to the rules of the Eurasian Economic Commission, the unified Nomenclature of dosage forms approved by the Decision of the EEC Board No. 172 of 12/22/2015 should be used.
Medicines registered under the unified rules and sold within the framework of the EAEU must be labeled in accordance with the uniform requirements for the labeling of medicines for medical use and veterinary medicines, approved by Decision of the Council of the Eurasian Economic Commission No. 76 of 03.11.2016.
Such drugs should also be accompanied by instructions for use that comply with the unified requirements approved by Decision of the ECE Council No. 88 of 03/03/2016.
EAEU Pharmacopoeia
Requirements for the quality of medicines, pharmaceutical substances, herbal raw materials, excipients, reagents, packaging materials used in industrial production, pharmaceutical manufacturing of medicines, to standard samples used in the quality control of medicines, methods for controlling the quality of medicines, their packaging , conditions and shelf life are determined in special technical regulatory legal acts - pharmacopeia articles.
At the level of national legislation of the EAEU Member States, the approved pharmacopoeial articles are combined into state pharmacopoeias, which are used for drug registration and quality control of medicines intended for circulation only in the territory of the corresponding Member State.
To standardize the requirements for medicines intended for circulation within the framework of a single market in the entire EAEU, the EAEU Pharmacopoeia is being created.
Work on the creation of a unified EAEU Pharmacopoeia has been carried out by the EAEU Pharmacopoeia Committee since 2016. The EAEU Pharmacopoeia Committee has approved a number of draft pharmacopeia articles, such as Equipment, Physical and Physico-Chemical Methods, Limit Testing of Impurities, and Quantification Methods ". The list of approved and discussed pharmacopoeial articles is published on the website of the Eurasian Economic Commission [6].
The requirements of the EAEU Pharmacopoeia are mandatory for the circulation of medicines within the EAEU. It is assumed that the EAEU Pharmacopoeia is updated at least 1 time in 5 years
Preclinical and clinical studies in the EAEU
As part of the work of the common market, preclinical and clinical trials of medicines in the EAEU Member States are carried out according to uniform rules.
Such rules are defined by Good Laboratory Practice (GLP) [7], Good Clinical Practice (GCP) rules [8] and drug research requirements.
The rules for conducting research on biological preparations of the EAEU [9] and the rules for conducting studies of bioequivalence of drugs within the EAEU [10] were also approved.
Production of medicines in the EAEU
In the production of medicines on the territory of the EAEU, the uniformed rules of Good Manufacturing Practice (GMP) of the EAEU are applied, approved by Decision of the EEC Council No. 77 dated 03.11.2016.
Compliance with Good Manufacturing Practice is mandatory for all manufacturers on the territory of the EAEU and is checked when issuing production licenses, as well as during inspection of manufacturers.
To establish guarantees of compliance with these rules, the status of the authorized person (Qualified Person) of the manufacturer is determined. An authorized person is appointed by the manufacturer of medicines and is certified in accordance with the procedure and requirements established by Decision of the EEC Council No. 73 of 03/03/2016. Certified authorized persons are included in the appropriate register, available on the EAEU information portal [11].
Wholesale, transportation and storage of medicines in the EAEU
Within the framework of the EAEU, the Good Distribution Practice (GDP) rules are approved by Decision of the EEC Council No. 80 dated 10.11.2017. These rules establish common requirements for the processes of procurement, storage, import (import), export (export), sale (with the exception of retail sales to the public) without limiting the volume, transportation of medicines as part of distribution in the EAEU.
At the level of national legislation of the EAEU Member States, only certain stages of the distribution of medicines are regulated in part that does not contradict the EAEU Good Distribution Practice.
In particular, this applies to the stages of distribution of narcotic, psychotropic drugs or their precursors, drugs that belong to the group of highly toxic (highly toxic) compounds, drugs that are sources of ionizing radiation.
In addition, the rules for the retail sale of medicines to the population are also determined by the national legislation of each of the EAEU Member States.
Unification of pharmaceutical inspection procedures in the EAEU
The EEC Council has defined unified requirements for one-time pharmaceutical quality system inspections, the results of which will be recognized in all EAEU member states. During such inspections, it is established whether the production of drugs meets the requirements of the EAEU Good Manufacturing Practice rules.
General requirements for pharmaceutical inspections are contained in Art. 10 Agreements on common principles and rules for the circulation of medicines within the EAEU, rules for pharmaceutical inspections, approved by Decision of the EEC Council No. 83 dated 03.11.2016.
Pharmaceutical inspections are carried out by pharmaceutical inspectorates of the EAEU Member States. In their activities, the inspectorates are guided by the General requirements for the quality system of pharmaceutical inspectorates, approved by Decision of the EEC Council No. 82 of 03.11.2016. The register of EAEU pharmaceutical inspectors is also available on portal.eaeunion.org [12].
The dates for scheduled pharmaceutical inspections, the procedure for making decisions on them, as well as the list of entities that have successfully passed the inspection and received the relevant certificates, are established by the relevant pharmaceutical inspectorate.
General requirements for pharmacovigilance in the EAEU
In the framework of pharmacovigilance (pharmacovigilance) - the identification, evaluation, understanding and prevention of undesirable consequences of the use of drugs is provided.
The requirements for the functioning of the pharmacovigilance system are established by the rules of the Good Pharmacovigilance Practice (GVP) of the EAEU, approved by the Decision of the EEC Council No. 87 dated 03.11.2016.
Organizations must develop and implement their own pharmacovigilance system to monitor the safety of medicines. For the functioning of the quality system of drugs, determined by the results of pharmacovigilance, all specialists of the pharmacovigilance system of the organization are responsible.
Authorized state bodies carry out inspections of pharmacovigilance systems. Such inspections may be sudden, so organizations should always be prepared for them.
Authors of the material: Valentin Anikin, Lawyer, Specialization Pharmaceuticals and Healthcare, REVERA, Belarus; and Dmitry Arkhipenko, Managing Partner, REVERA, Belarus
Material published in CIS GMP news No. 1 (8) Winter 2020, Arabic Issue
[1] As of January 20, 2020, the EAEU member states are the Republic of Armenia, the Republic of Belarus, the Republic of Kazakhstan, the Kyrgyz Republic and the Russian Federation.
[2] The official ECE website is available at http://www.eurasiancommission.org/
[3] Approved by Decision of the ECE Council No. 78 of 03/03/2016.
[4] https://portal.eaeunion.org/sites/commonprocesses/en-us/Pages/DrugRegistrationDetails.aspx .
[5] P. 7st. 7 Agreements on common principles and rules for the circulation of medicines within the EAEU.
[6] http://www.eurasiancommission.org/en/act/texnreg/deptexreg/LS1/Pages/pharmacopoeia_PO.aspx
[7] Approved by Decision of the ECE Council No. 81 of 03/03/2016.
[8] Approved by Decision of the ECE Council No. 79 of 03/03/2016.
[9] Approved by Decision of the ECE Council No. 89 of 11/03/2016.
[10] Approved by Decision of the ECE Council No. 85 of 03/03/2016.
[11] https://portal.eaeunion.org/sites/odata/_layouts/15/Registry/PMM02/TableView.aspx?ItemId=371&ListId=0e3ead06-5475-466a-a340-6f69c01b5687 .
[12] https://portal.eaeunion.org/sites/odata/_layouts/15/Registry/PMM09/TableView.aspx