Data Exclusivity in Russia and the EAEU: Legal Regulation

 

September 3, 2019

Anna Ivanova, Attorney at BRACE Law Firm

 

The legal regime of Data exclusivity (exclusivity of clinical trial data) in pharmaceuticals aims to protect clinical trial data and prevent the early registration of generic medicinal products (generics). generally, this legal regime provides for specific periods during which the confidentiality of information on preclinical and clinical studies of medicinal products submitted during registration is ensured. This regime implies a legislative consolidation of the period prohibiting the filing of an application for the registration of generic medicinal products, as well as the period prohibiting the release of generic medicinal products into circulation. Most often, these periods are calculated from the date of registration of the reference medicinal product.

Clinical Trial Data Exclusivity

Clinical trial data exclusivity is defined as the protection of the rights of the original medicinal product manufacturer to the sole use of its own clinical trial data for commercial purposes for a certain period [1].

Data exclusivity can be characterized as an administrative remedy based on two legal aspects:

• The legal obligation of third parties to refrain from using data from preclinical and clinical studies for commercial purposes and for the registration of generic products within a six-year period.
• The legal obligation of the regulatory body receiving the registration dossier to keep the received information secret from third parties [2].

Currently, the issue of the functioning of the legal institution of exclusivity of preclinical and clinical trial data is not finally settled within the EAEU legislation [3]. Thus, this issue is currently regulated by the EAEU member states in national legislation within the framework of the obligations that EAEU member states assume upon accession to the WTO (except for the Republic of Belarus, which has not joined the WTO).

In accordance with Art. 39 of the Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS), adopted within the framework of the WTO, members, when requiring, as a condition of approving the marketing of pharmaceutical or of agricultural chemical products which utilize new chemical entities, the submission of undisclosed test or other data, the origination of which involves a considerable effort, shall protect such data against unfair commercial use. In addition, Members shall protect such data against disclosure, except where necessary to protect the public, or unless steps are taken to ensure that the data are protected against unfair commercial use.

However, according to paragraph 1295 of the Report of the Working Party on the Accession of the Russian Federation to the WTO, for a period of at least 6 (six) years, no person other than the person who submitted the data may, without the explicit consent of that person, rely directly or indirectly on such data in support of an application for product approval/registration [4].

These legal norms are also reflected in the legislation of the EAEU member states. In particular, in accordance with Parts 20-21 of Art. 18 of Federal Law No. 61-FZ dated April 12, 2010, On Circulation of Medicinal Products (the "Law on Circulation of Medicinal Products"), an application for state registration of a generic medicinal product for medical use may be submitted to the authorized federal executive body carrying out state registration of medicinal products after the expiration of 4 years from the date of state registration of the reference medicinal product in the Russian Federation. An application for state registration of a biosimilar medicinal product (biosimilar) may be submitted to the authorized federal executive body carrying out state registration of medicinal products after the expiration of 3 years from the date of state registration of the reference medicinal product in the Russian Federation.

According to Part 18 of the above-mentioned article of the Law on Circulation of Medicinal Products, it is not permitted to use, for commercial purposes, information on the results of preclinical studies of medicinal products and clinical studies of medicinal products for veterinary use, submitted by the applicant for state registration of medicinal products, without the applicant's consent for 6 years from the date of state registration of the reference medicinal product in the Russian Federation.

It is important to note that this 6-year term, according to the legal position of arbitration courts in the dispute between Biointegrator and Novartis Pharma AG, does not represent Data exclusivity in the form of a ban on generic registration, but rather protection against the disclosure of closed information. The Supreme Court of the Russian Federation concluded that the ban on the disclosure and use of clinical trial data does not apply to any information on conducted preclinical and clinical studies of the original medicinal product. This ban does not concern information published in specialized printed publications. The use of such information is recognized, in the opinion of the Supreme Court of the Russian Federation, as lawful [5]. In this situation, it can be assumed that such a position of the court regarding the non-extension of protection to information obtained during clinical studies of medicinal products and published in specialized printed publications may negatively affect subsequent practice of protecting data exclusivity.

It is important to understand the difference between the mechanism for protecting clinical trial data exclusivity and the patent protection mechanism. Thus, according to Paragraph 1 of Article 1358 of the Civil Code of the Russian Federation, the patent holder owns the exclusive right to use the invention, utility model, or industrial design in accordance with Article 1229 of the Civil Code of the Russian Federation in any manner not contradicting the law. In this case, the manufacture, use, offer for sale, sale, other introduction into civil circulation, or storage for these purposes of a patented medicinal product will constitute a patent violation. However, conducting scientific research on a product or method in which an invention or utility model is used, or scientific research on an article in which an industrial design is used, or conducting an experiment on such a product, method, or article will not constitute a violation.

Judicial practice contains examples where the court sides with the medicinal product manufacturer due to the existence of a registered patent.

For example, the court prohibited the manufacture, offer for sale, sale, or other introduction into civil circulation or storage for these purposes of a medicinal product under any trade name containing the substance "Voriconazole" (INN), including the medicinal product registered by the Ministry of Health of the Russian Federation under the trade name "Biflurin," until the expiration date of the patent of the Russian Federation [6]. Other persons may not use the corresponding result of intellectual activity or means of individualization without the consent of the copyright holder. The Intellectual Property Court took a similar position in Case No. A40-30012/2015 [7].

At the same time, as confirmed by judicial practice, the manufacture and submission to Roszdravnadzor and the Scientific Center for Expertise of samples of a medicinal product for conducting a quality examination of this product cannot be recognized as a violation of patent rights. However, the manufacture or storage of a product until the expiration date of the patent for the purpose of sale or introduction into civil circulation after this date is not permitted [8].

Thus, it is important to note that Data exclusivity applies regardless of the validity of a patent and its existence.

Nevertheless, given the lack of extensive judicial practice regarding the application of Data exclusivity, a large number of questions arise regarding the scope of protection of clinical trials and the procedure for providing information on clinical trials for use in scientific purposes, rather than for introduction into commercial circulation.

In particular, according to Clause 3 of the Procedure for Forming a Registration Dossier for a Medicinal Product..., approved by Order of the Ministry of Health of the Russian Federation No. 409n dated July 12, 2017, the administrative documentation section of the registration dossier must include the consent of the developer of the reference medicinal product or a person authorized by them to use, for commercial purposes, information on the results of preclinical studies and clinical studies of the reference medicinal product for medical use, when submitting an application for state registration of a generic medicinal product before the expiration of 6 (six) years from the date of state registration of the reference medicinal product in the Russian Federation.

However, the procedure for manufacturers of reference medicinal products to provide clinical trial data for use in scientific purposes is not regulated by current legislation. Also, there is no clear indication of exactly which clinical trial data is subject to disclosure and which is subject to legal protection.

Specifics of Clinical Trial Data Protection in the Russian Federation

As we indicated earlier, Parts 18 – 22 of Art. 18 of the Law on Circulation of Medicinal Products do not permit the use for commercial purposes of information on the results of preclinical studies of medicinal products and clinical studies of medicinal products for medical use submitted by the applicant for state registration of a medicinal product without the applicant's consent for 6 (six) years from the date of state registration of the reference medicinal product in the Russian Federation.

The holder or owner of a Registration Certificate for a biotechnological or orphan medicinal product is obliged to provide, on a reimbursable basis, samples of the reference medicinal product to applicants for conducting clinical trials. The cost of a sample of a reference medicinal product included in the List of Vital and Essential Drugs (VED List) must not exceed the registered maximum selling price for the reference medicinal product or the price for the medicinal product in the manufacturer's country.

Based on the legal norms cited above, it follows that ensuring the preservation of preclinical and clinical trial data from disclosure applies to cases of their disclosure when used for commercial purposes.

At the same time, an application for state registration of a generic medicinal product for medical use may be submitted to the authorized federal executive body carrying out state registration of medicinal products after the expiration of 4 years from the date of state registration of the reference medicinal product in the Russian Federation.

An application for state registration of a biosimilar medicinal product (biosimilar) may be submitted to the authorized federal executive body carrying out state registration of medicinal products after the expiration of 3 (three) years from the date of state registration of the reference medicinal product in the Russian Federation.

Upon state registration of a medicinal product, submission of a report on the results of bioequivalence studies of the generic medicinal product for medical use is not required if generic medicinal products for medical use are being registered that:

• Are intended for parenteral administration and are aqueous solutions;
• Are solutions for oral use;
• Are produced in the form of powders or lyophilisates for the preparation of solutions;
• Are gases;
• Are ear or eye medicinal products produced in the form of aqueous solutions;
• Are intended for topical application and prepared in the form of aqueous solutions;
• Are aqueous solutions for use in the form of inhalations using a nebulizer or as nasal sprays applied using similar devices.

In this case, said medicinal products (except for medicinal products that are gases) must contain the same excipients in the same quantities as the reference medicinal product. If the compositions of excipients differ, the applicant must submit evidence that the excipients used in these concentrations do not affect the safety and (or) efficacy of the medicinal product for medical use.

Thus, for other generic medicinal products, state registration is mandatory.

Consequently, the obligation to transfer samples of reference medicinal products is established only for holders of Registration Certificates for biotechnological or orphan medicinal products (Part 19, Art. 18 of the Law on Circulation of Medicinal Products). For other holders of Registration Certificates, such an obligation is not directly established in current Russian legislation. We believe that this issue should be regulated [9].

At the same time, the liability of medicinal product manufacturers for failure to provide data on preclinical and clinical studies, as well as samples of medicinal products, has not been introduced at the legislative level.

Currently, a draft law (Project ID – 02/04/10-18/00085211) is in the regulatory impact assessment stage, which provides for supplementing the Code of Administrative Offenses of the Russian Federation (CAO RF) with Article 6.34, establishing administrative liability for the failure of a holder or owner of a Registration Certificate for a biotechnological or orphan medicinal product to provide samples of the reference medicinal product for conducting clinical trials to another legal entity acting in its own interests or authorized to represent the interests of another legal entity and intending to carry out state registration of a generic medicinal product. The administrative penalty for committing this offense will be a fine ranging from 200,000 to 1,000,000 rubles. It is planned to empower Roszdravnadzor and its territorial bodies with the authority to draw up protocols on these administrative offenses.

According to the explanatory note to this draft law, it is noted that according to Part 20 of Article 18 of the Law on Circulation of Medicinal Products, state registration of a generic medicinal product is carried out by the authorized federal executive body after the expiration of 4 (four) years from the date of state registration of the reference medicinal product in the Russian Federation, and a ban on conducting clinical trials of a generic medicinal product before the expiration of the specified period is not established by the Law on Circulation of Medicinal Products.

Since the clinical trial of a generic medicinal product is carried out prior to the submission of an application for its state registration, establishing restrictions regarding the applicant obtaining samples of the reference medicinal product for conducting a clinical trial after the expiration of 4 years from the date of its state registration in the Russian Federation will lead to an unjustified extension of the period established by Part 20 of Article 18 of the Law on Circulation of Medicinal Products.

In the conclusion on the regulatory impact assessment, the Ministry of Economic Development of Russia notes that a 4-year period from the date of state registration of a medicinal product is not provided for submitting a request to the holder or owner of the Registration Certificate for the medicinal product to provide a sample of the reference medicinal product for conducting clinical trials.

In addition, the legislation of the Russian Federation does not establish deadlines for providing a response to the above requests [10].

Establishing administrative liability for manufacturers of biotechnological and (or) orphan medicinal products for failure to provide interested parties with samples of such medicinal products for conducting clinical trials after the expiration of 4 years from the date of state registration is provided for by the Action Plan for the Development of Competition in Healthcare, approved by Order of the Government of the Russian Federation No. 9-r dated January 12, 2018 [11].

Thus, it can be concluded that within the framework of Russian legislation, many issues remain unregulated regarding the procedure for appealing to medicinal product manufacturers with requirements to provide data on preclinical and clinical studies, as well as samples of medicinal products (including the form of such an appeal to the manufacturer, deadlines for manufacturers to respond to such appeals, liability measures for failure to provide requested information, and the volume of data provision).

Given the above, the indicated draft law and clarifications, as well as judicial practice, have marked the beginning of the formation of an established procedure for relationships between manufacturers of original medicinal products and generics.

Also, at the legislative level, the issue of the volume of provided data on clinical and preclinical studies of reference medicinal products acceptable for provision to generic manufacturers is not specified. We believe that from a literal interpretation of the Law on Circulation of Medicinal Products, which does not allow the use for commercial purposes of information on the results of preclinical studies of medicinal products and clinical studies of medicinal products for medical use submitted by the applicant for state registration of a medicinal product, it follows that the volume of possible provision of materials is determined by the volume of clinical studies submitted for state registration of the reference medicinal product [12].

Additionally, it should be noted that another method of protecting the rights of manufacturers of original medicinal products is the existence of a patent for a particular medicinal product. In this case, when registering a generic during the patent validity period, there are risks of canceling such registration in court. For example, in a lawsuit filed by the foreign company AstraZeneca UK LIMITED against Jodas Expoim LLC and the Ministry of Health of the Russian Federation, the court established that without state registration of the medicinal product and state registration of maximum selling prices for the medicinal product included in the VED List, the introduction of the medicinal product into civil circulation is not permitted. Furthermore, admission to circulation (introduction into civil circulation) of a medicinal product is considered by the Law on Circulation of Medicinal Products as the main goal of the corresponding registration. Taking into account that one of the grounds for canceling the state registration of a medicinal product and excluding the medicinal product from the state register of medicinal products for medical use is a court decision on the violation of the rights of the intellectual property rights holder during the circulation of medicinal products (Clause 7, Article 32 of the Law on Circulation of Medicinal Products), and considering that when using RF Patent No. 2153495, the plaintiff manufactures and supplies to the Russian Federation a medicinal product registered in the State Register of Medicinal Products on November 30, 2004 under number 016075/01, which contains the chemical compound Gefitinib, used by the defendant in the registration of medicinal product No. LP-003076 by the Ministry of Health in the State Register of Medicinal Products on July 6, 2015, the court concluded that such actions by the company constitute preparation for an offer for sale of a medicinal product in which the Gefitinib substance patented by the plaintiff is used. As a result, the court obliged the defendant to file an application for cancellation of the state registration of the indicated medicinal product [13].

Considering the existence of a large number of unregulated problems regarding the circulation of generics on the Russian market while maintaining a balance of interests between manufacturers of reference medicinal products and generic manufacturers, it seems possible to borrow some foreign experience regarding the legal regulation of Data exclusivity.

In addition, when determining the volume of clinical trial data possible for transfer and disclosure, when carrying out legislative activities regulating actions in the Russian Federation regarding Data exclusivity, it is possible to propose the partial application (borrowing) of general requirements of legislation on trade secrets. In particular, according to Art. 13 of Federal Law No. 98-FZ dated July 29, 2004, On Commercial Secrecy, state power bodies, other state bodies, and local self-government bodies, in accordance with this Federal Law and other federal laws, are obliged to create conditions ensuring the protection of the confidentiality of information provided to them by legal entities or individual entrepreneurs.

Specifics of Legal Regulation of Data Exclusivity (Exclusivity of Clinical Trial Data) in EAEU Member States

Based on the legislative databases of EAEU member states available in the public domain, we provide information on how issues related to the legal regulation of Data exclusivity are settled in a number of these states.

Paragraph 19 of Art. 71 of the Code of the Republic of Kazakhstan No. 193-IV ZRK dated September 18, 2009, On People's Health and the Healthcare System, establishes that the state expert organization in the sphere of circulation of medicinal products, medical devices, and medical equipment and the state body in the sphere of circulation of medicinal products, medical devices, and medical equipment are not permitted, without the applicant's consent, to disclose and use for commercial purposes confidential information provided for the state registration of medicinal products contained in the application for state registration, medicinal product examination materials, and the registration dossier of a medicinal product containing new chemical entities for 6 years from the date of state registration of the medicinal product. This period is general and does not have a division into periods for chemical or biological preparations (unlike the Russian Federation). The provisions provided in the specified paragraph prohibiting the disclosure and use of confidential information for commercial purposes do not apply to:

• Individuals or legal entities issued a compulsory license for the use of the medicinal product in accordance with the Patent Law of the Republic of Kazakhstan;
• Use, manufacture, import, export, or distribution of the medicinal product for non-commercial purposes.

At the same time, based on a court decision, disclosure and use of the indicated information without the applicant's consent is permitted in the presence of one of the following cases:

• If supplies of the medicinal product are insufficient to meet the needs of the population within 12 months from the date of registration in the Republic of Kazakhstan;
• Necessity to protect public health in emergencies or for the purpose of ensuring national security;
• Detection of actions violating the requirements of the legislation of the Republic of Kazakhstan in the field of competition protection [14].

The registration dossier on electronic media is stored for 10 years. In case the medicinal product is on the market for more than 10 years, the storage of the electronic registration dossier is extended for the period the medicinal product is on the market of the Republic of Kazakhstan (Appendix No. 1 to the Order of the Minister of Health of the Republic of Kazakhstan No. 736 dated November 18, 2009) [15].

According to Part 15 of Art. 16 of the Law of the Republic of Armenia No. ZR-86 dated June 13, 2016, On Medicinal Products, during the registration of a generic medicinal product, the applicant is not required to submit data on preclinical studies and (or) clinical studies if the applicant submits documents proving that the medicinal product is reproduced from that original medicinal product which was registered in the Republic of Armenia or in a member country of an international professional organization established by a decree of the Government of the Republic of Armenia for at least 8 years. This generic medicinal product may enter into circulation 10 years after the registration of the original medicinal product. In the case of registration within the 10-year period of one or more new indications by the holder of the registration certificate rights, the period is extended by a maximum of another 1 year. The applicant does not submit data on the bioequivalence study of the generic medicinal product if the documents submitted by them confirm that this medicinal product has been used in the Republic of Armenia or in a member country of an international professional organization established by a decree of the Government of the Republic of Armenia for more than 8 years. In such cases, the applicant submits only relevant scientific literature data [16].

Other periods of protection for reference medicinal products against registration and introduction into trade circulation of generics are not established.

Thus, it can be concluded that currently, on the territory of EAEU member states, there is also a lack of clear legal regulation of many issues regarding the legal regulation of the effect of Data exclusivity. In this regard, there are grounds to believe that these states, similar to Russia, need to introduce additional legal mechanisms in the direction of regulating issues of legal protection of clinical trial data exclusivity.

Legal Regulation of Data Exclusivity Legal Institutions in Other Jurisdictions

It is worth noting that the introduction of the legal institutions of data exclusivity and data protection in the territory of the European Union, as well as in the USA, was implemented earlier than in the Russian Federation, and, therefore, the established rules are of a more specific nature.

According to Art. 10 of Directive 2001/83/EC of the European Parliament and of the Council of November 6, 2001, on the Community code relating to medicinal products for human use, submission of results of preclinical tests and clinical trials is possible if it can be demonstrated that the medicinal product is a generic of a reference medicinal product which is or has been authorized under Article 6 for not less than 8 years in a Member State or in the Community. However, a generic medicinal product authorized pursuant to this provision shall not be placed on the market until 10 years have elapsed from the initial authorization of the reference product [17]. This ten-year period implies a maximum extension to eleven years if, during the first eight years of those ten years, the marketing authorization holder obtains an authorization for one or more new therapeutic indications which, during the scientific evaluation prior to their authorization, were held to bring a significant clinical benefit in comparison with existing therapies.

Also, according to Part 11 of Regulation (EC) No 726/2004 of the European Parliament and of the Council of March 31, 2004, in the case of medicinal products for medical use, the period of protection of data relating to preclinical tests and clinical trials generally mirrors that provided for in Directive 2001/83/EC [18].

In the USA, depending on the registered drug, the "data exclusivity" period may vary and ranges from 3 to 7 years. At the same time, patent protection of the rights of medicinal product manufacturers operates in parallel with this [19].

Also, despite the fact that US legislation lacks an established liability measure for the failure of developers of original medicinal products to provide samples of such products to generic manufacturers for scientific development, the Food and Drug Administration (FDA) is taking measures regarding work with generic applicant-developers requesting such information. In particular, the FDA publishes on its official website a list of incoming requests from generic developers asking for samples of original medicinal products [20].

Thus, issues of protecting clinical trial data exclusivity in the EU and USA are more detailed, and the periods of protection of clinical trial data are longer compared to the periods established in EAEU member states.

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References

[1] Medicinal products as objects of patent rights. Pilicheva A.V. // Monograph. M.: Infotropic Media, 2016. 184 p.

[2] "Data exclusivity" and "Data protection": exclusivity and protection of CT results. D.A. Kopytin, PhD in Law, Associate Professor of the Department of Entrepreneurial Law of Lomonosov Moscow State University. Ed.: Remedium, No. 1, January 2013.

[3] Requirements of the EAEU single market are implemented in practice. Interview with a member of the Board (on technical regulation of the EEC V.N. Koreshkov). 09/19/2017 14:00. Rubric: Economy. Tatyana Bateneva. Rossiyskaya Gazeta – Special Issue No. 211(7377).

[4] Report of the Working Party on the Accession of the Russian Federation to the WTO dated November 16, 2011 // Legal Reference System "Consultant Plus".

[5] Ruling of the Supreme Court of the Russian Federation No. 305-ES16-2399 dated May 26, 2016 in case No. A40-188378/14.

[6] Decision of the Intellectual Property Court dated September 14, 2015 in case No. A40-30124/2015.

[7] Decision of the Intellectual Property Court dated August 2, 2016 in case No. A40-30012/2015.

[8] Resolution of the Presidium of the Supreme Arbitration Court of the Russian Federation dated June 16, 2009 No. 2578/09.

[9] According to the Ruling of the Supreme Court of the Russian Federation No. 305-ES16-2399 dated May 26, 2016 in case No. A40-188378/14, the court established that the state registration of the generic medicinal product "Nescler" was performed by the defendants under an accelerated procedure. To confirm the efficacy of fingolimod, the active substance used in the preparation "Gilenya," in the treatment of multiple sclerosis, the defendant relied on information contained in articles published in specialized printed publications. According to Clause 12 of Art. 4 of the Law on Circulation of Medicinal Products, a generic medicinal product is a medicinal product containing the same active pharmaceutical ingredient or a combination of such active pharmaceutical ingredients in the same dosage form as the original medicinal product and entered into circulation after the original medicinal product entered into circulation. In accordance with Part 1 of Article 26 of the Law on Circulation of Medicinal Products, the accelerated procedure for the examination of medicinal products for the purpose of state registration of medicinal products applies to generic medicinal products. During such a procedure, information obtained during clinical studies of medicinal products and published in specialized printed publications, as well as documents containing the results of a bioequivalence study and (or) therapeutic equivalence of the medicinal product for medical use, are submitted. The court of first instance, supported by the court of cassation, interpreting the provisions of Articles 18 and 26 of the Law on Circulation of Medicinal Products, concluded that the ban established by Part 6 of Article 18 of the said Law does not apply to information published in specialized printed publications. Denying the satisfaction of the claims, the courts of the first and cassation instances found it unproven that the defendants had illegally obtained, disclosed, or used information provided by the plaintiff during the state registration of the preparation "Gilenya"; the plaintiff did not submit materials of the registration dossier of the preparation "Gilenya," which indicates the unproven fact of the use by the defendants of information on preclinical and clinical studies of the medicinal product "Gilenya."

[10] Draft Law No. 02/04/10-18/00085211 "On Amendments to the Code of Administrative Offenses of the Russian Federation regarding the establishment of administrative liability for failure to provide samples of a reference medicinal product for conducting clinical trials."

[11] Action Plan for the Development of Competition in Healthcare, approved by Order of the Government of the Russian Federation No. 9-r dated January 12, 2018.

[12] In accordance with Clause 7 of the Rules of Good Clinical Practice, approved by Order of the Ministry of Health of the Russian Federation No. 200n dated April 1, 2016, a clinical trial is conducted in accordance with the clinical trial protocol, which contains, inter alia: 1) protocol title; 2) name and address of the organization organizing the clinical trial and monitoring (if different); 3) surname, first name, patronymic (if available) and position of the person authorized to sign the protocol on behalf of the organization organizing the clinical trial; 4) surnames, first names, patronymics (if available), position, address, and telephone number of the medical expert of this clinical trial, the investigator responsible for conducting the clinical trial, as well as addresses and telephone numbers of clinical centers, the physician responsible for making medical decisions; 5) names and addresses of clinical laboratories and other medical and (or) technical services and organizations participating in the clinical trial; 6) justification for the clinical trial; 7) goals and objectives of the clinical trial; 8) description of the general plan (design) of the clinical trial; 9) inclusion criteria for participants in the clinical trial; 10) non-inclusion and/or exclusion criteria for participants in the clinical trial/from the clinical trial; 11) information on all medicinal products used in the clinical trial; 12) list of efficacy parameters of the investigational medicinal product; 13) list of safety parameters of the investigational medicinal product; 14) requirements for reports, registration procedure, and reporting of adverse events and intercurrent diseases; 15) method and duration of follow-up of clinical trial participants after the occurrence of adverse events; 16) description of statistical methods of the clinical trial; 17) description of quality control and quality assurance actions; 18) description of ethical aspects of the clinical trial; 19) description of data handling and record keeping; 20) description of the procedure for financing the clinical trial and insurance of clinical trial participants; 21) indication of the possibility of publishing clinical trial results.

[13] Resolution of the Intellectual Property Court dated February 28, 2018 in case No. A40-106405/2018.

[14] Code of the Republic of Kazakhstan No. 193-IV ZRK dated September 18, 2009 "On People's Health and the Healthcare System" // Information-legal system of normative legal acts of the Republic of Kazakhstan "Adilet".

[15] Rules for conducting the examination of medicinal products, approved by Order of the Minister of Health of the Republic of Kazakhstan No. 736 dated November 18, 2009.

[16] Law of the Republic of Armenia No. ZR-86 dated June 13, 2016 "On Medicinal Products" // Database "Legislation of the CIS countries".

[17] Directive 2001/83/EC of the European Parliament and of the Council of November 6, 2001, on the Community code relating to medicinal products for human use.

[18] Regulation (EC) No 726/2004 of the European Parliament and of the Council of March 31, 2004 // Legal Reference System "Garant".

[19] Frequently Asked Questions on Patents and Exclusivity/ Home Drugs Development & Approval Process (Drugs) Frequently Asked Questions on Patents and Exclusivity. Content current as of: 05/02/2018. An official website of the United States government.

[20] Reference Listed Drug (RLD) Access Inquiries. Content current as of 02/07/2019. Home Drugs Development & Approval Process (Drugs) / How Drugs are Developed and Approved / Types of Applications / Abbreviated New Drug Application (ANDA) / Reference Listed Drug (RLD) / Access Inquiries.