Inclusion in and Exclusion from the VED List and Other Lists of Medicinal Products

 

April 9, 2024

BRACE©

 

Ensuring the safety, quality, and efficacy of drug therapy is a paramount task of the state. To implement this task, the government adopts restrictive lists of medicinal products, the costs of which are covered by budgetary funds and medical insurance funds. Establishing such lists allows, on the one hand, selecting the most effective medicines corresponding to the modern level of medical development from the variety of existing drugs, and on the other hand, taking into account the financial capabilities of the state.

This article discusses the main restrictive lists of medicinal products effective in the Russian Federation, as well as the procedure for including and excluding medicinal products from them.

History of the Formation of Medicinal Product Lists

The first Model List of Essential Medicines was published by the World Health Organization (hereinafter – "WHO") in 1977. It included slightly more than 200 products for treating the vast majority of diseases. Since then, WHO model lists have been updated every two years. Subsequently, similar lists began to be formed in many countries. Currently, more than 150 countries have national lists of essential medicines, but they vary significantly.

In Russia, the first list of medicines was approved in 1992. It was called the List of Vital and Essential Medicines (hereinafter – "VED List") and included many more items than the WHO model list. Until 2000, the work on its formation was effectively unregulated by normative acts, was conducted by various expert groups, and lacked formation criteria. Starting in 2000, the work on compiling the VED List was entrusted to the Formulary Committee of the Ministry of Health of Russia. It was then, according to researchers of this topic, that the examination of materials on a medicinal product was introduced as a necessary condition for making decisions on its inclusion in the list, and the main criteria for classifying a product as vital and essential were formulated: proven clinical efficacy, safety, and economic acceptability [1]. Since 2004, the authority to form the List has transferred directly to the Ministry of Health of Russia.

On August 28, 2014, the Government of Russia adopted Decree No. 871 "On Approval of the Rules for Forming Lists of Medicinal Products for Medical Use and the Minimum Assortment of Medicinal Products Necessary for Providing Medical Care" (hereinafter – "Decree No. 871"), which established the procedure for forming four lists of medicinal products:

• The List of Vital and Essential Drugs (hereinafter – "VED List");
• The List of Medicinal Products Intended for the Provision of Persons Suffering from Hemophilia, Cystic Fibrosis, Pituitary Dwarfism, Gaucher Disease, Malignant Neoplasms of Lymphoid, Hematopoietic and Related Tissues, Multiple Sclerosis, as well as Persons after Organ and/or Tissue Transplantation (hereinafter – "List of High-Cost Medicinal Products");
• The List of Medicinal Products for Medical Use Prescribed by Decision of Medical Commissions of Medical Organizations;
• The List of the Minimum Assortment of Medicinal Products Necessary for Providing Medical Care (hereinafter – "Minimum Assortment").

Since 2021, the formation of the List of Medicinal Products Prescribed by Decision of Medical Commissions of Medical Organizations has been cancelled.

Below we will consider in detail the objectives and procedure for forming said lists.

Inclusion of Medicinal Products in the VED List

According to Part 6 of Article 4 of Federal Law No. 61-FZ dated April 12, 2010, "On the Circulation of Medicines" (hereinafter – "The Law on Medicines", "Law No. 61-FZ"), the VED List is a list approved by the Government of the Russian Federation of medicinal products for medical use that ensure the priority needs of healthcare for the prevention and treatment of diseases, including those prevailing in the disease structure in the Russian Federation.

The main function of the VED List is state regulation of prices for vital and essential medicinal products. Such regulation is implemented by registering the manufacturer's maximum selling prices and establishing maximum limits for wholesale and retail markups on these products.

Another important function of this list is the free provision of medicines to citizens during the provision of medical care. Thus, by virtue of Part 3 of Art. 80 of Federal Law No. 323-FZ dated November 21, 2011, "On the Fundamentals of Health Protection of Citizens in the Russian Federation" (hereinafter – "Law No. 323-FZ"), when providing medical care within the framework of the Program of State Guarantees of Free Provision of Medical Care to Citizens, the medical organization ensures the provision of citizens with medicinal products for medical use included in the VED List. The prescription of other medicinal products is carried out by substitution only in cases of individual intolerance or for vital indications by decision of the medical commission.

Based on the above, state procurement of medicinal products is also carried out in accordance with the VED List in most cases, except for cases of procurement of medicinal products for specific patients in case of individual intolerance or for vital indications by decision of the medical commission.

The VED List is formed by International Nonproprietary Names (INN) of medicinal products (in the absence of such names – by grouping or chemical names), taking into account standards and clinical guidelines on medical care issues.

As a general rule, single-component medicinal products are included in it; combination medicinal products are included only if the assessment results prove their advantage in application and cost compared to single-component medicinal products. At the same time, along with combination products, all single-component medicinal products registered in the Russian Federation that make up such a combination are simultaneously included.

In accordance with Clause 2 of Decree No. 871, medicinal products included in the VED List must meet the following criteria:

• Be registered as a medicinal product in the manner established in the Russian Federation;
• Be used for the diagnosis, prevention, treatment, and rehabilitation of diseases, syndromes, and conditions, including those prevailing in the disease structure in the Russian Federation;
• Have an advantage over other medicinal products in the treatment of a specific disease or condition.

Prior to the inclusion of a medicinal product in the VED List, a comprehensive assessment is performed, including an analysis of information on the comparative clinical efficacy and safety of the medicine, an assessment of the economic consequences of using the medicine, and a study of the additional consequences of using the medicine.

Inclusion in the List of High-Cost Medicinal Products

Article 14 of Law No. 323-FZ imposes on federal state power bodies the obligation to provide persons suffering from rare and high-cost diseases with necessary medicinal products. Currently, Article 44 of the Law classifies such diseases as: hemophilia, cystic fibrosis, pituitary dwarfism, Gaucher disease, malignant neoplasms of lymphoid, hematopoietic and related tissues, multiple sclerosis, hemolytic-uremic syndrome, juvenile arthritis with systemic onset, mucopolysaccharidosis types I, II, and VI, unspecified aplastic anemia, hereditary deficiency of factors II (fibrinogen), VII (labile), X (Stuart-Prower), and provision for persons after organ and (or) tissue transplantation. These diseases are called "14 Nosologies", but the list of such diseases is periodically expanded.

The provision of medicinal products to patients with the indicated diseases and syndromes for outpatient treatment is carried out at the expense of the federal budget in accordance with the List of High-Cost Medicinal Products.

It is formed by INN (in the absence of such names – by grouping or chemical names) within the limits of budgetary allocations provided in the federal budget for the corresponding financial year.

According to Clause 3 of Decree No. 871, to be included in said List, a medicinal product must meet the following criteria:

• Be registered as a medicinal product in the manner established in the Russian Federation;
• Be included in the VED List;
• Have an advantage over other medicinal products in the treatment of persons suffering from the indicated diseases and syndromes.

It is also important that the inclusion of a medicinal product in the List of High-Cost Medicinal Products and, if necessary, the exclusion of an alternative medicinal product from it, should not lead to an increase in the volume of budgetary allocations provided in the federal budget for the corresponding financial year.

The formation of this List is also carried out in accordance with the norms of Decree No. 871.

List of Medicinal Products for the Provision of Certain Categories of Citizens

Another list mentioned in Decree No. 871 is the List of Medicinal Products for the Provision of Certain Categories of Citizens. It was assumed that certain categories of federal and regional beneficiaries, such as disabled persons and veterans of the Great Patriotic War, liquidators of the consequences of the Chernobyl NPP disaster, disabled persons, and others, would be provided with medicinal products during outpatient treatment in accordance with it.

However, currently, the provision of these categories of citizens is carried out based on the VED List. In connection with these upcoming changes, the removal of the reference to this List from the text of Decree No. 871 is planned.

Minimum Assortment of Medicinal Products Necessary for Providing Medical Care

Part 6 of Article 55 of the Law on Medicines establishes the obligation of pharmacy organizations and individual entrepreneurs holding a pharmaceutical license to ensure the availability of the minimum assortment of medicinal products necessary for providing medical care when carrying out retail trade.

The Minimum Assortment is also formed by INN (in the absence of such names – by grouping or chemical names) from medicinal products for medical use.

Criteria for including a medicinal product in the Minimum Assortment:

• Registration as a medicinal product in the manner established in the Russian Federation;
• Inclusion in the VED List;
• Availability of at least 2 generic or biosimilar (biologic) medicinal products corresponding to the product by INN (or the grouping or chemical name replacing such name) in similar dosage forms and dosages, produced by two or more manufacturers (except for medicinal products produced by a single domestic manufacturer);
• Demand by the healthcare system and the population throughout the entire calendar year according to data on sales volumes in the pharmaceutical market of the Russian Federation.

Procedure for Forming Lists of Medicinal Products

In accordance with Clause 7 of Decree No. 871, the VED List is formed and reviewed at least once a year. The List of High-Cost Medicinal Products and the Minimum Assortment are formed at least once every 3 years.

The formation of lists is carried out by a commission established by the Ministry of Health of Russia. The full name of this commission is the Commission of the Ministry of Health of the Russian Federation for the Formation of Lists of Medicinal Products for Medical Use and the Minimum Assortment of Medicinal Products Necessary for Providing Medical Care (hereinafter – "The Commission") [2]. The Commission includes representatives of federal executive bodies (Ministry of Health, Ministry of Industry and Trade, Ministry of Labor, Roszdravnadzor, Rospotrebnadzor, FAS, FMBA, Ministry of Education and Science), executive bodies of constituent entities of the Russian Federation in the sphere of health protection, federal educational institutions of higher medical and pharmaceutical education, and federal medical and pharmaceutical scientific organizations.

Organizational support for the Commission's activities is provided by the Department of Drug Supply and Regulation of the Circulation of Medical Devices of the Ministry of Health, which, inter alia, ensures:

• Conducting documentary expertise of proposals for the lists and Minimum Assortment regarding compliance with the requirements of the Rules for Drafting Proposals, completeness and reliability of the submitted information on medicinal products, including its compliance with information contained in the state register of medicinal products;
• Preparing draft conclusions based on the results of the documentary expertise of proposals for the lists and Minimum Assortment and sending them to applicants via information and communication technologies, including preparing and sending proposals for the lists to the Center for Expertise, the expert organization, and chief experts;
• Summarizing conclusions based on the results of the comprehensive assessment of proposals for the lists and recommendations of chief experts;
• Preparing invitations to Commission meetings for Commission members, chief experts, representatives of the expert organization, as well as representatives of interested federal executive bodies, public associations carrying out activities in the spheres of healthcare, circulation of medicines, and protection of citizens' rights in these spheres;
• Preparing documents and information received by the Commission for consideration at Commission meetings;
• Sending documents and information on issues of forming lists and the Minimum Assortment to the Department of Digital Development and Information Technologies of the Ministry for posting on the official website on the Internet [3].

To be included in the lists of medicinal products or the Minimum Assortment, the applicant sends a proposal to include a medicinal product to the Commission electronically by the 10th day of the first month of the quarter. Proposal forms are approved by Appendices No. 1 and 2 to Decree No. 871. Information on proposals is posted on the official website of the Ministry of Health of Russia on the Internet.

Consideration of the proposal is carried out in several stages:

1. Documentary Expertise.

Within 7 working days from the date of receipt of a proposal for inclusion in the Lists or Minimum Assortment, the Commission organizes its documentary expertise. Based on the results of the documentary expertise, the proposal is rejected in the following cases:

• Improper formatting or submission of documents and information in incomplete volume;
• Submission of unreliable or distorted information;
• Repeated submission within one calendar year of a proposal for inclusion within the same INN if a decision was made by the Commission in the current year to refuse inclusion of a medicinal product with the same INN or regarding which documentary expertise or comprehensive assessment is already being carried out;
• Submission of a revised proposal after repeated rejection based on the results of documentary expertise.

The conclusion on the rejection of the proposal is sent to the applicant within 3 working days from the date of its issuance. A revised proposal with eliminated deficiencies may be re-sent to the Commission within 10 working days from the date of receipt of the first negative conclusion.

Information on proposals that have passed documentary expertise is posted on the official website of the Ministry of Health on the Internet.

2. Comprehensive Assessment.

No later than 2 working days from the date of issuance of a positive conclusion of the documentary expertise, the Commission sends proposals for a comprehensive assessment to authorized organizations:

• FSBI "Center for Expertise and Quality Control of Medical Care" of the Ministry of Health of Russia (hereinafter – "Center for Expertise");
• A specialized federal state educational organization of higher (medical or pharmaceutical) or additional education carrying out research activities as a statutory activity, or a medical and (or) pharmaceutical scientific organization subordinate to the Ministry of Health or the Ministry of Education and Science (hereinafter – "Expert Organization").

The list of expert organizations is approved by the Ministry of Health of Russia and posted on the official website on the Internet.

During its stage of the comprehensive assessment, The Center for Expertise performs:

• Analysis of the methodological quality of clinical-economic studies of medicinal products and studies using budget impact analysis of the budgetary system of the Russian Federation. The parameters and requirements for the analysis are established in Appendix 5.1 to Decree No. 871.
• Study of the additional consequences of using the medicinal product based on the scale for quantitative assessment of additional data on the medicinal product provided in Appendix No. 6 to Decree No. 871.

The Expert Organization is entrusted with the analysis of information on the comparative clinical efficacy and safety of the medicinal product, as well as the assessment of the economic consequences of its use. These are conducted based on the following integral scales (Appendix No. 6 to Decree No. 871):

• Scale for assessing levels of evidence of results of clinical trials of medicinal products;
• Scale for assessing levels of credibility of evidence of clinical trials of medicinal products;
• Integral quantitative assessment of the quality of a clinical trial of a medicinal product;
• Quantitative assessment of the efficacy of using a medicinal product within the framework of clinical trials;
• Quantitative assessment of the safety of using a medicinal product within the framework of clinical trials;
• Quantitative assessment of the additional therapeutic value of a medicinal product;
• Scale for assessing the cost of a course (year) of treatment with a medicinal product;
• Scale for clinical-economic assessment of a medicinal product;
• Scale for assessing the impact of a medicinal product on the budgets of the budgetary system of the Russian Federation;
• Scale for quantitative assessment of additional data on a medicinal product.

We do not aim to examine these integral scales and the procedure for assigning points according to the criteria indicated therein in this article, as they are of a highly specialized nature. More details on the assessment procedure using scales can be found in a scientific work on this topic [4].

The comprehensive assessment is conducted within 30 working days from the date of receipt of the proposal from the Commission. Based on the results of the comprehensive assessment, the Expert Organization and the Center for Expertise compile conclusions and submit them to the Commission.

3. Obtaining the Recommendation of the Chief Expert.

The proposal and conclusions based on the results of the comprehensive assessment are sent by the Commission to the Chief Expert within 2 working days from the date of their receipt for the preparation of a scientifically substantiated recommendation on the inclusion of the medicinal product in the Lists and Minimum Assortment. When forming the Minimum Assortment, as well as upon receipt of a proposal to exclude a medicinal product from the lists and Minimum Assortment, at least 2 Chief Experts are involved.

Requirements for the Chief Expert are not established in Decree No. 871, except for the correspondence of the activity profile; in practice, these are the Chief External Specialists of the Ministry of Health of Russia.

Within 10 working days from the date of receipt of the documents, the Chief Expert submits a scientifically substantiated recommendation to the Commission in the form according to Appendix No. 9 of Decree No. 871. In case of complete or partial disagreement with the conclusions based on the results of the comprehensive assessment, the Chief Expert indicates comments in the recommendation with detailed justification and references to publications on clinical trial data or efficacy and safety monitoring data, calculations justifying the conclusions, with these publications attached.

4. Holding a Commission Meeting to Consider the Proposal.

Decisions on proposals are made at Commission meetings. Meetings are held quarterly, by the 10th day of the second month of the quarter, and are broadcast on the official website of the Ministry of Health on the Internet. No more than 15 medicinal products are considered at one Commission meeting. At the same time, note that according to data from the Ministry of Health of Russia website, Commission meetings were repeatedly canceled in 2023 for technical reasons.

Representatives of the Center for Expertise and representatives of the Expert Organization are invited to the Commission meeting. Representatives of the pharmaceutical market or public associations carrying out activities in the sphere of healthcare, circulation of medicines, and protection of citizens' rights may also be present at the meeting, subject to a preliminary written request no later than 5 working days before the day of the corresponding Commission meeting.

The decision is made by voting. In the event of a tie, the vote of the presiding officer at the Commission meeting is decisive.

Based on the results of the meetings, draft Decrees of the Government of the Russian Federation are prepared, which are posted on the official website on the Internet for a period of at least 10 working days. Before approval by the Government, they are subject to coordination with federal executive bodies.

Please note that by virtue of Clauses 9(1) and 9(2) of Decree No. 871, in addition to the general procedure, operative introduction of changes to the Lists and Minimum Assortment is provided for:

• Based on and within the timeframe in accordance with an instruction of the Government of the Russian Federation;
• Upon submission by the Ministry of Health of Russia regarding medicinal products possible for prescription and use for the treatment and prevention of diseases posing a danger to others in emergency situations and (or) upon the emergence of a threat of the spread of such diseases.

Inclusion is carried out in a simplified manner, but the procedure is not regulated in the normative act under consideration.

Currently, said lists of medicinal products and the Minimum Assortment are approved by Decree of the Government of Russia No. 2406-r dated October 12, 2019 [5].

In practice, there are cases of refusals to include medicinal products in lists of medicinal products or the Minimum Assortment for various reasons. Thus, according to the specialized publication Pharmvestnik [6], in 2022, the Commission refused to include two products in the VED List: the antitumor drug "Trabectedin" by R-Pharm and "Fampridine", used in patients with multiple sclerosis, by Valenta Pharm. For one of them, a discussion arose regarding clinical indications; the other did not score enough points based on the results of the expertise. In 2021, Valenta Pharm had already submitted an application and received a refusal, also due to the expertise.

Disputes Regarding Inclusion in Lists of Medicinal Products

Challenging a refusal or inaction must be carried out in accordance with Chapter 24 of the Arbitration Procedure Code of the Russian Federation "Challenging non-normative legal acts, decisions and actions (inaction) of state bodies, local self-government bodies, other bodies, organizations vested with separate state or other public powers by federal law, and officials". However, due to procedural features and the complexity of assessment procedures, this can be difficult.

Thus, in 2024, the pharmaceutical company Biocad applied to the arbitration court with a statement to declare illegal the inaction of the Deputy Minister of Health of the Russian Federation, who acts as the chairman of the commission for forming lists of medicinal products, and the Ministry of Health of Russia (Case No. A40-12763/24-33-97). It demanded holding a commission to include its medicines for multiple sclerosis therapy in the VED List and the List of High-Cost Medicinal Products. As explained by company representatives, "for more than six months, it was not possible to arrive at any visible result regarding the consideration of the submitted dossiers; the company was forced to use all available methods to protect its interests and the interests of Russian patients" [7]. However, before the start of the case consideration by the court, the company withdrew the statement, and the case was terminated.

A potentially effective legal remedy may be an appeal to the Federal Antimonopoly Service. In the previously considered case, Biocad also filed a complaint with FAS demanding that the Deputy Minister be held administratively liable for "hindering patients' access to domestic drugs, thereby creating preferential conditions for foreign suppliers of medicinal products". In our opinion, such an appeal is possible regarding the violation of prohibitions on actions (inaction) of federal executive bodies that restrict competition, established by Chapter 3 of Federal Law No. 135-FZ dated July 26, 2006, "On Protection of Competition."

Procedure for Exclusion from Lists of Medicinal Products and Minimum Assortment

Medicinal products are subject to exclusion from lists of medicinal products and the Minimum Assortment in the following cases:

• Inclusion of alternative medicinal products possessing proven clinical and (or) clinical-economic advantages, and (or) features of the mechanism of action, and (or) greater safety in the diagnosis, prevention, treatment, or rehabilitation of diseases, syndromes, and conditions;
• Appearance of information on toxicity or high frequency of adverse side effects when using the medicinal product;
• Suspension of the use of the medicinal product in the Russian Federation;
• Cancellation of the state registration of the medicinal product;
• Cessation of production of the medicinal product or its supplies to the Russian Federation and (or) absence of the medicinal product in civil circulation in the Russian Federation for a period exceeding one calendar year;
• Exclusion of the medicinal product from the VED List (regarding MPs included in the List of High-Cost Medicinal Products and the Minimum Assortment);
• Submission of a scientifically substantiated recommendation of the Chief External Specialist of the Ministry of Health of the Russian Federation;
• If within 6 months after the inclusion of the medicinal product in the VED List, the manufacturer's maximum selling price for the medicinal product has not been registered.

Forms of proposals for exclusion from lists of medicinal products and the Minimum Assortment are approved by Appendices No. 3 and 4 to Decree No. 871.

Thus, in October 2022, the Commission planned to consider at a meeting proposals to exclude several hundred dosage forms from the VED List due to absence from the market, termination of registration, and other reasons. Some products were excluded from the VED List.

Upcoming Changes in Legal Regulation

Public discussion of the draft amendments to Decree No. 871 (Project ID 01/01/02–24/00145808) has been completed on the portal of draft regulatory legal acts. We note the following key points:

• In the VED List, it is planned to indicate not only the INN of the medicinal product but also the method and (or) routes of administration of the product, as well as the main or additional elements of dosage forms, including the type of release of the active substance (if available).
• When considering issues of inclusion in the VED List, it is planned to request the position of state power bodies of constituent entities of the Russian Federation in the sphere of health protection regarding the expediency of inclusion, given that such a decision may change the burden on the budget of the constituent entity.
• Requirements for the analysis of the quality of clinical-economic studies of medicinal products and budget impact analysis studies will change.
• The applicant, in case of disagreement with the recommendation of the Chief Expert or the results of the comprehensive assessment, will be able to provide additional documents and information, which are subject to re-evaluation.
• The possibility of remote voting by commission members is excluded in order to establish maximum transparency of the procedure.

In general, the importance of restrictive lists of medicinal products is difficult to overestimate. They are a guarantee of ensuring the availability of medicinal products at all stages of medical care. In this regard, the introduction of rules for forming the Lists was an important step towards ensuring the transparency of decisions made. At the same time, problems continue to be identified in the work process regarding both the assessment scales of the medicinal product and the procedure for conducting procedures, which require adjustment.

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References

[1] Omelyanovskiy V.V., Sura M.V., Avksentyeva M.V., Khachatryan G.R. Rules for forming lists of medicinal products for medical use at the federal level: current state and development prospects // Medical Technologies. Assessment and Choice, 2018; 3(33), pp. 9–17.

[2] Order of the Ministry of Health of Russia dated September 9, 2014, No. 498n "On approval of the regulation on the commission of the Ministry of Health of the Russian Federation for the formation of lists of medicinal products for medical use and the minimum assortment of medicinal products necessary for providing medical care" (registered with the Ministry of Justice of Russia on September 29, 2014, No. 34182).

[3] Clause 9 of the appendix to the Order of the Ministry of Health of Russia dated September 9, 2014, No. 498n "On approval of the regulation on the commission of the Ministry of Health of the Russian Federation for the formation of lists of medicinal products for medical use and the minimum assortment of medicinal products necessary for providing medical care" (registered with the Ministry of Justice of Russia on September 29, 2014, No. 34182).

[4] Tolkushin A.G., Kholovnya-Voloskov M.E., Pogudina N.L. Preparation of a proposal for including a drug in the VED List. Critical points // Remedium. 2021, 2, pp. 91–99.

[5] Decree of the Government of Russia dated October 12, 2019, No. 2406-r "On approval of the list of vital and essential medicinal products, as well as lists of medicinal products for medical use and the minimum assortment of medicinal products necessary for providing medical care".

[6] E. Kalinovskaya. Drugs of R-Pharm and Valenta Pharm companies were again refused inclusion in the VED List. April 27, 2022 // Pharmaceutical Bulletin (Pharmvestnik).

[7] Biocad filed a lawsuit against the Deputy Head of the Ministry of Health. January 29, 2024 // RBC Companies.