Introduction

1. State of the Russian pharmaceutical industry

1.1 Strategy for the revival of the pharmaceutical industry

1.2 Large enterprises

2. Global pharmaceutical industry

2.1 GMP standard

2.2 Large foreign pharmaceutical enterprises

3. An innovative way to create drugs is a way to revive industry

3.1 Development of a new drug

3.2 Molecular modeling

3.3 Virtual screening

3.4 Programs for computer simulation

4. Research in the field of molecular modeling in Russia Conclusion

Literature

Introduction

Currently, the economies of almost all developed and many developing countries are aimed at creating and developing a “high-tech sector”. In a modern economy, the “high-tech sector” is seen as the main and perhaps the most important driver of economic growth. The pharmaceutical industry is now the fastest growing, most important, high-tech industry. It is subject to a variety of laws and regulations regarding drug patenting, clinical and preclinical testing, and the specifics of marketing and marketed products. Currently, the pharmaceutical industry is one of the most successful and influential industries, the reviews of which can be controversial. However, there is a clearly distinguishable line between the development of pharmaceutical production in Russia and abroad. This is largely due to the painful transition to a new type of economy in 1990. Nevertheless, the Russian pharmaceutical industry continues to develop and in many ways this becomes possible thanks to the use of the latest methods of targeted search for new drugs.

1. The state of the Russian pharmaceutical industry

The Russian pharmaceutical market occupies one of the leading places in the world in terms of growth rate - more than 19% annually. The “high-tech” sector in Russia is currently at its nascent stage. Although there are several high-tech industries that contribute a significant share to the Russian economy, many industries, such as computers and office equipment, telecommunications equipment, medical devices, and precision instruments, are in their infancy. At this stage of development, the issue of survival is critical for these industries, which requires government support, attraction of venture capital, as well as the availability of the necessary infrastructure, which is just beginning to be created in our country. For companies in these industries, vital problems are the formation of a client base, reaching the breakeven level, and return on initial investments. Of the domestic high-tech industries, two have largely emerged: aerospace manufacturing and pharmaceuticals. The aerospace industry in Russia is, of course, more developed than pharmaceuticals; in addition, it is the products of the Russian aerospace industry that are the most competitive in comparison with other sectors of the Russian economy. For example, the contribution of the aircraft industry to Russian GDP ranges from 2 to 2.5%, while the contribution of the pharmaceutical industry to GDP is 10 times less and equals 0.2%. However, the pharmaceutical industry is a more competitive industry within the national economy. As noted above, currently the contribution of the Russian pharmaceutical industry to the country's GDP is very small and amounts to only 0.2% (as of 2010). By comparison, the pharmaceutical industry's share of US GDP was more than 5.5% in 2002. Considering the scale of the countries, the population, as well as the demand from neighboring countries (CIS), one can see that the potential of the domestic pharmaceutical sector of the economy is great. The production volume of the domestic pharmaceutical industry in 2008 amounted to 360 billion rubles, in 2009 - 430 billion rubles, thus, the growth rate reached 19.28% per year. The pharmaceutical industry in Russia is represented by two main areas of activity of the companies that form it, namely, medical equipment and medicines. At the same time, the share of medicines in the total volume of pharmaceutical production is growing. So in 2008, the share of medicines accounted for 79.93%, and already in 2009 – 85.64%. Such a redistribution of shares is accompanied by the growth of the entire industry. The number of players in the industry is large; the 10 largest enterprises account for only 58.29% of total production. Currently, many domestic manufacturers of pharmaceutical products and especially medicines are producing so-called “generics” (from the English generic - generic drug), i.e. “copies” of drugs that have lost patent protection abroad. At their core, “generics” are copies of already outdated drugs, which leads to a slowdown in the pace of development of domestic biotechnologies. This situation is exacerbated by the extremely low share of domestic pharmaceutical companies' R&D expenditures. According to statistics from the Ministry of Economic Development of the Russian Federation, domestic companies spend approximately 1-2% of annual revenue on R&D. For example, in the USA or Western Europe, pharmaceutical companies spend an average of 10-15% of annual revenue on R&D, which allows them to build their product portfolio using innovative medicines

1.1 Strategy for the revival of the pharmaceutical industry Pharma-2020

The Strategy for the Development of the Pharmaceutical Industry of the Russian Federation until 2020, developed by the Ministry of Industry and Trade of the Russian Federation and approved by the Government of the Russian Federation in 2009, is intended to resolve such issues. This document contains a list of the main problems of the Russian pharmaceutical industry, and also proposes a set of measures to solve them and achieve competitiveness of domestic pharmaceutical manufacturers in the world market.

The strategy is intended:

Determine priority directions for the development of the pharmaceutical industry of the Russian Federation (hereinafter referred to as the pharmaceutical industry) and ways of their implementation;

To be a conceptual basis for public-private partnerships on the development of the pharmaceutical industry;

Ensure consistency of actions of government authorities at various levels in the areas of industry development in the long term;

Determine the strategic vector for the development and adjustment of the regulatory framework of the pharmaceutical industry;

Serve as the basis for decision-making at the state level on the development and implementation of targeted programs and projects for the development of the pharmaceutical industry.

Thus, one of the main goals of the Strategy is to increase the share of Russian manufacturers in the domestic pharmaceutical market to 50% (currently 80% of the market is held by foreign-made drugs), as well as to increase the share of innovative drugs in the product portfolios of domestic manufacturers, for which the Strategy provides measures to stimulate investment in R&D. Also, the set of measures provided for in the Strategy concerns the improvement of regulatory regulation of the industry, which is primarily aimed at improving technical standards, as well as creating favorable conditions for competition (and minimizing unfair competition). As can be seen from the characteristics of the Russian pharmaceutical industry, the main players in the industry are companies of approximately the same size, whose market shares are also comparable. In addition, most of these companies carry out identical activities, namely: the production and sale of generic drugs, the development of their own import-substituting drugs, as well as the development of innovative drugs. Despite the fact that the range of domestic manufacturers is inferior to Western market players, domestic products are competitive. Thus, many analogues of foreign drugs are not inferior to them in terms of price-quality ratio, and are also included in the list of necessary drugs for which preferential prices are set, which helps to increase demand. Of course, in order to be able to compete with foreign manufacturers on equal terms, domestic pharmaceutical companies need to actively develop their product portfolios through the creation of innovative products. However, this requires additional investment and expanded production capabilities.

1 .2 Large Russian pharmaceutical enterprises

One of the largest domestic companies is Pharmstandard OJSC. Pharmstandard accounts for more than 12% of all drug production in Russia. Pharmstandard was founded in 2003 by Profit House (a Millhouse Capital structure that managed the assets of Roman Abramovich). At that time, the company owned only two Russian pharmaceutical plants: Fitofarm-NN in Nizhny Novgorod and Ufavita in Ufa. Five more were purchased from the American pharmaceutical giant ICN Pharmaceuticals: “October” in St. Petersburg, “Marbiopharm” in Yoshkar-Ola, “Leksredstva” in Kursk, “Polypharm” in Chelyabinsk and “Tomskkhimpharm” in Tomsk. Subsequently, three factories were sold or closed for various reasons: “October” (inconveniently located in the very center of the city), “Marbiopharm” (focused on the production of substances secondary to the Pharmstandard strategy), “Polypharm” (required too much investment). In 2005, Pharmstandard bought the Tyumen plant of medical equipment and instruments. All Pharmstandard enterprises are constantly modernized [source not specified 271 days] to comply with international GMP quality standards. By 2006, the company had spent more than $70 million for these purposes. In 2006, Pharmstandard bought the Masterlek company, whose assets included 15 well-known brands. In particular, the rights to Arbidol, Amiksin and Flucostat were obtained. By this time, the holding’s production capacity exceeded 1 billion packages per year; Pharmstandard’s factories produced all forms of medicines (tablets, suspensions, capsules, sprays). By the end of the year, Arbidol came out on top in sales in Russia, overtaking Viagra and hawthorn tincture. In 2006, the company launched several more high-tech drugs: Russia's first growth hormone Rastan, developed at the Institute of Bioorganic Chemistry, and genetically engineered human insulin Biosulin. At the moment, Pharmstandard is the largest Russian manufacturer of insulin. The company’s capacity would be enough to meet 100% of Russians’ needs for this drug, but Russia still imports most of its insulin from abroad. Since 2007, Pharmstandard has been actively working with foreign partners: for example, Tomskkhimpharm, together with Solvey Pharma (France), began production of the drugs IRS19 and Imudon. In 2008, Pharmstandard entered into an agreement with the Latvian company Grindeks (Latvia) for the exclusive distribution and promotion of the drug Mildronate, mastered the production of Afobazol, and introduced the genetically engineered drug Neipomax into production. In 2009, Pharmstandard became the first and currently only Russian member of the International Council of Producers, Distributors and Consumers of Active Pharmaceutical Ingredients (Excipients) in Europe (IPEC Europe). In the same year, the company implemented an operation to implement a specialized IP solution for the central office and factories.

The company's revenue according to IFRS in the first half of 2009 amounted to 10.062 billion rubles. (an increase of 62% compared to the first half of 2008), net profit - 2.588 billion rubles. (an increase of 47%). The company's revenue according to IFRS in 2008 amounted to 14.3 billion rubles, net profit - 3.5 billion rubles. The company's revenue in 2007 amounted to 11.3 billion rubles. (in 2006 - 8.5 billion rubles, growth 22%), net profit - 3.2 billion rubles. (2 billion rubles).

In 2005, the company took 1st place in the ranking of Russian pharmaceutical manufacturers. The drug Arbidol, which is part of the company's portfolio, took 1st place in sales in 2007 on the Russian over-the-counter drug market. In 2007, Pharmstandard was awarded the title of “Company of the Year” and received first place in the rating of Russian manufacturers compiled by the Pharmexpert marketing research center. At the beginning of 2008, Pharmstandard entered the top 100 fastest growing companies in Europe according to BusinessWeek experts, took first place in retail sales in Russia and second among operators of the Russian pharmaceutical market. The company was included in the list of systemically important enterprises in Russia, which, if necessary, will be provided with government support. In 2008, the drug Pentalgin became the winner of the “PEOPLE’S BRAND / BRAND No. 1 in Russia” award in the “Painkiller” category. In 2009, the drug Complivit won in the “Vitamins” category.

2. Global pharmaceutical industry

The global pharmaceutical industry ranks 2nd in terms of investment in research and development. This conclusion is contained in the leading source of analytical information on the 800 British and 1,250 global companies that invest the most in R&D - the R&D Scoreboard 2009 of the UK department of trade and industry.

Pharmaceutical companies took a step between hardware manufacturers (technology hardware, 1st place) and the automotive industry (3rd place), and software companies were in 5th place (In Fig. 1 (" R&D Scoreboard 2006") - the contribution of industries to investments in R&D around the world, %). The top 1250 included companies from 39 countries, with the share of companies from five countries - the USA, Japan, Germany, Great Britain and Switzerland - accounts for 82% of investments in R&D. In total, about £249 billion was invested in R&D across all industries in 2009, of which £46.7 billion was invested in the pharmaceutical sector, which is 8.3% more than in 2004. The top 100 companies that spent the most on innovation in the 2009/2010 financial year (across all industries), including 18 pharmaceutical companies (Table 1); At the same time, the top 20 includes 6 pharmaceutical companies - 2 from the USA and 4 from Europe (for comparison: in 1992, there was not a single representative of the pharmaceutical sector in the top 20).

It should be noted that despite the global presence of pharma, funds for R&D come mainly from companies in the USA, Switzerland and the UK.

The pharmaceutical industry in the European Union is one of the leading and high-tech industries. It creates about 3.5% of the total added value of products produced in the EU, and is the recipient of about 18.2% of business investments, which in 2004 amounted to about 21.1 billion euros (in 1990 - 7.8 billion euros). Trade surplus – 32.2 billion euros in 2004 (7.1 billion euros in 1990). The industry has created 612 thousand jobs in Europe, including 102.2 thousand employed in R&D departments. Undoubtedly, large companies find it easier to discover and develop new drugs. First of all, because the cost of developing a new drug increases every year, and the return on drug development is less and less (due to an increase in the number of drugs within one therapeutic group, tightening regulatory requirements, the simultaneous existence of me-too drugs on the market, that is, not having significant therapeutic advantages in comparison with each other). The most winning strategy for companies with large research budgets is to develop several areas at once. In this case, it is necessary to allocate at least $100 million. per year in order to conduct research at a high modern level and not be inferior to competitors, but if the company wants to achieve greater results than its competitors, it will have to allocate more than $300 million. in year. To make the process of discovering new therapeutic agents more efficient and streamlined, laboratory techniques are being automated, bioinformatics and new methods for screening the human genome are being used. Company managers face a difficult task in determining the direction of research, in choosing the technologies that the company will use, and in the size of the budget for each of the areas. Some companies, aimed at excessive profits, develop their own “field” of diseases, and obtain intellectual property rights to all biological targets identified through sequencing of the human genome (which requires huge investments in the creation of new screening technologies) in order to solely benefit from the fruits of the investment. Others are content with fragmentary data obtained as a result of investments in research from other companies and create me-too drugs. Despite the high cost of using the latest scientific achievements, many companies decide to use them in their own programs, although the risk associated with such investments is high. Thus, Bayer allocated $465 million. a deal with Millennium Pharmaceuticals that will identify hundreds of drug targets; Novartis has entered into an $800 million contract with Vertex Pharmaceuticals to gain access to substances generated using technologies at the intersection of chemistry and genomics to predict the effectiveness of drug candidates and potential side effects from their use. On average, companies spend about 25% of their R&D budget on discovery of substances, but if they want to get ahead of the rest in a certain therapeutic area, they will have to spend up to 1/3 of the research budget on this if the company's sales by prescription group are 7-10 billion dollars , and up to 1/3 of the budget - the giants with sales of prescription drugs exceeding $20 billion. Smaller companies prefer to pursue a different research strategy, focusing on modifications that improve the effectiveness of existing substances. Some analysts, on the other hand, believe that a large budget does not guarantee greater return on investment, and argue that small and mid-sized biotech companies have better conditions for research and development. Biotech companies drive the majority of innovation in healthcare, and more than 40% of drug candidates (at all stages of development) are in their hands. They can compete with pharmaceutical giants in terms of the number of new drugs. Therefore, Big Pharma companies are trying to stabilize their revenues by pursuing aggressive merger policies or entering into licensing agreements with biotech companies that have a strong, promising product pipeline. For the period 2002–2008 There were about 35 mergers and acquisitions between pharma and biotech, during which pharmaceutical companies had to part with $19.8 billion. in 2005, 11 billion in 2004, 14.8 billion in 2003 and 25.5 billion in 2002.

Every year, the reported amounts of transactions between pharmaceutical and biotechnology companies are becoming larger. Small and mid-sized biotech companies are better financed and less dependent on pharmaceutical companies for funding, expertise or infrastructure because they already have sufficient capital and human resources.

2.1 Standard GMP

The GMP standard ("Good Manufacturing Practice") is a system of norms, rules and guidelines for the production of medicines, medical devices, diagnostic products, food products, food additives and active ingredients. In contrast to the quality control procedure of examining samples of such products, which ensures the suitability of only the samples themselves (and possibly the batches manufactured closest to the given batch), the GMP standard takes a holistic approach and regulates and evaluates the production parameters themselves. and laboratory testing. The Russian GMP standard was prepared by the Association of Engineers for the Control of Microcontaminants (ASINCOM) and in 2004, by resolution of the State Standard of Russia dated March 10, 2004 No. 160-st, GOST R 52249-2004 “Rules for the production and quality control of medicines” was approved, which is harmonized with the rules GMP (Good Manufacturing Practice for medicinal products) of the European Union. Currently, GOST R 52249-2009 is in force. The international standard GMP (Good Manufactured Practice) includes a fairly extensive range of indicators that enterprises producing certain products must comply with. GMP for pharmaceutical companies defines the parameters of each production stage - from the material from which the floor in the workshop is made and the number of microorganisms per cubic meter of air to the clothing of employees and the markings applied to product packaging. Currently, the most important elements of the GMP concept are: compliance of all technological and control documentation in production with the contents of the registration dossier for the corresponding drug; strict control over compliance with the rules, implying not only declared, but also the actual application of sanctions to violating enterprises. A sign of the times can also be considered the introduction of strict methodological rules in the work of state bodies for regulatory control of drugs: quality systems, measures to prevent conflicts of interest among employees, measures to maintain the confidentiality of documentation.

2.2 Large foreign pharmaceutical enterprises

Pfizer, Inc. is an American pharmaceutical company, one of the largest in the world. The company produces the world's most popular drug Lipitor (Atorvastatin, used to lower blood cholesterol). The company also sells the following popular drugs: Lyrica, Diflucan, Zithromax, Viagra, Celebrex. Pfizer shares were included in the Dow Jones Industrial Average on April 8, 2004. The company produces drugs for a wide range of consumers under the well-known brands Benadryl, Sudafed, Listerine, Desitin, Visine, Ben Gay, Lubriderm, Zantac75 and Cortizone. Pfizer is the inventor and manufacturer of the world famous drug Viagra.

The production of drugs is carried out at the company's factories located in the USA, Great Britain, France, Italy, Holland, Germany, Turkey (in total - in 46 countries around the world). There are representative offices in more than 100 countries, including Russia. According to the British information and publishing agency URCH Publishing, Pfizer is the leader in the global pharmaceutical market (2007) with a market share of 6.2% (closest competitors: GSK - 5.4%, Roche - 4.3%). The company's main divisions are Human Health, Animal Health and Corporate Groups. The total number of personnel (at the end of 2008) is 83 thousand people (106 thousand people in 2005). Annual sales in 2008 were $48.3 billion ($48.4 billion in 2007, $51.3 billion in 2005). The company's profit is $8.1 billion ($8.14 billion in 2007). According to Jeff Kindler, Pfizer no longer intends to depend on the success of a few blockbusters. This is the main reason for the acquisition of Wyeth, one of the first major companies to invest in biotechnology. Pfizer will focus on biologics vaccines and treatments for Alzheimer's disease and cancer, rather than focusing on conventional drugs such as cholesterol-lowering and antihypertensive drugs (Lipitor, US sales of 13% of the company's total (more than $6 billion) drugs, as well as antidepressants. The company also intends to actively work in the drug market for older people. Until 2014, the company's brands such as the cholesterol-lowering drug Lipitor, the antihypertensive drug Norvasc, the drug for the treatment of erectile dysfunction Viagra and the drug for the treatment of glaucoma Xalatan will lose patent protection. Annual consolidated sales of these drugs are $16.7 billion.

3. An innovative way to create drugs is a way to revive industry

3.1 Creation of a new drug

The development of a new drug takes a long time - from 8 to 12 years. This is due to the high and constantly increasing level of safety and efficiency requirements. Therefore, the creation of a new drug requires considerable funds. Abroad, this figure is estimated at $350-500 million. In Russia, costs are significantly lower, but nevertheless, by our standards, they are quite high. In addition, there is a high probability of obtaining a negative result: the pharmacological agent being developed may turn out to be toxic, and the data obtained on experimental animals may not be confirmed in the clinic, etc. Therefore, all pharmaceutical companies are very interested in obtaining new technologies that would reduce the risk of obtaining negative results, and the time spent on development, and the cost of development. Drug developers have always been interested in identifying unique substances that have significant novelty compared to known drugs. The search for the basic structures of new drugs aims to identify substances from chemical classes where the activity being studied has never been found before. The emphasis on “new substances” dominated the drug discovery strategy previously, but now, along with this, research has shifted towards the search for new targets for drug action. A target is a biological macromolecule, such as a protein, that is associated with the pathogenesis of a specific disease. For example, viruses have proteins, the “switching off” of which leads to the death of the virus. They can be considered as targets for the action of new drugs. For example, when decoding the genome of the hepatitis C virus, a protease protein was discovered, which is involved in maintaining the life cycle of this virus. If it were possible to find inhibitors of this protease that would kill the virus, but would have virtually no effect on similar proteins in the human body, such substances would become an effective treatment for hepatitis C. Similar approaches are being developed today for the treatment of many bacterial and viral infections. At the turn of the 20th-21st centuries, through the efforts of molecular biology, a unique situation was achieved when the genomes of about 30 microorganisms were completely deciphered, and more than 100 more are at the stage of deciphering. The human genome has already been completely deciphered. This has created new conditions for a systematic search for macromolecules that are targets for the action of new drugs. This is the work of a special field of science - bioinformatics, which compares the genetic sequences and primary structures of proteins found in various pathogenic organisms with a set of sequences in humans normally and in pathologies. On this basis, potential targets of drug action are identified. After identifying such a target, the task arises of searching for ligands - substances acting on this protein (inhibitors or activators). This is where computer-assisted drug design methods come into play. In the so-called direct search for ligands, it is necessary to determine the spatial structure of the target macromolecule. This can be done either by experimental methods or by computer simulation. The first path is quite long and does not always lead to success, since many proteins are difficult to isolate in an intact (undamaged) form. Currently, the gap between the number of proteins with a deciphered primary structure and the known spatial structure is several orders of magnitude, which is why the development of methods for computer modeling of spatial structure is so important. Such methods are quite successful if it is possible to carry out homology modeling, when among proteins with a known spatial structure there is a macromolecule “similar” in amino acid sequence to the new target macromolecule being studied. After obtaining the three-dimensional structure of the target macromolecule and establishing the characteristics of its active center, it is possible to search for substances in databases of samples of chemical compounds that are potentially ligands of this target macromolecule. If such ligands are identified, they are considered as probable basic structures of a new drug. After experimental confirmation of the biological activity of the basic structures, again using computer methods, the so-called optimization of the properties of the basic structure is carried out. In this case, analogues of the originally discovered basic structure are designed, synthesized and tested for biological activity, having higher biological activity, lower toxicity and better bioavailability. If the three-dimensional structure of a target macromolecule cannot be determined experimentally or its model cannot be constructed using computer methods, the only way left is to search for the initial basic structures using experimental high-throughput screening. Currently, robotic installations are used abroad for this purpose, making it possible to test up to 100 thousand substances on 100-200 targets within a week. If basic structures are identified during such screening, then they can then be used as a training sample to search for analogous substances (by biological action) using complex methods in databases containing many millions of chemical compounds.

3.2 Molecular modeling

Molecular modeling (MM) is a collective name that refers to theoretical approaches and computational methods for simulating or depicting the behavior of molecules. These methods are used by computational chemistry, computational biology, and materials science to study molecular systems of various sizes. The simplest calculations can be done by hand, but computers become absolutely necessary when calculating systems of any reasonable scale. A common feature of MM methods is the atomistic level of description of molecular systems - the smallest particles are atoms or small groups of atoms. This is the difference between MM and quantum chemistry, where electrons are also explicitly taken into account. Thus, the advantage of MM is the lower complexity in describing systems, which allows consideration of a larger number of particles in calculations. Molecules can be modeled either in a vacuum or in the presence of a solvent such as water. Calculations of systems in a vacuum are called "gas phase" calculations, while calculations involving solvent molecules are called "explicit solvent" calculations. Another group of calculations takes into account the presence of a solvent evaluatively, using additional terms in the potential function - the so-called “implicit solvent” calculations. Currently, molecular modeling methods have become commonplace in the study of the structure, dynamics and thermodynamics of inorganic, biological and polymer systems. Among the biological phenomena that are studied by MM methods are protein folding, enzymatic catalysis, protein stability, conformational transformations and molecular recognition processes in proteins, DNA and membranes.

3.3 Virtual screening

Virtual screening is a computational procedure that involves automated scanning of a database of chemical compounds and selecting those predicted to have desired properties. Most often, virtual screening is used in the development of new drugs to search for chemical compounds that have the desired type of biological activity. In the latter case, the virtual screening procedure can be based either on knowledge of the spatial structure of the biological target or on knowledge of the structure of the ligands to the molecule of a given biological target. The key procedure for virtual screening based on knowledge of the spatial structure of a biological target is molecular docking, which makes it possible to predict the spatial structure of the ligand-protein complex and, based on it, using scoring functions, calculate the binding constant of the ligand to the protein. In this case, a focused library is formed from the compounds for which the highest binding constants to the protein molecule are predicted, from which material is selected for further biological experiments. An example of the use of virtual screening of this kind is work aimed at searching for potential ligands of NMDA and AMPA receptors

3.4 Computer modeling programs

DockingServer offers an easy-to-use web interface that manages all aspects of molecular docking with ligand and protein settings. Its user-friendly interface allows calculations and evaluation results carried out by researchers from all areas of biochemistry; DockingServer also provides full control over setting specific ligand and protein parameters and docking and calculations for more advanced users. The application can be used for single ligand docking and analysis, as well as high throughput ligand docking to a target protein. DockingServer integrates a large number of computational chemical programs specifically aimed at correctly calculating the parameters required at different stages of the docking procedure, i.e. precise optimization of ligand geometry, energy minimization, charge calculation, protein-ligand calculation and docking, integrated representation. Thus, the use of DockingServer allows the user to carry out highly efficient and reliable docking calculations by integrating a number of popular programs combined into one web service.

The DockingServer program consists of three modules containing the following main stages of docking calculations

Proteins can be downloaded as *PDB files, or can be downloaded directly (after a keyword search in the database, if necessary) from the Protein Data Bank (www.rcsb.org). Small molecules present in the PDB file can be added to the ligand folder. More accurate protein partial charge calculations using quantum chemical methods.

Ligands can be downloaded directly from the PubChem database, or in SDP file format

The user can select the desired pH, affecting the protonation state of the ligand.

The calculated information is presented to the user in the most convenient format - in the form of tables, lists. For more experienced users, it can be presented as a file for independent work

QuteMol- an open source program for interactive visualization of molecular systems. QuteMol takes advantage of the available capabilities of modern computer graphics using the OpenGL library. The program offers a wide range of graphic effects. QuteMol visualization techniques aimed at improving the realism and facilitating the perception of 3D shape and structure of large molecules or complex proteins.

Rosetta@Home

An online project that allows everyone to contribute to the modeling of drug molecules for serious diseases. All the user needs is to download the distribution of the program and leave it running on the computer in their free time. The goal of our current research is to develop an improved model of intra- and intermolecular interactions and to use this model to predict and design macromolecular structures and interactions. Prediction and design applications, which can be of great biological interest in their own right, also provide rigorous and objective tests that improve the model and increase fundamental understanding. We use the computer program Rosetta to perform protein and design calculations. The Rosetta core has potential functions for calculating the energy of interactions within and between macromolecules, and methods for finding the lowest energy structure for an amino acid sequence (protein structure prediction) or protein-protein complex, and for finding the lowest energy amino acid sequence for a protein or protein-protein complex (protein engineering). Feedback from prediction and design tests is used continuously to improve potential search features and algorithms. The development of a single computer program to handle these diverse problems has significant advantages: first, the different applications provide additional tests of the underlying physical model (fundamental physics/physical chemistry is of course the same in all cases); Second, many problems of current interest, such as flexible backbone protein design and protein-protein docking with backbone flexibility, involve a combination of different optimization techniques.

4. Research in the field of molecular modeling in Russia

The laboratory of molecular modeling and spectroscopy in Moscow is engaged in this work. The Laboratory of Molecular Modeling and Spectroscopy was created in 1975. It was organized by Professor (now Corresponding Member of the Russian Academy of Sciences) Lev A. Gribov. Initially, the laboratory was called the “laboratory of molecular spectroscopy and quantum chemistry” and it included a theoretical group and groups of optical, in particular, time-resolved, EPR and NMR spectroscopy. Then a laser spectroscopy group appeared in the laboratory and the direction related to the development of the theory and methods for calculating the spectra of complex molecules, quantum chemistry and special software was significantly strengthened. Gradually, research in this field of science became the main one. The laboratory employs seven doctors and two candidates of science. The main results of the activities of the laboratory staff are the following. The theory and methods for calculating energy levels and the probabilities of transitions between them for all types of internal motions of atoms in molecules, polymers and crystals, including internal rotations and movements of atomic groups, have been developed. The approaches are general and have no restrictions on the structures and sizes of the analyzed molecular objects and on the choice of generalized coordinates, among which there can be any number of dependent ones. This makes it possible to easily operate with molecular models with a very wide variety of input parameters and easily move from one representation to another. It is important that the proposed computational algorithms for polymers and crystals allow working not only with infinitely extended systems, but also with nanoobjects of finite sizes, studying surface phenomena, etc. This forms the basis for solving many problems associated with the creation of modern nanodevices and the development of nanotechnologies. A method for accumulating settlement data in a special bank is proposed. Computational algorithms are implemented in the form of a set of LEV programs, which has no analogues in its capabilities, and according to its general ideology, is aimed at a gradual transition from single calculations to mass calculations, suitable for designing molecular systems with specified properties at the engineering level. Methods have been created that for the first time made it possible for real large molecules to carry out predictive calculations of electronic vibrational absorption and emission spectra taking into account the fine structure of the bands and to analyze the results of precision experiments using arbitrary observation methods, including pulsed excitation in the femtosecond range, and with any changes in the structure of molecules during transitions between states. The result of a significant part of these studies is summarized in an extensive (more than 600 pages) monograph, “Theory and methods of Calculation of Molecular Spectra” (Wiley, 1988), written entirely on original materials. For the first time, attention was drawn to the adequacy of chemistry as a science with the apparatus of discrete mathematics and the foundations of a new scientific direction - mathematical chemistry - were laid. A general theory has been created and a logical and algorithmic structure of an expert system has been proposed for diagnosing and establishing the properties of unknown molecular objects based on a set of experimental data. This task is basic for organic analytical chemistry. A laboratory sample of the system was used to create branded computer products (Germany, Canada). A presentation of the fundamentals of the theory formed the content of an entire issue of Crit magazine. Rev. Anal. Chem. (No. 8, 1979). The development of the theory of expert systems (artificial intelligence systems) required an in-depth analysis of the fundamental principles of constructing scientific knowledge. The results obtained were included in a textbook on the philosophy of natural sciences for universities. In 1999, the works of this cycle were awarded the State Prize of Russia - the highest national award in the field of science - with the wording: “For the development of the theory and methods for calculating molecular spectra and the creation of expert systems.” In the last decade, an original general theory of molecular processes based on the concept of resonance of states has been proposed. For the first time, it was possible to form a unified system of equations for spectral and chemical transformations in molecules and conduct a series of computer experiments for real complex systems. As an example, the figure shows the results of calculations of spectra reflecting the progress of the chain isomerization process. Spectral manifestations of the effect of double bond migration: time-dependent fluorescence spectra of isomers a, b, c, d of heptadienylbenzene upon excitation of isomer a. The resonance effect does not depend on the reaction conditions. This makes it possible to describe fast and slow reactions, photochemical, thermal, cryogenic, etc. from a unified point of view. The new theory made it possible to clarify the physical nature of the transfer of energy and information in molecular space both through spectral and chemical channels; the action of molecular objects as receiving-transforming (up to pattern recognition) systems; understand the mechanism of molecular learning and subsequent recording of deterministic complex signals. For the first time, on the basis of first principles without the use of empirical experience, the basic chemical laws are explained: short-range action, Arrhenius's law, reduplication, etc. The result of a large series of works in this direction is summed up in the unique monograph “Theory and methods of calculation of molecular processes: spectra, chemical transformations and molecular logic” published in 2006. The primary importance of these studies is determined by the fact that further exploration of the infinite number of objects and variety of properties of the molecular world becomes impossible without advanced theoretical elaboration and engineering calculations, especially in those areas in which the empirical rules and recommendations accumulated in chemistry turn out to be completely insufficient. The laboratory initiated the use of spectral theory and quantum chemistry methods in analytical chemistry. A theory of the action of polar substituents and the influence of the electric field of molecules on the course of ion-molecular reactions has been created. The nature of the chemical bond in compounds with unusual valency of the constituent elements has been clarified. A new approach to describing the electronic states of molecules, based on the Fock formalism, is proposed, based from the very beginning on the exact solution of the problem of the movement of one electron in the field of nuclei (an analogue of the solution of the problem of the hydrogen atom in atomic theory). The corresponding theory is free from empirical elements, eliminates the self-consistency procedure and allows one to analyze both ground and excited, including highly excited Rydberg, states of electrons in molecules. Significant results were obtained in the theory of special functions, where new relations between them were proposed, simplifying the summation of hypergeometric series. A method for the quantitative analysis of substances based on their optical spectra is proposed and justified, which does not require the use of samples of standard composition. Combining theoretical calculations and experiment makes it possible to eliminate the “scissors” between the universality of the spectrometer and the narrow specialization of standards. Methods have been developed for spectral determination in real conditions of ultra-small amounts of a substance (detection limits 10-13 - 10-14 g/ml) with maximum exclusion of background and the influence of matrices. The method is based on two-stage laser excitation of atoms followed by their ionization in an electric field. The experimental design is shown in the figure. Currently, a new method is being developed for detecting trace amounts of organic substances using laser ionization and subsequent desorption of ions from rough and porous surfaces. Many results were obtained for the first time and are significantly ahead of foreign developments.

Abroad, such developments are being carried out in the USA, Texas. LaboratoryofMolecularSimulation.

The Laboratory of Molecular Modeling (LMS) brings molecular modeling and computational chemistry techniques closer to experimental science by offering training to both inexperienced and advanced users. Advanced simulation software is available to perform quantum computations on small molecules or solid systems; molecular mechanics/dynamics modeling for large systems such as proteins, DNA, nanomolecules, polymers, solids and liquids. The LMS also provides support for instructors who want to incorporate molecular modeling into their courses.

Conclusion

At the moment, the Russian pharmaceutical industry is still in a backward state. In total, three groups of enterprises can be distinguished. Enterprises that were able to find funds and rebuild their production in accordance with European standards (for example, Akrikhin), enterprises that were formed from former research institutes and are engaged in the production of 2-3 highly specialized drugs (for example, Pulmomed) and enterprises that re-launched production (Pharmstandard). Russia's share in the production of medicinal substances in the world is still very small and amounts to about 2-3%. Russia is also dependent on the import of vital medicines. According to some data, the ratio of imports to domestic production is 85:15. Based on all of the above, it is extremely necessary to revive and increase the pace of pharmaceutical production. One way is to search for new drugs using computer technology. This method allows you to reduce the search for a cure from 8-10 years to 3-4 years. In our country, specialized laboratories are already being implemented, which already have sufficient progress in such developments.

Literature

1. Tikhonova I. G., Baskin I. I., Palyulin V. A., Zefirov N. S. Virtual screening of databases of organic compounds. Creation of focused libraries of potential ligands for NMDA and AMPA receptors // Proceedings of the Academy of Sciences. Chemical series. - 2004. - No. 6. - P. 1282-1291.

2. A. V. Pogrebnyak Molecular modeling and design of biologically active substances. - Rostov-on-Don: Publishing house SKNTs VSh, 2003. - ISBN 5-87872-258-5

3. H.-D. Helltje, W. Zippl, D. Ronyan, G. Volkers, Molecular Modeling Theory and Practice, 2010, ISBN 978-5-9963-0156-0

4. N. I. Zhokhova, E. V. Bobkov, I. I. Baskin, V. A. Palyulin, A. N. Zefirov, N. S. Zefirov (2007). "Calculation of the stability of complexes of organic compounds with β-cyclodextrin using the QSPR method." Bulletin of Moscow State University, ser. 2, Chemistry 48(5): 329-332.

5. N. I. Zhokhova, I. I. Baskin, V. A. Palyulin, A. N. Zefirov, N. S. Zefirov (2005). "Investigation of the affinity of dyes for cellulose fiber within the fragmentation approach in QSPR." Journal of Applied Chemistry 78(6): 1034-1037.

6. D. A. Filimonov, V. V. Poroikov (2006). "Forecast of the spectrum of biological activity of organic compounds." Ross. chem. and. (Journal of Russian Chemical Society named after D.I. Mendeleev) L (2): 66-75.

7. I. I. Baskin, G. A. Buznikov, A. S. Kabankin, M. A. Landau, L. A. Leksina, A. A. Ordukhanyan, V. A. Palyulin, N. S. Zefirov ( 1997). "Computer study of the relationship between embryotoxicity and structures of synthetic analogs of biogenic amines." Izvestiya RAS, biological series (4): 407-413.

Pharmaceutical industry - an industry concerned with the research, development, mass production, market research, and distribution of drugs primarily intended for the prevention, relief, and treatment of disease. Pharmaceutical companies can work with generics or original (brand-name) drugs. They are subject to a variety of laws and regulations regarding drug patenting, clinical and preclinical testing, and the marketing of off-the-shelf products. Currently, the pharmaceutical industry is one of the most successful and influential industries, the reviews of which can be controversial.

History of development

The production of medicines has been known since ancient times. The emergence of industrial enterprises for the production of medicines dates back to the end of the 19th century. They began to emerge especially quickly at the beginning of the twentieth century. after the discovery of synthetic drugs. The production of medicines developed most intensively in Germany, Great Britain, and Switzerland; Of many types of medicines, Germany dominated the world market during the Second World War 1939-45. In the 70s, the production of synthetic medicines and antibiotics increased greatly in the USA and Great Britain. The development of industry is based on the achievements of chemical science.

Development of the pharmaceutical industry in Ukraine

The chemical pharmaceutical industry in Ukraine developed quite a long time ago, which was facilitated by the availability of local raw materials (mineral salts, alcohol, water, water, etc.). Its pioneers were With a request. foreigners: laboratories - I. Singer (founded 1874), P. Legrand (1875) and K. Leviton (1884) - all three in Odessa, later others appeared, pharmaceutical laboratories of F. Del in Lubny, S. Snapir in Kremenchug, K Debu from Slavyansky, K. Schmidt and A. Martsinchik in Kyiv. 1914 largest pharmaceutical enterprises n. there were laboratories of the head. “Sanitas”, “Stella”, “Labor”, “Farm-galen”. Before the Second World War, pharmacies played an important role, where medicines were prepared from the constituent (often imported) materials according to doctors’ prescriptions. One of the first pharmacies in Ukraine was a pharmacy in Lviv (1392 - 1400); only from the beginning 18th century pharmacies appeared in Glukhov (1707) and Lubny. 1896 there were only 7 pharmacies in Kyiv; the first of them was the Bunge pharmacy (1728).

In the Ukrainian SSR after the First World War, all indestructible enterprises were concentrated in the so-called “Ukrmedtorzi” and large pharmaceutical factories were created from the united smaller enterprises. (named after Sverdlov, “Workers’ Health”, “Red Star”). Activities have begun to produce honey from medicinal plants. drugs in Lubny and Zhitomir. Immediately before the Second World War, new pharmaceutical plants were built. in Odessa and Lvov. But the production of complex drugs and preparations (or vitamins) was still in the experimental stage, so far only money circulation from institutes was made from laboratories (the main ones: the Ukrainian Institute of Experimental Pharmacy and the All-Ukrainian N.-D. Institute of Endocrinology and Organotherapy, both in Kharkov) . The population's need for medicines was covered only by 50-60%; only large hospitals and clinics received more important medicines. Before 1930 - 35 pp. large pharmaceutical enterprises of the Ukrainian SSR were under the jurisdiction of the r. Commissariat of Health of the Ukrainian SSR, but in 1935 - 37 pp. big managers transferred to Moscow, and from that time on H.-F. p. works according to plans and programs determined by the “Commander in Chief” of Moscow. min-st.

State of H.-F. p. improved noticeably only in the 1950s pp. Then the production of antibiotics was established, primarily such as penicillins and streptomycins (headed by Sverdlov); neocide and glucose cadases began to be produced in 1963 - 65 pp.; imacin and levymycentin later. New plants have been built in Ukraine. vitamins and herbal antibiotics (in Uman, Borshchagovka and Darnitsa). 1957 began to mass produce anti-typhoid vaccines, as well as biogenic stimulants (in Lubny and Odessa). The production of dental preparations in Kharkov, medical gypsum in Shchirets, and absorbent cotton wool in Chernivtsi has been developed. 1964 at Darnitsky plant. production of injection solutions in ampoules has been established. In 1950 - sixties pp. started viroblaty phytochemical preparations for the treatment and control of the cardiovascular system (strophanthin, hetoxin, davkarin, korglykon, reserpine) their production is concentrated at the head. “Workers' Health” (Kharkov) and at the Lviv Chemical and Pharmaceutical Plant.

1980 There were 24 large pharmaceutical companies working in Ukraine. and 30 auxiliary profiles. Product range H.-F. n. covered the beginning. 1970s pp. OK. 900 names, including a number of vitamin preparations. The share of ready-to-use mass-produced drugs in Ukrainian pharmacies’ formulations amounted to 1974 approx. 65% (in the USA 95%); 35% of medications are prepared in pharmacies. Deaka preparations are produced in separate workshops by the head. other industries, for example, glucose is produced by the Verkhnedneprovsky starch plant, organotherapy preparations from animal raw materials are produced by the workshop-laboratory of the meat processing plant in Poltava, Vinnitsa, Donetsk, Voroshilovgrad. At the same time, a large number of new, experimental drugs with a complex structure are produced by laboratories of monetary circulation institutes, not only of the pharmaceutical profile, but also the Institute of Colloid Chemistry and Water Chemistry of the Academy of Sciences of the Ukrainian SSR, institutes of the endocrinology and toxicology sector (in Kharkov and Kyiv), and the Institute of Organic Chemistry of the Academy of Sciences Ukrainian SSR, etc. Growth in production of H.-F. p. for post-war pp. can be seen from the table:

Ukrainian SSR in 1950 - 1975 pp

Products of some chemical and pharmaceutical products in the Ukrainian SSR in 1950 - 1975 pp.

In the 1970s pp. H.-f. n. bedspreads approx. 80% of the drug needs of institutions and patients. There is a shortage of some sulfoamide drugs, analgesic anticoagulants, galenic drugs, etc. The packaging of ready-made drugs was quite primitive; only the construction of two new special heads. (in Maryanovka and Bakovtsy in the Zhitomir region and in the village of Kodra in the Kiev region) 1975 somewhat improved the situation. The production of nebulizers for diseases of the nose and throat was established late (at the Belgorod-Dnestrovsky plant, it reached full power only at the end of the 1970s pp.), as well as x-ray and automatically recording film films for modern equipment associated with computer diagnostics technology In the early 1980s, medical treatment automation and computers were already stagnant in several specialized hospitals of the Ukrainian SSR, in particular in the sector of oncology and endocrinology.

The institutes issue monetary circulation in two journals: “Pharmaceutical Journal” (6 times a year), and “Ukrainian Biochemical Journal” (6 times a year), as well as the periodical collection “Pharmacology and Toxicology”.

The specificity of pharmaceutical production is the release of a product aimed at improving or maintaining human health. This determines the strategic role of the pharmaceutical industry for the country and the importance of state regulation of the drug production process. In the modern world, the future of the nation depends on the state of the national healthcare system. And the pharmaceutical industry plays one of the leading roles in the overall healthcare system.

The dynamics of global healthcare throughout its development clearly demonstrate that the use of drug therapy is constantly expanding. Currently, the industry's products are available in the form of tablets, injection solutions, inhalations, ointments, gels and other finished forms containing one or more active pharmaceutical ingredients. High efficiency in the treatment of many diseases, speed, convenience and ease of use, non-invasiveNoninvasive - (noninvasive) - The term is used to characterize methods of research or treatment during which there is no impact on the skin using needles or various surgical instruments nature of treatment, reduced dependence depending on the specific place of treatment - the advantages that modern drugs provide compared to other types of treatment. The range of use of modern pharmaceutical products is extremely wide, and at the same time constantly covers new areas of therapeutic indications. With the help of chemical pharmaceuticals, most infectious diseases, many cardiovascular pathologies, and some types of malignant tumors can be cured. Modern medications can significantly alleviate the condition of patients with diseases of the central nervous system (CNS), reduce drug and alcohol addiction, and relieve pain and inflammatory syndromes.

Today it is impossible to imagine the life of a modern person and society as a whole without such drugs. The constant availability of a certain set of medicines is a key link in the system of ensuring national security. The pharmaceutical industry should be considered as one of the key sectors of national industry, the influence of which, directly or indirectly, extends to all spheres of life of modern society and the state.

The pharmaceutical industry is a complex set of interconnected elements, and the effective operation of this entire system depends on the harmonious interaction of all its parts. The most important of them: research work on the creation of new drugs; development of technological approaches to the industrial production of medicinal substances, including chemical and biotechnological approaches; large-scale production of substances and finished dosage forms; organization of a drug sales system; implementation of effective marketing activities; organization of an effective personnel training system; establishing and improving mechanisms for financing developments; effective activities of regulatory government organizations. Also, the control system for this most complex mechanism, which requires the involvement of highly qualified specialists and advanced management technologies, deserves special mention.

Current state of the Russian pharmaceutical market

The modern pharmaceutical industry can be considered one of the most high-tech and knowledge-intensive sectors of the world economy, and this applies to the greatest extent to the development of new drugs. And this is seen as another important role of the pharmaceutical industry at the present stage of the existence of the Russian state: under certain conditions, it can become the engine of real innovative development of the country

The Russian pharmaceutical market is one of the most promising in Central and Eastern Europe due to its size, continued economic growth and improvements in intellectual property rights protection. The market size is the largest in the said region and will remain so for the foreseeable future. According to the Information and Analytical Portal www.remedium.ru

Table 1

Market volume

At the same time, the growth potential of the Russian market is very significant, although significant efforts are required to fully realize this potential. In 2006, the market capacity in absolute terms reached $12.2 billion. According to the DSM Group. In 2007, intensive growth continued, and the market capacity amounted to $14.3 billion (117.21% more than the previous year ). Over the past 2008, the market capacity amounted to 18.4 billion dollars, which is 128.68% more than in 2007. According to various forecasts, market growth will continue in 2009-2011. with an average rate of 10-12% per year in national currency and an even higher rate in dollar terms. As a result, its volume (the final cost for consumers) will reach $20 billion already in 2011, and by 2020, according to various estimates, $25-35 billion. Growth will be primarily ensured by increased incomes of the population and the associated increase in the size of the private health insurance market.

Let's look at the share of imports in total sales in Table 2.

table 2

Specific share of imports in total volume

Fig.1

The share of imports in total sales has been increasing in recent years, mainly due to the import of expensive medicines. The volume of imports of medicines (drugs) in 2006 was $8.93 billion, or 3.19 billion packages. In 2007 it reached 10.2 billion US dollars, or 3.36 billion packages. The volume of imports of medicines at the end of 2008 amounted to 13.09 billion US dollars, or 3.44 billion packages. In value terms, the import of medicines increased by a third, in physical terms - an increase of 102.2%. According to data from the Federal Customs Service, imports of medicines into the Russian Federation in the first half of 2009 decreased by 6.1% to $3.19 billion from $3.397 billion in the same period last year. The main volume of medicines worth $3.181 billion, as last year, was purchased in non-CIS countries.

Consumption of finished medicinal products (FPP) per capita has doubled over the past 4 years, but this figure is still significantly lower than in the EU countries and the USA. According to the Information and Analytical Portal www.remedium.ru. This indicates the existence of significant pent-up demand, as well as high potential for market growth as economic indicators improve.

Current state of the pharmaceutical industry and production

According to data from the Ministry of Industry and Energy of the Russian Federation for 2008, the Russian pharmaceutical industry is represented by 525 enterprises employing 65.1 thousand people. These enterprises produce marketable products worth 62 billion rubles. The industry average profitability is 17%. The degree of depreciation of fixed assets is 60%, and production capacity utilization is 78%.

In recent years, there has been significant growth in production in the domestic pharmaceutical industry. Due to the development of domestic sales, the processes of mergers and acquisitions and licensing of leading products have intensified within the Russian pharmaceutical sector in recent years. Companies' spending on research and development (R&D) and product promotion has increased significantly.

Pharmaceutical production is one of the most stable segments of Russian industry. The pharmaceutical industry is oriented mainly towards the domestic market, which means, unlike export-oriented industries, it is less sensitive to exchange rate fluctuations. Demand for pharmaceutical products depends little on the phase of the economic cycle, which has a positive effect on the development of the industry as a whole. Even during the recession in the mid-1990s, the decline in pharmaceutical volumes was not as significant as in other industries. It is enough to note that the share of unprofitable enterprises in this market segment at the beginning of 2000 was 12.6%, while in the industry as a whole it was about 50%. According to the data presented on the website www.marketing.spb.ru/mr/healthcare/ farm.

Foreign manufacturers are actively investing their funds in the development of Russian ones. In recent years, several groups of companies have formed, uniting the largest pharmaceutical plants in Russia. The Russian market gradually began to Europeanize and resemble the markets of developed countries. Russia has also become attractive in terms of entering the markets of neighboring countries (CIS countries and Asia).

The most important characteristic of the Russian pharmaceutical market is the controlling role of the state, which is carried out through fairly strict licensing and certification, legislative restrictions on the advertising of medicines, and the organization of drug sales. Compared to other countries, Russia has a more significant share of government procurement of pharmaceuticals.

In general, Russian pharmaceutical production has serious investment attractiveness. Moreover, domestic pharmaceutical manufacturers achieved such a position in the industry by relying solely on their own strength and without special access to external investment. They managed to reverse negative trends and move towards qualitative and quantitative growth. According to the Pharmexpert marketing research center

Problems of the pharmaceutical industry

Two systemic problems of the Russian pharmaceutical industry should be noted. Firstly, this is the low level of provision of the population of the Russian Federation with affordable and high-quality domestically produced medicines, which is a threat to national security. Secondly, the low level of innovation and technology used in the development and production of medicines. This general problem of the Russian economy is fully characteristic of its pharmaceutical sector. The constituent factors of systemic problems are:

1. Lack of a national concept for the development of the pharmaceutical industry.

2. Lack of funding mechanisms for drug development.

3. Many gaps in critical chains of interactions that ensure the creation of new domestic innovative brands.

4. The absence of large national pharmaceutical companies capable of determining the strategic development of the industry and fulfilling government orders to ensure drug safety.

5. Regulatory barriers to the creation of new drugs, insufficient predictability of the pharmaceutical market.

6. Insufficient level of Russian patent legislation and law enforcement practice relative to international standards.

7. The continuously depleting human resources potential of domestic science and production.

Analysis of the competitive situation in the Russian pharmaceutical market

The pharmaceutical industry in Russia is of strategic importance both for the current supply of medicines to the population and, accordingly, maintaining the level of health at an acceptable level, and for the long-term provision of economic and political security of the state. Traditionally, pharmacy has such characteristics as innovation, science intensity, low price elasticity, high barriers to entry, and monopoly power on unique patented drugs.

The Russian pharmaceutical industry is characterized by high imbalances between exports and imports, a high proportion of counterfeit, low-quality products that threaten the health of consumers, and excessive “regulation”. The main consumers of the pharmaceutical industry are the least socially protected segments of the population.

According to Professor of Pharmaceutical Sciences, Deputy Director of the Research Institute of Pharmacy for Scientific Work I.A. Samylina, one of the ways to improve the situation here is the comprehensive, integrated development of competition.

Global changes that have occurred over the past decades in the Russian pharmaceutical market, accompanied by the denationalization of property, an increase in the number of pharmaceutical market entities (especially in the wholesale and small retail chains), price liberalization, and an increase in the range of goods and services sold by pharmaceutical enterprises, have led to the need to acquire new knowledge in the field. survival in a competitive environment.

The increase in the number of pharmacies was one of the reasons for increased competition in the pharmaceutical market. If previously the main market players were simply large pharmacies, now there is a rapid process of combining individual pharmacies into networks (mergers and acquisitions). In St. Petersburg, the obvious leader is the pharmacy chain “First Aid”; at the end of 2009, it was represented in 3 regions of Russia (St. Petersburg, Moscow, Yekaterinburg) and has about 200 pharmacies. According to the pharmacy chain "First Aid"

In addition, the range of goods sold has expanded significantly. Non-traditional groups of goods sold in pharmacies have appeared (dietary supplements, homeopathy, valeo-pharmacological preparations), and the traditional product group for pharmacies - medicines - has also become more diverse. The range of drugs has increased almost 3 times, largely due to the introduction of synonymous drugs from various manufacturing companies into the assortment list. According to www.labex.ru

Leading experts, such as Doctors of Pharmaceutical Sciences S.V. Pervushkin, and M.N. Ivashev believe that currently the leading strategy in enterprise management should be the strategy of competitive rationality, which represents targeted actions to find a sustainable advantage over competitors by satisfying consumer needs. This strategy is considered the modern concept of marketing.

Pharmaceutical industry development strategy

Based on Order of the Ministry of Industry and Trade of Russia No. 965 of October 23, 2009, “Strategy for the development of the pharmaceutical industry for the period until 2020,” the main goal of the state policy of the Russian Federation is to create conditions for its transition to an innovative development model, which should lead to an increase in the provision of the population and institutions healthcare and the Armed Forces of the Russian Federation, federal executive authorities, in which the law provides for military and equivalent service, domestically produced medicines, with a general increase in the provision of those in need with medicines to the average European level, both in terms of quantitative and qualitative indicators.

The main objectives of the Strategy are:

1. Increasing the provision of the population, healthcare institutions and the Armed Forces of the Russian Federation, federal executive authorities, in which the law provides for military and equivalent service, with vital and essential medicines of domestic production, as well as medicines for the treatment of rare diseases;

2. Increasing the competitiveness of the domestic pharmaceutical industry by harmonizing Russian standards for the development and production of medicines with international requirements;

3. Stimulating the development and production of innovative medicines;

4. Protection of the domestic market from unfair competition and equalization of market access conditions for domestic and foreign manufacturers;

5. Implementation of technological re-equipment of the Russian pharmaceutical industry;

6. Improving the system for confirming the quality of medicines, including measures to eliminate excessive administrative barriers to registration of domestic medicines;

7. Training of specialists for the development and production of pharmaceutical products in accordance with international standards.

The development strategy of the national pharmaceutical industry is based on the following priorities:

Priority of an innovative model for industry development;

Priority to the quality, effectiveness and safety of medicines;

Priority of the national pharmaceutical industry in the implementation of state programs in the field of provision of medicines;

Priority for the production of high-tech pharmaceuticals

substances on the territory of the Russian Federation;

Priority for the development of export-capable industries and new developments;

Priority for replacing imported medicines with domestic ones, the full production cycle of which is located on the territory of the Russian Federation;

Priority of pharmaceutical products produced on the territory of the Russian Federation in procurement according to the list of vital and essential medicines, as well as in the supply of medicines for the Armed Forces of the Russian Federation, federal executive authorities, in which the law provides for military and equivalent service.

The expected result of the implementation of the Strategy for the Development of the Pharmaceutical Industry of the Russian Federation for the period until 2020 should be:

Increasing the share of domestically produced products in the total volume

consumption in the domestic market up to 50% in value terms by 2020;

Changing the range of production of medicinal products produced on the territory of the Russian Federation, including increasing the share of innovative drugs in the portfolios of local manufacturers to 60% in value terms;

Increase in exports of pharmaceutical products by 8 times compared to 2008;

Ensuring drug safety of the Russian Federation in accordance with the nomenclature of strategically important drugs and vaccines.

Stimulating the organization of production of pharmaceutical substances on the territory of the Russian Federation in the amount necessary to ensure the production of 50% of finished dosage forms in monetary terms, including at least 85% of the nomenclature from the list of strategic drugs.

Today, the development of the pharmaceutical industry is a strategic direction for the development of the national economy and healthcare. The profitability of the pharmaceutical industry in terms of net profit is quite high. The development of a knowledge-intensive, innovative and investment-attractive pharmaceutical industry can become one of the engines of the Russian economy, a source of growth in the country's GDP and a channel for the influx of large investments into the domestic economy.

To increase the internal and external competitiveness of the Russian pharmaceutical industry, increase the provision of citizens and healthcare institutions with domestically produced medicines, the National Strategy for the Development of the Pharmaceutical Industry until 2020 (Pharma-2020) was developed.

Based on the relevance of the issue of effective development of the Russian pharmaceutical industry, on March 29, 2016, the international forum “Pharmevolution 2016. Building an environment for pharmaceutical innovations in Russia: challenges and prospects” was held in Obninsk, organized by the business newspaper “Vedomosti” together with the government of the Kaluga region, the Agency for Innovative Development "Cluster Development Center of the Kaluga Region" with the support of the Kaluga Pharmaceutical Cluster.

Assessing the prospects for the development of the Russian pharmaceutical industry, the conditions for ensuring the leading positions and competitiveness of pharmaceutical companies, which are impossible without the introduction of the latest technologies, and the influx of new investments by increasing the investment attractiveness of the industry are the most important issues that require solutions for the effective development of the country's pharmaceutical industry.

The problem of investment attractiveness of the pharmaceutical industry largely depends on systemic support and sufficient financing, investment in innovative developments, and the development of pharmaceutical clusters. According to the governor of the Kaluga region, Anatoly Artamonov, the localization of pharmaceutical production in Russia is paramount. For example, the pharmaceutical cluster created in the Kaluga region has a full production cycle, starting with scientific research and ending with the disposal of used pharmaceutical products. The economic benefits of investing in the pharmaceutical industry today are as obvious as their importance for improving public health. The authorities of the Kaluga region provide all possible assistance for the location and effective functioning of pharmaceutical production on their territory. And they continue to plan to locate new pharmaceutical enterprises in the region.

The cost of drugs is a strategically important factor in the successful development of the domestic pharmaceutical industry, especially for VED drugs. The issues of political pricing and import substitution in Russia, the problem of compulsory licensing, issues of revaluation of drugs in pharmacies, the topic of cheap drugs and government support require close attention. Elena Maksimkina, Director of the Department of Drug Supply and Regulation of Circulation of Medical Products of the Ministry of Health of Russia, analyzing the Russian drug market, reports that the department she heads currently administers almost 93 billion rubles. for drug provision of the population, about 40 billion rubles. falls on the program for high-cost nosologies. Therefore, you need to think that when a drug becomes so expensive, it is possible to replace it. The topic of centralizing the procurement of medicines in accordance with the instructions of the President of the Russian Federation on the centralization of procurement of drugs against HIV, tuberculosis and hepatitis is very important, says Elena Maksimkina.

The main task is to make these drugs as accessible as possible. Regarding the problem of compulsory licensing, the position of the Ministry of Health is that it is necessary to consider any measures that will facilitate the availability of medicines for the population, but compulsory licensing is not the only correct way and a panacea; there must be a set of measures that would allow patients to receive affordable medicines. Currently, drug coverage of the population is about 25%, and according to WHO recommendations, it should be at least 60%.

The topic of import substitution, which concerns various sectors of the economy, is also very relevant for the domestic pharmaceutical industry. According to Olga Kolotilova, Director of the Department for Development of the Pharmaceutical and Medical Industry of the Ministry of Industry and Trade of the Russian Federation, after the adoption of the Strategy for the Development of the Pharmaceutical Industry in Russia in 2009, the production of medicines doubled and amounted to 231 billion rubles in 2015, the share of Russian medicines on the market is 27 ,18%, in 2013 it was 23%, in 2014 - 24% (in value terms). As of last year, the industry attracted about 120 billion rubles of its own funds, and the state attracted about 40 billion rubles from budgetary funds, i.e. For every ruble raised by the state, the industry independently raised three rubles. The share of Russian drugs from the list of vital and essential drugs is 72%; by 2018, according to the decree of the President of the Russian Federation, it should be up to 90%.

For the development of a competitive domestic pharmaceutical industry based on innovative technologies and scientific developments, the most important condition is the localization of leading pharmaceutical enterprises in the country. According to Kenneth Mortensen, Vice President, Plant Director of Novo Nordisk in Kaluga, the Russian Federation has made great strides in the field of healthcare in recent years. Today, the pharmaceutical industry is transitioning to a more modern model, reducing the country's dependence on imports. The operation of the high-tech Novo Nordisk plant in the Kaluga region for the production of modern insulins fully complies with the goals set in Pharma-2020: it helps to strengthen drug safety, transfer advanced technologies and improve the treatment of diabetes in Russia. Today, the company produces the entire range of modern insulins and provides the entire necessary volume of supplies of drugs for its patients in Russia.

Despite the difficult economic situation in the country, Novo Nordisk management is optimistic about the prospects for production development. Over the year, the number of employees employed in production increased from 150 to 200 people. The company's plans are related to increasing capacity and commissioning new production processes: the production of finished dosage forms of modern insulin preparations using the company's original substances. While emphasizing that diabetes is a complex problem, Kenneth Mortensen believes that addressing it in a sustainable manner requires the collaborative efforts of many stakeholders. For Novo Nordisk in Russia, the main goal is to increase the availability of modern insulin preparations to improve the lives of patients.

Today, the need for optimal transformations in the pharmaceutical industry is obvious. It involves the development of an innovative domestic pharmaceutical industry with effective mechanisms for financing innovative projects in the pharmaceutical industry of the Russian economy. Strengthening the innovative path will provide Russian pharmaceutical production with worthy competition to foreign manufacturers, both in domestic and foreign markets. As a result, a solid foundation for the national pharmaceutical industry will be created.

Volume of the Russian pharmaceutical market in final prices in 2015 - RUB 1.12 trillion(+10.34% compared to 2014).

Volume of production of medicines for 2015 at manufacturer prices – RUB 231.0 billion(+26.3% compared to 2014). Compared to 2009 (RUB 96 billion), production volume more than doubled.

The share of domestic drugs in the total volume of purchases under the “7 nosologies” program has increased since 2011 from 4.5% to 35,4% in monetary terms.

The share of domestic drugs according to the nomenclature of the list of vital and essential drugs is 72,4% (from the stage of production of the finished dosage form), which exceeds the planned figure by 69% (according to the State Register of Medicines).

The share of domestically produced medicines in monetary terms at final prices in 2015 in the total market volume – 27,2% (in 2014 – 24%).

Share of domestic drugs in market volume ( 5.5 billion packages) in physical terms in 2015 is 58% .

The share of domestic medicines in the total volume of government procurement was 25% in monetary terms and 69% in kind.

Over the past 5 years, the pharmaceutical industry has attracted over 120 billion rubles. private investments of foreign and domestic companies with a volume of federal budget funds in the amount of RUB 35 billion.

Opened in 2015 6 pharmaceutical factories. Totally open since 2013 19 pharmaceutical production sites, including 7 with the participation of foreign capital.

Production of medical devices in 2015 amounted to RUB 39.1 billion(+9.08% compared to 2014).

Exports of medical devices produced on the territory of the Russian Federation in 2015 amounted to RUB 3.2 billion(+13.7% compared to 2014)

Since 2011, the amount of actual costs incurred in implementing projects in the medical industry has been RUB 29.6 billion, of which: own funds RUB 14.4 billion; budget funds RUB 15.2 billion.

The Industrial Development Fund for 2015 in the field of the pharmaceutical industry was approved for financing 5 projects with total loan amount RUB 2.1 billion:

• JSC "Generium" - production of a drug for the treatment of rheumatoid arthritis;
• Geropharm LLC - production of pharmaceutical substances for the production of peptide and protein drugs;
• 2 project of JSC "R-Pharm" - production of drugs for the treatment of multiple sclerosis in syringes; production of pharmaceutical substances and drugs for the treatment of cancer;
• JSC "Pharmasintez" - production of pharmaceutical substances for drugs against tuberculosis and cancer.

By providing loans, the Industrial Development Fund supported 8 medical industry projects for a total amount RUB 1.8 billion:

1. Joint endoprostheses and other implanted medical products made of titanium alloys for orthopedics and traumatology.” Performer: Ilkom LLC.
2. Hip endoprostheses." Performed by ZAO NEVZ-CERAMICS.
3. Production of small-sized defibrillators of three types for use in public places, ambulances and intensive care vehicles, and medical institutions.” Performed by Altomedika LLC.
4. Creation of import-substituting production of innovative children's urinals for collecting tests." Performed by Paritet LLC.
5. Production of medical equipment for comprehensive equipment of multidisciplinary operating rooms, intensive care wards and intensive care units.” Performed by Modern Medical Technologies LLC.
6. Production of medical infusion filters based on a track membrane for use in pediatrics and neonatology, for anesthesia and chemotherapy.” Performed by Nano Cascade LLC.
7. Absorbent products for the care of sick and elderly people.” Executor: Hygiene-Service Med LLC.
8. Creation of a comprehensive high-tech production of woven-based dressings that meet the requirements of Russian and European standards.” Performed by KhBK Navtex LLC.

In 2015, 26 projects to organize the production of medical devices were financed from the federal budget for a total amount RUB 137.4 million

Funds from the federal budget were allocated for the implementation of projects to organize the production of substances RUB 199.8 million for 2015–2017 (antitumor agents, autoimmune diseases).

The List of organizations that have a significant impact on industries and trade includes 29 medical industry organizations. Of these, within the framework of the resolution of the Government of the Russian Federation - subsidizing the interest rate on loans to replenish working capital, support in the amount 78.39 million rubles. was provided 7 enterprises.

Resolution of the Government of the Russian Federation dated 02/05/2015 No. 102 “On establishing restrictions on the admission of certain types of medical products originating from foreign countries for the purpose of procurement to meet state and municipal needs” was adopted.

The Government of the Russian Federation adopted Resolution No. 1045 dated October 1, 2015, “On approval of the Rules for the provision of subsidies from the federal budget to Russian organizations to reimburse part of the costs of implementing projects for organizing and conducting clinical trials of drugs within the framework of the subprogram “Development of Drug Production.”

Resolution of the Government of the Russian Federation dated October 1, 2015 No. 1046 “On approval of the Rules for the provision of subsidies to Russian organizations to compensate for part of the costs of implementing projects for organizing and conducting clinical trials of implantable medical devices” was adopted.

The Government of the Russian Federation adopted Resolution No. 1047 dated October 1, 2015 “On approval of the Rules for the provision of subsidies from the federal budget to Russian organizations to compensate for part of the costs incurred in the implementation of projects for the organization of medicines and (or) production of pharmaceutical substances, within the framework of the subprogram “Development of the production of medicines” funds" of the state program of the Russian Federation "Development of the pharmaceutical and medical industry" for 2013–2020."

Resolution of the Government of the Russian Federation dated October 1, 2015 No. 1048 “On approval of the Rules for the provision of subsidies from the federal budget to Russian organizations to reimburse part of the costs of implementing projects to organize the production of medical devices” was adopted.

Decree of the Government of the Russian Federation dated November 30, 2015 No. 1289 “On restrictions and conditions for the admission of medicinal products originating from foreign countries, included in the list of vital and essential medicinal products, for the purpose of procurement to meet state and municipal needs” was adopted.

Resolution of the Government of the Russian Federation dated December 30, 2015 No. 1518 “On amendments to the state program of the Russian Federation “Development of the pharmaceutical and medical industry” for 2013–2020” was adopted; The new version of the Program provides subsidies to reimburse part of the costs of Russian organizations for the implementation of projects to organize the production of medicines and organize and conduct clinical trials of medicines.

The Government of the Russian Federation adopted Decree No. 1503 dated December 30, 2015 “On approval of the Rules for the provision of subsidies from the federal budget to Russian organizations to reimburse part of the costs of implementing projects to develop innovative medicines with similar pharmacotherapeutic effects and improved analogues.”

As of January 1, 2016, within the framework of the State program, it has been developed and brought to market 29 medications. The production volumes of medicinal products developed under the Program in 2015 exceeded 5 billion rubles. In 2015 the following were registered:

• Natamycin (antifungal antibiotic, indicated for vaginitis, vulvitis, vulvovaginitis caused by fungi of the genus Candida);
• Valganciclovir (an antiviral drug indicated for CMV retinitis in patients with AIDS, as well as for the prevention of CMV infection after solid organ transplantation in patients at risk);
• Acetazolamide (a diuretic, used for edema syndrome, attacks of glaucoma, etc.);
• Methylprednisolone aceponate (for the treatment of inflammatory skin diseases: atopic dermatitis, eczema, childhood eczema, simple contact dermatitis, etc.);
• Norepinephrine (acute decrease in blood pressure during trauma, surgery, poisoning, moderate cardiogenic shock);
• Salmeterol + Fluticasone (combined bronchodilator, indicated for regular treatment of bronchial asthma, for maintenance therapy for chronic obstructive pulmonary disease);
• Trastuzumab (Disseminated breast cancer);
• Bevacizumab (Metastatic colorectal cancer).

As of January 1, 2016, it was registered under the Federal Target Program 17 medical products (including 5 medical devices have passed voluntary registration):

• an automatic smear coloring machine with the ability to implement the Papanicolaou method for processing preparations with a set of dyes and reagents;
• apparatus for histological processing of tissues;
• apparatus for hypo-hyperoxytherapy;
• artificial lung ventilation device with adaptation of mechanical ventilation parameters based on biofeedback signals;
• hemostatic agent Hemoflex Pro;
• hemostatic agent Hemoflex Combat sterile;
• polymer heart valve prosthesis “EvRos-MI”;
• biological heart valve prosthesis “MEDING-BIO”;
• full-flow prosthetic heart valves “MEDING-ST” made of pyrolytic carbon with an attached cuff, with accessories;
• cryosurgical apparatus and a set of cryoinstruments for abdominal surgery;
• range of motorized and automated microtomes;
• vacuum tubes for collecting venous blood;
• automated diagnostic PCR complex;
• biological endoprosthesis “Hernioplant”;
• osteoplastic matrix “Bio-Ost”;
• model range of thermostats for histology;
• combined effect physiotherapeutic device.

Comparative analysis of data on the pharmaceutical industry for the period from 2011 to 2015

* vital and essential medications
** state program of the Russian Federation “Development of the pharmaceutical and medical industry” for 2013-2020.