ANALYSIS OF THE MAIN CHANGES IN THE RULES OF REGISTRATION AND EXAMINATION OF MEDICINES WITHIN THE FRAMEWORK OF THE EURASIAN ECONOMIC UNION

ANALYSIS OF MAJOR CHANGES IN THE RULES OF REGISTRATION AND EXAMINATION OF MEDICAL PRODUCTS INSIDE THE EURASIAN ECONOMIC UNION

Olga Nefidova

Graduate student, Sechenov First Moscow State Medical University,

Russia, Moscow

Dmitrii Babaskin

Associate Professor, Doctor of Medical Sciences, Sechenov First Moscow State Medical University,

Russia, Moscow

The Agreement on Common Principles and Rules for the Circulation of Medical products within the EAEU represents the fundamental legal document governing the formation of a common pharmaceutical market in the space of the Eurasian Economic Union (hereinafter referred to as the EAEU, the Union) [1]. A full-fledged transition to a single market is a complex, time-taking and costly process both for the authorities that regulate medical products as well as for the companies, that manufature them. The key task is to develop and observe the supranational rules for the registration and examination of medicinal product for human use within the Union [2]. In a rapidly changing external environment the rules developed, being constructive, dynamic and complex, require, however, further harmonization and unification within the EAEU. The decision of the Council of the Eurasian Economic Commission as of March 2022 established significant changes to the rules for registration and examination of medicines [3].

The purpose of the work is a comprehensive analysis of the main changes in the rules for registration and examination of medical products for human use within the Eurasian Economic Union and identification of their specifics.

Methodology and methods. In its methodology the study relies on legal documents, scientific works of domestic and foreign authors devoted to the issues of registration and examination of pharmaceuticals. The process of scientific research employes systemic, structural-functional and factorial approaches. Changes in the rules for registration and examination of medicines were studied using the methods of comparison, generalization, abstraction, deduction and induction.

Results and discussion. The significance of establishing a special legal regulation status for particular areas and spheres lies in the option of creating potentially different conditions for the implementation of activities. Making the above more specifically fot registration and examination of medical products, it is important to emphasize that the regulation of these aspects is a significant activity focused on listing the rules for registration and examination of medicines, together with management and regulation of all related processes, as well as standardization of a number of systemically important procedures. The absence of regulation gives way to spontaneous activity of manufacturing companies. This significantly expands the range of risks associated with non-compliance with all kinds of standards for the manufacture, transportation, storage, registration of medicines, as well as a number of related fairly significant procedures. It needs emphasizing, that activities within the EAEU (of which the Russian Federation, the Republic of Belarus, the Republic of Kazakhstan, the Republic of Armenia and the Kyrgyz Republic are currently participating countries) are subject to a special status of regulation, customs registration procedures, simplification of a number of economic aspects and other measures aimed at on the maximum implementation of the integrative function of the participating countries [4]. In other words, regulatory procedures reflected in the legislation is a rather significant systemic aspect enabling to establish general requirements for the circulation of pharmaceutical products on the territory of the EAEU and making possible the unified regulation of these issues within the national economies of the participating countries. The adoption of a single procedure for registration and examination of medicines is a guarantee of maximum convergence of all countries - the members of the Union [5]. At the same time, the current situation accentuates the frequency of changes in legislation, as soon as medical products manufacturers need to implement ongoing monitoring activities and take into account current changes in order to avoid various unwanted procedures.

The latest version of the Rules for Registration and Expertise of Medicinal Products for Human Use (hereinafter referred to as the Rules) [2, 3], provides a particular group of changes to be distinguished concerning the application of the Rules in various situations. Specifically, in accordance with the new edition, the Rules are applicable in emergency situations (paragraph 3) [3]. Previously, the Rules were not suitable for the above. At the same time, the new edition provides access to citizens of the participating countries to unregistered medical products in cases where they are prescribed for the treatment of life-threatening conditions or belong to high-technology ones (paragraph 5).

Another aspect is the simplification of the registration procedure for medicines intended for the treatment of orphan diseases (rarely common, poorly studied, and also not having a wide range of specialized medicines and unified approved methods of treatment) (paragraph 6). Presently the accelerated timeframe for their registration is up to 140 working days, and 10 working days for examination. This regulation allowed reducing the period of registration and examination of medicines by 74 days in the reference state. Mutual recognition also diminishes the medication registration procedure by more than 30 days. Time period for other special procedures, reflected in the legislation and directly related to the issues of registration and examination of medicines was limited as well [3].

The new version of the Rules allows for obtaining a perpetual registration certificate (clause 18). It is issued if the medicinal product has been registered for at least five years on the territory of the EAEU, and provided that the list of  participating countries has not been expanded. In the latter case, the open-ended time frame of the registration certificate is void, and a new, five-year certificate is issued (clause 18).

The new version of the Rules introduces improved definitions, namely “real clinical practice data”, “evidence obtained on the basis of real clinical practice data”, which allow expanding the possibilities for registration and examination of new medical products within the Union, with an emphasis on simplifying the same (paragraph 19) .

Yet, the current version of the Rules is defificent with certain significant aspects. For example, “... mutual recognition in each State of the Union in the form of a sequential procedure” (paragraph 20) is excluded. The issues of appointment of the inspection are rephrased, like earlier the notions “unscheduled or scheduled” were attributable to the inspection; after the revision is was amended as pharmaceutical inspection (paragraph 38).

In addition to the main changes in the Rules, it is necessary to point out a number of selective, still quite significant changes. Thus, in section VI, which deals with the registration and examination of medicinal products in the territory of the reference state, the following changes were made [3]:

• registration terms are reduced to 140 working days;

•  possibility of conducting an on-site (or remote) pharmaceutical expertise, with a detailed description is noted;
•  the terms for assessing the regulated document have been reduced from two weeks to 10 working days;
•  the time of the actual response to the request has been reduced in a way that previously the response was formed within three months, taking into account only calendar working days, now this period is strictly 90 working days;
•  A 105-days examination procedure was introduced in the reference state, from the date of receipt of the task for examination;
•  A procedure of rejection in the registration and examination in the absence of an appropriate response to a request has been introduced.

The current version of the Rules is marked with a clear contradiction, namely the reduction in the terms of registration and examination, implies no changes in the field of response to the request (the previous 90 calendar days remain). Moreover, attention is drawn to the inconsistency in the timing of the response to the request: according to paragraph 58, it is 180 working days, while paragraph 46 states 140 days.

Section VII, which addresses the same issues with a focus on the implementation of mutual recognition procedures, highlights the following changes[3]:

•  there is a similar possibility of a remote form for submitting applications;
•  additional features of making changes are formed (however, they must occur before the recognition is submitted, with the exception of special cases, which include urgent changes in safety issues);
•  the terms of registration in the Member State concerned are reduced to 60 working days from the moment of receipt of all necessary versions of the regulated document, expert reports of the reference state and other updated documents, with due consideration of all changes;
•  the terms for accepting/rejecting an application are reduced from 14 to 10 working days;
•  the terms for sending the opinion of the Member State concerned in relation to the reference state are reduced to 5 working days;
•  the terms for issuing all documents and their publication are reduced to 5 working days.

Section VI, which deals with issues of decentralized registration and examination, introduces similar reductions in the time for filing registration and examination applications, emphasizes the possibility of electronic referral of procedures and obtaining remote pharmaceutical examination, and the possibility of reject due to failure to provide a response to the request is elaborated [3].

The main range of post-registration measures has also undergone significant changes. Thus, the new version of the Rules completely excludes the obligation to undergo an annual “benefit-risk” reassessment, and expands the possibilities for e-submission of documentation. In addition, the following items have been added [3]:

•  the opportunity of registration of a medicinal product in exceptional cases (which implies the annual re-evaluation of the market conditions);
•  the opportunity of conditional registration of the medicinal product (with a description of the conditions for the use in such cases cases, namely for the provision of emergency care, maintenance of vital processes and the use of treatment in case of unmet medical needs of the patient);
•  The main criteria for conditional registration is a favorable “benefit-risk” ratio, the period for issuing a registration certificate in this case is 5 years;
•  Possibility of accelerated examination under conditions of three groups of diseases, namely orphan diseases, diseases of underaged and especially significant diseases, based on the decision of the Expert Committee.

The current version of the Rules envisages reduced terms for confirming registration and re-registration of medicinal products, enhancing the procedures for additional importation and sale of medicinal products, and expanding the conditions for the circulation of medicinal products in the Union territory (it has been clarified that they can be circulated before the expiration date). New definitions of certain types of high-tech medicines are established, and procedures for filing applications, paperwork, regulated document requirements and registration issues have been clarified.

Thus, it should be emphasized that the latest version of the Rules is aimed at optimizing the time for issuing decisions, as well as expanding the cases of registration and examination of medicines within the EAEU. This creates the necessary conditions for the active circulation of, for instance, orphan medical products, and their accelerated administration in a number of individual cases. These changes are exclusively positive, since they create the possibility of providing accelerated medical care in cases of lack of necessary medicines in the territory of the Union. The approach used to amend the Rules in the event of an emergency, the use of unregistered medications, as well as the issuing open-ended registration certificates is another step towards liberalizing the circulation of medicines and strengthening the quality and accessibility of medical care. The COVID-19 pandemic has shown that accelerated registration of medicines allows the fastest overcoming crisis situations [6]. The current editions of the Rules (including the possibility of electronic submission of applications) enable to mitigate such risks, and as a result, to reliably improve the situation with the circulation of medicines within the EAEU.

Analysis of editorial interpretations revealed several inaccuracies. Thus, there is an inconsistency in relation to the terms, which can be characterized as a rather negative phenomenon; reduction of registration and examination terms implies a comprehensive management of these processes, among other things, due consideration of additional aspects in elimination of inaccuracies.

Conclusion. Consequently, despite some inaccuracies identified in the amendments to the Rules for Registration and Expertise of Medicinal Products for Human Use within the EAEU, like, terms of approval of submission of applications, or responses to a request, generally, there changes may be acknowledged as positive. The processes of liberalization of registration and examination procedures are clearly traced, the availability of unregistered medical products in some cases is increasing, which in a good manner affects the provision of timely necessary medical care. In addition, reduction of the terms of registration and examination of medicinal products represents a significant simplification of the registration and examination procedure.

References:

1. Agreement on uniform principles and rules for the circulation of medicines within the Eurasian Economic Union: [ratified by Federal Law No. 5-FZ dated January 31, 2016]. Electronic fund of legal and normative-technical documents. – URL: https://docs.cntd.ru/document/420307203 (date of access: 07.05.2022). [Soglasheniye o yedinykh printsipakh i pravilakh obrashcheniya lekarstvennykh sredstv v ramkakh Yevraziyskogo ekonomicheskogo soyuza: [ratifitsirovano Federalnym zakonom ot 31.01.2016 N 5-FZ]. Elektronnyy fond pravovykh i normativno-tekhnicheskikh dokumentov. – URL: https://docs.cntd.ru/document/420307203 (data obrashcheniya: 07.05.2022).]
2. Rules for registration and examination of medicinal products for medical use: approved by the Decision of the Council of the Eurasian Economic Commission dated November 3, 2016 N 78. Electronic fund of legal and regulatory documents. – URL: https://docs.cntd.ru/document/456026097 (date of access: 07.05.2022). [Pravila registratsii i ekspertizy lekarstvennykh sredstv dlya meditsinskogo primeneniya: utverzhdeny Resheniyem Soveta Yevraziyskoy ekonomicheskoy komissii ot 3 noyabrya 2016 goda N 78. Elektronnyy fond pravovykh i normativno-tekhnicheskikh dokumentov. – URL: https://docs.cntd.ru/document/456026097 (data obrashcheniya: 07.05.2022).]
3. On amendments to the Rules for registration and examination of medicinal products for medical use: Decision of the Council of the Eurasian Economic Commission dated March 17, 2022 N 36. Electronic fund of legal and regulatory documents. – URL: https://docs.cntd.ru/document/350014244 (date of access: 07.05.2022). [O vnesenii izmeneniy v Pravila registratsii i ekspertizy lekarstvennykh sredstv dlya meditsinskogo primeneniya: Resheniye Soveta Yevraziyskoy ekonomicheskoy komissii ot 17 marta 2022 goda N 36. Elektronnyy fond pravovykh i normativno-tekhnicheskikh dokumentov. – URL: https://docs.cntd.ru/document/350014244 (data obrashcheniya: 07.05.2022).]
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