Rules for Registration and Expertise of Medicinal Products for Medical Use in EAEU

1.1 General provisions

These Rules determine the procedure for registering, confirming registration (re-registration), amending the registration dossier and examining drugs for medical use with the aim of forming a common market for medicines within the Eurasian Economic Union (hereinafter - the Union), as well as the other procedures related to the registration of drugs (hereinafter referred to as procedures related to registration), including:

Bringing the registration dossier of a drug registered in the Member States of the Union (hereinafter referred to as the Member States) before the entry into force of the Agreement on Uniform Principles and Regulation for the circulation of medicinal products within the Eurasian Economic Union from December 23, 2014 (hereinafter referred to as the Agreement) until December 31, 2020, in compliance with these rules (hereinafter referred to as bringing to conformity with the requirements of the Union);
Suspension and cancellation of registration of drugs or application limitation of a medicinal product;
Issuance of duplicates of the registration certificate of a drug.

The requirements of these Rules apply to developers and manufacturers of drugs, holders of drug registration certificates, their proxies, authorized bodies (expert organizations) of Member States in the field of medicinal products circulation.

Registration in accordance with these Regulations shall be applied to the drugs intended for circulation in the common market of pharmaceutical products within the framework of the Eurasian Economic Union or in the territory of one of the Member States.

Registration under one trade name of medicines having a different qualitative composition of active substances is prohibited.

One drug with different trade names may be registered in different Member States in the following cases:

Use of the proposed trade name may be contrary to the norms of law and morals or otherwise does not take into account the national cultural and (or) linguistic properties;
intellectual rights to a trade name in the form of a trademark belonging to a person who is different from the person who applied for the registration of the medicinal product (hereinafter referred to as the applicant) or the holder of the registration certificate, and the applicant or holder of the registration certificate cannot provide the relevant license agreement on granting of the right Use of the trademark;
the drug has been registered under different trade names in accordance with the legislation of Member States until December 31, 2020.

Registration of a pharmaceutical product, confirmation of registration (re-registration), an introduction of changes to the registration dossier, as well as procedures related to registration, are carried out by authorized bodies.

Expert examination of a medicinal product is carried out by an expert organization determined in accordance with the legislation of a Member State.

Authorized bodies and expert organizations ensure the confidentiality of information contained in the registration dossier of the drug in the process of registration and examination of medicinal products, including information contained in the closed part of the master file for active pharmaceutical substance.

The applicant, in accordance with the legislation of a Member State, incurs expenses on registration, confirmation of registration (re-registration), changes to the registration dossier and examination of drugs, procedures related to registration, and inspections in order to determine compliance with the requirements of appropriate pharmaceutical practices initiated due to the implementation of these procedures.

The authorized body (expert organization) of the reference state upon receipt of the application for registration, confirmation of registration (re-registration), modification of the registration dossier and procedures related to drug registration, assigns to it a unique number via the integrated information system of the Union (hereinafter referred to as the integrated system), and informs the applicant.

The authorized body (expert organization) of the Member State shall provide information related to drug registration, confirmation of registration (re-registration), amendments to the registration dossier, as well as procedures related to registration, authorized bodies (expert organizations) of other Member States, and To the Commission using the integrated system according to the application number in accordance with the formation and maintenance procedure of the Unified Register of Registered Medicines (hereinafter - the Register).

The authorized body (expert organization) of the reference state shall in no later than 5 working days from the date the applicant submits the registration dossier electronically provide access to the registration dossier information upon the request of the authorized bodies (expert organizations) of the recognition states through the use of the means of the integrated system.

Based on the results of drug registration, the authorized body of each Member State that registered the medicinal product issues a registration certificate of the pharmaceutical product confirming the fact of its registration.

A drug registration certificate is issued in accordance with the unified form and rules for filling a medicinal product registration certificate for medical use according to Appendix No. 17 to this Regulation by the authorized body which registered the drug.

The validity period of the registration certificate for a drug registered for the first time in the referring state is 5 years. At the end of this period, a perpetual registration certificate of the medicinal product is issued, provided that the registration (re-registration) is confirmed.

In cases specified in Section VII of these Rules, as well as in cases related to the matters of pharmacovigilance, the authorized body may re-issue a registration certificate with a validity period of 5 years following the confirmation of registration (re-registration). The registration certificate of drug registered in accordance with the legislation of the Member States before December 31, 2020 and circulating for 5 years or more on the market of at least 3 member states is issued for an indefinite period in accordance with the procedure for filing it in conformity with the requirements of the Union under section XIII of these Rules.

1.2 Definitions

For the purposes of these Rules, the terms used have the following meanings:

"Holder of the registration certificate" is a legal entity that received the registration certificate for a drug and became responsible for the safety, effectiveness and quality of the medicinal product;
"Unified Register of Registered Medicinal Products of the Union" is a common information resource formed within the integrated system and containing information on drugs registered or completed the other procedures related to registration in accordance with these Regulations;
"Applicant" is a legal entity competent to submit an application for drug registration, confirmation of registration (re-registration), introduction of changes to the registration dossier of a pharmaceutical products, other procedures related to registration, and responsible for the reliability of information contained in the documents submitted to it and the registration dossier data;
"Normative document" is a document that establishes requirements for the quality control of a drug (containing the specification and description of analytical techniques and tests or references to them, as well as the relevant eligibility criteria for these quality indicators, etc.) based on the conducted expertise of a drug; it is approved by the authorized body in case of registration of a drug in the territory of the Union and designed to control the quality of the medicinal product during the post-registration period in the territory of the Union;
"General characteristics of the medicinal product" is a document approved by the authorized body of the Member State, in accordance with the acts issued by the bodies of the Union, containing information for the medical workers on safety and effectiveness of the drug;
"Representative of the registration certificate holder" is a legal entity registered in accordance with the legislation of a Member State or a separate subdivision of a legal entity located in the territory of a Member State and authorized by the holder of a registration certificate for performance of actions related to the circulation of drugs in the territory of a Member State;
"Registration dossier" is a set of documents (including an application), compiled in accordance with these Rules, submitted for conducting procedures related to drug registration or confirmation of registration (re-registration) of the medicinal product;
"Registration certificate of a medicinal product" is a document of a unified form issued by an authorized body that confirms registration of a pharmaceutical product and is a permit for its medical use in the territory of a Member State;
"Registration number" is the code designation assigned to the drug winning registration in the territory of a Member State;
"Registration of a medicinal product" is the procedure aimed at obtaining a permit for medical use of a drug in the territories of one or more Member State carried out in accordance with these Regulations;
"Reference state" is a member state that prepares an expert report on evaluation of safety, efficacy and quality of a drug on the basis of drug examination in accordance with these Regulations;
"Reference drug" is a drug used as a reference product and is the standard by which the properties of a examined medicinal product are determined (normalized);
"Specification" is a list of quality indicators, references to analytical techniques as well as on tests and norms that represent numerical (quantitative) limits, ranges and other criteria for the specified quality indicators;

1.3 General principles of registration of drugs

Registration of drugs may be performed at the request of the applicant in succession in the several Member States in accordance with the mutual recognition procedure or simultaneously in the several Member States in accordance with the decentralized registration procedure.

The procedure for mutual recognition is carried out by:

A) the reference state in accordance with these Rules with the aim of applying the pharmaceutical product in the market of that state only (national drug registration procedure);
B) in the states of recognition - upon request of the applicant after registration of the drug in the reference state using the procedure of mutual recognition.

The decentralized registration procedure is carried out simultaneously by the several Member States to which an application for drug registration of has been filed, with the choice of the reference state.

The applicant independently chooses the reference state and, if necessary, the state of recognition when applying for registration of the drug.

Only one state can act as a reference state.

The requirements for documents and data of the registration dossier in the format of the general technical document submitted for drug registration have been established by Annexes 1 to 5 to these Regulations.

Prior to submission of an application for registration of a drug in EAEU, the authorized bodies or expert organizations of the Member States shall have the right, at the request of the applicant, to conduct scientific and pre-registration consultations in accordance with the legislation of the Member States on the issues related to the execution of analytical tests, preclinical and clinical studies (trials), aspects of drug Registration procedures, including the qualification issues, a variation of the application for registration of a drug for the purpose of the volume of documents and registration dossier data, the completeness of the registration dossier, the definition of affiliated persons in the states of recognition, the format for submitting the application and the drug registration dossier, the necessity to provide samples of the drug, reference standards, materials, specific reagents, consumables required for conducting a laboratory quality examination in the expert organization or for its intended purpose, and on the other issues.

During drug registration procedures, or confirmation of registration (re-registration), or amendments to the registration dossier or procedures related to drug registration, an authorized body or an expert organization of the reference state initiates the inspection for compliance with the relevant good pharmacy practices conducted by the Pharmaceutical inspectorate of this State in case of detection facts that call into question the reliability of the information provided by the applicant in the registration dossier regarding the conducted pre-clinical (non-clinical) studies (trials) of drugs and clinical trials (trials) of drugs or production of the pharmaceutical product, including production of pharmaceutical substances or pharmacovigilance system organization. Such inspections can also be initiated in the cases specified in paragraphs 31, 33, 35, 37,38, 39 of these Rules. Responsibility for the timely initiation of appropriate unscheduled inspections, if necessary, is borne by the authorized body of the reference state.

The production of drugs must comply with the Rules of Good Manufacturing Practices of the Eurasian Economic Union.

When applying for drug registration, confirming registration (re-registration), aligning with the requirements of the Union of a medicinal product, the applicant must submit, as a part of the registration dossier, an existing document confirming compliance with the requirements of good manufacturing practices of the Union, the production site (production sites) where the production of the finished dosage form is performed and batch release quality control of the drug claimed for registration, confirmation of registration (re-registration), brought into conformity with the requirements of the Union.

Until December 31, 2018, with regard to the production site (production sites) of the medicinal product, the applicant, instead of a document confirming compliance with the requirements of good manufacturing practice of the Union, has the right to present a document confirming compliance with the requirements of good manufacturing practices issued by the authorized body of the Member States to the manufacturer of the medicinal product, production site (sites) of a medicinal product that carries out the production of the finished dosage form and release quality control.

If it is not possible to present the current document confirming the compliance of the production site (production sites) of the drug with the requirements of the Good Manufacturing Practice of the Union, the applicant, when filing an application for registration of a drug before December 31, 2018, or to bring it in conformity with the requirements of the Union, provides the following documents and information instead of this document:

A) current documents confirming the compliance of the production site (production sites) that produces the finished dosage form and issues quality control of the drug to the requirements of Good Manufacturing Practices issued to the manufacturer of the drug by the competent authority of the country of production of the drug;
B) a copy of the report on the results of the last inspection of the production site (production sites at production stages) conducted by the authorized body of the producing country and/or other authorized bodies during the last 3 years;
C) information on the results of all inspections of this production site (production sites) for compliance with the requirements of good manufacturing practices conducted over the last 3 years;
D) information on complaints regarding the quality of medicinal products produced at the given production site (production sites) over the last 3 years;
E) consent for a pharmaceutical inspection to be conducted in accordance with the requirements of Good Manufacturing Practice of the Union;
F) a copy of the main dossier (site master file) of the production site (production sites).

The reference state, based on the documents submitted by the applicant specified in clause 30 of this Regulation, taking into account the assessment of possible risks, makes a decision on whether to conduct an unscheduled pharmaceutical inspection for compliance with the GMP requirements of the Union for the time of drug registration procedures or to include an inspection of the drug production site (sites) in the plan of inspections in the first 3 years after completion of the registration procedures.

In case of documentary justification by the authorized body of the reference state, the impossibility of conducting an unscheduled inspection of the production site (production sites) of the drug by the reference state at the time of drug registration procedures, the applicant has the right, upon agreement with the reference state, file an application to one of the Member States for conducting an inspection of this production site (production sites) in compliance with the GMP requirements of the Union.

In case of a written refusal by the authorized state agencies of recognition in conducting an unscheduled inspection of the production site (production sites) of a drug, the authorized body of the referent state is obliged to organize and conduct an unscheduled inspection within the period of this drug registration procedures.

The decision on whether to conduct an unscheduled pharmaceutical inspection for compliance with the GMP requirements of the Union is made by the authorized body of the reference state in the process of:

A) drug registration procedures - for pharmaceutical products produced at the sites where the finished dosage forms are manufactured and the batch release control is performed, and which were not subject to the inspection by the authorized body (organization) of at least one Member State before;
B) the procedures for bringing to conformity with the requirements of the Union - for medicines previously registered in Member States, in case of indication (introduction, modification) of the production site (production sites) previously not inspected by the authorized body (organization) of at least one Member State.

Pre-clinical drug safety studies conducted in non-member states are considered during the expertise of medicinal products provided that these studies are planned, conducted and described in the pre-clinical study report in accordance with the requirements of Good Laboratory Practice equivalent to the requirements of the Union (or not below).

Clinical studies of medicinal products conducted in non-member states are reviewed during the expertise of medicinal products provided that these trials are planned, conducted and described in the clinical trial report in accordance with the requirements of GCP, equivalent to the requirements of the Union (or at least equal), as well as the principles of the Helsinki Declaration of the World Medical Association "Ethical principles of medical research with human participation as an object of research".

In the process of drug registration, the reports on previously conducted clinical trials included in Module 5 of its registration dossier are reviewed during the examination in case of one of the following conditions:

clinical studies shall be conducted in accordance with the legislation of the Member States and in their territory before January 1, 2016 (by the date of the last visit of the last patient (volunteer)) or continued as of January 1, 2016 (with a complete set of patients (volunteers) in the study);
the clinical trials shall be conducted partially or completely in the territories of the countries of the region of the International Conference on Harmonization of Technical Requirements for Registration of Medicinal products for Medical Use (ICH) before January 1, 2016 (on the date of the last visit of the last patient), on the basis of which the medicinal product was registered in the territories of countries of the Region of International Conference on the Harmonization of Technical Requirements for Registration of Medicines for Medical Use (ICH);
clinical studies initiated after January 1, 2016, shall be conducted in accordance with the international treaties and acts constituting the law of the Union, with at least one of the clinical studies conducted in full or in part (with respect to data obtained from the subjects of the study) in the territory of the Union.

The authorized body of the reference state on the basis of the documents and information submitted by the applicant, taking into account the assessment of possible risks, decides whether it is necessary (or not necessary) to conduct an unscheduled inspection of clinical trials of the drug, including bioequivalence studies, within the period of registration of the drug for compliance with the requirements of a GCP of the Union, or on the inclusion of a clinical research inspection in the plan for conducting inspections in the first 3 years after registration of the medicinal product.

An unscheduled inspection of the pharmacovigilance system of the holder of the registration certificate as a part of the registration procedure for the medicinal product is carried out in cases stipulated by the rules of good pharmacovigilance practice approved by the Commission.

1.4 General principles of expertise of medicinal products

Examination of drugs is carried out to obtain a scientific assessment of the quality, safety and efficacy of drugs and the risk-benefit ratio, and may include:

evaluation of documents and information provided by the applicant in the registration dossier of the drug (evaluation of the dossier);
conducting the laboratory tests for compliance with the requirements of the Normative Document and verification of analytical quality control procedures;
preparation of an expert report on evaluation of the medicinal product by the reference state;
assessment of the expert evaluation report by the state of recognition, taking into account the documents and information contained in the registration dossier of the drug.

During development of the pharmaceutical product, execution of pre-clinical (non-clinical) and clinical trials (trials) of the drug, its production, pharmacovigilance and preparation of documents for drug registration procedure, confirmation of registration (re-registration), changes in the registration dossier or other procedures related to registration , Developers, manufacturers and Marketing Authorization Holders and their authorized persons must comply with legislation of Member States, international treaties and acts constituting the right of the Union, as well as to be guided by the best approaches, the implementation of which will ensure the fulfillment of such requirements, and which are set out in decisions and recommendations adopted by the Commission. In case of non-compliance with these recommendations, the applicant must provide a rationale for the admissibility of the chosen approach in terms of ensuring the quality, efficacy and safety of the drug. The presented rationale must be evaluated when examining the medicinal products.

Examination of the drug is not interrupted for the period of conducting unscheduled pharmaceutical inspections for compliance with the requirements of the Union's proper practices (production, laboratory, clinical, pharmacovigilance), but the final expert evaluation report can be drawn up by the authorized body (expert organization) of the reference state only taking into account the results of unscheduled pharmaceutical inspections (if conducted). These inspections should be carried out within a period not exceeding 180 calendar days from the date of the authorized body's decision to initiate the inspection.

1.5 The procedure for registration and examination of medicinal products under the procedure of mutual recognition

1.5.1 Registration and examination of medicinal product in the reference state

The period of drug registration and examination in a reference state shall not exceed 210 calendar days from the date of filing an application for registration of a drug until the day of issuing a registration certificate.

For the purpose of a drug registration (Marketing Authorization Application), the applicant shall submit the following documents and materials to the authorized body (expert organization) of the reference state:

Application for registration of a drug in the established form on paper and (or) electronic media in accordance with Appendix no. 2 of these Regulations;
Documents confirming the payment of the fee (toll) for registration and examination of the pharmaceutical product according to the procedure established by the legislation of the reference state;
Drug Registration dossier in accordance with Annexes 1 to 5 to these Regulations on electronic media (in addition module 1 of the registration dossier is submitted on paper (except for the risk management plan, the main dossier (master file) of the production site (production sites) and the master file on pharmacovigilance));
Samples of medicinal products.

In the cases specified in the eighth paragraph of clause 47 of these Regulations, laboratory tests are carried out in the laboratory of quality control of the manufacturer of the medicinal product in the presence of representatives of the expert organization or in the contract laboratory used by the manufacturer in the presence of representatives of the expert organization.

Examination of a medicinal product in a reference state includes:

evaluation of completeness and correctness of the documents submitted in the drug registration dossier;
evaluation of documents and information on safety, efficacy and quality of the drug provided by the applicant in the registration dossier;
execution of the laboratory tests for compliance with the requirements of the normative document on quality and reproducibility of the declared quality control procedures carried out in the accredited testing laboratories;
initiation, if necessary, of an unscheduled or planned pharmaceutical inspection in the cases specified in these Regulations;
preparation of an expert report on the evaluation of the drug by the reference state.

The authorized body (expert organization) of the reference state shall, within 14 working days from the date of submission of the application for drug registration, assess the completeness, contents and correctness of registration of the documents submitted in the registration dossier before sending the registration dossier materials for expertise. The applicant is granted 90 calendar days maximum not included in the registration and examination period of the pharmaceutical product, for submission of materials missing in the drug registration dossier, according to the comments of the authorized body (expert organization) of the reference state.

The authorized body (expert organization) of the reference state rejects the application for drug registration in the event of failure to submit the registration dossier materials on the remarks of the authorized body (expert organization) of the reference state and (or) failure to confirm payment of the fee (fee) for registration and examination of the medicinal product in cases and order Established by the legislation of the reference state.

The authorized body and (or) the expert organization of the reference state when conducting drug registration and (or) examination of the medicinal product has the right to send a request to the applicant in written and (or) electronic form concerning submission of missing additional information, and request necessary explanations or document clarifications and data presented in the registration dossier.

The period for submitting a response to the request specified in paragraph 52 of these Rules shall not exceed 90 calendar days from the date of receipt of the request.

If necessary, the period established in paragraph 53 of these Rules may be extended by the authorized body (expert organization) of the reference state on the basis of the relevant justification of the applicant. The total response time for inquiries should not exceed 180 calendar days.

The period for documents submission for the applicant upon the request of the authorized body or expert organization during expertise of the drug is not included in the period of examination and registration of the pharmaceutical product.

If the applicant fails to submit the requested documents and information within the prescribed period, examination and registration of the drug shall be terminated. The authorized body (expert organization) notifies the applicant in writing and (or) by e-mail services within 14 working days from the date of adoption of this decision.

The interaction of the authorized body (expert organization) with the applicant when sending requests is carried out electronically using an integrated system.

The expertise of the medicinal product in case of initiating a pharmaceutical inspection for compliance with the proper pharmaceutical practices of the Union shall not be suspended. Wherein preparation of an expert evaluation report is completed by the reference state only after the expert organization of the reference state receives the results of the inspection. An unscheduled pharmaceutical inspection with a report on the completed inspection must be conducted at the time of registration of the medicinal product not exceeding 180 calendar days from the date the decision to conduct the inspection was adopted by the authorized body or an expert organization. The applicant organizes a visit to the production site and / or the research center and / or the inspection of the pharmacovigilance system of the Marketing Authorization holder within 30 calendar days after receiving a request to hold an inspection or offers the dates of visits, but no later than 90 calendar days after receiving the notification that the inspection shall be performed.

To prepare an expert evaluation report, the expert organization of the reference state prepares the expert reports on the forms in accordance with Appendices no. 6, 7, 8,9, 10, 12 and 22 to these Regulations.

Based on the results of the expert examination of the drug, the expert organization of the reference state prepares the final expert report on evaluation of the drug submitted for registration, including an assessment of the explanations received from the applicant, documents and information submitted in response to the request of the expert organization or authorized body, in accordance with Appendix no. 16 to these Regulations.

Expert reports on quality aspects, preclinical, clinical aspects, and final expert evaluation report are compiled in accordance with appendices No. 13, 14, 15 and 23 to this Regulation.

The expert evaluation report should be updated by the expert organization of the reference state with the appearance of new information that is important for assessing the quality, safety or efficacy of the drug and may affect the benefit-risk ratio of the medicinal product as part of the procedure for amending the registration dossier.

If, based on the results of the examination of the pharmaceutical product, the authorized body of the reference state takes a positive decision on registration of the drug, the authorized body of the reference state within a period not exceeding 10 working days shall:
issue a drug registration certificate to the applicant in the form in accordance with Appendix No. 17 to these Regulations;
place information about the medicinal product and its active pharmaceutical substances in a single registry with the application of approved summary of product characteristics, instructions for medical use, package mock-ups, the quality standard document, and the final expert evaluation report compiled in accordance with Appendix No. 16 to these Regulations, after confiscation of confidential data and data on experts, the agreed risk management plan for the use of the drug (if necessary) in accordance with the procedure for the formation and maintenance of a unified register.

The authorized body of the reference state refuses to register the drug based on the results of the examination in the following cases:

the expected risk-benefit ratio associated with the use of the medicinal product is not favourable;
the effectiveness of the drug is not confirmed by the information provided by the applicant;
the quality of the drug is not confirmed;
the proposed quality control methods and techniques are impracticable;
the applicant provided false information;
according to the results of the appointed inspection during drug registration, its compliance with the relevant pharmaceutical practices of the Union is not confirmed.

In case the authorized body of the reference state adopts a decision to refuse to register a drug, the authorized body (expert organization) of the reference state shall notify the applicant about it in electronic and/or written form within 10 working days from the date of adoption of such decision.

1.5.2 Registration and expertise of a drug under the mutual recognition procedure in the state (states) of recognition

The applicant, after registration of a drug in the referenced State, may initiate registration in the other Member States selected by the applicant as recognition States by way of a mutual recognition procedure by submitting to the competent authorities of such Member States (expert organization) the following:

Applications for drug registration under the procedure of mutual recognition on paper and (or) electronic media in accordance with the form provided in Appendix No. 2 to these Regulations;
Documents confirming the payment of the fee (fee) for drug registration and examination of the medicinal product in case and according to the procedure established by the legislation of the state of recognition;
Module 1 of the registration dossier on electronic media.

The authorized body (expert organization) of the reference state at the request of the applicant within a period not exceeding 5 working days from the date of receipt of this request shall provide access to the authorized bodies (expert organizations) of the recognition states to the drug registration dossier and the evaluation expert report through an integrated system with the use of additional documents and information submitted by the applicant upon the requests of the authorized body (expert organization) of the reference state.

The registration of a pharmaceutical product in the state of recognition in the absence of disagreements between the authorized bodies of this member state and the reference state and the availability of an opinion on the possibility of recognizing the expert evaluation report shall be made no later than 90 calendar days after the day of obtaining access to the expert evaluation report.

Examination of a medicinal preparation under the procedure of mutual recognition in the states of recognition is carried out by:

reviewing the application, documents and information provided in the registration dossier of a drug;
reviewing the expert evaluation report prepared by the expert organization of the reference state.

The authorized body (expert organization) of the state of recognition within 14 working days from the date of filing the application rejects the application for registration of the drug under the procedure of mutual recognition in case of non-compliance of the application with the requirements of these Rules and (or) failure to confirm payment of the fee (fee) for registration and examination of the medicinal product In the cases and in the manner stipulated by the legislation of the state of recognition.

When registering a drug under the procedure of mutual recognition, the authorized body (expert organization) of the state of recognition shall, not later than 50 calendar days after obtaining access to the expert evaluation report, forward the request to the authorized body (expert organization) of the reference state in accordance with Appendix No. 18 to these Regulations.

The applicant sends a response to the request to the authorized body (expert organization) of the state of recognition within a period not exceeding 90 calendar days. The authorized body (expert organization) of the state of recognition shall within 5 working days from the receipt of the applicant's response provide access to the authorized body (expert organization) of the reference state through an integrated system.

If the applicant fails to provide the documents and information requested by the authorized body (expert organization), the examination and registration of the pharmaceutical product in the given state of recognition is ceased.

The applicant shall be notified (in electronic form and/or hard copy) of the decision of the authorized body and (or) expert organization within 10 working days from the date of the decision.

The authorized body (expert organization) of the state of recognition on the basis of the examination of the drug within a period not exceeding 50 calendar days from the date of submission to the state of recognition of the application for drug registration (in the absence of inquiries to the applicant) or within a period not exceeding 20 calendar days from the date of receipt of the applicant's response to a request sent by the authorized body (expert organization) of the state of recognition, using an integrated system, sends a conclusion on recognizing or non-recognizing the expert evaluation report prepared by the reference state to the expert body (expert organization) of the reference state. The authorized body of the reference state brings the obtained conclusion to the attention of the applicant.

If, based on the results of the examination of the drug, the authorized body of the state of recognition makes a positive decision on registration of the drug, the authorized body of the state of recognition in no later than 10 working days shall do the following:

issue the registration certificate of the pharmaceutical product to the applicant in accordance with Appendix No. 17 to this Regulation, as well as the guidelines for medical use approved by the summary of product characteristics, the mock-ups of the packages in the national language of the State of Recognition, subject to the relevant requirements in the legislation of the State of Recognition;
coordinate the regulatory document on quality issued by the reference state;
place information about the medicinal product and its active pharmaceutical substances in the unified register with the application of approved summary of product characteristics, guidelines for medical use, package mock-ups, an agreed risk management plan if the medicinal product is used (if necessary) in accordance with the procedure of forming and keeping the unified register.

The registration certificate of the drug is issued by the authorized body of the state of recognition with the validity period of the registration certificate established by the reference state.

The registration of a drug registered in accordance with these Regulations in the other Member States not listed in the initial application for registration as recognition states, as well as in the states that joined the Union after registration of the pharmaceutical product, is carried out under the mutual recognition procedure based on reviewing the current version of the expert evaluation report prepared by the expert organization of the reference state.

If the expert evaluation report prepared by the expert organization of the reference state cannot be recognized, the authorized body (expert organization) of the state of recognition shall send the conclusion on impossibility of recognizing this expert report to the authorized body (expert organization) of the reference state, the other states of recognition participating in the drug registration procedure, to the applicant and to the Expert Committee.

The expert committee shall, within a period not exceeding 60 calendar days from the date of receipt of the conclusion of the authorized body of the state of recognition on the impossibility of recognizing the expert assessment report prepared by the expert organization of the reference state, implement the procedure for considering disagreements in accordance with the procedure established by the Commission.

The authorized body of the State of Recognition refuses to register the drug if, following the examination of the medicinal product and after conducting the dispute resolution procedure in the Expert Committee, it has been decided that the data presented in the expert evaluation report cannot be recognized as sufficient to confirm the quality and (or) effectiveness, and (or) favorable benefit-risk ratio of the pharmaceutical product.

In case of disagreement between the authorized bodies regarding the recognition of the expert evaluation report and their revision by the Expert Committee, the authorized body of the recognition state that made a positive decision to recognize the expert evaluation report prepared by the expert organization of the reference state issues a drug registration certificate, the summary of product characteristics, instructions for medical use, package mock-ups and coordinates a risk management plan for the use of the medicinal product (if necessary), Normative Document before the decision of the Expert Committee. At the request of the applicant, the issuance of the drug registration certificate by the authorized body of such state of recognition may be suspended until the disagreements between the authorized bodies of other recognition states and the reference state are eliminated.

The registration certificate of the drug issued in such cases is valid in the territory of the state of recognition.

1.6 The drug registration process and expertise sequence under the decentralized procedure in the reference state and in the states of recognition

For the purpose of drug registration according to the decentralized procedure, the applicant shall choose the reference state and the state of recognition.
The duration of the decentralized procedure for drug registration and examination of the medicinal product shall not exceed 210 calendar days from the day of filing of the last of the applications for registration of the medicinal product in the State of recognition until the day the registration certificates of the drugs are issued by the authorized bodies of all Member States participating in the decentralized procedure.

The drug registration process for a decentralized procedure consists of the following stages, conducted simultaneously:

registration of a drug in the reference state;
recognition of the expert evaluation report and drug registration in states of recognition.

For the purpose of registration of a medicinal product, the applicant submits the following documents to the authorized body (expert organization) of the reference state:

An application for registration of a drug in the established form on paper and (or) in the electronic form in accordance with Appendix No. 2 to these Regulations;
Documents confirming the payment of the fee (tax) for drug registration and examination of the medicinal product according to the procedure established by the legislation of the reference state;
Drug registration dossier in accordance with Annexes 1 to 5 to these Regulations on electronic media;
Samples of medicinal products.

Within 14 working days from the date of submission of documents to the authorized body (expert organization) of the reference state, the applicant shall submit to the authorized bodies (expert organizations) of the states of recognition the following documents:

A statement on paper and (or) in soft copy in the established form in accordance with Appendix No. 2 to these Regulations;
Electronic version of Module 1 of the drug registration dossier;
Documents confirming the payment of the fee (tax) for drug registration and examination according to the procedure established in accordance with the legislation of the state of recognition.

The examination of a drug in a reference state according to the decentralized registration procedure includes:

evaluation of completeness and correctness of preparation of the submitted documents of the registration dossier of the drug;
evaluation of documents and data submitted by the applicant in the registration dossier of the medicinal product for safety, efficacy and quality;
conduction of the laboratory tests for compliance with the requirements of the normative document on the quality and reproducibility of the declared quality control procedures carried out in the accredited testing laboratories;
initiation, if necessary, of an unscheduled or planned pharmaceutical inspection in the cases specified in these Regulations;
preparation of an expert report on the evaluation of the drug by the reference state.

The expertise of the pharmaceutical product in the states of recognition according to the decentralized drug registration procedure is carried out by consideration of:

statements, documents and data of the registration dossier of the drug;
an expert evaluation report prepared by the reference state.

The authorized body (expert organization) of the reference state shall, within 14 working days from the date of submission of the application for drug registration, evaluate the completeness and correctness of the submitted documents of the registration dossier of a drug before sending the materials of the registration dossier for expertise. The applicant is granted no more than 90 calendar days not included in the registration and examination period of the drug, for submission of missing materials to the registration dossier to consider the remarks of the authorized body (expert organization) of the reference state.

The authorized body (expert organization) of the reference state shall, not later than in 14 calendar days from the date of filing the application for registration of the drug in the reference state, after evaluating the completeness of the submitted registration dossier files, submits the registration dossier of the pharmaceutical product to the authorized bodies (expert organizations) according to the procedure of decentralized registration of a drug through an integrated system.

The authorized body (expert organization) of the reference state rejects the application for drug registration in case the documents and materials of the registration dossier on the remarks of the authorized body (expert organization) of the reference state are not submitted in due time and (or) in case of failure to confirm payment of the fee (tax) for registration and examination of a pharmaceutical product in cases and in the manner established by the legislation of the reference state, and informs the applicant and the authorized bodies (expert organizations) of the states of recognition through the integrated system within a period of not more than 5 working days from the date of the decision.

The authorized body (expert organization) of the reference state within the period of drug registration and examination of the medicinal product has the right to send the request on submission of the missing additional information, necessary explanations or clarifications concerning the submitted documents and data of the registration dossier to the applicant, in writing and (or) electronically, in accordance with the application No.6,7, 8 attached to these Regulations.

The authorized body (expert organization) of the reference state shall, within 90 calendar days from the date of commencement of the examination, send to the authorized bodies (expert organizations) of the states of recognition a copy of the reports with the formulation of comments and requests to the applicant in accordance with the Appendices No 6,7, 8 to these Regulations and the preliminary report on evaluation in accordance with the Appendix No. 11 to these Regulations.

If there are requests sent to the applicant, the authorized body (expert organization) of the state of recognition within 30 calendar days from the date of receipt of the preliminary report on evaluation of the reference state shall send the requests to the authorized body (expert organization) of the reference state, which within 5 working days from the date of receiving the last request from the state of recognition, forms a unified request and sends it to the applicant in accordance with clause 93 of these Regulations.

The period for submitting a response to the above request by the applicant should not exceed 90 calendar days. Procedures for sending requests and presenting the answers are established by requirements of the legislation of the Member States.

If necessary, on the basis of the relevant application of the applicant, the response time to the request may be extended by the authorized body of the reference state. The total period for responding to inquiries should not exceed 180 calendar days.

The examination is resumed after the applicant responds to the inquiries of the authorized body (expert organization) of the reference state.

If the applicant fails to submit the documents and materials requested by the authorized body (expert organization) in due time, the expertise and registration of the drug shall be terminated. The authorized body (expert organization) notifies the applicant and the authorized bodies (expert organizations) within 14 working days from the date of adoption of such decision in the written and (or) electronic form.

The expertise of the drug in case of initiating a pharmaceutical inspection for compliance with the proper pharmaceutical practices of the Union shall not be suspended. Upon that the preparation of an expert evaluation report is completed by the reference state only after the expert organization of the reference state receives the results of the inspection. An unscheduled pharmaceutical inspection with a report on the inspection carried out should be conducted within the period of registration of the drug, but not exceeding 180 calendar days from the date the decision on initiating the inspection was made by the authorized body (expert organization).

The applicant organizes a visit to the production site, the research centre, the pharmacovigilance system of the holder of the registration certificate within 30 calendar days after receiving information on the need for an inspection or specifies a specific visit period, but no more than 90 calendar days after receipt of the information.

In case of no information from any state of recognition regarding the expertise of the medicinal product (the submission of comments, the results of the examination of the preliminary assessment report), the reference state considers that the state of recognition agrees with the opinion (including comments, if applicable) contained in the preliminary report on evaluation.

Written consultations between the authorized bodies (expert organizations) of the reference state and the recognition states, if necessary, are carried out electronically using the means of an integrated information system.

The expert reports on quality aspects, pre-clinical, clinical aspects, final expert evaluation report are compiled in accordance with the instructions given in Annexes 13,14, 15 and 23 to these Regulations. The final expert report on the evaluation of the reference state is drawn up in accordance with the form provided in Appendix No. 16 to these Regulations.

Within 155 calendar days from the date of submission of the application for drug registration, the authorized body (expert organization) of the reference state shall send the draft of final evaluation report to the recognition state and the applicant in accordance with Appendix No. 16 to these Regulations along with the applicant's responses to the requests, the draft summary of product characteristics, the draft guidelines for instruction for medical use (leaflet), the draft of package mock-ups, the draft of Normative Document, and, if necessary, the draft of risk management plan for the use of the drug. If the expert organization of the reference state prepares a negative draft of the final expert evaluation report and decides not to register a drug in accordance with clause 114 of this Regulation, the examination and registration of the drug shall be terminated. The authorized body (expert organization) notifies the applicant about the decision made within 14 working days from the date of adoption of such decision in the written and (or) electronic form with the above-mentioned final expert evaluation report attached. If the expert organization of the reference state prepares a positive draft of the final expert evaluation report, it is reviewed by the authorized bodies (expert organizations) of the states of recognition.

In case of no comments were received from the authorized bodies (expert organizations) of the states of recognition or after their withdrawal in accordance with paragraph 106 of these Regulations, the authorized body (expert organization) of the reference state and the recognition states complete the expertise procedure for the pharmaceutical product within 10 working days (175th calendar Day from the date of application for registration).

If the comments from the competent authorities (expert organizations) of the states were issued regarding the draft of final evaluation report, the draft of summary of the product characteristics, the draft of instruction on medical use, the draft of package mock-up or the draft of Normative Document, the draft of risk management plan for the use of the drug (if necessary), the authorized bodies (expert organizations) of the recognition states, if necessary, carry out consultations with the authorized body (expert organization) of the reference state or recognition states in the electronic form within 10 working days in accordance with the form provided in Appendix 18 to this Regulation (the 165th calendar day from the date of application for registration of the drug).

In case there are unresolved disputes as a part of mutual consultations, the authorized body (expert organization) of the state of recognition within a period not exceeding 10 working days from the date of receipt of the final expert report on evaluation of the reference state, taking into account the conditions of paragraph 106 of these Rules, using the means of the integrated system, produces the impossibility of recognizing the expert evaluation report prepared by the expert organization of the reference state, with justification of reasons for a negative decision to the authorized body (expert organization) of the reference state and states of recognition, as well as to the Committee of Experts, including issuing such report on paper.

The expert committee shall conduct a dispute settlement procedure in accordance with the procedure established by the Commission, within a period not exceeding 60 calendar days from the date of conclusion declared by the states that it is not possible to recognize a positive expert evaluation report prepared by an expert organization of the reference state.

In case the disagreements between the authorized bodies of the referenced State and the States of recognition regarding the recognition of the expert evaluation report are settled, they proceed to completion of drug expertise and issuance of the final documents in accordance with paragraphs 105 and 109 to 113 of these Rules.

In case the disagreements between the authorized bodies of the referenced State and the States of recognition regarding the recognition of the expert evaluation report are not settled, the authorized bodies of the reference state and the recognition states that have accepted the positive decision to recognize the expert evaluation report shall proceed to completion of expertise and the procedure for issuing the final documents in accordance with paragraphs 105 and 109 - 113 of these Rules. Upon the request of the applicant, the issuance of a registration certificate by the authorized bodies of such Member States may be suspended until the disagreements of the authorized bodies of other recognition and reference States are settled.

The authorized bodies (expert organizations) of the reference state and states of recognition that have made a positive decision on the expertise results and consider to issue registration of the drug in accordance with paragraphs 105 and 108 of these Rules proceed to the procedure for issuing final documents within a 30-calendar-day period. As well as within the specified period of 10 working days, the applicant is obliged to translate the summary of product characteristics, the draft of instruction for medical use, the mock-ups of the packages into the languages of the Member States, if there is a corresponding requirement in their legislation.

Within no more than 30 calendar days (the 205th calendar day from the date of submission of the application for drug registration):

the authorized body of the reference state issues the registration certificate of the drug to the applicant in accordance with Appendix No. 17 to these Regulations, approved by the summary of product characteristics, the medical application guidelines, Normative Document, the package mock-ups, the evaluation expert report (if necessary, the applicant is given the approved summary of product characteristics, the guidelines for medical use and package mock-ups of the medicinal product in the national language of the reference state), and also, if necessary, the agreed risk management plan for the use of the drug;
the authorized bodies of the recognition states issue the registration certificates of the drugs to the applicant in accordance with the form provided in Appendix No. 17 to these Regulations, approved by the summary of product characteristics, the instruction for medical use, package mock-ups of the drug in the official languages of the recognition states (if applicable in the legislation of the Member States), and, if necessary, an agreed risk management plan for the use of the medicinal product.

The authorized bodies of the reference state and the states of recognition publish the information on registration of the drug and the active pharmaceutical substances that are included in its composition into the unified register with the attachment of the approved summary of product characteristics, instructions for medical use, package mock-ups, Normative document, and the final expert evaluation report, compiled in accordance with Appendix No. 16 to these Regulations, after confiscation of confidential data and data on the experts, summary of an agreed risk management plan for the use of the medicinal product (If necessary) in accordance with the procedure for forming and maintaining the unified register.

The registration certificate of the medicinal product is issued by the authorized body of the state of recognition with the validity period of the drug registration certificate established by the authorized body of the reference state.

The authorized body of the reference state refuses drug registration under a decentralized procedure in the following cases:

the ratio of the expected benefit to the possible risks associated with the use of the medicinal product is not favourable;
the effectiveness of the drug is not confirmed by the data provided by the applicant;
the quality of the medicinal product is not confirmed;
the proposed methods and techniques of quality control are impracticable;
the applicant provided false information;
according to the results of the designated inspection, compliance with the relevant pharmaceutical practices of the Union has not been confirmed during the drug registration process.

The authorized body of the state of recognition does not recognize the expert evaluation report prepared by the expert organization of the reference state and thereby denies drug registration under the decentralized procedure if following the results of examination of the registration dossier of the medicinal product and conclusions of the dispute resolution procedure in the Expert Committee, a decision has been taken that the data presented in the expert evaluation report cannot be deemed sufficient to confirm quality, and (or) objectivity, and (or) favorable benefit-risk ratio of the medicinal product.

1.7. Establishment of post-registration measures (registration on terms)

The authorized body (expert organization) of the reference state with respect to the drug registration process and the procedures related to registration may establish one or more of the following additional requirements:

Inclusion of certain measures into the risk management system to ensure the safe use of the drug;
Execution of post-registration clinical studies to measure safety of a drug;
Establishment of additional requirements for drug registration and reporting on suspected adverse reactions;
Conducting the post-registration studies of the medicinal product effectiveness, the studies of various aspects of the efficacy of the medicinal product, if necessary, that cannot be investigated before the product is sold;
Other conditions or restrictions for safe and effective use of the medicinal product in accordance with the requirements of the Rules of Good
Pharmacovigilance Practice of the Eurasian Economic Union.

The established conditions and restrictions, as well as the time periods for their implementation, are indicated in the registration certificate, the unified register, as well as in the summary of product characteristics and the instruction for medical use.

The continuation of presence of the drug in the Union market being the object of the above mentioned procedures, is possible only on the basis of re-assessment of the benefit-risk ratio conducted annually by the authorized body (expert organization) of the reference Member State, with preparation of an expert report on evaluation of the medicinal product. The authorized body of the reference state has the right to cancel the registration certificate of the medicinal product in cases when the holder of the registration certificate does not fulfill the additional requirements established by the authorized body (expert organization) of the reference state with regard to this particular drug when registering it and implementing procedures related to drug registration in accordance with clause 116 of this Regulation, and if the positive decision on the benefit-risk ratio in the process of re-assessment of the benefit-risk ratio conducted annually by the authorized body (expert organization) of the reference state is not confirmed.

A condition for registration of a drug and confirmation of registration (re-registration) of a medicinal product by an authorized body may be the obligation to be fulfilled by the holder of the registration certificate:

post-registration safety studies of the medicinal product in case there are risk concerns about this product. In case the risks are related to more than one medicinal product, the authorized bodies of the Member States encourage joint conducting of post-registration safety studies by the holders of the registration certificates of such products,
post-registration studies for efficacy of the product, if the understanding of the disease or the clinical methodology show that previous assessments require a major revision.

The holder of the registration certificate has the right to submit written explanations in response to the introduction of the obligation provided in clause 118 of these Regulations within 90 calendar days from the date of receiving the relevant notification from the authorized body (expert organization) on the introduction of the obligation.

Based on the written explanations provided by the holder of the drug registration certificate in accordance with clause 118 of these Regulations, the authorized body (expert organization) is required to remove or confirm the obligation to conduct the studies specified in clause118 of these Regulations within 30 calendar days. If the obligation specified in clause118 of these Regulations is confirmed, the conditions for registration of the medicinal product must be changed by including the relevant provisions therein, and the risk management systems should be modified.

1.8. Confirmation of registration (re-registration) of a drug

The date of the registration confirmation (re-registration) of the medicinal product for all Member States where the medicinal product is registered is determined by the date of registration of the drug in the referenced State under the mutual recognition procedure or decentralized procedure.

For medicinal products that are not recognized as orphaned in the territory of a Member State in accordance with its legislation, the date of confirmation of registration (re-registration) is determined by the date of registration of a drug in a given Member State under the mutual recognition procedure.

Confirmation of registration (re-registration) is carried out on the basis of re-assessment of the benefit-risk ratio conducted by the authorized body (expert organization) of the referent Member State, with the preparation of an expert report on the evaluation of the medicinal product.

The examination of the medicinal product upon confirmation of registration (re-registration) in the states of recognition is carried out by:

Processing of application, documents and data of the registration dossier;
Processing of the expert evaluation report prepared by the reference state.

During the procedure of confirming the registration (re-registration) of a drug, its circulation on the territory of the Union is allowed.

The applicant submits applications for confirmation of registration (re-registration) to all Member States where the medicinal product is registered.

In case the holder of the registration certificate of the medicinal product does not submit an application for confirmation of registration (re-registration) before the expiry of the validity period of the registration certificate, the registration certificate of the medicinal product shall be recognized as invalid.

The procedure for confirming registration (re-registration) should not exceed 120 calendar days from the date of submission of the application for drug registration confirmation (re-registration).

The application for registration confirmation (re-registration) of the drug must be submitted not earlier than 210 calendar days before expiry of the validity period of the drug registration certificate in the reference state, but not later than the expiry date of the validity of the registration certificate.

In order to confirm the registration (re-registration) of the medicinal product, the applicant submits the following documents to the authorized body (expert organization) of the reference state:

application for confirmation of registration (re-registration) of the drug in an established form on paper and (or) in the electronic form in accordance with Appendix No. 2-1 to these Regulations;
documents confirming the payment of the fee (fee) for confirmation of drug registration (re-registration) and expertise in a case and according to the procedure established in accordance with the laws of the reference state;
modules 1 and 2 of the registration dossier, prepared in accordance with Annexes 1 to 5 to these Regulations, in an electronic media.

The authorized body (expert organization) of the reference state within a period not exceeding 5 working days from the date of submission by the applicant of the documents specified in paragraph 127 of these Rules shall ensure access to the registration dossier of the drug for the authorized bodies (expert organizations) using the integrated system means.

Within 14 working days maximum from the date of submission of the application for confirmation of drug registration (re-registration) to the referenced State, the applicant shall submit the following documents to the authorized body (expert organization) of each state of recognition:

an application on paper and (or) electronic media in accordance with Appendix No. 2 to these Regulations;
documents confirming the payment of the fee (toll) for confirmation of drug registration (re-registration) and expertise in the case and procedure established in accordance with the legislation of the states of recognition;
module 1 of the registration dossier, in the electronic form;
in the presence of relevant requirements in the legislation of the Member State, the summary of product characteristics, guidelines for medical use and mock-ups of medicinal product packages in the state language of the state of recognition are also submitted.

The authorized body (expert organization) of the reference state within 14 working days from the date of submission of the application for confirmation of drug registration (re-registration) shall inspect the completeness, contents and correctness of registration of the submitted documents of the registration dossier before sending the materials of the registration dossier for examination.

The applicant is granted no more than 90 calendar days beyond the time of confirmation of registration (re-registration) and examination of the medicinal product, for submission of missing materials to the registration dossier following the remarks of the authorized body (expert organization) of the reference state.

The authorized body (expert organization) of the reference state rejects the application for confirmation of registration (re-registration) of the drug in case of failure to submit missing documents to the registration dossier according to previously submitted remarks within the established period and (or) failure to confirm payment of the fee (toll) for confirmation of drug registration (re-registration) and expertise for the medicinal product in cases and according to the procedure established by the legislation of the reference state, as well as due to the violation of the period of submission of the application for confirmation of drug registration (re-registration) specified in paragraph 126 of these Regulations, and notifies the authorized bodies (expert organizations) of the recognition and applicant countries in writing and (or) electronically about it.

During drug examination conducted by the authorized body (expert organization) of the reference state within 50 calendar days from the date of submission of the application for confirmation of drug registration (re-registration), the preliminary expert report is prepared and sent using the means of the integrated system to the authorized bodies (expert organizations) of the states of recognition according to the form in accordance with Appendix No. 11 to these Regulations.

In case of disagreement with the conclusions presented in the preliminary expert report on evaluation of the reference state in terms of the benefit-risk ratio of the drug, or if there is a requirement on the part of authorized bodies (expert organizations) of the states of recognition to introduce changes to the summary of product characteristics, instructions for medical use, package mock-ups of a drug or other documents of the registration dossier, the authorized body (expert organization) of the state of recognition no later than in 20 calendar days from the date of sending by the authorized body (expert organization) of the reference state of the preliminary expert evaluation report, sends, via the integrated system, a respective justified request to the authorized body (expert organization) of the reference state.

In the course of reviewing by states of the recognition of the preliminary expert evaluation report prepared by the expert organization of the reference state, reviewing by the authorized bodies (expert organizations) of the reference state of the requests of the authorized bodies (expert organizations) of states for recognition and reviewing by the authorized bodies (expert organizations) of states of the recognition of the final expert evaluation report prepared by the expert organization of the reference state, the authorized bodies (expert organizations) of the Member States participating in the procedure, using the integrated system means, in accordance with Appendix No. 18 to this Regulation, consider and agree upon the final expert evaluation report prepared by the authorized body (expert organization) of the reference state.

The authorized body (expert organization) of the reference state during the procedure of confirmation of drug registration (re-registration) and examination of the medicinal product has the right to send the request about submission of the missing additional information, necessary explanations or clarifications concerning the submitted documents and data of the registration dossier to the applicant in writing and (or) electronically. The deadline for submitting a response to the above request by the applicant should not exceed 90 calendar days.

The time period for submission of documents by the applicant upon the request of the authorized body (expert organization) of the reference state in the process of confirming drug registration (re-registration) and examination of the medicinal product is not included in the time of confirmation of drug registration (re-registration) and examination of the medicinal product.

The authorized body (expert organization) of the reference state conducts the examination of the applicant's answers, including responses to the requests of authorized bodies (expert organizations) of the states of recognition within a period of no more than 20 calendar days as a part of the expertise of drug.

If the applicant fails to submit the requested documents and data within the prescribed period, the confirmation of drug registration (registration renewal) and examination of the medicinal product shall be terminated. The authorized body (expert organization) notifies the applicant and the authorized bodies (expert organizations) within 14 working days from the date of making such decision in the written and (or) electronic form.

According to the results of examination of the drug within a period not exceeding 90 calendar days from the date of submission of the application for confirmation of drug registration (drug registration renewal), the authorized expert body (expert organization) of the reference state shall prepare and approve, in accordance with Appendix No. 16 to these Regulations, the final expert evaluation report, which is sent using the integrated system to the authorized bodies (expert organizations) of all states of recognition involved in the verification procedure of drug registration (drug registration renewal) of the product. The expert evaluation report is drawn up in accordance with Appendices No. 13, 14, 15 and 23 to these Regulations.

The authorized body (expert organization) of the state of recognition on the basis of the results of examination of the medicinal product within a period not exceeding 20 calendar days from the date of receiving the final expert report on evaluation of the reference state conclusion whether to recognize the expert report on the evaluation of the reference state or not shall be compiled, approved and, using the the integrated system, sent to the authorized body (expert organization) of the reference state in accordance with Appendix no. 18 to this Regulation.

Proposals of the authorized bodies (expert organizations) of the reference state and states of recognition on changes in the summary of product characteristics, instructions for medical use, drug package mock-ups or other documents of the registration dossier in the event that the applicant agrees with them cannot serve as grounds for refusal to confirm registration (renewal) of the drug.

If, based on the results of examination of the medicinal product in the reference country, it is established that the benefit-risk ratio is assessed positively and the drug registration dossier, taking into account the changes introduced, meets the requirements:

the authorized body (expert organization) of the reference state issues a timeless drug registration certificate to the applicant in accordance with the form provided in Appendix No. 17 to these Regulations;
the authorized bodies of the recognition states issue the timeless registration certificates of the drug to the applicant in accordance with Appendix No. 17 to these Regulations, as well as, if necessary, approved by the summary of product characteristics, instructions for medical use, medicinal product package layouts in the national language of the recognition states, within the legislation of these states;
the authorized bodies of the Member States participating in the procedure of confirming drug registration (re-registration) include the necessary information on the drug and its active pharmaceutical substances in a single register, along with a summary of the agreed risk management plan for the use of the drug (if necessary).

If it is impossible to recognize the expert evaluation report prepared by the expert organization of the reference state, the authorized body (expert organization) of the state of recognition shall send, in soft and (or) hard copy, the conclusion on the impossibility of recognizing this expert report with the justification of the decision made by the authorized body (expert organization) of the reference state and state of recognition, participating in the procedure for confirming drug registration (drug registration renewal), as well as to the Expert Committee within the period specified in clause 137 of these Regulations.

The expert committee shall, within a period not exceeding 60 calendar days from the date of receipt of the opinion of the authorized body of the state of recognition of the impossibility of recognizing the expert report on the assessment of the reference state, implement the procedure for considering disputes in accordance with the procedure established by the Commission.

The authorized body of the State of Recognition refuses to confirm drug registration (drug registration renewal) if, following the examination of the medicinal product and after the procedure for resolving the disagreements in the Expert Committee, it is established that the expert evaluation report prepared by the expert organization of the reference state cannot be recognized by the authorized body Expert organization of the state of recognition for the reasons specified in
paragraph 146 of these Rules.

When drug registration (drug registration renewal) is confirmed by the authorized body (expert organization) of the Member State, the fulfillment by the holder of the registration certificate of the conditions related to the registration of the medicinal product set forth in Section VII
of these Regulations is carried out if these obligations were applied to this holder of the registration certificate. When new data on the safety and efficacy of a medicinal product is revealed, the authorized body may introduce changes to the conditions of drug registration and (or) new conditions may be put forward.

During evaluation of the registration dossier of the drug in the process of confirming drug registration (drug registration renewal) by the authorized bodies (expert organizations) of the Member States, it verifies the fulfillment by the holder of the registration certificate of the obligation to maintain information about the medicinal product in the up-to-date state in the light of current scientific knowledge, taking into account the conclusions of the results assessments and recommendations of the authorized body (expert organization).

If the authorized body (expert organization) of the reference state identified, at expertise of the medicinal product during confirmation of drug registration (re-registration of the drug), that the obligations specified in clause142 of this Regulation were not fulfilled for objective reasons and changes in the registration dossier of the drug are required, then after the reference state makes a positive conclusion on confirmation of the registration (re-registration) of the medicinal product, the regulatory document (If applicable) should be updated by initiating, by the holder of the registration certificate, the appropriate procedure for introducing changes to the registration dossier within a period not exceeding 180 calendar days from the date the authorized body (expert organization) of the reference state is requested to make changes to the registration dossier of a drug.

The authorized body (expert organization) of the reference state may allow the introduction of changes to the registration dossier of a medicinal preparation of type I in accordance with Appendix No. 19 to these Regulations upon confirmation of drug registration (re-registration of the medicinal product) in order to avoid additional application for changes to the registration dossier of a drug.

Based on the pharmacovigilance data, and taking into account the circumstances specified in paragraphs 143 and 144 of these Regulations, upon confirmation of the drug registration (re-registration of a drug) by the authorized body of the reference state, upon the examination of the medicinal product, a decision may be taken to issue a registration certificate with a validity period of 5 years with necessity for subsequent confirmation of drug registration (drug registration renewal) after expiration of the validity period of the drug registration certificate.

Grounds for refusal to confirm drug registration (drug re-registration) by the authorized body of the reference state and recognition by the authorized state body of the recognition of the expert evaluation report can be the following:

the preservation of the following serious health risks associated with the use of the medicinal product at the time of confirmation of drug registration (drug registration renewal):
the proven unfavourable benefit-risk ratio or the apparent lack of therapeutic efficacy provided that the conditions for the use of the drug described in the approved summary of product characteristics are met;
the facts established by the pharmacovigilance data indicating an unfavourable benefit-risk ratio (including a significant excess of the reporting frequency of any undesirable reactions in comparison with the data specified in the approved summary of product characteristics);
the discrepancy between the qualitative and quantitative composition of the declared product or repeated quality discrepancy of the drug during its circulation in the market of the Union declared at the time of registration;
inaccurate or outdated data in registration dossier of a drug accompanying the application for confirmation of drug registration (re-registration of a drug);
failure of the holder of the drug registration certificate to comply with the remarks or to respond to questions raised during the examination of the medicinal product within the allotted time;
failure by the holder of the registration certificate to fulfil the obligations under the pharmacovigilance or obligations under the drug registration procedure on the terms.

Rules for Registration and Expertise of Medicinal Products for Medical Use in EAEU

1.1 General provisions

1.2 Definitions

1.3 General principles of registration of drugs

1.4 General principles of expertise of medicinal products

1.5 The procedure for registration and examination of medicinal products under the procedure of mutual recognition

1.5.1 Registration and examination of medicinal product in the reference state

1.5.2 Registration and expertise of a drug under the mutual recognition procedure in the state (states) of recognition

1.6 The drug registration process and expertise sequence under the decentralized procedure in the reference state and in the states of recognition

1.7. Establishment of post-registration measures (registration on terms)

1.8. Confirmation of registration (re-registration) of a drug

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Rules for Registration and Expertise of Medicinal Products for Medical Use in EAEU

1.1 General provisions

1.2 Definitions

1.3 General principles of registration of drugs

1.4 General principles of expertise of medicinal products

1.5 The procedure for registration and examination of medicinal products under the procedure of mutual recognition

1.5.1 Registration and examination of medicinal product in the reference state

1.5.2 Registration and expertise of a drug under the mutual recognition procedure in the state (states) of recognition

1.6 The drug registration process and expertise sequence under the decentralized procedure in the reference state and in the states of recognition

1.7. Establishment of post-registration measures (registration on terms)

1.8. Confirmation of registration (re-registration) of a drug

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Leave a Comment

Latest report

Belarus Pharmaceutical & Healthcare Industries Overview 2017 & Forecast to 2017-2019

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