CIS GMP news 2 (3) / autumn 2018

Nikolai Bespalov

Albert Karimov

Rate of import substitution and localization

Government support can multiply companies’ R&d budgets

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36

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Theme of the Issue:

44

The “Pharma-2030” Strategy

Novo Nordisk Insulin Full-Cycle Production Launched in Kaluga

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No 2 (3) / Autumn 2018

CIS GMP news

EAEU & CIS PHARMACEUTICAL INDUSTRY AND CURRENT GMP TRENDS REVIEW

RAFARMA – Full-Cycle Pharmaceutical Enterprise see page 72

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with the support of:

CIS GMP news

2 (3) / autumn 2018

“We create a business alliance between the EU a CIS pharmaceutical markets”

We have launched a new website and design of our unique distribution portal www.imcopharma.com www.imcobuy.com

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supported by

In 2018, IMCoPharma company has celebrated several important moments in its history – 25 years ago, the company "Ivan Mikes – IMC" had been founded, which was transformed into the company "IMC Ostrava a.s." in 2011. Later the company "IMCoPharma a.s." successfully joined its activities, celebrating this year the 10th anniversary of the company's modern history.

One of the siginificant moments in the development of the company this year has been the finalization of the 2nd stage of reconstruction of the administrative and logistics complex, which started to be restored in 2013.

Currently, the company has real estate of more than 15,000 m2, as well as warehouse and office space of about 4,300 m2. These are necessary for favorable conditions and further development of the company "IMCoPharma a.s.", which is nowadays the leader of the group of companies "Vivesa".

Another important goal that has been achieved this year is the connection to the direct operation of the CRM Dynamics 365 information system, which is important both for a more efficient solution of business processes and for trading activities.

Thanks to such software deployments, company employees can optimally respond to the increasing pressure from the market related to the quality, speed and range of services provided, which is associated with

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increase in profits, the number of customers and their requirements.

The goals of IMCoPharma for the near future are focused, first of all, on the interests of customers, both on suppliers and consumers. The company directs its investments to improve the quality of IMCoPharma´s services, namely: increase of capacities and assortment, speed of processing and delivery of

State Institute of Drugs and Good Practices

the order, accuracy and reliability of service, as well as increase of knowledge and competence. In addition to the aforementioned expansion of warehouse and administrative premises, the staff focuses on improving regulatory support for the products delivered to the CIS countries through the unique imcobuy web portal for APIs and excipients used in the pharmaceutical industry.

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CIS GMP news

2 (3) / autumn 2018

Pharmaceutical Industry Magazine

CIS GMP News Specialized publication dedicated to Good Manufacturing Practice, modernization of pharmaceutical production, and modern pharmaceutical manufacturing technologies This issue was published with the support from Federal Budgetary Institution “State Institute of Drugs and Good Practices”

Published by GMPnews.Net s.r.o.

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Editorial board

Redakce

Executive Director Irina Litovkina, i.litovkina@gmpnews.net

Výkonný ředitel vydání Irina Litovkina, i.litovkina@gmpnews.net

Editor-in-chief Vyacheslav Fedorenko, v.fedorenko@gmpnews.net

Šéfredaktor Vyacheslav Fedorenko, v.fedorenko@gmpnews.net

External Editor Michal Avdonin, m.avdonin@gmpnews.net

Redaktor Michal Avdonin, m.avdonin@gmpnews.net

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The opinions and views expressed by the authors in this journal are not necessarily those of the Editor or Publisher and, while every care has been taken in preparation of the journal, the Editor and Publisher are not responsible for such opinions and views, or for any inaccuracies in the articles.

Názory vyjádřené autory v tomto časopisu nemusí být nutně názory redakce a vydavatele. Redakce a vydavatel nenese žádnou odpovědnost za názory vyjádřené autory. Přestože byla věnována veškerá péče při přípravě časopisu, redakce a vydavatel nejsou zodpovědní za jakékoli nepřesnosti v článcích.

2 (3) autumn / 2018 *** Published biannually ISSN 2570-7191

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2 (3) podzim / 2018 *** Vychází 2× ročně ISSN 2570-7191

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Editor’s Note

CIS GMP news

Dear reader, The autumn issue of the magazine continues to report on the development of the pharmaceutical industry, its export opportunities, and future prospects. There is no doubt whatever about the fact that the era of GMP has already began, however, many challenges still remain both at the level of regulators, and at the level of manufacturers. Nevertheless, Good Manufacturing Practice Regulations are regularly reviewed and updated around the world, and that is as it should be. We are trying to follow the events taking place in the industry of the CIS countries, and reflect its current status on the pages of our publication.

In this issue, we would like to draw the reader's attention to the materials on the “Pharma 2030” draft strategy of the Ministry of Industry and Trade of Russia (Minpromtorg). Today, this topic is widely discussed among experts.

The article “The Pharma-2030” Strategy: Promoting Globalization” reveals the top priorities of the project of the federal target-oriented program “The Development of Pharmaceutical and Medical Industry”.

The analysis of the expert on the pharmaceutical market Nikolai Bespalov “Software-based replacement” is also focused on this issue. By using figures and facts, the expert consistently shows the unfolding situation with regard to the drug

production in Russia, and also draws attention to the problems that sooner or later will have to be solved, or it will not be possible to achieve the goals and objectives.

In the autumn issue of the magazine, we continue to publish reports from plants and factories, which were reconstructed, new production sites that were constructed, trains that were brought on stream, new technologies that were mastered; and share the experience of today's “good manufacturing practice” of modern pharmaceutical enterprises; draw the reader's attention to new developments and achievements; talk about important events related specifically to the pharmaceutical market.

The editorial staff would like to give thanks to all active authors, experts, specialists, representatives of press services of companies, translators, advisors – all those who prepared and provided unique material to the magazine. As editor-in-chief, I also would like to express my gratitude to all the employees who helped to create and release the autumn issue.

Many thanks to our partners! We always appreciate your cooperation and partnership. The editorial office of “CIS GMP news” hopes that the readers will enjoy reading this autumn issue. We are pleased to invite all individuals and companies to cooperate with us!

Vyacheslav Fedorenko Editor-in-chief

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CIS GMP news

2 (3) / autumn 2018Contents

Founder:

We work closely with our main partners to promote the services and expertise that they offer.

CIS GMP news magazine has a strong presence within their businesses as they do within ours.

EVENT ANNOUNCEMENTS

......... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 8-14 Dmitry Chagin: “What is Happening in Pharmaceutical Industry is Unprecedented!” . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16-17 Pharmtech & Ingredients ................... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 International Conference on Drug Development . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . 20 Discover the Russian Pharma Industry ..... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . 22 Penetrating the European Market

REGULATORY ISSUES

24-29 A. Meshkovski. On Regulation of the Pharmaceutical Market in Uzbekistan . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30-31 The “Pharma-2030” Strategy: Promoting Globalization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

GMP INSPECTION I. Gulyaev. Manufacturers’ Preparedness for Follow-Up GMP Inspections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

32-35

PHARMACEUTICAL MARKET N. Bespalov. Substitution Policy Rate of Import Substitution and Localization

36-41 A. Prokopiev. How to Protect People from Counterfeit Medicines ...................................................... 42-43 Government Support Can Multiply Companies’ R&D Budgets .......................................................... 44-49 Kaluga Pharmaceutical Cluster ........................................................................................... 50-55 on Russian Pharmaceutical Market ......................................................................................

LOCALIZATION

56-57 Successful Localization in Russia ......................................................................................... 58-59 Pharmstandard Released the First Batch of the Innovative Drug ........................................................ 60-61 R-Pharm and AbbVie Announce the Launch of Full-Cycle Production of Kaletra® in Russia ......................... 62-63 Wörwag Pharma has Localized Manufacture of Magnesium Orotate at the Facilities of PIQ-PHARMA .............

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supported by

State Institute of Drugs and Good Practices

CIS GMP news

Exclusive partners:

Takeda to Produce Innovative Drug for Multiple Myeloma Patients in Yaroslavl, Russia

................................ 64-66

CONTRACT MANUFACTURING

.............................. 68-71 Full-Cycle Pharmaceutical Enterprise .................................................................................... 72-75 AVVA RUS Invites for Long-Term Cooperation in the Field of Contract Manufacturing

GOOD MANUFACTURING

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76-81 Full-Cycle: From Substance Manufacture to Original Drug Product Release . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82-87 Petrovax Pharm has Launched Production of Grippol® Quadrivalent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88-90 Novo Nordisk Insulin Full-Cycle Production Launched in Kaluga

PACKAGING AND MARKING

M. Khazanchuk, E. Belov. Track & Trace in Russia: Race for Survival . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 92-96

MEDICINE DEVELOPMENT

Innovative Drug Development of the Kazan Federal University . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 98-99 B. Sysuev, A. Rudko. How can the Russian R&D Industry Help the Global One?

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 100-101

EXHIBITIONS, FORUMS, CONFERENCES ............................. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ........ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

III All-Russia GMP Conference with International Participation in Kazan . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Russia's BIOTECHMED Conference – an International Hit . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

ACHEMA 2018. Final Report

GMP news in Partnership with ACHEMA 2018

102-104 105-107 108-119 120-125

ABOUT GMP NEWS

. ....................................... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126 Media Partnership ....................................... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126 About GMP news

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CIS GMP news

2 (3) / autumn 2018 Event Announcements

Penetrating

the European Market

10 September 2018

As a part of CPhI Worldwide 2018, a collective exposition of Russian pharmaceutical companies will be displayed.

The Russian pavilion (stand № 12F40) is operated by S.GROUP Corporate Communications LLC. On 9 to 11 October, 2018, Madrid (Spain) will be hosting CPhI Worldwide 2018, the 29th global pharmaceutical exhibition and the world’s leading event in the industry.

Exhibiting under the auspices of the Ministry of Industry and Trade of the Russian Federation, Russia will be represented by thirteen pharmaceutical companies, including both well-known players of the domestic and global pharmaceutical markets and those who have started conquering these markets relatively recently. The joint exposition of pharmaceutical manufacturers is one of the effective measures to promote non-commodity exports.

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GEROPHARM

GEROPHARM At the exhibition, the company will present some proprietary genetically engineered human insulins produced on a full-cycle basis, i. e. from synthesis of a substance to a finished dosage form, as well as medicine alternatives to insulin manufactured by only a few pharmaceutical companies in the world.

The objective of the company is to find partners interested in marketing Russian insulins locally. Currently, the distribution of products manufactured by GEROPHARM covers 12 neighbouring countries, with European markets next in turn.

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CIS GMP news

2 (3)Â / autumn 2018

NANOLEK The company boasts extensive experience in the implementation of projects with global biopharmaceutical partners on the joint development, licensing, technology transfer and localisation of medicines for the prevention and treatment of socially significant human diseases.

At the moment, the company demonstrates dynamic growth of its

presence in the CIS countries, and plans to penetrate the markets of non-CIS states in the future. For the company, CPhI is one of the tools for searching local partners from different countries with high export potential.

Besides, the company is willing to establish partnerships to bring new hightech pharmaceutical products that allow localisation and technology transfer on a full-cycle basis to the Russian market.

PERM CHEMICAL COMPANY In 2017, exports of the company accounted for 89 % of its total revenues. The company products were exported to Japan, USA, Ireland, Great Britain, Germany, Korea, and India.

PCC LLC demonstrates its expertise in customised synthesis, primarily the synthesis of organic, organic fluorine and iodine compounds, and in the development of synthesis technologies, from experimental laboratory synthesis to pilot batches.

NOVAMEDICA INNOTECH NovaMedica Innotech is a first-timer at CPhI WorldWide. This is the first opportunity for the company to introduce its products to the European market. NovaMedica Innotech Technology Centre opened its doors in April 2017 in Moscow. It possesses a unique range of innovative technology platforms for the development and pilot production of advanced, competitive, and effective pharmaceuticals.

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NovaMedica Innotech

At present, the company has around 20 research projects in progress, including those under contracts with Russian and foreign partners. One of the targets on the roadmap is to expand the scope of its international cooperation. Besides, NovaMedica Innotech offers its manufacturing facilities for the localisation of high-tech dosage forms in Russia, which may be of interest to global companies applying for public procurement programmes.

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SOTEX Visitors will get the chance to find out more about Sotex pharmaceutical products, which include medicines for the treatment of nervous system disorders, musculoskeletal disorders, renal failure, influenza, and acute respiratory viral infections. Each of them is manufactured in compliance with the European GMP standards, which facilitates

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distribution of these products on the Western markets.

So far, the company has conquered fifteen markets. Alongside proprietary production, Sotex is just as actively involved in technology transfers. This exhibition will become an excellent platform for negotiating with existing partners and making new business contacts with representatives of the global pharmaceutical industry.

Active Component

ACTIVE COMPONENT Active Component has been successfully operating on the market for over 10 years and is one of the major Russian manufacturers of generic active pharmaceutical ingredients. Substances produced by the company are supplied to the EAEU states and abroad.

Active Component collaborates with international pharmaceutical giants,

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such as Abbott, STADA, Polpharma, etc.

With the launch of a new plant, by 2020 the volume of exports is expected to grow from 10% to 25%, which is more than double. The new manufacturing facilities will enable Active Component to expand its product range by 10 items a year. The company intends to negotiate with potential partners and offer cooperation opportunities on a number of items for further production.

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CIS GMP news

2 (3) / autumn 2018

PETROVAX PHARM One of the strategic goals of the company is the expansion of its export potential and geography of sales. In 2017, the share of exports in the company sales accounted for 11.2%. Pharmaceutical products are shipped to 11 foreign countries, including the states of the Eurasian Economic Union, the European Union, and Iran. The company expects to expand its presence on the existing markets, and penetrate the markets of the EU, the Middle East, North Africa, and Southeast Asia.

Petrovax Pharm specializes in the manufacturing of original pharmaceuticals, including both proprietary products,

and products developed in collaboration with local and foreign companies. The exhibits will include the whole range of proprietary products such as adjuvanted influenza vaccines, including the first Russian quadrivalent inactivated subunit adjuvanted influenza vaccine Grippol® Quadrivalent.

MATERIA MEDICA HOLDING None of the company’s pharmaceutical products has alternatives in the world. The company exports its medicines to 16 countries, which accounts for 15% of its overall production. The manufacturer’s pool of medicines includes innovative pharmaceuticals for the treatment of acute respiratory viral infections and flu, stress and anxiety, and erectile dysfunction. Among other things, Materia Medica will present its one-of-a-kind calming medicine specifically engineered for children considering their peculiar mental behaviour, which can be used by children aged 3 and older.

Petrovax Pharm

USOLYE-SIBERIAN CHEMICAL AND PHARMACEUTICAL PLANT The company is actively engaged in cooperation with the CIS states, such as Belarus, Uzbekistan, Ukraine, Georgia, and Armenia, and is planning to export its products to the Kyrgyz Republic and the EU countries. One of the key targets for the company now is to enter the global pharmaceutical market. To this end, the plant is not only improving the existing manufacturing technology, but is also developing new methods of synthesis to make the production cost significantly lower.

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The company portfolio includes 73 active pharmaceutical ingredients, including psychoactive, and some of the vital and essential medicines, which will be displayed at the exhibition in Madrid.

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GENERIUM The company is actively engaged in the development of its global business: the pharmaceutical products are subject to marketing authorisation in the

State Institute of Drugs and Good Practices

countries of Latin America, Southeast Asia, and the Middle East. Export of supplies to Venezuela is already in place. The participation in CPhI Worldwide on an annual basis allows the company to hold dozens of meetings with its foreign partners to discuss ongoing projects and prospects for cooperation, and, of course, to make new contracts.

Consistent interest in Generium from abroad ensures in-house manufacturing of biotech products for the treatment of rare diseases, which is at the cutting edge of the pharmaceutical industry and is in high demand all over the globe. In Madrid, the company is going to present its Recombinant Clotting Factor VII for treating inhibitors in patients with haemophilia.

There are only two more companies that manufacture it alongside Generium. Another development of the company is Diaskintest, a one-of-a-kind innovative medicine designed for the screening diagnosis of tuberculosis.

Generium

AVVA RUS The highest priority of the company’s business is the development of innovative pharmaceutical products with a unique patient safety

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profile. The company obtained a European certificate of compliance with Good Manufacturing Practices (GMP EU) for the manufacturing of pharmaceutical products for human use, having proved that its products conform to the highest quality standards. One of the advantages of the company’s products is the presence of lactulose, i. e. a prebiotic that supports the indigenous gut flora and promotes the growth and development of native beneficial bacteria.

This combination enables the medicines to have comprehensive therapeutic effect on the body.

At the moment, AVVA RUS pharmaceutical products are present in most CIS countries, with some of the products (including one beta-lactam antibiotic) subject of the process of obtaining marketing authorisations for distribution in the European Union. Moreover, the company has extensive experience in contract manufacturing and regulatory support services.

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CIS GMP news

2 (3) / autumn 2018

SAMSON-MED Today, Samson-Med is one of the most dynamic pharmaceutical companies in Russia. It is delivering a unique investment project for the construction of a GMP compliant pharmaceutical plant. The manufacturing facilities of the investment project allow us to develop and implement the programmes and contract manufacturing of various dosage forms and pharmaceutical substances.

The portfolio of the Company includes active pharmaceutical ingredients and finished dosage forms representing various pharmaceutical groups, such as proteases, enzymes, immunostimulants, metabolic and anti-inflammatory agents, and urological medicines. One of the top-priority areas of Samson-Med’s business is the development of the company’s export potential and expansion of the share of international supplies. In 2017, the top five countries the company exported its drugs to included Mongolia, the Kyrgyz Republic, Uzbekistan, Azerbaijan, and Belarus.

PIQ-PHARMA

PIQ-PHARMA The company has been offering its products both on the Russian market and in the CIS states for 25 years. At CPhI Worldwide 2018 in Madrid, PIQ-PHARMA presents comprehensive services for contract manufacturing of solid and liquid non-sterile dosage forms at a new, fully GMP-compliant manufacturing site, and also plans to present its new capabilities for contract manufacturing of pharmaceutical products on the premises of the Technology Laboratory PIQ-PHARMA TECH. PIQ-PHARMA is not only interested in cooperation with suppliers of active pharmaceutical ingredients and excipients, but also with potential customers interested in services such as pharmaceutical development, contract manufacturing and localization, as well as with suppliers of solutions for launching innovative products on the Russian market.

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State Institute of Drugs and Good Practices

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CIS GMP news

2 (3) / autumn 2018 Event Announcements

Dmitry Chagin: “What is Happening in Pharmaceutical Industry is Unprecedented!”

Honorable collegues!

WE INVITE YOU TO PARTICIPATE IN "LIFE SCIENCES INVEST PARTNERING RUSSIA" THE VIII ANNUAL INTERNATIONAL PARTNERING FORUM November 14-15th, 2018, St. Petersburg, Russia.

We warmly welcome all of you!

Dmitry Chagin

Director of the «Medical Pharmaceutical Projects. The 21st century» Union

14 September 2018

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Firstly, we are going to talk with Dmitry Chagin, the director of the "Medical Pharmaceutical Projects. The 21st century" Union, an organization that unites manufacture, educational and scientific institutions in St. Petersburg. Our topic today is the importance of the forum for the market and its participants www.gmpnews.net

supported by

Dmitry Alexeevich, why did you choose Saint-Petersburg as the hosting city for the Forum?

Saint-Petersburg is the leader for a number of projects in the Pharmaceutical industry in Russia and the Eurasian Union. And this is not surprising, as the fact that this city is the place where there is a huge scientific potential and a large part of advanced developments is concentrated; about 30 universities are taking part in the implementation of the industry development program. Therefore, appearing of the new projects of large companies, both domestic and global are absolutely clear.

It seems that over the years, Russian Pharmacy has gone through international expansion, is this true?

The expansion in pharmaceutical industry for last three years is unprecedented! The level of scientific knowledge, technical support, evaluation and collection of large data is incredible. It was not possible to get such deep analysis. The companies got stronger! Initially if we talk about bioanalogs and generics within the framework of import substitution, and at the same time there was no significant success in the development of original drugs, now companies develop such molecules that are in different phases of preclinical and clinical trials.

The cluster policy has given huge opportunities for development in St. Petersburg. The companies conduct their own research in the special economic zones, for instance, more than half of the employees are involved in scientific development in Biocad. Today, the development of the Russian market of pharmaceutical substances, characterized not only by large production volumes, but also by the creation of science-intensive, patentable technologies in the production of expensive drugs for the treatment of rare diseases, is moving to the forefront. Domestic companies have their own scientific developments and projects that can be related to both independent activity and subsequent transfer of technology. Many Western companies understand that it is impossible to play by the old rules, when you just deliver drugs or are engaged in packaging of drugs.

What is the Cluster's contribution to the development of companies?

Our common goal is the development of full-cycle companies producing

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drug products, starting with the substance synthesis of the active pharmaceutical ingredients before the release of the finished dosage form. Now, two similar projects are already being implemented – these are the "Active component" and "Baltfarma".

When forming the Strategy for the Development of the Pharmaceutical Industry until 2030, the main issue is that government support is needed for companies that will allow to develop the export opportunities of the domestic pharmaceutical industry, as well as stimulating companies to conduct research and development. The structure of the Russian market has undergone significant changes in recent years, but first of all, these changes occurred in the government procurement. One of the objectives is to reach an agreement on securing the state order not for three to five years, but for a much longer period. After all, a number of drugs requires a long time for preparation, for example, the release of vaccines is preceded by two to three years of technological regulations.

State Institute of Drugs and Good Practices

produce not ephemeral things, but substances for saving lives. I am glad that in the medical community, there are fewer prejudices about the insufficient quality of domestic medicines.

The state program has already had a tremendous effect in the pharmaceutical industry and now we are working in the mode of "import substitution", projects in the field of cellular technologies and biomedical cellular products, monoclonal antibody drugs are being carried out.

The success of their major product consolidate the film’s position in the market of Russia and Saint-Petersburg.

Is there a lack of employees in the industry ?

Today, St. Petersburg gives huge opportunities for the use of infrastructure by the city government, the Committee on Industry and Innovation provides support, subsidies, compensation, and technical support. The development of pharmaceutics is a complex scheme, scientific and cultural methodology, which unites a number of specialties: chemists,

Our common goal is the development of full-cycle companies producing drug products, starting with the substance synthesis of the active pharmaceutical ingredients before the release of the finished dosage form

The transition to procurement at the expense of budgets for all levels is fundamental, including additional preferences in the amount of at least 25% of the initial maximum contract price for the production of the full cycle or from local substances. With the volume of the public procurement market of 400 billion rubles annually, these are huge additional resources in the tasks implementation of sectoral development, in addition to the resources of the core state program. It is important for us not just to produce the drug, but to understand that it will be in demand and timely.

The personalized medicine is another new direction, when drugs are selected, taking into account individual characteristics of an organism, for a specific patient. We closely cooperate with the medical and patient community; we

mathematicians, bioinformatics. Therefore, it is extremely important to train new personnel. We create a holistic organism together with universities, with companies, with a cluster, technology parks, and city committees.

Students of biomedical classes visit factories, laboratories – this is an opportunity to interest young people in specific areas. We see the influx of young talented students into the industry. We track gifted youth and involve them in scientific work since school days. We have interesting youth projects in the relevant – areas, for example, Pharma Slam, where students choose topics of interest to them by themselves. Now it is obvious to everyone that pharmaceutics is modern research, that is interesting to do and that you can devote your life to!

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CIS GMP news

2 (3) / autumn 2018 Event Announcements

Pharmtech & Ingredients 12 September 2018

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The 20th anniversary international exhibition of equipment, raw materials and technologies for pharmaceutical production – Pharmtech & Ingredients will be held on 20-23 November 2018 in Russia, Moscow, Crocus Expo IEC!

ast year, the exhibition hosted more than 7,500 visiting pharma professionals from 41 countries and 61 Russian regions over four days. More than 400 exhibitors from 30 countries gathered at the event to network and benefit from strengthening relationships with existing clients and met potential new ones.

“The exhibition has been held for 20 years already, and during this period, it had earned authority among specialists in the pharmaceutical and healthcare sectors. It is annually visited by professionals from Russia and other countries throughout the world, developers, manufacturers and distributors of healthcare products, manufacturers of pharmaceutical equipment, representatives of pharmacies, scientists, and others”, – Alexander Borisov, Сonsumer Market Development Committee Chairman, Chamber of Commerce and Industry of the Russian Federation.

Every sector of the pharmaceutical market is represented under one roof.

By September, more than 360 exhibitors confirmed participation, including more than 50 newcomers. Major companies like, Marchesini Group, Artlife-Techno, BASF, Capsugel, Comecer, FAVEA, Sartorius trust Pharmtech & Ingredients to

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help them meet the right customers and get huge brand visibility in Russia.

Exhibition is constantly developing: in addition to the national expositions of Germany and Switzerland, the exposition of India will be presented this year for the first time.

Visitors attending the exhibition will network with leading international pharmaceutical figures, source solutions from the entire pharma supply chain, and learn more about innovative trends of pharma growing market with FREE on-site content.

13th International Pharmtechprom Forum, to be held on 21-22 November, will focus on innovations and the most current trends in the pharmaceutical industry with 30+ hours of live content from industry experts and exhibitors.

Specialists of the companies DIOSNA GmbH, Servolift GmbH, Getinge GmbH, Franz Ziel GmbH accepted the speaking invitations within the

Round table “Materials transfer in the production process of sterile, hormonal, and highly toxic preparations”, organized by Pharmamixt company, to be held on 22 November. The questions of the safe product transfer, eliminating cross contamination, protection of personnel health, and validated cleaning processes of equipment will be discussed.

With so many industry leaders attending and so many new opportunities to build new business relationships at Pharmtech & Ingredients, can you really afford to miss out?

To attend Pharmtech & Ingredients FOR FREE – USE promo code pha18pGGNG to register now at www.pharmtech-expo.ru/en-GB We look forward to seeing you to the event on 20-23 November 2018, IEC Crocus Expo, 2 hall, Moscow, Russia!

Sponsor of the registration area

Silver sponsor

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CIS GMP news

2 (3) / autumn 2018 Event Announcements

International Conference on Drug Development

P

eoples' Friendship University of Russia (RUDN University) is a unique higher educational institution, a large internationally oriented educational and scientific center.

RUDN University is known in the world for its achievements in the organization of the educational process, innovative research in the field of fundamental and applied sciences, broad international connections.

RUDN University takes high places in international and Russian scientific ratings due to the active scientific work of the University’s scientists.

28 November 2018, RUDN University, Moscow

goals and objectives in the new knowledge development and promotion.

Maintaining the tradition of international cooperation, on November 28,

Slogan of the University is “Uniting people of different cultures, by knowledge RUDN University creates leaders to make the world better”

In 2015, RUDN University was among the competition winners to receive the state support within the 5-100 Project framework. The goal of Project 5-100 is to maximize the competitive position of a group of leading Russian universities in the global research and education market.

Over 150 science events are held annually in RUDN University. More than 14 thousand people take part in these activities including 15% of foreign participants.

The RUDN University’s scientific events are authoritative platforms for business communication among scientists, postgraduate and international students, thereby ensuring a possibility of testing scientific research results, setting new

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2018, RUDN University is holding an international conference with the participation of leading scientists in the field of pharmaceutical development of Russia, Germany, Switzerland, Finland, Israel, and other countries and with the participation of relevant federal ministries and departments. The main aims of the Conference are the exchange of scientific theories, concepts, hypotheses, innovative ideas, innovative approaches and modern practices; creation of international research teams.

Scientific and technological progress in the pharmaceutical industry is accompanied by the search, development, and continuous improvement of technologies for the production of active pharmaceu-

tical substances and pharmaceuticals. A modern trend in the development of the pharmaceutical industry is the building of a system of cooperation between industry and higher education. Within the framework of the conference, the following topical issues will be discussed: Integration of education, business and science: new scientific and educational practices and perspective models.

Current trends in effective cooperation with Russian and foreign partners in the field of pharmaceutical development.

Interaction and harmonization of good practices. Сlinical research. Personalized medicine.

Pharmacognosy and plant metabolomics in the development of natural origin medicines.

Use of green bioreactors for the production of monoclonal antibodies.

International practice of pharmaceutical development.

Participation in the international conference is free of charge.

We invite scientists, employees of Russian and foreign pharmaceutical companies to participate in the conference.

Additional information is available at pharmdevelopment.rudn.ru.

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CIS GMP news

2 (3) / autumn 2018 Event Announcements

Discover

the Russian Pharma Industry 17 September 2018

IPhEB Russia gives you the opportunity to showcase your brand to an international and domestic audience of pharmaceutical and nutraceutical manufacturers and providers, network with over 4,000 attendees, and stay up to date with all the latest industry knowledge.

IPhEB is the most Russian pharma event, hosting a wide range of exhibitors in the field of ingredients, APIs, functional supplements, finished dosage, machinery, equipment, technology, and outsourcing. This event is the unique opportunity to initiate business and build partnerships in the booming Russian and CIS pharma markets.

O

ver the past eight years, IPhEB Russia has become a traditional meeting place for the pharmaceutical industry professionals. Deputy Minister of Industry and Trade of the Russian Federation Sergey Tsyb noted that IPhEB Russia is a business platform for innovations, modern technologies and new approaches that

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could change the Russian pharmaceutical market.

The Russian pharma market is positioned at the forefront of pharmerging markets and is projected to reach the value of 31.2 billion USD by 2019. With Russia’s Pharma 2020 plan in mind, the country continues to rely on foreign partners in an effort to boost the domestic pharma industry.

There are many good reasons for exhibiting at IPhEB Russia 2019. So don’t miss out when your industry colleagues meet up in Saint-Petersburg.

The No. 1 marketplace for the pharmaceutical and healthcare industries.

Meeting hub with domestic and international industries partners and government institutions.

Interact with over 4 000 pharma professionals and key decision-makers.

Looking at the future – the latest pharma trends "live".

Russia is API producing country, looking for new partners and suppliers.

IPhEB Russia is the unique opportunity to initiate business and build partnerships in the blooming Russian market – don’t miss IPhEB Russia 2019, taking place at Expoforum, Saint-Petersburg on 2 – 4 April 2019.

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CIS GMP news

2 (3) / autumn 2018 Regulatory Issues

The “Pharma-2030” Strategy: Promoting Globalization

Until the end of the year, the Government of the Russian Federation should approve the program “Development of the Pharmaceutical Industry of the Russian Federation until 2030” (“Pharma-2030”), a document that will give the domestic pharmaceutical industry new directions for global development. While the goal of the previous “Pharma-2020” strategy program was the infrastructure development for pharmaceutical production, import substitution and stimulating innovations, in other words, laying the foundation for the domestic pharmaceutical industry, the new program is focused on large-scale market integration of domestic innovations in Russia, as well as export of drugs and technology transfer.

10 September 2018

P

Nanolek

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ublic discussions of the new strategy began at the beginning of July, when the Ministry of Industry and Trade of the Russian Federation published this document in the federal information system “Management”, and ended at the beginning of August. Within the next two months, the ministry should finalize the project, taking into account proposals and recommendations from the Chamber of Commerce and Industry of the Russian Federation, the Russian Union of Industrialists and Entrepreneurs, industry associations and market participants, and submit it for approval to all relevant agencies, after which it will be approved by the Government of the Russian Federation.

The new strategy will continue the course outlined in the previous document “Pharma-2020”, but it has already set more ambitious goals. Denis Manturov,

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Generium

the Minister of Industry and Trade, stated that among the priorities of the strategy will be “the breakthrough scientific and technological and socially-oriented development of the pharmaceutical industry, the creation of a high-performance export-oriented pharmaceutical sector and, as a result, in the volume of exports of drugs at least four times compared to 2017 – up to approximately $3 billion by 2024”. The level of the basic infrastructure of the domestic pharmaceutical industry, formed within the framework of the “Pharma-2020” strategy, opens up the possibilities of the expansion into the international market.

The main objective of the previous strategy presented in 2009 and estimated at that time at 188 billion rubles was to overcome the crisis in which the domestic pharmaceutical industry was in that period. According to the Ministry of Industry and Trade, the share of consumption of the Russian drugs was a little more than 20% of the market in monetary terms, and no more than 65% – in real terms. “Domestic manufacturers of drugs lose in market competition not

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only to the world's largest pharmaceutical corporations developing innovative products, but also to manufacturers of reproduced drugs and raw materials for their production mainly from China and India”, – the explanatory note to the “Pharma-2020” program says. Even in spite of the growing consumption of pharmaceutical products by the population of the Russian Federation on the whole as a result of the Health national project, the growth in the consumption of Russian drugs had been reducing every year by 1–2%.

The mid-2000s federal programs, for example, “Federal program on prevention and control of socially significant diseases” (2007–2011), “National technological base” (2007–2011) were focused mainly on the development of new technologies in the respective segments, but did not propose systemic organizational mechanisms that could integrate research results into industrial production and ensure large-scale introduction of innovations in the pharmaceutical industry. At the same time, one of the factors of the insufficiently high share of domestic

drugs in the market was the low technological level of the production capacities of pharmaceutical plants, which lagged behind modern production standards, and did not meet the international standards of GMP. So there were two critical problems for the industry at that time: a significant lag of the pharmaceutical plants in terms of technological equipment, which impeded the establishment of a stable output of competitive domestic products, as well as a lack of a system of government measures to stimulate domestic pharmaceutical production.

Accordingly, the key direction of the “Pharma-2020” strategy was the modernization of domestic pharmaceutical plants, their gradual transition to GMP standards, as well as the establishment of the domestic analogues of imported drugs (generic drugs) production and provision of conditions for the growth of domestic demand for Russian drugs.

Even then, part of the strategy was the development of the scientific potential of the Russian pharmaceutical industry, as well as the development and launch of innovative domestic products. The

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CIS GMP news

2 (3) / autumn 2018

Active Component

tools of the program were a set of state measures, including government contracts for the development of technologies for the production of drugs according to the list of strategically important drugs, vital and essential drugs (VEDs), and drugs used for the prevention and treatment of the most common cancer, cardiovascular, and other diseases; government subsidies for foreign innovative drug development and pre-clinical and clinical research; public funding for re-equipment and construction of the pharmaceutical plants, creation of pharmaceutical clusters on the basis of hightech plants, and much more.

According to Sergei Tsyb, the Deputy Minister of Industry and Trade, during the “Pharma-2020” program, realization of more than 400 projects for the creation of new drugs were supported, more than 100 molecules entered the stage of clinical trials, and 30 new pharmaceutical plants were built according to the most advanced international standards. Foreign pharmaceutical manufacturers built 7 new plants in Russia,

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and 78 foreign manufacturers localized their production on local plants. In particular, in the period from 2011 to 2014, the program included 130 government contracts for the development of technology and organization of production of the drugs included in the list of VEDs, for which in 2011–2015, 4.5 billion rubles from the federal budget and 8.2 billion rubles of extra-budgetary investments were raised. As part of co-financing from the government programs of the Russian Federation, 60 Russian competitive drugs, including new molecules – elsulfavirin (HIV), narlaprevir (tuberculosis), gosogliptin (diabetes mellitus) have been registered since 2009. The production of Russian medicines in the last 5 years has grown 1.7 times, and by 2017, the volume of this market was estimated at 295 billion rubles.

The activities of the program led to significant changes in the market. According to the DSM Group, the share of local drugs in the segment of public procurements in 2017 was already 30% in value terms, in hospital purchases in particular –

47%, and in the commercial market – 28.5%. According to the Ministry of Industry and Trade of Russia data on 1 August 2018, the share of domestic drugs in the nomenclature of the VEDs list reached 85.8% (in 2012 this figure was 63%)1.

A significant increase in the share of domestic drugs also occurred in the other segments: up to 36.65% in the 7 High-Cost Nosologies segment (10.2% in 2012), to 32.94% in the cancer segment (12.22% in 2012), to 29.66% in the HIV treatment segment (9.91% in 2012). According to the DSM Group, the increase in sales of local drugs in 2017 was significantly higher (7.4% in terms of value and 4.3% in real terms) than the increase in sales of imported drugs (6.1% in value terms and 2.3% in real terms). Thus, the activities of the “Pharma-2020” program enabled to reverse the unfavorable trend in the development of the domestic pharmaceutical industry, and create a basis for its further growth.

The new “Pharma-2030” strategy program, on the one hand, continues the course outlined in the previous document, on the other hand, it sets fundamentally new goals, especially with regard to the global development of the domestic pharmaceutical industry.

The strategy for the domestic market is focused on strengthening the positions of domestic products, the symbiosis of science, production and the market, the integration of innovations into practice, linking pharmaceutical production and the healthcare system in a broad sense. Accordingly, the project assumes linking of the production, educational and scientific infrastructure, providing the industry with sufficient raw materials, chemical and biological synthesis products and other materials, as well as stimulating full-cycle pharmaceuticals, including research laboratories and production lines.

According to the project of the strategy, these goals will be reached thanks to the new system of measures for regulating drug circulation in Russia. The document proposes, for instance, to establish a single regulator, “responsible for the entire scope of powers related to the health care system and drugs”, which would enable the state to achieve the most ef1 The share was calculated according to the presidential decree of 07 May 2012, No. 598 “On the improvement of public health policy”, which says that the volume of production of Russian drugs by the list of VEDs should be brought up to 90% by 2018.

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fective spending of budget funds. It is assumed that additional regulation will affect both public procurement and the commercial market of drugs. For example, the strategy proposes providing all pharmaceutical companies with a full cycle of a price preference of 25% for public procurement of drugs, which, according to the document, will attract additional investments of 50 billion rubles to this segment. In fact, the new strategy is more “patient-oriented” and focuses on bringing the innovations to the consumer.

The stimulation of the full-cycle pharmaceutical production is connected with another key point of the strategy: a significant increase in the volume of export of domestic pharmaceutical products to foreign markets, as well as the creation of joint ventures for the production of drugs in emerging markets.

According to the document, although the Russian pharmaceutical industry as of 2017 had insufficient representation in international markets, local plants are now successfully increasing their export volumes. For example, in 2017

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the volume of export of drugs reached $750 million, which is 16% more than in 2016. According to the Ministry of Industry and Trade of Russia, some of the Russian drugs are already registered in more than 60 countries, not only in the market of the Eurasian Economic Union, but also in South-East Asia, Africa and Latin America. Such international coverage should ensure a multiple increase in exports of Russian pharmaceuticals production by 2030.

According to the strategy, further export growth is possible, first of all, due to the development of innovative drugs in narrow therapeutic niches. A specialized venture fund is considered as a possible financial mechanism for further support of technological and industrial innovations. The establishment of such fund is especially important as the existing development funds demonstrated their inefficiency and are not able to provide necessary level of financing.

The ambitious task of increasing the export of local products should, of course, be accompanied by Russia's

large-scale integration into the international pharmaceutical community, for example, by participating in the International Conference Harmonization (ICH), so that exported local drugs can be included in relevant registers and validated abroad. In addition, according to the strategy, the export development is impossible without the protection system of drugs as objects of intellectual property when entering foreign markets. This task also should be in the focus of attention for the government program of pharmaceutical industry development.

In case of implementation of all proposed measures of government support, the volume of local drugs export, as it is said in the strategy, will increase significantly. Taking into account the goals set by the President of Russia in May 2018 to develop non-primary non-energy exports, and additional support measures being developed within the framework of the national project “International Cooperation and Export”, the fourfold growth in exports of local drugs is becoming more than real.

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CIS GMP news

2 (3) / autumn 2018

The pharmaceutical market has been actively discussing Pharma-2030 Strategy, which is currently being developed. The opinions and assessments that we hear are often quite different, if not diametrically opposite. The concept of the program must incorporate the interests of all market participants, including manufacturers, who must understand the general trend, the goals and objectives for further development, and the resources they have available for that work.

We asked Alexander Kuzin, General Director of NovaMedica Company, to share his opinion of the program as a representative of the manufacturing sector.

The main priority behind the Pharma 2020 program was localization and import substitution, and its main goal was to develop the pharmaceutical industry of Russia and to bring it to a higher level. We could call it the “first level.” And now that we have, in essence, successfully completed the first level, we are entering the second level, the Pharma-2030 program. Its objectives are far more complex. We can define several priority areas for the next stage. These priority areas will include development of R&D capabilities, increase of export, and stimulating production of own APIs; these are the tasks that we could not set before us 10 years ago; now this work is possible and the goal is achievable.

It is too early to say if Pharma 2030 will be able to solve these issues within this period of time. First and foremost because this is just a draft and the discussion is underway with market participants and inside the government. When we consider the opinions and interests of all market participants, and after we discuss the project strategy we will be able to come to a common understanding of the overall picture; it is then that we will be able to predict how much of the program is doable and in what timeframe these ends could be achieved.

But the overall picture also needs a frame: the rules that regulatory agencies establish. In the opinion of the market, as this strategy is amended, its authors will need to interact with the Ministry of Industry and Trade and other departments who will be setting the corresponding rules. These will include the Ministry of Health, the Federal Anti-Monopoly Service, the Ministry of Economic Development and the Ministry of Finance.

Without setting these boundaries that will define the route for implementing the program, we will be unable to understand the full picture. Speaking mathematically, this system of equations can only be solved when we determine the limiting conditions. As of today, the market is lacking this information, and we have no clear understanding of the rules of the game. Can a team score five goals? Perhaps, but we need to know if we will be playing hockey or football.

And now, to turn this document into an actionable program, the authorities will have to interact with the market. The pharmaceutical community has already provided feedback to

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the Ministry of Industry and Trade, and included a number of critical comments and suggestions. This is a very normal, natural process. It is excellent that the feedback in our industry is working, and that it has been of use. You cannot achieve the ideal result in just one go; it is therefore important that different participants of the process share their perspectives, and that everyone’s interests are taken into account. This is exactly what is happening now. Michelangelo had famously said that to create his masterpieces he had to take a slab of marble, and carve away what is extra. Metaphorically speaking, we have not carved the David of our industry yet; we are still in the process of creating it.

In essence, Pharma-2030 must be a logical continuation of Pharma-2020. For instance, whereas our previous goal was to localize production and guarantee import substitution, now the deeper form of localization will be the localization of R&D projects. Therefore, within the framework of the new strategy, it becomes important to take the next step and establish the regulatory process so as to create such an eco-system that will allow R&D activities in this country to become economically feasible and financially profitable. Moreover, it should appear lucrative to the global market as well. This is what, in my opinion, the 2030 program should focus on.

Now when it comes to preferences for Russian manufacturers, and in order to develop the export component, I believe the authors of the Pharma-2030 program must consider how much influence one has on the other, and diligently search for a balance point. I understand that Russian pharmaceutical companies would love to get the maximum protection and work under conditions of minimal competition inside the country, but they must understand that as a result, their global competitiveness will suffer. The competitiveness of our enterprises must take root inside the country; this is where it should start on its way to becoming stronger globally. Creating excessive preferences inside the country – what I would call “overprotection” – will do a poor service for Russian manufacturers in terms of developing their export potential. In such overprotective conditions, we will not be able to stand our ground against the aggressive external competitive environment or develop our

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capabilities more intensively. It is just like keeping a child away from bacteria: when parents keep their child in sterile conditions, they will not have the strong immune system necessary for further growth and adult life. The same can be said of any enterprise.

You cannot cover the entire Russian market with preferential conditions, and then ride onto the markets of other countries on the shoulders of the state. Local grants, regulatory measures, diplomatic or any other form of support inside just one country will not help, either. Those companies that are globally more competitive win on the global scale; this is the law of economics. So, if you ask me: “Is it okay to provide these preferenc-

State Institute of Drugs and Good Practices

es?” my answer would be: “Yes, but they must be very precisely defined in terms of conditions, numbers, and deadlines.”

Overall, I would like to see the Pharma-2030 program in its final version as a roadmap for our entire industry. It should reflect the future trends, and each manufacturer must be able to define its place in the system and understand precisely how to change and where to proceed, because this document will define clearly how the entire environment will change, and in which direction the entire industry must proceed.

This is why I believe that this document is of crucial importance and much needed by every pharmaceutical company in our country.

Denis Chetverikov, the President of AKRIHIN: At present, the elaboration of the strategy is the matter of numerous debates

What is, in your opinion, the fundamental difference between the Pharma-2020 and Pharma-2030 programs?

Even now, the new program provides for many essential and appropriate ideas, for example, exports and import substitution are prioritized over other matters.

Both areas of activity are critical for our company. We believe that export is a good opportunity for development of both the entire business, and our facility. Currently, Akrikhin’s products are mainly exported to the CIS countries; however, we aim at going beyond these limits and generally work on establishing an export development program for far abroad.

In my opinion, import substitution will be of current interest for many years as the share of imported drugs in Russia is still very large. At present, Akrihin is developing the so-called first-to-market-generics, i.e. generic drugs, the cost of which is less than the cost of alternatives, hence, they are expected to be more accessible. We are also involved in improvement of the drugs, which are already available in the market, developing new dosage forms and combinations.

Considering the Pharma-2030 strategy from the manufacturer’s viewpoint, do you think it is possible to achieve the goals and objectives provided for by the Strategy within the specified period of time?

I am not sure that we’ll succeed in achieving all of the objectives. However, every one of us understands that they must be addressed.

Are there any major deficiencies or problems with the developed Pharma-2030 program which must be addressed by regulatory authorities before certain goals can be set for the industry?

In my opinion, first of all, it is necessary to focus on establishing own manufacturing processes, and simplifying import of pharmaceutical substances. Today, even if a company has a Marketing Authorization for a new drug, but the substance is not registered, we cannot bring this drug into circulation, because we cannot import the substance required for its manufacture.

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Development of which areas of the pharmaceutical industry, in your opinion, shall be prioritized to take many other areas/divisions of the industry to an adequate level?

One of the key objectives of the new strategy is to provide the pharmaceutical industry with a sufficient range and amount of raw materials and supplies, first of all, with pharmaceutical substances, products of chemical and biological synthesis, and other materials used in the high-tech industry.

It seems to me that this is the first objective to be achieved.

It is necessary to set up production of Russian substances, however, of course, not all of the substances will be Russian. We cannot instantly switch to using domestically produced raw materials only; this is a time-consuming process requiring the utmost attention as well as improvement of both legislation and manufacturing processes.

Can we generally consider the Pharma-2030 program sort of a “roadmap” enabling us to understand the current position of certain manufacturers, developers, or investigators and their possible path forward?

At present, the elaboration of the Strategy is the matter of numerous debates. I hope that after adaptation, it will indeed be used as a “roadmap”. However, experienced market players do have a pretty clear idea of the positions of their own companies, as well as of the courses of their development.

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CIS GMP news

2 (3) / autumn 2018 Regulatory Issues

On Regulation

of the Pharmaceutical Market in Uzbekistan

Andrei Meshkovski

24 September 2018

In

Uzbekistan, the regulatory system in the area of medical products (pharmaceuticals, vaccines, sera, medical equipment) was recently reorganized. Innovative approaches are introduced in its functioning. Therefore it may be regarded as an evolving structure. Formally the National Regulatory Authority is the Agency for the Development of the Pharmaceutical Sector reporting to Ministry of Public Health.

The Agency was established by the Presidential Decree of 7 November 2017 on “Measures for the Radical Improvement of Governance over the Pharmaceutical Sector” (№ UP-5229).

According to the implementing Cabinet of Ministers (Government) Ordinance of the same date the structure of the Agency includes the Head office, provincial field offices, the State Centre for the Evaluation and Standardization of Medical Products, the National Chemico-pharmaceutical Research and Development Institute, the Research Centre for Vaccines and Sera, the Re-

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Sechenov 1st Moscow State Medical University, Moscow, RF

search Institute for Oriental Medicine and the joint stock company O‘zmedimpeks. The latter is responsible for import and export operations, tendering mechanisms etc. Under the previous structure, the Centre for the Evaluation and Standardization of Medical Products was a part of the Department for Quality Control of Pharmaceuticals and Medical Instruments, also within MoH. Status, functions, authority, and responsibilities of the Agency, as well as of its HQ and field offices were determined by the Government Ordinance of 18 December 2017 (№ 993). Its director is appointed by the President of the country. The office staff (HQ plus field stations) should not exceed the limit of one hundred posts. The director, jointly with the Health Minister, are accountable to the Cabinet and to the respective segment of the Presidential Administration.

The activities of the Agency are unusually diversified. For the purpose of the brief review below functions related to the Pharma sector may be grouped into the following major areas:

Regulation of the medical products market: product registration (MA), post-marketing QC and pharmacovigilance, GMP, GLP, and GCP audits (inspections), the pharmacopoeial programme, promotion of international harmonization of norms, standards, regulations and best practices. In respect of this activity, the Agency is supported by the State Centre for the Evaluation and Standardization of Medical Products. Its principle competencies are related to registration (marketing authorization), QC, and certification of medicinal products and medical instruments. In practical terms, the State Centre is the regulator.

Development of manufacturing capabilities: preparation and implementation of strategies and programmes for the strengthening of local Pharma industry, coordination and support of R&D of products that can be competitive both on local and global markets, management of investment projects including public-private partnership and free economic zones, encouragement of foreign investments, support

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Uzbekistan is one of the NIS (New Independent States) emerged after the collapse of the USSR in 1991. The country of over 32 million people is situated in the Turkestan (ancient Turan) area of Central Asia. The rich history of Uzbekistan is associated with kingdoms of Horezm and Sogdiana, as well as with conquers of Amir Temur, known in the West as Tamerlan (Amir means military commander, Temür or Tēmōr means iron) with his slogan “Strength in justice”.

of import substitution projects, elaboration of proposals regarding modernization of manufacturing technology.

Improved access to products: implementation of the National Medicines Policy, market research, utilization studies, optimization of import operations, support of selection of essential medicines, centralized purchase of vitally needed and essential medical products, management of tenders for the purchase of critical medical supplies, participation in the development of measures to prevent shortages of medical products.

International relations: support to broadening of contacts and strengthening of collaboration between local and foreign manufacturers through organization of meetings, exhibitions etc., promotion of participation of local interested parties in activities of international organizations.

One of the current priorities of the Agency is the acceleration of public access to innovative pharmaceuticals in accordance with the Presidential Decree of 20 June 2018 (№ UP-5460). To this

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end, it was proposed to use a simplified registration procedure for products approved in countries with stringent regulatory requirements. One of the options under discussion is the straightforward recognition of products marketed in the EU, USA, Japan etc.

It should be noted that WHO recommends reliance on information and decisions of countries with mature regulatory systems. One of the recent documents might be quoted in this context: Collaborative Procedure in the Assessment and Accelerated National Registration of Pharmaceutical Products and Vaccines Approved by Stringent Regulatory Authorities (originally circulated as a working document QAS/17.704/Rev.1. 2017 and later published in WHO TRS 1010, 2018, Annex 11). According to the recommended procedure, a certain product data set, a shortened version of a dossier, ought to be obtained from the company-Marketing Authorization holder. In addition, an assessment report is received from the mature authority that previously approved the product.

On the basis of such documents the authority using the accelerated registration procedure determines the relevance of medical and pharmaceutical information on the product (e.g. indications, stability, etc.) to its national setting. This means that recommendations from WHO in this area are far from automatic acceptance of decisions taken by foreign authorities. This example indicates the need for national regulatory authorities to monitor normative documents issued by WHO and other relevant international organizations, as well as collaborate between themselves.

The Agency for the Development of the Pharmaceutical Sector together with the State Centre for the Evaluation and Standardization of Medical Products are in the process of establishing contacts with WHO, both at Headquarters and Regional Office for Europe levels, as well as with some national regulatory authorities such as China, Russia.

This allows to determine the appropriate regulatory pathways. The next step would be to explore new vistas, such as cooperation with PIC/S, ICH, FIP etc.

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CIS GMP news

2 (3) / autumn 2018 GMP inspection

Manufacturers’ Preparedness for Follow-Up GMP Inspections

Current issues of pharmaceutical manufacturers Ivan Gulyaev

Ph.D. Pharm, Senior Expert of the Department of Pharmaceutical Manufacture Inspections, State Institute of Drugs and Good Practices

7 September 2018

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D

uring the preparation phase of the 3rd All-Russia GMP conference, the State Institute of Drugs and Good Practices (SID & GP) received more than 100 questions from 34 open and anonymous sources. They were mostly about follow-up inspections and Corrective Action/Preventive Action (CAPA) plans.

SID & GP experts analyzed the received information to determine the number of businesses planning to re-submit applications for follow-up inspections. Tentative assessment revealed 112 companies from 38 countries.

Please note the provisions of Federal Law No. 61 ‘Pharmaceutical circulation’ dated April 12, 2010 (as amended on June 4, 2018) article 45 section 1 ‘Phar-

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Fig. 1. Decisions of the Russian Ministry of Industry and Trade are weekly updated at: http://minpromtorg.gov.ru (please choose ‘GMP decisions register’ in the Lists and Registers folder)

maceutical manufacture’, ‘Pharmaceutical manufacture shall comply with the GMP rules approved by the Federal Government Authority. GMP certificates are issued based on the outcomes of pharmaceutical manufacturers’ inspections per procedure established by the Government of the Russian Federation… ’ In accordance with Decree No. 1314 ‘Verification of GMP compliance among pharmaceutical manufacturers’ dated December 3, 2015, ‘…an Inspection is a sequence of actions undertaken by the Russian Ministry of Industry and Trade (for human-use pharmaceuticals) and by the Russian Federal Veterinary and Phytosanitary Service (for veterinary pharmaceuticals) – hereinafter referred to as Regulating Authorities – or by the Federal State Institution subordinate to the above Authority (hereinafter referred to as Regulating Agency) – aimed at verification of the pharmaceutical manufacturer’s compliance with the GMP rules…’

Section 19 reads, ‘Inspections of foreign manufacturers fall under the jurisdiction of the Regulating Agency…’

The State Institute of Drugs and Good Practices has been assigned to conduct inspections of foreign manufacturers of pharmaceutical products for human use.

Decree No. 1314 ‘Verification of GMP compliance among pharmaceutical manufacturers’ issued by the Russian Government on December 3, 2015 prescribes to conduct an inspection within

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160 work days from the decision of the Regulating Authority. Presently, an average wait time after the Russian Ministry of Industry and Trade issues an inspection warrant (Order) does not exceed 110 – 112 work days. Upon receipt of the inspection warrant issued by the Russian Ministry of Industry and Trade, SID & GP arranges for a follow-up inspection of the production site in a timely manner.

The Russian Ministry of Industry and Trade decides on the issuance of GMP-certificates as provided for by Order No. 916 of the Russian Ministry of Industry and Trade dated June 14, 2013 (as amended by Order No. 4148 of December 18, 2015) ‘Approved GMP rules’ registered by the Russian Ministry of Justice under No. 29938 on September 10, 2013 (hereinafter referred to as GMP Rules). Decisions of the Russian Ministry of Industry and Trade are weekly updated at: http://minpromtorg.gov.ru, please choose ‘GMP decisions register’ in the Lists and Registers folder (fig. 1.).

The Inspection procedure was established by Decree No. 1314 ‘Verification of GMP compliance among pharmaceutical manufacturers’ issued by the Russian Government on December 3, 2015. The same procedure is equally applicable for both initial and follow-up inspections.

A follow-up inspection is conducted in the following events: Expiration of the GMP certificate; in accordance with Decree No. 1314 ‘Ver-

ification of GMP compliance among pharmaceutical manufacturers’ issued by the Russian Government on December 3, 2015, a GMP certificate remains valid 3 years.

Request from the manufacturer to adjust the valid GMP certificate (for example, in case of expanding the Production List) to make sure that deviations revealed during the previous inspection have been eliminated.

If the adjustment happens during the validity of the current GMP certificate issued for pharmaceutical products manufactured at the same facility and in the same conditions specified in the GMP certificate, the Regulating Authority releases a new one with the same expiry date without conducting an inspection.

In order to determine that the conditions of pharmaceutical manufacture remain unchanged, experts of the State Institute of Drugs and Good Practices analyze every submission following the internal procedure and taking the risk-based approach to evaluate quality of the drugs: joint production on the same production lines, with the same equipment, in the same premises, using the same engineering systems, as well as the previously approved flows of stock, raw materials, finished products, and personnel, paying special attention to risks of cross contamination; launching new production lines,

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using new equipment, in new premises, using new engineering and introducing new flows of stock, raw materials, finished products, and personnel; adding new dosages of manufactured pharmaceuticals, changing the commercial name of the product, changing the name of the manufacturer, etc.

Based on the findings, it is decided whether an on-site visit is necessary, or the Production List can be extended without an inspection.

Another reason calling for a follow-up inspection is making sure that the deviations revealed during the previous visit have been removed.

If the previous inspection revealed deviations, the manufacturer should provide documentary evidence of corrective measures along with a request for a follow-up inspection.

Experts of the State Institute of Drugs and Good Practices review each application. Their analysis is based on the risk-based approach in line with the SOPs and evaluation of risks pertaining to the detected deviation. The review focuses on paperwork that can demonstrate elimination of identified GMP deviations. First, it is expected that all previous deviations have been cleared, and corrective and preventive actions (CAPA) have been fully implemented.

In case of well-grounded doubts in reliability of the information presented, or if the information does not prove elimination of the identified deviations by the manufacturer, a follow-up inspection is deemed necessary.

Preparation steps for a follow-up inspection on the manufacturer’s end include: analysis of the previously revealed deviations; investigation of the root reason of the said deviations; development and enforcement of a CAPA plan, evaluation of its efficiency; request for a follow-up inspection, including submission of paperwork for evaluation.

The risk-based approach cannot be underestimated in analyzing the revealed deviations. Deviations are categorized by Order No. 261 issued by the Russian Ministry of Industry and Trade on February 4, 2016. The categories are harmonized with respective regulations used by inspectorates in the EAEU countries, Europe, Canada, Australia, and others.

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It is important to realize that an individual inspection is organized for each separate applicant with all deserved confidentiality. A plethora of factors should be considered, e.g. drug characteristics, equipment, technology, manufacture process, documentation (including the drug registration dossier, the list of products to be inspected), the pharmaceutical quality system, etc. Deviations revealed at different manufacturers may belong to the same GMP Rule, however – depending on the above listed factors – they could mean different levels of risk in product’s quality, and consequently, will be categorized differently in each particular case. For one, it is obvious that the degree of risk in product quality cannot be the same in manufacture of sterile and non-sterile products exposed to contamination.

Inspectors’ responsibility for protection of confidential information about the applicant is part of the Inspection Agreement signed between the applicant and the State Institute of Drugs and Good Practices. Each inspector signs a confidentiality statement to be able to proceed with the site inspection.

A CAPA dossier for a follow-up inspection should demonstrate documented evidence of all actions within the pharmaceutical quality system aimed at eradication of the detected deviations. The dossier should include documentation of all involved systems: quality risk management; deviations management, including documented investigation and establishment of the root/genuine cause or the most likely cause; change control management; staff training; CAPA management, including performance evaluation of the undertaken measures.

A CAPA dossier reflects the quality system at the pharmaceutical facility.

The following principles should be observed in its preparation: 1) Documentation culture: structure. The documents should be filed by the type of deviations in a logical and chronological order; consistency. The documents should not bear contradictions; visibility. The attached photographs should be of high quality to demonstrate the mended deviations; correct translation.

2) Relevance. The presented paper-

work should be relevant and provide evidence of the measures undertaken to reconcile the deviations.

3) Traceability. It is necessary to ensure traceability of data in various types of documentation, i.e. registration records and reports.

4) System approach. There should be presented an evidence of measures undertaken to prevent the risk of deviations in similar circumstances. For instance, if a deviation is connected to insufficient training of the process manager it might be worth considering a new training course for all the team in charge of this particular process.

When submitting a request for a follow-up inspection the manufacturer should be able to prove during the follow-up visit all corrections of the previously detected deviations: If positive, then the previously revealed deviations will be lifted; If not, it deems impossible to evaluate performance of the planned actions. In this case, the deviations will again show on the inspection report.

Per existing procedure – governed

by Decree No. 1314 ‘Verification of GMP compliance among pharmaceutical manufacturers’ issued by the Russian Government on December 3, 2015 – no CAPA plan can be reviewed during preparation of the report immediately after the inspection was completed. An opportunity exists – however – to submit additional paperwork that was not produced during the site inspection for objective reasons. Please visit the webpage of the State Institute of Drugs and Good Practices to find out what documents can be additionally submitted: https://gilsinp.ru (fig. 2.).

In the future, with introduction of the EAEU GMP certificates (Decision No. 77 issued by the Eurasian Economic Commission Council on November 3, 2017) CAPA materials can be reviewed immediately after the inspection, which is provided for in Decision No. 83 issued by the EEC Council on November 3, 2017.

In accordance with Decree No. 1011 of the Russian Government dated August 25, 2017, the Russian Ministry of Industry and Trade is assigned to act as Regulatory Authority for coordination of pharmaceutical circulation, including the manufacture and sharing with the EEC information on pharmaceutical manufacture inspectors in order

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State Institute of Drugs and Good Practices

Fig. 2. Please visit the web-page of the State Institute of Drugs and Good Practices to find out what documents can be additionally submitted https://gilsinp.ru

to open a register of EAEU inspectors.

Apart from that, the Russian Ministry of Industry and Trade is in charge of the database of the issued and recalled GMP certificates; conducting GMP inspections; and issuance, suspension or cancellation of EAEU GMP certificates of pharmaceutical manufacturers.

The State Institute of Drugs and Good Practices is preparing to conduct inspections by Eurasian Economic Union rules. SOPs have been finalized and the staff is taking relevant training.

In April 2018, the FSI & GP hosted a WHO Global Learning Opportunities course for GMP inspectors from EAEU countries, i.e Armenia, Kazakhstan, Kyrgyzstan, and Russia.

In anticipation of joint GMP inspections, mock inspections are conducted in cooperation with the inspectorates of the EAEU regulating authorities.

Two Work Groups operate in the Eurasian Economic Commission to establish common pharmaceutical market in the Eurasian Economic Union: Work Group for common approach to pharmaceutical products circulation in the EAEU. The WG operates under the Board of the Eurasian Economic Commission (Decision No. 204 issued by the EEC Board on October 30, 2012. The WG composition is regulated by Resolution No. 52 updated by the EEC Board on June 9, 2015). The WG’s main task is to draft blueprints of EEC regulations for the common EAEU pharmaceutical mar-

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ket. The WG meets on a monthly basis.

Work Group for GMP inspections in the Eurasian Economic Union. The WG was initiated by the State Institute of Drugs and Good Practices with the support of the Russian Ministry of Industry and Trade. The WG operates on an ongoing basis; the EEC Board has not yet issued an institutionalizing decision, but it is on the way; the WG convenes every three months, starting 2018. The group focuses on articulation and application of unified technical and practical approaches in GMP inspections to be conducted on the common pharmaceutical market of the Eurasian Economic Union.

The EEC Work Group for pharmaceutical manufacture inspections not only pursues cross-country relations between their Regulatory Agencies, but it also strives to find practical solutions to guarantee a transparent, efficient, and productive functioning of the common EAEU market.

The EEC inspectorates encounter a number of particular issues in certain areas of the common pharmaceutical market, i.e. conducting pharmaceutical inspections in line with the unified EAEU rules; mechanisms and principles of interagency communications between the EAEU member-states during pharmaceutical inspections by the unified EAEU rules; unified rules of pharmaceutical in-

spections; a range of specific questions pertaining to filling out and design of registration documents by the unified EAEU rules.

Per internal procedure, the State Institute of Drugs and Good Practices sends an advance notification to the Regulating Authority of the host country with the dates of the planned inspection of the foreign manufacturer.

Should the inspection reveal critical deviations, the Russian Inspectorate relays this information to the host country Regulating Authority with a reference to the relevant GMP Section without specification of the deviation for facility’s confidentiality. Representatives of local regulators are invited and in many cases show up for the inspection of foreign manufacturers.

Above said, in submitting a request for a follow-up inspection special attention should be given to preparedness of the production site after all deviations have been cleared and necessary changes introduced. The developed and implemented CAPA plan must be properly evaluated, relevant, and exhaustive. Evaluation of the site preparedness for the inspection includes production capacity (staff, premises, equipment, drug quality control, etc) as well as proper documentation.

We wish you all successful inspections!

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Substitution Policy

Rate of Import Substitution and Localization on Russian Pharmaceutical Market 10 September 2018

In early July, a project of a new program for expansion of the Russian pharmaceutical industry, this time up to 2030, was submitted for discussion. The document continues with a range of aims and goals provided for by its current version and brings a number of innovations aimed, in particular, at the expansion of manufacture of active pharmaceutical ingredients (APIs) and drug export promotion.

Meanwhile, the existing program is not completed yet; it has given a start to a number of successful projects for import substitution and localization. To a large extent, the results demonstrated by domestic pharmaceutical industry for the last 2.5 years, both in the field of formation of the relevant production infrastructure and development of product portfolios, were provided by this program. Those trends, definitely, need further development.

GENERAL STATE OF DRUG MANUFACTURE IN RUSSIA Following the results of the 1st half-year of 2018, our country produced drugs worth 157.4 billion rubles (at producers' values, including VAT), which is 1.2% less than the year before (Fig. 1). The physical output also decreases: here the long-term dynamics reached 10%. We could observe something similar in 2014: back then performance of domestic pharmaceutical industry was estimated at 3.3% in rubles and -9.6% in packages, although both the macroeconomic situation and the demand conditions on Russian pharmaceutical market during the said time periods were markedly different.

Fig. 1. Volume and dynamics of drug shipment from warehouses of Russian pharmaceutical companies (manufacture of drugs), billion rubles, including VAT Source: RNC PharmaÂŽ, automated database Manufacture of Drugs in the Russian Federation

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The drop in production of drugs in the 1st half-year of 2018 didn't affect only Russian manufacturers – activity of importers during that period was also low enough: against the backdrop of significant contraction of demand caused by the low consumer purchasing power the Russian pharmaceutical market accumulated substantial commodity stocks, actually, the decrease in shipping resulted from market participants’ intention to prevent further glut of inventory.

In a sense, this situation is temporary: starting from February 2018, Rosstat has reported an increase in real disposable household income, in particular, for the first 6 months of 2018, this parameter increased by 1.7% year-over-year.

But, of course, it doesn’t pay to wait for a prompt reaction expressed in growth of demand for drugs, all the more so because before that, the household income had been decreasing for the entire 2017.

However, it is worth noting that despite the low effective demand, consumers predominantly do not strive to switch to using domestic products instead of foreign ones, the demand for drugs is generally conservative, and only cardinal, if not dramatic events, for example, a sharp rise in prices, or a flu epidemic can fundamentally change the preferences. During the current year, by the way, a combination of both, has not worked in favour of domestic manufacturers, the inflation for drugs in January-June 2018 was negative (-2.6%), and

State Institute of Drugs and Good Practices

Nikolai Bespalov Development Director at RNC Pharma

the flu and ARVI rates also decreased (by 25.4% and 2.3%, respectively).

Thus, during the current year, the traditional growth of the share of domestic products on the pharmaceutical market has not been observed, moreover, as of the first half of 2018, we had to note some downward adjustment of this parameter, which is now equal to 30.6% (Fig. 2), whilst following the results of 2017, it was about 30.8% (in monetary terms). Such an adjustment, by the way, is unprecedented starting from 2008, however the year has not ended yet, thus, domestic companies still have some time to restore standing.

LOCALIZATION ACTIVITY Notwithstanding the relatively modest quantitative results, the domestic pharmaceutical industry continued active expansion of assortment, inter alia by means of localization of drug manufacture in the territory of Russia.

It is understood that this is a multistage process, generally starting from transfer of certain stages of the production cycle: primary and secondary packaging as well as release quality control). It is natural that these localization stages provide for import of in-bulk drugs into

Fig. 2. Share of domestic drugs on Russian pharmaceutical market in general, %, rubles.

Source: RNC Pharma®, Monitoring of import substitution in the Russian Federation

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Fig. 3. Imports of in-bulk drugs and share thereof in the total imports Source: RNC Pharma®, automated database Manufacture of Drugs in the Russian Federation

Russia, where they undergo final production stages.

It is interesting that after the last year's drop in the volume of in-bulk shipments (in monetary terms), this year the said product category resumed its growth again. Following the results of the 1st half-year of 2018, our country imported in-bulk drugs worth 52.1 billion rubles, which is 22% more than in the corresponding period of the previous year (Fig. 3).

It is particularly remarkable that following the results of 2017, the dynamics of in-bulk shipments were oppositely directed for volumes in monetary and physical terms: in the first case, a decrease in volume was registered (-14%), while in the second, the output increased (+6%). It was due to the fundamental changes in the assortment of delivered products; in particular, several companies stopped importing particular in-bulk drugs (including the ones from the upper-mid market). In some cases, it had to do with the deepening of the production cycle; therefore, the companies switched from in-bulk shipments to delivery of pharmaceutical substances and a full-cycle formulation in the territory of Russia. Such a path was taken, for instance, by Pfizer, which starting from 2017, completely stopped shipments of in-bulk Prevenar vaccine and currently delivers antigen for its manufacture at the facilities of Russian company Petrovax.

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There were other examples where foreign companies had to deal with the pressure of Russian alternatives and, having broken down under the strain, had to cut down the above-mentioned production stages, stop in-bulk shipments, and return to import of the finished dosage form, volumes of which, of course, were much less than the initial ones. Such processes were observed, for example, with respect to Velcade (Johnson & Johnson) or Copaxone (TEVA).

Interestingly, the volume of inbulk shipments in physical terms to our country demonstrated quite remarkable positive dynamics instead of a possible decrease. In particular, following the results of 2017, our country imported 4.6 billion minimal dosing units (MDU), and the dynamics as compared to the previous year reached 6.1%. During the first half of 2018, the growth continued, the volume of physical supplies increased by 1.1% – localization activity did not cease, moreover, this process smoothly continues at the expense of mass products of mid-price segment.

Localization policy of certain foreign companies in Russia is based on a number of lists determining either a possibility of publicly funded procurement of drugs, or direct national policy in the field of import substitution. As of April 2018, 111 corporations bore some or other marks of localization within VED, ESSENTIAL DRUG REIMBURSEMENT PROGRAM (ONLS), SEVEN NOSOLOGIES

PROGRAM (VZN), 57 INN, Industrial Plan of Minpromtorg (Ministry of Industry and Trade) and lists of orphan drugs. In aggregate, at different stages they localized 388 INNs, which corresponds to 618 tradenames.

Most INNs are currently localized within the VED list: here certain marks of localization are borne by 255 molecules (Fig. 4), however, the same list is the most extensive – the “new” list contains 713 INNs (taking into consideration various vaccines). However, almost half of the said 255 items undergo only the secondary packaging and release quality control procedures in our country, while localization of full-cycle formulation is only available for 69 items, and another 65 items are localized at the stage of inbulk primary packaging.

The list of 57 INNs is characterized by the largest share of full-cycle localized drugs: 12 drugs can be fully formulated in our country, another 5 items are localized at the level of in-bulk packaging. All in all, taking into consideration other localization levels (secondary packaging and release quality control), 32 out of 57 items included into the list bear certain marks of localization, which accounts for more than 56% of the total number of drugs.

The worst situation is with the list of orphan drugs: only 2 items bear individual marks of localization and none of them is even remotely close to full-cycle formulation.

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Fig. 4. Rate of localization of foreign pharmaceutical companies according to the current version of MA Source: RNC Pharma®, Monitoring of import substitution in the Russian Federation

IMPORT SUBSTITUTION PROCESS Localization activity is closely associated with import substitution. Hereinabove, we have provided examples of how certain companies affected by competitive factors lose their market share, therefore, withdrawing from the

localization process. Despite the lack of significant industrywide quantitative growth, import substitution continues to develop actively by means of product expansion; moreover, during the current year, we have seen a number of episodes of an unprecedented competitive struggle where Russian manufacturers of alternative drugs succeeded in judicial contesting of exclusive rights

and securing the issue of a compulsory license. In particular, in June 2018, similar judgement was delivered in favor of Nativa with respect to the Revlimid (Celgene) alternative, however at the time of preparing this material, the alternative drug has not ­entered the Russian market yet. It is worth noting that Nativa handles several similar cases against other manufacturers.

Fig. 5. Availability of alternative drugs from Russia and EAEU with respect to certain drug lists in accordance with the current version of MA as of April 2018.

Source: RNC Pharma®, Monitoring of import substitution in the Russian Federation

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Fig. 6. Import of pharmacopoeial and technical APIs to Russia Source: RNC Pharma®, automated database Manufacture of Drugs in the Russian Federation

In early July 2018, the patent of Eli Lilly for certain dosage forms of Cialis was declared void. Severnaya Zvezda (North Star) contested the effect of this patent, while as early as June, the company produced several batches of Tadalafil-SZ. The bare fact of contesting patents constitutes an important marker characterising the development of pharmaceutical market, as domestic companies not only bring alternative drugs to the market, which lose their patent protection, but also start to demonstrate a proactive position substantially regaining their right to produce and sell particular drugs. Such a position, undoubtedly, raises the prospect of success many times; therefore, it is used by a number of generics manufacturers all over the world. In a sense, struggle against the so-called “evergreen patents” is a judicial top class and the fact that certain Russian companies make major gains in this field is an extremely positive sign.

At the same time, at present, most alternatives from Russia and EAEU member states are included into the VED list: here 341 INNs have 2 or more alternatives, and 157 molecules have at least 1 domestically produced alternative (Fig. 5).

However, the same VED list is in the lead by number of INNs that have no registered Russian alternatives yet, and today, the market totals 215 similar molecules.

Nevertheless, the competitive struggle

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on the market continues, including that among INNs that have no alternatives included into VED list; 50 items are subject to clinical trials (CT), which means that in a couple of years these items will also have Russian alternatives. It is particularly remarkable that alternatives of certain drugs are being developed by several different manufacturers at once. In particular, Ganciclovir undergoes different stages of clinical trials carried out by five domestic companies. But, interestingly, it was a Belorussian, not Russian, alternative drug which was the first to obtain a Marketing Authorization for that INN: Ganciclovir (Belmedpreparaty) was registered in Russia in April 2018.

Another 9 INNs having no domestically produced alternatives are now subject to clinical trials carried out by two different companies; thus, actual number of competitors in particular areas of medicine will significantly increase in the short run. Furthermore, Russian companies will have to compete not only with the manufacturers of original drugs, but also with each other, as well as with the colleagues from EAEU member states, which can claim the same privileges as Russian manufacturers.

The best situation is with respect to 57 INN list: only 18 INNs included therein have no alternatives registered in Russia, of which 11 are now subject to CT; if all of them succeed and are brought to the market, there will be only 7 drugs with-

out alternatives. It should also be noted that none of those 7 molecules is currently localized in our country, even at certain stages of production cycle.

In addition, it is worth noting that import substitution of finished dosage forms by no means always aligns with import substitution of delivery of raw materials for manufacture of certain drugs, while an overwhelming majority of manufacturers still have to acquire pharmaceutical substances abroad. In a broad sense, dependence of the domestic pharmaceutical market on foreign pharmaceutical substances (APIs) not only plays a key financial role as it enables Russian companies to pursue an autonomous pricing policy and rely less on foreign-exchange fluctuations, but also determines actual fulfillment of a number of strategic tasks provided for by the program of development of the Russian pharmaceutical industry.

As of 2017, 12.3 tons of foreign APIs worth 73.9 billion rubles were imported into our country (Fig. 6). For the last 5.5 years, the volume of supplies of foreign raw materials to our country has been growing steadily, both in physical, and monetary terms. In particular, in 2017 as compared to 2016, import in monetary terms increased by 22% (rubles), while the dynamics of supplies in physical terms were 9% (tons). At the same time, the range of imported APIs expanded by 61 items.

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In 2018, this trend continued: following the results of the 1st half-year of 2018, the dynamics in rubles reached 30%. However, it is worth noting that certain substances imported into Russia are significantly overpriced, especially when it comes to deliveries to companies that have localized full-cycle formulation in our country. A difference in prices for the same item may reach 10-20 times, hence, the increase in the volume of deliveries in monetary terms shall be associated not so much with real processes of import substitutions, but with particular profit shifting schemes. Furthermore, the dynamics in physical terms are negative (-4.5% for the first 6 months of 2018).

Of course, the fact that the companies localized in Russia acquire substances abroad is by no means always associated with profit shifting. In most cases, local manufacturers of raw materials are simply unable to offer the required assortment at a competitive price. In fact, in Russia, the fine and medium-sized chemical industry is rather underdeveloped, with its share in the total chemical industry volume amounting to 10%-15% according to different estimates, and the essential share in the volume of Russian output belonging to so-called large-scale production (base polymers, petrochemistry, fertilizers, etc.), whereas in developed countries, this share is at least 35-40%.

Such a situation is historically created and, undoubtedly, it cannot be simultaneously settled, which is why development of own pharmaceutical substance manufacture should become a top priority task. One of the main goals of the new program of development of the Russian pharmaceutical industry brought for consideration of community of professionals in early July was as follows: “Provision of the pharmaceutical industry with the required assortment and amount of locally produced raw materials and supplies...”.

This is not to say that Russia does not produce APIs at all: we do have about 55 facilities producing certain pharmaceutical substances, amongst which the unconditional leaders in terms of volume and assortment are Polisintez, Bion, Irbitskiy Chemical-Pharmaceutical Plant, and other facilities. However, it is clear that the problem of development of APIs manufacture in our country cannot be solved without establishment of new facilities.

It is interesting that implementation of the above project was declared prior to the revision of the “Strategy”.

Moreover, particular projects are already

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being implemented, in particular, Aktyvny Komponent (Active Component) is involved in construction of a facility in Pushkin (Saint Petersburg) where they plan to start production in 2018-2019, and in the Irkutsk Region in June 2018, construction of Pharmasyntez-Chemie was started, the launch of which is expected in 2021.

Development of own APIs manufacture in Russia, among other things, will determine future success of Russian companies on the global stage. First, it is the only way to ensure competitive prices for the products; second, without development of own manufacturing facilities, it is hard to talk of proprietary design, which is of main interest on the world stage.

EXPORT ACTIVITY Export of drugs from Russia (exclusive of deliveries to EAEU member states) is worth a rather modest amount yet: following the results of 2017, it is about 22 billion rubles (including customs duties), for the entire year, this amount has not changed significantly, and the dynamics was only 1.7% (Fig. 7).

The volume in physical terms grows a little faster (1.9%). The figures for January-April 2018 do not give much cause for optimism: the, growth in monetary terms continues (+3%), but the physical volumes still amount to 7.8%.

In a broad sense, Russia exports not only domestic products: thus, following the results of 2017, except for the drugs produced in Russia, we exported products produced in 71 regions, with the maximum share in the volume belonging

State Institute of Drugs and Good Practices

to the products from Germany (5%) and Belarus (3.9%). We’re talking about the so-called re-export, which can be associated both with export of drugs to unrecognized and partially recognized regions, among which are LPR, DPR, Pridnestrovian Moldavian Republic etc., and with return of certain consignments of goods.

At the same time, the share of Russian drugs export is the largest – about 65% in monetary terms.

The Russian exports geography is wide enough – in 2017, it included 100 different directions (excluding deliveries to EAEU member states), with certain goods being delivered to quite exotic destinations, such as North Korea.

From amongst the largest drug exporters, it is important to note Stada, which is the ultimate leader in export of drugs from Russia in monetary terms – following the results of 2017, the company’s share has amounted to 8.9% of the total exports. The company’s products are exported to 26 different countries, the main importer being Ukraine. The second place is taken by FSBSI M.P. Chumakov Institute of Poliomyelitis and Viral Encephalitides (8.0%) – products made by the Institute are well known in 45 countries all over the world.

It is natural that no-one on the global market is going to welcome Russian products with open arms. Furthermore, some countries design their regulatory policy in such a way as to limit the entry of new competitors. In this respect, Russian export-oriented pharmaceutical companies definitely need special support. It shall include both financial and other support of advisory

and fiscal nature.

Fig. 7. Export of drugs from Russia (excluding deliveries to EAEU member states) Source: RNC Pharma®, automated database Manufacture of Drugs in the Russian Federation

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How to Protect People from Counterfeit Medicines 13 September 2018

R

eports of deaths from falsified medicines regularly appear in the media. Horrifying statistic are published, too. For example, about 700 thousand people die DAILY in the world because of fake medications. According to the American Center for Medicines, the annual income from the sale of "unreal medicines" is estimated at USD 75 billion. WHO is also sounding the alarm: the share of counterfeit medicines in the world is 12%, and in countries with a low standard of living, it reaches 80%.

Here, Russia is not an exception.

According to the Ministry of Internal Affairs, until recently, every tenth tablet sold in our country was a counterfeit, and the sales of fakes were 10-15%.

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Pharmaceutical piracy and falsification of medical products is a problem of international scale. Relying on the statistics, according to its incomes, it is quite possible to compare it with the turnover of drugs or weapons. That is why mechanisms to counter this are being developed at the international level.

For example, it is precisely these issues that are covered by the Medicrime Convention (an international treaty on the counterfeiting of medical products and similar crimes). In ratifying the Convention in 2017, Russia became the 12th country to join it.

COUNTERFEIT LEAVING PHARMACIES Speaking recently at a government hour in the State Duma, Health Minister Veronika Skvortsova noted "a significant reduction in the number of falsified

medical products in the legal supply chains of the Russian Federation in recent years." The fact that in Russia, substandard drugs have become less likely to find was noted at the Federal Service for Supervision in Health Care. For example, in 2017, the number of falsified, counterfeit, and inadequate medications withdrawn from sale decreased 2.1 times compared to 2016.

As noted by experts, all this is the result of previous decisions. Namely: the creation of laboratory complexes that have international accreditation, labeling of drugs, the formation of the necessary legislative framework. As for the latter, a number of amendments to Russian legislation have recently been adopted in order to bring it in line with the requirements of the Medicrime Convention. So the amendments to the Criminal Code of the Russian Federation and the Administrative Code increased criminal responsibility for counterfeiting

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State Institute of Drugs and Good Practices

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drugs and their circulation. When they were examined by the State Duma, they insisted that the relevant norms should appear in the Criminal Code – since the turnover of counterfeit drugs is not so much an economic crime, as directed against the life and health of people.

Therefore, the measure of restraint for such crimes was introduced quite harshly – 12 years in prison. By the way, during the time of these new norms, the number of related criminal cases has significantly increased. If in 2015 the Investigative Committee only opened 10 such cases, then in 2016 instituted 25 already, and in 2017, it instituted 39. The situation with fakes in the medicines market has gradually begun to straighten out.

NEW MARKETS FOR COUNTERFEIT However, we are faced with one more problem – the spread of counterfeits via the Internet. According to experts, this is a problem of a great many countries – 50% of counterfeit medicines in the world are distributed through the Internet.

Recently, Federal Service for Supervision in Health Care together with the Department of Economic Security and Anti-Corruption in the Moscow Region conducted a study showing that only in Moscow and the Moscow Region, more than 1000 Internet sites and groups in social networks participate in illegal activities related to the sale of counterfeit and falsified medicines. According to some estimates, the turnover of this trade ranges from RUB 350-600 million.

According to the head of Federal Service for Supervision in Health Care Mikhail Murashko, while in the network of pharmacies the amount of falsification was cut in half over 4 years, and does not exceed 0.01%, the risk of buying counterfeit medicines through websites remains high; for some sites, the risk is almost 100%.

Concern by remote sales of medicines via the Internet is expressed in the Ministry of Health. From Veronica Skvortsova's speech: "Efforts should be intensified to adopt legislative norms that put a barrier to unsafe and harmful activities, including the draft law that was adopted by the State Duma on first reading on December 13, 2017, establishing rules for the safe remote sale of non-prescription medicines."

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Alexander Prokopiev

Deputy of the State Duma, initiator of legislations under the Medicrime Convention

CRIME AND PUNISHMENT One such legislative norms could be heavier penalties for distributors of fakes through the Internet sites. Moreover, this also requires fulfillment of obligations in accordance with the provisions of the Medicrime Convention.

My colleagues and I have already prepared corresponding legislation.

What do we offer? Establish criminal responsibility for distributing counterfeit medicines via the Internet similar to other turnover of counterfeit goods.

Relevant amendments are being made to the Criminal Code of the Russian Federation and the Code of Administrative Offenses, where at present, an offense is not envisaged as an aggravating circumstance using means of wide distribution, such as information systems, including the Internet. We consider that the term of punishment for such crimes should be similar for those committed in offline;

it should be at least 12 years in prison.

When we worked on the law, we clearly understood that these crimes should be regarded not from the point of view of economic crimes, but from the point of view of forming a real threat to the life and health of our population. And the measures of responsibility should be as strict as possible, respectively. Other countries have already come to it. For example, in the United States, the sale of counterfeit drugs is punishable with life imprisonment, or a fine of up to USD 200 million. There is also life imprisonment in India. There is imprisonment from 30 to 50 years in Turkey.

Now, the legislation on increasing the responsibility for the distribution of drug falsification through the Internet is being expertly assessed in the Government of the Russian Federation.

We expect that we will be able to consider it already in the autumn session of the State Duma.

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Government Support Can Multiply Companies’ R&D Budgets

7 September 2018

Interview with Deputy Prime Minister and Minister of Industry and Trade of Tatarstan Albert Karimov

The Republic of Tatarstan is known, first of all, as an oil producing region with developed oil refining and petrochemical sectors.

Are there any tasks set for the development of more high-tech industries in the republic today, such as low-tonnage chemicals, pharmaceuticals, and biotechnology? What is the role of the Tatarstan Ministry of Industry and Trade in these processes?

Petrochemical complex of Tatarstan has been and remains the backbone for the economic development in the region, generating over 5% of the industrial output and about 20% of the gross regional product.

Nevertheless, in the long-term, as outlined in the Strategy for Social and Economic Development of Tatarstan until 2030, the priority within the framework of the flagship project titled “Tatarstan’s Technological Initiative” is given to high-tech industries at the junction of disciplines (IT, chemistry, biology, physics), such as “smart materials” (new plastics and composites, nanostructured materials), additive technologies, biotechnology, and robotics.

In the context of the Strategy that provides for the creation of development institutions, including sectoral ones, the Ministry initiated the establishment of the “PharmMedPolis of the Republic of Tatarstan” project office, whose tasks are

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strategic and operational management of Tatarstan's pharmaceutical industry development, the initiation of joint projects with Russian and foreign biotechnology and pharmaceutical companies, both in the sphere of production and in the research and educational fields.

If we talk about other activities of the Ministry in the sphere of pharmaceutical industry development, it is, first of all, the popularization of Tatarstan's opportunities at Russian and foreign industry-specific exhibition sites (such as the BioTechMed Forum, the IPhex International Exhibition for Pharma & Healthcare in New-Delhi, the ACHEMA International Exhibition Congress in Frankfurt-on-Main), visits to innovative sites and enterprises (pharmaceutical cluster in Kaluga, Novo-Medica, Pharma City and Biotech Cluster in India, etc.), shaping the marketing strategy for the sector, initiating and supporting supposedly promising projects, including international ones.

The Ministry also generated a package of proposals for developing the Pharma 2030 programme with ideology in the coordination and concentration of efforts and capabilities of all concerned parties (Russian R&D centres, enterprises, universities) and more targeted governmental support of innovations, projects, and companies.

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State Institute of Drugs and Good Practices

For instance, in order to ensure the country’s medicinal security, a proposal has been made to compile a list of imported low-tonnage products, followed by incentives for the production of items from this list (including semi-processed products and intermediates for the synthesis of pharmaceutical ingredients) within the Russian Federation.

To facilitate the domestic production of original drugs, we suggested developing support mechanisms for contract research organizations and platforms operating full-cycle, from seeking new ideas and bio-targets, synthesising and producing experimental batches, performing preclinical and clinical studies, to registering and releasing ready-made dosage forms.

To encourage investment activities in Russian regions and shift investments from related industries into pharmaceutical industry and biotechnology development, it is advisable, in our opinion, to initiate public co-financing of region-wise sectoral programmes and projects, which would allow setting the development budget for the pharmaceutical sector, including through extra-budgetary resources.

For the development of the contract manufacturing system in the country, we suggest to devise a mechanism of allocating subsidies for the renovation of domestic pharmaceutical enterprises through placing production facilities by foreign companies on their sites.

SEZ Alabuga, the most successful special economic zone of Russia: open to pharmaceutical industry residents

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Pharmaceutical facilities of Tatkhimpharmpreparaty

Please tell us more about the PharmMedPolis project. What goals were pursued in its creation, what indicators do you intend to achieve eventually?

In short, during the formation of the project concept, we proceeded from the fact that Tatarstan, while boasting of a developed chemical industry, significant scientific and educational potential in the field of pharmaceuticals, has a very modest share of the pharmaceutical industry in the total industrial output (lower than the Russia’s average) and the key task of the project is to reach the average Russian level by 2020, and the level of developed countries in the future (where it is about 4% to 7%). For your information, the republic’s industrial output in 2017 amounted to over RUB 2.2 trillion.

Tatarstan is a home for a number of pharmaceutical companies, first of all, Tatkhimpharmpreparaty with more than 85 years of history (it is among Top 20 Russia’s companies by output value and among Top 10 by volume).

In 2016, the state-of-the-art production facility of Nanopharma Development was opened. This is a successful

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forward business model of cooperation between Izvarino Pharma (Russian division of the Swiss-based Ferring), Rosnano, and Tatarstan.

The Karpov Chemical Plant and Laskraft also produce active pharmaceutical ingredients.

However, the explosive development of the pharmaceutical industry in Tatarstan can only be achieved by attracting external investment and by outstripping growth of research services based on its R&D centres and clinics.

With this in mind and given the current trend formed by Russia’s government policies for placing foreign production facilities in the country, we focus on the emergence of new pharmaceutical and biopharmaceutical facilities in the republic, on the flow of investments into the industry, by employing the advantages that we posses.

For three years in a row since 2015, the republic headed the National Rating of Investment Climate in Russian Regions developed by the Agency for Strategic Initiatives to Promote New Projects. The development infrastructure (special economic zones Alabuga and

Innopolis, the priority social and economic development areas in Naberezhnye Chelny, Zelenodolsk, Chistopol, and Nizhnekamsk, a network of industrial parks, business incubators, industrial sites and platforms) allows providing areas, ready-to-use floor spaces for any production facility. Investors can acquire both a turnkey site and preferences for federal, republic’s and local taxes, reduced rates of social security payments.

At the same time, a production facility with a sanitary protection zone of 1000 metres can also be built in the republic.

One of the pioneer projects of PharmMedPolis nearing completion is the Pharmaceutical Atlas of Tatarstan with selected sites for pharma production, an interactive resource with a focus on potential residents that consider options for localizing their production facilities in Russia. This will be followed by the anticipatory establishment of specialized sites for placing relevant facilities, which are expected to be in demand.

We plan that there will be at least 5-6 new pharmaceutical enterprises in the republic by 2020.

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The industry's demand for highly qualified professionals is very high, but relevant universities do not always provide an opportunity to test new equipment. Is sufficient attention given to these aspects in the republic, what results can we already speak about and what is planned in the future?

Tatarstan is rightfully considered one of the Russia’s leader regions in education and science, 25 out of 45 Tatarstan’s universities are lead ones. The total number of students is more than 150,000. Experts in pharmaceuticals and related fields are trained within the walls of the Kazan Federal University, the Kazan National Research Technological University, the Kazan Medical University, and the Kazan Medical Academy. More than 1000 students are graduate each year in fundamental, preventive medicine, and pharmacy.

The development of innovative medicines is carried out in the Research and Education Centre for Pharmacy under the Kazan Federal University, in the Central Research Laboratory of the Kazan Medical University, and in the International Scientific and Innovation Centre

Production processes at Nanopharma Development take place in the isolator version, which allows producing drugs that contain cytotoxic and highly active substances

Starting from July 2016, Tatkhimpharmpreparaty produces ointments, gels, and drops that can replace foreign anti-inflammatory gels

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of Neurochemistry and Pharmacology based on the Arbuzov Institute of Organic and Physical Chemistry. These sites are actively used for students as job training and research placements.

Created under the Pharma 2020 Federal Targeted Programme and fitted with unique equipment, the Research and Education Centre for Pharmacy under the Kazan Federal University, in collaboration with Tatkhimpharmpreparaty, implemented ten projects to develop innovative medicines, successfully completed three studies of antitumor, antibacterial, and anti-inflammatory drugs.

Three projects to develop antifungal, antiseptic, and antiepileptic drugs are in the preclinical research stage. Another project for an anti-inflammatory and analgesic drug was supported by the Ministry of Industry and Trade of the Russian Federation and the Skolkovo Foundation and is currently in the transition to Phase I clinical trials. Development of another 10 projects for innovative medicines (anti-glycaemic, antitumor, anticholinesterase, anti-burn, anti-tuberculosis, etc.) are underway. The university also has a pilot production site.

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Institute of Fundamental Medicine and Biology under the Kazan (Volga Region) Federal University: the Medical Simulation Centre

Other research centres strive to build similar chains from development to production.

The Kazan Federal University boasts of a high-level training for students of medical specialties in the Institute of Fundamental Medicine and Biology. A unique world-class Medical Simulation Centre was built for the IFMB, including a hospital model, a Dental Phantom Class, and a Medical Engineering Centre.

The IFMB also accommodates a simulation equipment production unit; the regional engineering centre of medical science already produces and exports a number of simulators intended for training doctors. For this purpose, an interdisciplinary approach is used, physicists, engineers, physicians, and IT experts are involved in the centre’s activities.

The Kazan Federal University is very active in the field of education and science, cooperating with dozens of universities; teaching conducted in Russian and English. Graduates of the Institute of Fundamental Medicine and Biology have skills in microscopy, gene diagnostics, nanotechnology, NMR, ESR, and are equipped with professional skills of a

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high-class expert. The Institute’s structure includes the Biomedical Centre for Collective Use, which comprises a genomic centre, a proteomic centre, a neurobiology laboratory, a biobank, a biomedical microscopy centre, a vivarium, a clinical diagnostic laboratory, a pharmacy research & education unit, a translational medicine centre, and other highly specialised laboratories.

As you can see, the Kazan Federal University currently has competences in both pharmaceutics and medicine, a biomedical cluster has been created, and companies coming to the republic can now rely on high qualifications of both production engineers and medical workers.

Moreover, in anticipation of the staffing requests from future pharmaceutical resident companies, the PharmMedPolis has plans to organise training programmes and projects aimed at the needs of future residents and existing republic’s enterprises.

Can you name any recently completed projects of pharmaceutical companies in Tatarstan and what projects for the

production of medicinal preparations are nearing completion?

As you know, the process of manufacturing absolutely new innovative drugs is very long and very expensive: on the average, global pharmaceutical companies can spend 7 to 10 years and up to one billion dollars to create one such drug. Nevertheless, our enterprises are developing and producing both generics and original products.

Tatkhimpharmpreparaty implemented a project in 2016 for the production of ointments and gels with a capacity of 20 million packages per year, investments to which amounted to EUR 12.5 million; the general contractor was FAVEA. Within the framework of the Pharma 2030 programme, 6 innovative medicines are at various stages of development, of which 3 drugs have completed the preclinical studies in animals and are preparing for human clinical trials. Another drug is in the preclinical study phase and two products are in the R&D phase (these are projects implemented jointly with the KFU’s Research and Education Centre for Pharmacy). Areas of application of these

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innovative products are non-steroidal anti-inflammatory drug, antibiotic, cancer medicine, antifungal, antiepileptic, and antiseptic drugs.

The above-mentioned Nanopharma Development produces three drugs against HIV infection, cancer diseases, as well as drugs used in transplantation: Civalgan for the treatment of AIDS retinitis; Imatinib for the treatment of leukaemia; Tacrolimus for the treatment and prevention of allograft rejection of internal organs (liver, kidney, heart).

In the future, the company's portfolio will include 9 more state-of-the-art drugs for the treatment of socially significant diseases.

There are plans to create contract manufacturing facilities at the Karpov Chemical Plant: negotiations are underway to locate the Advanced (India) production; technical and economic feasibility are being assessed for the localisation of pulmonary drug production by Boehringer Ingelheim (Germany) based on Tatkhimpharmpreparaty.

One of the sites at the Zelenodolsk Priority Social and Economic Development Area is hosting the construction from scratch of a pharmaceutical facility to produce state-of-the-art medicinal products in tablets, capsules and ampoules, that is now reaching completion.

Does your region have any requests from pharmaceutical companies for the conclusion of SPICs or offset contracts?

There were no such initiatives for the time being, but as I said, we have several territories with preferential tax treatment and ready-to-use infrastructure, while a legislative support of investment-active companies is provided in the republic starting from January 9, 1998, when a law was adopted “On Investment Activities in the Republic of Tatarstan”.

What do you think is acutely missing in Tatarstan today, or maybe in the Russian Federation in general, for the full-fledged development of the pharmaceutical industry (legislative initiatives, regulatory standards, legal aspects, R&D, etc.)?

In my opinion, Russia, as a matter of priority, today needs to restore the process chain leading to the development of innovative medicines. Launching a full-cycle development of pharmaceuticals in the country, from idea to pro-

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State Institute of Drugs and Good Practices

Research and Education Centre for Pharmacy under the Kazan (Volga Region) Federal University. Clean facilities for holding small laboratory animals (Grade D according to EU-GMP standards)

duction, is the main task that should be solved within the framework of the Pharma 2030 programme. We have a project that is now being discussed with industry’s experts, with a focus on collaboration and coordination of efforts among the R&D centres established earlier at Russian universities. Its main goal is the organisation of a full-cycle development of pharmaceuticals in the country, the production of at least 10 innovative drugs in the future 5-7 years for the treatment of socially significant diseases, and a steady annual production of up to 5 drugs by 2030.

Another sensible spot in the Russia’s pharmaceutical industry is the insufficient amount of investment into R&D. According to the Industrial R&D Investment Scoreboard annually published by the European Commission that reviews the performance of the top 2500 R&D investing companies in the world, pharmaceuticals and biotechnologies are now the most knowledge-intensive industries with an R&D intensity of 1415%. This rating does not include Russian pharmaceutical companies, which may be indicative of low investment

activities of domestic manufacturers.

Which in turn can be caused by a number of reasons, such as the increase in the total costs for the introduction of new drugs on the pharmaceutical market over the past few years, the need to bring production to compliance with the requirements of GMP standards and the introduction of a drug labelling system, the high cost of borrowed funds.

Thus far, government support measures consist in reimbursing for a portion of the costs already incurred by the manufacturer for a limited list of project-related activities. More active government support can increase the companies’ research budgets manifold, at least up to the level of no less than 15% of the proceeds.

As to legislative initiatives, it is appropriate to ensure, when necessary, in parallel with their adoption, reimbursement mechanisms for recovery of costs incurred by domestic producers of medicines and medical products, which are caused by changes in regulatory requirements. This measure would become a guarantee for sustainability of industrial enterprises.

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Kaluga

Pharmaceutical Cluster Business gave credence to the government course of developing pharmaceutics Interview with Vice-Governor of Kaluga Region Vladimir Popov 18 September 2018 Kaluga Region achieved substantial success in attracting pharmaceutical companies in the region. What are results for 2017, and what are further short-term priorities of the regional government in developing pharmaceutical industry?

Really, our pharmaceutical cluster achieved strong results over seven years of operation. Volume of industrial production grew five-fold over these years. More than 60 Russian and foreign companies work in the cluster. Today, it

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consolidates key elements of production chain: from pre-clinical and clinical studies, development and production of pharmaceutical substances, industrial production of finished pharma products to manufacturing of pharmaceutical packaging and recycling of waste.

Upon results of 2017, industrial production index in the segment amounted to 167%. Volume of products manufactured by the cluster companies achieved 35 billion rubles – this is the best development dynamics not only

among other segments of the regional industry, but also among the entire Russian market of pharma products.

The growth is explained by opening of new plants (six more companies joined the cluster in 2017), and also by expansion of the existing production sites. Last year, AstraZeneca, BerlinFarma and Bion achieved planned output, strongly increasing their production volumes. For example, Bion, Obninsk manufacturer of pharmaceutical substances, increased its production vol-

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ume three-fold over the last two years.

This year, two more plants, Pharm-Syntez and Sphera-Pharm will start operations. By the end of the year, we expect commissioning of the integrated laboratory block of Hemofarm LLC. I am sure that the industry demonstrates high growth rates also because businesses gave credence to the head for pharmaceutics development adopted by the government. I mean state program of import substitution and legislative acts for higher local content in pharma production adopted by the Ministry of Industry and Trade.

Two of our companies have already got substantial preferences under the terms of Special Investment Contracts.

AstraZeneka Company was the first pharma production company not only in our region, but also for entire Russia, which concluded special investment contract in 2017.

This year, NovaMedica Company got approval for the conclusion of special investment contract. NovaMedica Company will additionally invest more than 3 billion rubles in modernization of its plant and in technology transfer within the frame of this contract.

The main target of our cluster activities is to roll-out efficient, qualitative, and affordable pharma products to the Russian market. It should be noted that we are moving rather swiftly to this target. Today, the plants of the cluster manufacture more than 150 drugs requested by the market, 30 more names are at the registration stage, and more than 20 are at prospective implementation stage; they are oriented mainly for import substitution.

We have development strategy of pharma industry in Kaluga Region for the coming two years. All projects of the roadmap are agreed upon, and sometimes they are initiated by our pharma manufacturers.

Their implementation will allow attracting more than 5.9 billion rubles worth of investments before 2020. And this means not only opening of new production sites; we are oriented to higher local content and expansion of already existing production capacities.

Only one example: Novo Nordisk Company additionally invests more than 2 billion rubles in local production of three finished pharmaceutical forms.

Achieving at least 10% overall share at the Russian pharmaceutical market is also, among the targets for 2020.

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Is export one of development vectors of Kaluga pharma industry? What programs and measures are considered by the government of Kaluga Region to develop export potential?

Export development is in principle one of our priorities. If quite recently, goods were mainly imported to the region, then, beginning from 2016 we see substantial growth of export supplies.

Export to non-CIS countries increased three-fold in 2017.

Speaking about export development in pharma segment, I would like to note that we consistently cooperate with leading international companies and clusters of the segment. Over the last 5 years cooperation, agreements were signed with French Eurobiomed cluster and German Bavaria medical cluster.

Since 2012, our cluster has been full member of European Cluster Platform, consolidating more than 200 clusters worldwide. Also, an agreement was reached to maintain scientific and technical cooperation with MediconValley, one of the major pharma clusters in Europe. I can also name among our partners All-Greece Association of Pharma Manufacturers (PUPI), BIOTURKU Finnish cluster, C.H.I.C.O. (CLUSTER OF HEALTH, INNOVATION AND COMMUNITY) Italian major cluster, and many others. Last year we signed agreement for Life Sciences development in Kaluga Region with Merck (leading international company in health care technologies) and with German Steinbeis Global Institute Tubingen affiliated to Steinbeis University. It is important that international cooperation is accompanied by real joint activities; it means new investors in the region and promotion of Russian-made drugs and technologies at the international markets.

I would like to say, as far as programs and measures are concerned, that today, all conditions for export of any categories of goods are in place in Kaluga Region. Few regions currently have such opportunities for optimization of logistics processes. I mean New Silk Road Project, I mean already formed railways routes, which link the region with the countries of Europe and South-Eastern Asia. No doubt that direct access to qualitative logistics infrastructure opens great opportunities for export-oriented companies, including pharma production companies.

We apply serious efforts to assist small and medium pharmaceutical

State Institute of Drugs and Good Practices

companies in developing export-oriented projects: this includes direct financial support, interaction with various funds, agencies and tax preferences. It means, for example, advantages for the property tax. The investors, which were included in the register of investment projects, participants of federal and regional Special Investment Contracts and Regional Investment Programs, which sales revenue is at least 70% in the total revenue volume, and which total amount of investments over first three years amounts at least to 500 million rubles, are completely exempt from the tax during 5 consecutive tax periods.

What are main advantages of Kaluga Region, in your opinion, for investor making decision on the placement of its production site, or its Research & Development unit?

Beneficial geographic location meaning receptive consumer market of the Central Russia, and modern transport and logistics infrastructure providing access to pharma markets of European and Asian countries are advantages of Kaluga Region as the center of pharma production placement.

Effective system of innovation support: engineering center, business incubators, high-tech technology park etc, is implemented in the region in order to develop pharmaceutical industry.

We constantly improve our infrastructure; today we offer clear and transparent conditions of the placement at the regional industrial sites, mitigating investors’ infrastructural risks, we provide consultancy support in ‘one-stop’ format. 12 industrial parks and two sites of Kaluga Special Economic Zone offer conditions, which exceed in many ways the needs of investors. Now there is active placement process at Borovsk site of the Special Economic Zone. We plan to concentrate there major pharma manufacturers. Taking into account specifics of the industry, beginning of exemption period for pharma companies is linked not to construction processes, but to the moment when their license is obtained.

What measures of regional support are now available for developing research and technology potential, incentivizing research & development activities and developing new pharmaceutical products?

I have already told you about some

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of them, when I answered previous questions. I can add that about 62 million were spent in the period between 2013 and 2017 from the regional budget for the development of pharmaceutical cluster, and 184 million were spent from the federal budget. In general, financial support is provided in two directions. It is development of innovation and educational infrastructure of the cluster, and ensuring activities of cluster-specific organization, which is in charge of development of cluster infrastructural facilities.

One of such facilities is the regional engineering center. The center is created upon initiative of entities-cluster participants in order to provide the companies with set of technology work and services necessary for the implementation of innovative biopharmaceutical projects. We consolidated funds from federal and regional budgets and equipped the center with analytical, laboratory and process equipment. Today, small and medium biopharmaceutical enterprises of the cluster actively use the services provided by the center. The range of services allows

solving both separate tasks, and the entire set of process-related activities necessary for the implementation of innovative biopharmaceutical project: from an idea to final product. And also, substantial reduction of development and marketing time is ensured for project companies.

Availability of qualified personnel is one of the success factors for the attraction of investors in the region. Kaluga Region achieved positive results in personnel formation for pharmaceutical production. What further steps are planned in this area?

Our highest priority is the investment into education: industry-specific orientation of education, its integration in real economy. Since 2012, namely from the moment when formation of pharmaceutical cluster in the region was announced, Specialist Training Center for pharmaceutical industry has been created upon initiative of the regional government.

Specialized educational institution combines base theoretical education and practical training using real production equipment. If we talk about education-

al projects over the last two years, I can mention creation of Practical Training Center for pharmaceutical industry on the basis of MEPhI National Research Nuclear University in Obninsk. Equipment installed at the Center allows training of specialists in the environment as close to real production facility as possible.

Today, training and demonstration laboratories of the Center are equipped with clean premises module for training and research purposes. The volume of financing for this project is 27.5 million rubles. The funds are allocated from federal subsidy associated to the support program for pilot innovation clusters.

Second project is the creation of innovation and training center Virtual and Simulation Technologies in Medical Education on the basis of Tsiolkovsky Kaluga State University. Administration pf Obninsk Technology Park took part in the project implementation. Laboratories of the Center are equipped with simulation equipment. Volume of financing from federal subsidy allocated for the development of pharmaceutical cluster is 23.4 million rubles.

NovaMedica Innotech

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“Our cluster policy is targeted at the global market and development of unique innovative sectors…”

Interview with General Director Agency for Innovation Development – Center for Cluster Development of Kaluga Region JSC Anatoly Sotnikov The modern history of innovations of Kaluga Region is fairly recent. However, the speed of its progress is quite impressive. Apart from the pharmaceutical cluster, the region is currently developing several other innovative clusters. What are the principles for their formation and what forms the basis of the idea?

The principal idea for creation of clusters has been around for a long time and it reinforces the belief that an innovation economy is formed as a clustertype economy, i.e. when one technological direction consolidates investments, business, science and industry. Cluster development is expected to stimulate economic growth and support territory development. This idea is incorporated also into the regional strategy for social and economic development. We are currently implementing its third stage: having built a new industrial economy, we are proceeding to creation of a knowledge economy.

It is important to remember that a cluster cannot be created in an empty space. The objective of our agency, which acts as the operator for creation of regional clusters, is to identify the industries with the highest growth potential and to build clusters around them.

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This was the principle used to create the pharmaceutical cluster – an infrastructure for recruitment of investors and innovation development was formed around Obninsk with its impressive intellectual potential.

A slightly different approach was chosen for creation of the ICT cluster.

The first thing we tried to figure out was the number of companies operating in the segment. We identified approximately 350 regional ICT companies involved in various aspects of IT technologies. These companies are generally very small.

At the same time, when major clients like Rostelecom look for contractors to solve their objectives, they tend to focus on large companies. That is why our global objective was to create an alliance, i.e. to consolidate efforts of small companies in implementation of big projects. Today, the ICT cluster includes 120 companies, both suppliers and equipment manufacturers. Together they are developing several projects, including innovative design methods (BIM-technologies).

The initiative to create a cluster of composite materials and structures belongs to scientific and production enter-

prise Technologiya: the Obninsk-based company is a center of competences in the sphere of scienceintensive products from non-metal materials. The idea underlying the creation of the cluster was to attempt to gain access to global markets through collaboration with specialized international associations. Today, the cluster includes 23 companies, collaborates with composite clusters of Limoges and Hamburg, with Airbus aircraft building company, and develops partnerships with unique Kaluga Region companies like the Center for Sports Technologies in Balabanovo.

Finally, the youngest cluster is that of nuclear technologies, which was created one year ago. The cluster was formed around Obninsk enterprises operating in the relevant field. Its main specialization is application of nuclear technologies in non-nuclear sectors.

The cluster alliance of competences has already put together a range of proposals, developments, and products for Kaluga Region’s industrial clusters.

For the automotive cluster – projects for introduction of spare part markers, and development of new sources for accumulation and storage of electrical energy. Seven projects for new power

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a­ ccumulators are currently being patented. For the agroindustrial complex – solutions involving low-dosage exposure for treatment of seeds and harvest storage, as well as a project for construction of digital greenhouses.

For the pharmaceutical cluster – a technology for decontamination of packaging, clothes, etc. Apart from that, the nuclear and pharmaceutical cluster are conducting joint development of radiopharmaceutical products. This implies the project for manufacturing of microcapsules for brachial therapy.

Their development will open tremendous prospects – the price of similar German methodologies is three times higher that the price of our drugs.

Clinical testing has already been completed, and the certification process is nearing completion as well. Thus, we expect to satisfy local demand for this drug in the nearest future.

Today, the term “innovation” can be applied to virtually any industry sector.

How justified is this, in your opinion?

Indeed, there are several spheres that, based on associated competence levels, can be inherently classified as innovation ones. These include the IT sector, biotechnologies, manufacturing of composite materials. At the same time, traditional sectors like the automotive industry, construction, and agriculture are also active consumers of innovations.

Thus, more and more economic sectors are becoming involved with innovations.

As the line between innovation and traditional sectors becomes more blurred, the state begins to provide support to innovation activities in general, without assigning priority to specific industry sectors. I am speaking about the formation of an infrastructure for development of innovations, about federal and regional measures of support provided to various sectors of the econ-

omy. Thus, industrial policy becomes more merged with innovation policy. I think this is a reasonable trend.

How will innovation clusters develop?

In accordance with development strategies designed for each of them.

Their concepts take into account interests of virtually each cluster participant and are targeted primarily at creation of new products. Obviously, all these clusters are currently growing faster than the economy of Kaluga Region in general. Efficient development of the innovative system in the region is supported by close collaboration of business, sciene, education, and authorities. Our region provides an example for forming such type of partnership, for consolidating resources for research financing, commercialization of inventions, development of education, and creation of an innovative infrastructure.

An environment for development of innovations Interview with Executive Director of the Kaluga Pharmaceutical Cluster association Irina Novikova The pharmaceutical cluster is a unique eco-system, with all links in its chain operating with high efficiency.

What contributed to its development and viability?

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I am certain that the system’s efficient operation is largely due to the cluster approach. Kaluga Region was one of the first to choose this development model. This principle is the foun-

dation for successful development of a range of clusters, including the pharmaceutical. The cluster model provides a clear understanding of investor needs, allowing training centers to pre-

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pare required specialists and participants to implement projects of any complexity within the shortest terms.

Effective cluster development requires coordinated efforts of regional management bodies at all levels, their active collaboration with the business community and with cluster management companies.

Kaluga Region has established such a system, and this allowed us to maintain leadership in industrial production growth and new investments for many years.

Kaluga’s cluster is gaining significance in supplying Russian consumers with high-quality medical products.

What ICD drugs do the region’s pharmaceutical companies currently produce?

Virtually all products in portfolios of “anchor” companies, as well as product and innovation portfolios of the cluster’s small and medium enterprises, are applied in the most promising fields of therapy. These include cardiology, oncology, endocrinology, treatment of respiratory and gastroenteric diseases.

Our pharmaceutical companies manufacture neurological drugs, drugs for treatment of the musculoskeletal system, immunomodulators, genitourinary system drugs, and reproductive hormones. Importantly, cluster participants manufacture vital and essential drugs: diclofenac, articaine, xylometazoline, indapamide, dalargin, and many others.

One of the most important directions is the development of pharmaceutical substances. How is this work carried out?

Finished pharmaceutical substances and source materials for their synthesis are developed, among others, by BION LLC. In 2016 alone, the company brought seven new products to the market. It has established a new production line for manufacturing of substances for advanced antitumor drugs. BION has so far registered, or is in the process of registering over 30 pharmaceutical substances. Each product is unique.

I would also like to note MirPharm’s success in development of finished form products. The company’s strategy is a continuous search for highly-efficient drugs that are

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either not available on the national market, or available in quantities insufficient to satisfy current demand.

They introduced drugs like Mifepristone, Mirolute, Ginepristone, Ginestril, Traneskam, Meksiprim. Those were later included in the STADA product portfolio, and are now manufactured to its order. In 2017, the company registered 6 drugs, and early this year – another three.

It is currently in the process of development and registration of 50 new drugs intended for use in gastroenterology, gynecology, urology, emergency treatment, neurology, and oncology. Among them are highly-demanded import substituting gynecological drugs – Atosiban and Carbetocin. They are expected to become the first Russian generics of original drugs.

What projects will be implemented in the cluster format in the nearest future? Are there plans to launch new production plants?

Recruitment of investors, improvement of localization and integration processes, expansion of production capacities at existing plants, and opening of news ones, infrastructure development – there are major projects planned for each of these directions.

Two new plants will be opened this year for manufacturing of finished medical products – by Russian companies Pharm-Sintez and Sphere-Pharm.

We are also expecting the commissioning of an integrated laboratory complex by Hemofarm by the end of the year. The complex will support the expansion of the company’s research and development efforts.

New investors are being recruited, among other things, by expanding the specialized site for pharmaceutical manufacturers at Kaluga SEZ. Another direction is associated with infrastructure development by expanding services and creating a network of local service suppliers. One of the examples is construction of the Sozvezdiye 220 kV substation to support new technological connections to the Obninsk power hub.

Among educational projects is further equipment of the Practical Training Center and creation of a laboratory for synthesis of active pharmaceutical substances at the National Research Nuclear University MEPhI.

State Institute of Drugs and Good Practices

Another priority is support of exports of cluster participants. The regional government has achieved considerable progress in this direction by providing direct financial support, tax preferences, and by establishing collaboration with various foundations and agencies.

Support of exports is identified as a priority in the new Pharma-2030 program. What is your assessment of its predecessor – Pharma-2020?

Most of the support measures defined in Pharma-2020 were originally suggested by pharmaceutical manufacturers themselves. The Ministry of Industry and Trade offers support to local companies, including by subsidizing transfer of technologies. The governmental regulation “On restriction and conditions of admission of drugs originating from foreign countries…” simplified the path to success in securing state contracts for local manufacturers.

One of the undisputed successes of Pharma-2020 was the volume of investments made by foreign companies into local pharmaceutical production. Since 2007, participants of our cluster alone have invested over 50 billion rubles. This process is continuing: we have signed four agreements for establishment of pharmaceutical plants within the region.

Cluster participants are actively participating in program directions like organization of manufacturing of substances, development of innovation drugs, and manufacturing of import substituting medical products.

Thus, Sanatmetal CIS is planning to open a plant for manufacturing of various implants and prosthetic appliances in 2018.

What novelties do you expects from the Pharma-2030 program?

On the one hand, we are expecting an expansion of current subsidies for financing of clinical research, organization of manufacturing – not manufacturing of specific substances, but creation of technological lines.

On the other hand, we are relying on export support measures. The current economic situation in Russia allows our participants to expand production volumes, and creates good prospects for exports of finished pharmaceutical products.

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Wörwag Pharma Has Localized Manufacture of Magnesium Orotate at the Facilities of PIQ-PHARMA The German company Wörwag Pharma and the Russian company PIQ-PHARMA have announced a successful completion of localization in Russia, and commencement of routine manufacture of Magnerot® (magnesium orotate) at the facilities of PIQ-PHARMA LEK LLC, in the Belgorod Region 12 September 2018

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agnerot® is an overthe-counter (OTC) drug from Germany, a brand owned by Wörwag Pharma, which has been providing a benefit to Russian patients for over 20 years. Magnerot® (magne-

sium orotate) is used to treat the conditions caused by magnesium deficiency, including those in pregnancy (on medical advice), such as irritability, fatigue, sleep disturbances, muscle pains and spasms. Magnerot® has readily come into practice of physicians of various specialties – gynecologists, general practitioners (therapists), neurologists; moreover, in 2018, it holds a leading position among other magnesium products in cardiology.

The project of manufacturing process transfer has been implemented by a highly qualified team. Following the transfer of the manufacturing process, the product quality control will be performed jointly by Wörwag Pharma and PIQ-PHARMA specialists. Fast and wellworked transfer of the Magnerot® manufacturing process to the local site has ensured the maintenance of the high quality of the products and required quantity of the product for patients.

Olga Streltsova, Director General of Wörwag Pharma LLC: "The launch of the contract manufacture of Magnerot® in Russia is a major step forward in development of longterm mutually beneficial relationship.

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We consider the Russian market as one of top priority and endeavor to build a strong partnership with the State and local pharmaceutical manufacturers. Our mission statement is "Close to people. For people", and this collaboration will definitely increase availability of high-quality drug products for enhancing quality of life, which is in line with our philosophy".

The presentation of the solid dosage forms manufacturing line, where the localized Magnerot® is manufactured, was attended by representatives of the Administration of the Belgorod region, Ministry of Industry and Trade of the Russian Federation, National Association of Manufacturers of Pharmaceuticals and Medical Devices, Russian Representative Office of Wörwag Pharma, PIQ-PHARMA management company.

The implementation of contract manufacture was rated very high by Alekhin Aleksey Viktorovich, the head of the Department of Pharmaceutical and Medical Industry Development.

The PIQ-PHARMA LEK manufacturing plant has the capacity to produce annually more than a million of packages of the most popular dosage form of Magnerot®.

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State Institute of Drugs and Good Practices

ABOUT WÖRWAG PHARMA GMBH & CO. KG WÖRWAG Pharma GmbH & Co. KG is an international pharmaceutical company founded in Germany specializing in development of biofactors. The portfolio of WÖRWAG Pharma includes prescription preparations, OTC products, and biologically active dietary supplements.

Drug products are indicated for treatment of neurological diseases, cardiovascular disorders, complications of diabetes, and they promote women's health, and support immune system.

ABOUT PIQ-PHARMA GROUP OF COMPANIES PIQ-PHARMA Group of companies is a Russian full-cycle pharmaceutical holding with a 25-year history carrying out development, authorization, manufacture, as well as sale and marketing of solid and non-sterile liquid dosage forms. Besides two manufacturing sites in Russia, PIQ-PHARMA Group has an R&D laboratory for development of finished dosage forms, and conducts own synthesis of strategically crucial active pharmaceutical ingredients. PIQ-PHARMA Group is expanding its product portfolio in the following therapeutic fields: neurology, gastroenterology, cardiology, pediatrics. Currently, the pipeline comprises 5 innovative products and generics to be introduced to the market in 2020s.

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Successful Localization in Russia 21 August 2018

MSD and AKRIKHIN announce successful localization in Russia of manufacturing of finished dosage form of sitagliptin for treating type 2 diabetes

MSD, an innovative global pharmaceutical company, and AKRIKHIN, a leading Russian pharmaceutical manufacturer, announced the successful launch of local production of a 100 mg finished dosage form of sitagliptin, an oral anti-hyperglycemic drug for type 2 diabetes. The project was implemented as a part of the strategic partnership between the companies for the transfer of pharmaceutical manufacturing technology to Russia that began in 2012.

Sitagliptin is manufactured at AKRIHIN’s production facility in the Moscow region (Staraya Kupavna) in full compliance with GMP standards. The manufacturing process includes incoming quality control, preparation of the active pharmaceutical ingredient and excipients, preparation of the finished dosage form, packaging, and release quality control.

To date, 75,000 packages of sitagliptin have been produced and released. The Russian-made medicine will become available in Russian pharmacies in Q2 2018. The batches of sitagliptin that are currently in circulation have been packaged at AKRIHIN’s plant. By the end of 2018, the company plans to manufacture up to 200,000 packages of sitagliptin, starting with the stage of finished dosage form preparation.

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Marwan Akar General Director, MSD, Russia and Eurasian Economic Union

Localizing production of medicines for the treatment of socially significant diseases is one of the key pillars of MSD’s strategy in Russia. Sitagliptin has become the second MSD medicine, production of which has been localized as part of our long-term partnership with AKRIKHIN, beginning with the dosage form preparation stage. This is an important step towards improving access to highly effective and safe therapy for Russian patients in line with state priorities in healthcare and development of the pharmaceutical industry.

Denis Chetverikov President, AKRIKHIN

Localizing pharmaceutical production in Russia is one of the most effective ways of quickly populating the domestic market with modern medicines. AKRIKHIN and MSD’s strategic partnership encourages the development of the Russian pharmaceutical industry, the application of new technologies and the production of more effective, and at the same time more affordable medicines. I am confident that such close cooperation will significantly expand Russian consumers’ access to the

most in-demand medicines produced in accordance with the highest quality standards at AKRIKHIN’s production facility.

According to the International Diabetes Federation (IDF), in Russia there are 9.3 million people with diabetes, while the number of undiagnosed patients with diabetes is approximately 5 million people.

Roughly 90% of registered patients in Russia have type 2 diabetes.

Sitagliptin, developed by MSD, is the first DPP-4 inhibitor in its class. In Russia, the medicine has been approved for use in treatment of type 2 diabetes since 2007 and has been included in the List of Vital and Essential Drugs (VED) since 2015.

The joint MSD and AKRIKHIN project to localize production was initiated in 2012. Over five years of joint work, production of seven key MSD medicines has been established, for the treatment of cardiovascular, allergic and respiratory diseases, diabetes and fungal infections. Under the project, technology is transferred, production lines and laboratories are refitted and staff are given additional training.

In 2014, a project was launched to set up production of the finished dosage form of four localized products, which is planned for completion before the end of 2018. The total investment by MSD and AKRIKHIN in the project will be 330 million rubles.

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State Institute of Drugs and Good Practices

ABOUT MSD

ABOUT AKRIKHIN

For more than a century, MSD has been one of the leading global healthcare companies. We create, develop, produce and sell innovative prescription medicines, including biologics and vaccines, that help maintain and improve people’s health. MSD’s portfolio includes products to treat and prevent cancer, diabetes, hepatitis C, HIV and other infectious diseases, autoimmune inflammatory diseases, respiratory diseases, circulatory diseases, and more. We also conduct and support programs and partner projects designed to boost the accessibility of medical care. MSD has been operating in Russia since 1991, focusing on ensuring access to innovative medicines and vaccines, partnership with local manufacturers and leading medical institutions, as well as supporting medical education. We apply our extensive global experience to contribute to the development of healthcare and the pharmaceutical industry in Russia. More information is available at www.msd.ru or www.msd.com.

AKRIKHIN is one of the leading Russian pharmaceutical companies producing effective, affordable, and high quality medicines in the most popular therapeutic areas in Russia. The company is in the top five leading local pharmaceutical producers by sales on the Russian market, and continues to demonstrate significant growth and development rates. AKRIKHIN’s product portfolio comprises some 200 medicines, more than 100 of which are manufactured at a production facility in the Moscow region. AKRIKHIN’s key therapeutic areas are tuberculosis, diabetes, dermatology, cardiology, neurology, gynecology, and more. All products are manufactured in full compliance with GMP standards.

In line with state and industry priorities, AKRIKHIN is actively involved in localization and import substitution of medicines through its own R&D center and also through partnership with international pharmaceutical producers. In 2014 – 2015, as part of its import substitution program, the company released 10 medicines to the market.

AKRIKHIN is committed to regularly updating its product portfolio through its own developments and also via effective cooperation with other pharmaceutical companies and leading R&D institutions in Russia and other countries. AKRIKHIN’s production facility is located 20 km from Moscow, and includes a facility for the manufacturing of soft and solid dosage forms, annual output of which is more than 80 million packages. In 2010-2016, the company implemented an investment program to modernize production facilities that involved a total investment of more than 35 million Euros. AKRIHKIN employs 1,500 staff, 800 of which work at the production facility in Staraya Kupavna in the Moscow region.

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2 (3) / autumn 2018 Localization

Pharmstandard Released the First Batch of the Innovative Drug

Takeda has Produced the First Batch of an Innovative Oncohematological Drug for Patients with Hodgkin's Lymphoma at the Pharmstandard-UfaVITA Plant

11 September 2018

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akeda LLC (Takeda Russia) and Pharmstandard JSC announced the release of the first batch of brentuximab vedotin, trading as ­ADCETRIS®, an innovative oncohematological drug for the treatment of patients with Hodgkin’s lymphoma at the plant of Pharm-

ABOUT TAKEDA Takeda Pharmaceutical Company Limited is a global, R&D-driven pharmaceutical company committed to bringing better health and a brighter future to patients by translating science into life-changing medicines. Takeda focuses its research efforts on oncology, gastroenterology and central nervous system therapeutic areas. It also has specific development programs in specialty cardiovascular diseases as well as late-stage candidates for vaccines. Takeda conducts R&D both internally and with partners to stay at the leading edge of innovation. New innovative products, especially in oncology and gastroenterology, as well as its presence in emerging markets, fuel the growth of Takeda. More than 30,000 Takeda employees are committed to improving quality of life for patients, working with our partners in health care in more than 70 countries.

Takeda Pharmaceuticals, LLC located in Moscow, is the Russian marketing and sales organization of Takeda Pharmaceutical Company Limited, Osaka, Japan.

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standard-UfaVITA OJSC (Ufa). Localization of production will increase the availability of the drug for patients in Russia, open up possibilities for export deliveries to the CIS countries, as well as help to reduce cost of the product in the longer term.

“We are committed to provide Russian patients with innovative medicines from the Takeda global portfolio,” says Andrey Potapov, General Director of Takeda Russia, head of the CIS area, – thanks to cooperation between Takeda and Pharmstandard, we establish the production of brentuximab vedotin in Russia, and patients with Hodgkin’s lymphoma have a chance to extend their lives. On August 1, we implemented a second technology transfer project and started the production of an innovative orphan drug ixazomib for the treatment of patients with multiple myeloma at our plant in Yaroslavl. We constantly move towards our goal, and I am confident that the advanced oncological drugs that we can offer to doctors and patients today will make a significant contribution to the treatment of certain cancer types and significantly improve the quality of life of patients.”

“The localization of an innovative drug production is a complex labor-intensive process that requires the

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well-coordinated work of an international team of specialists. Brentuximab vedotin is a part of Takeda’s global portfolio of innovative medicines, and it was crucially important for us that the transfer of the production of the drug be carried out on a production site that meets aall the international and Russian requirements. We approached the choice of a partner for the implementation of this project very carefully and are glad that we chose Pharmstandard,” commented Andrey Obruchnikov, Commercial and Logistics Director, Takeda Russia. “Already this year we plan to release several thousands of packages and in a partnership with Pharmstandard we consider the possibility of increasing production next year in order to improve access to innovative treatment for patients in the CIS countries through export supplies.”

“Today, one of the focus areas of Pharmstandard is a local manufacturing of innovative drugs for treatment of oncologic and hematologic diseases.

That is why cooperation with Takeda is strategically important for us. As a result of this project, patients will get access to innovative target therapy that is a breakthrough in control of this serious disease, impairing lymphatic system.

Preservation of patients’ life and a prospect of rehabilitation are priority objectives of the Russian national policy. I am glad that we make a substantial contribution to oncologic diseases therapy and development of healthcare delivery,” noted Grigory Potapov, General Director of Pharmstandard JSC. The oncohematological drug brentuksimab vedotin for patients with Hodgkin's lymphoma was registered in Russia in February 2016 and is for use for patients with recurrent / refractory CD30 + Hodgkin's lymphoma and recurrent/refractory systemic anaplastic large cell lymphoma (SACCL)1. The drug is a conjugate of a monoclonal antibody and an antineoplastic agent that acts on tumor cells that have a CD30 marker on the surface, causing a controlled process of their death.

The introduction of this antibody into clinical practice provides patients who have exhausted the resources of classical treatment regimens, the possibility of long-term remission, and gives

a chance for a cure.

1 Instruction leaflet for medical use of the medical product ADCETRIS®. Product license ЛП 003476

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State Institute of Drugs and Good Practices

ABOUT PHARMSTANDARD Pharmstandard is a leading pharmaceutical company in Russia, included in the List of strategic country enterprises. The Company’s total manufacturing capacity exceeds 1.7 billion packs per year, and 700 thousand liters of pharmaceutical substances. Pharmstandard produces more than 330 pharmaceutical products, including medications to treat cardiovascular diseases, diabetes mellitus, growth hormone deficiency, gastroenterological, neurological, infectious diseases, and metabolic disorders, oncologic, and other diseases. More than 140 pharmaceutical products (considering all dosage forms and dosages) are included in the “Vital and Essential Drugs List”. Pharmstandard is one of Russian leading pharmaceutical companies in local manufacturing of innovative medical products of leading global producers.

Manufacturing sites of the Company meet the requirements of Good Manufacturing Practice, and are completed with state-of-theart manufacturing and laboratory equipment. The Company supplies its products throughout Russia and abroad.

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R-Pharm and AbbVie Announce the Launch of Full-Cycle Production of Kaletra® in Russia

21 August 2018

R

-Pharm Group and AbbVie, a research-based global biopharmaceutical company, announced that technology transfer for production of Kaletra® (lopinavir + ritonavir) drug for HIV/AIDS treatment in adults is completed. Kaletra® finished dosage form

will be produced at the R-Pharm manufacturing complex in Yaroslavl, Russia.

R-Pharm will use Kaletra® substance produced by AbbVie. There are 943,999 people living with HIV in Russia now. About 346,000 people constantly receive antiretroviral therapy (ART)1. The therapy coverage is steadily increasing as stipulated by the government and public goals to combat the HIV/AIDS epidemic in Russia. The number of patients receiving ART has increased by 2.76 times compared to 20122.

"Completion of the technology transfer and organization of the full cycle production of the drug for HIV/AIDS treatment is an important stage in implementation of Pharma-2020 Strategy," said Vasily Ignatyev, General Director, R-Pharm Group. “Our partnership with AbbVie should increase efficiency of combat against diseases caused by the human immunodeficiency virus".

"At AbbVie, we are committed to make remarkable impact on patients' lives. Antiretroviral therapy helps patients to live normal live, control the disease, 1 Excerpt from the speech of Olga Golodets, Deputy Chair of the Russian Government, at the 6th Eastern Europe and Central Asia HIV/AIDS Conference on April 18, 2018 http://government.ru/ news/32325/ 2 Action against HIV and other socially dangerous diseases: some figures for 6 years. http://government.ru/info/32200/

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and restrains epidemic," said Anthony Wong, Regional Vice-President, Russia, Ukraine & CIS, AbbVie. "The full cycle production is a step forward to improve access to antiretroviral therapy for Russian patients".

In order to localize the production cycle of Kaletra® in Russia, R-Pharm upgraded equipment at production facilities and laboratories, transferred analytical methods of drug and pharmaceutical substance quality control, implemented additional engineering technologies.

Great attention was paid to training of R-Pharm’s quality control employees.

The Yaroslavl-based R-Pharm's manufacturing complex for production of finished dosage forms and biotechnological substances is fully certified in compliance with the GMP requirements, and was approved by the Russian Ministry of Healthcare on March 19, 2018 for all process stages of the finished dosage form of Kaletra® production.

R-Pharm is one of the key partners of many international pharmaceutical companies. Together they execute a vast number of projects that aim at providing patients throughout the world with access to modern medicines and technologies. The projects of the company in Russia significantly contribute to the development of the pharmaceutical industry, and are implemented with respect for strategic goals and initiatives of the government.

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ABOUT R-PHARM MANUFACTURING COMPLEX IN YAROSLAVL The pharmaceutical complex for production of finished dosage forms in Yaroslavl was founded in 2010. At the moment, it employs more than 500 highly qualified specialists. Development, design, and validation of the plant were effectuated by NNE – one of the leading pharma engineering companies in the world. The facility fully meets EMA (European Medical Agency), FDA (Food and Drug Administration, USA) and GMP (Good Manufacturing Practice) standards.

The plant successfully passed several dozens of external audits executed by such companies as AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boryung, Dr.Reddy’s, Eli Lilly, Ferring, Glaxo Smith Kline, Johnson & Johnson, Mallinckrodt, MSD, Pfizer, Roche, Sanofi, and others.

The technologies that were implemented at the plant provide the highest level of consumer, personal, and environmental protection.

The product portfolio is comprised of various medicines used for treat-

State Institute of Drugs and Good Practices

ment of diseases in such spheres as oncology, hematology, cardiology, immunology, virology, neurology, endocrinology, anesthesiology.

In 2016, a new monoclonal antibodies manufacturing line developed by Xcellerx (GE Healthcare) was launched at R-Pharm complex in Yaroslavl. This allows the company to produce biopharmaceuticals and biosimilars with high export potential.

ABOUT ABBVIE AbbVie is a global, research-driven biopharmaceutical company committed to developing innovative advanced therapies for some of the world's most complex and critical conditions.

The company's mission is to use its expertise, dedicated people and unique approach to innovation to markedly improve treatments across four primary therapeutic areas: immunology, oncology, virology, and neuroscience. In more than 75 countries, AbbVie employees are working every day to advance health solutions for people around the world.

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Takeda to Produce Innovative Drug for Multiple Myeloma Patients in Yaroslavl, Russia 21 August 2018

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State Institute of Drugs and Good Practices

ABOUT TAKEDA PHARMACEUTICAL COMPANY LIMITED Takeda Pharmaceutical Company Limited (TSE: 4502) is a global, research and development-driven pharmaceutical company committed to bringing better health and a brighter future to patients by translating science into life-changing medicines. Takeda focuses its R&D efforts on oncology, gastroenterology, neuroscience, and therapeutic areas (plus vaccines). Takeda conducts R&D both internally and with partners to stay at the leading edge of innovation.

Innovative products, especially in oncology and gastroenterology, as well as Takeda’s presence in emerging markets, are currently fueling the growth of Takeda. Approximately 30,000 Takeda employees are committed to improving quality of life for patients, working with Takeda’s partners in health care in more than 70 countries.

T

akeda Pharmaceutical Company Limited (TSE: 4502) on 1 August, 2018 announced the opening of a production site for NINLARO® (ixazomib), an innovative drug for patients with multiple myeloma, at its Yaroslavl plant. The move takes the Company’s total investment in local Russian manufacturing and production of the product to 477 million rubles.

NINLARO®, which is part of Takeda’s global portfolio of innovative medicines, is indicated in combination with lenalidomide and dexamethasone for multiple myeloma patients who have previously received at least one line of therapy. NINLARO®, which has orphan drug status, was first registered in Russia in 2017, and was made available to patients locally in 2018.

“Takeda Russia celebrates 25 years of operations this year. Throughout these years, we have always sought to increase the availability of innovative drugs and new treatments for local people. I am proud that in our silver jubilee year, we have brought an innovative medicine to Russian patients with multiple myelo-

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ma, and also began its production at our Yaroslavl plant,” commented Andrey Potapov, General Director of Takeda Russia, head of the CIS area. “Yaroslavl will become only the second production site for ixazomib in the world. Critically, local production will better help meet the unmet medical needs of patients in Russia and, as we will also be able to export ixazomib produced at this facility, patients in CIS countries.”

Andrei Obruchnikov, Commercial and Logistics Director, Takeda Russia said: “We started work on transferring the production of ixazomib in 2015 and as early as the fourth quarter of the year, plan to start full cycle production. That means that even more patients will be able to access this innovative, high quality treatment.”

Dmitry Koloda, Medical Director, Takeda Russia-CIS said: “The main goal for the treatment of patients with multiple myeloma is to achieve the maximum possible clinical response with long-term disease control, while maintaining patient quality of life. Ixazomib in combination with lenalidomide and dexamethasone,

is the first fully oral triplet therapy that allows patients to receive out-patient treatment, which also reduces the burden on doctors in hospitals, and allows patients to continue to lead an active life.”

Multiple myeloma is an incurable disease and accounts for 1% of all malignant tumors, and 13% of instances of hemoblastosis (cancers of hematopoietic and lymphatic tissues) 1, 2. The disease incidence of multiple myeloma in Russia is 2.0 cases per 100,000 people, and has a mortality rate is 4.1 cases per 100,000 people, per year3. The average age of patients in Russia with multiple myeloma is 64 years3.

1 Anderson KC, Alsina M, Atanackovic D, et al. NCCN Guidelines Insights: Multiple Myeloma, Version 3.2016. J Natl Compr Canc Netw. 2016;14(4):389400.

2 Ferlay J, et al. GLOBOCAN 2008 (version 1.2), Cancer Incidence and Mortality Worldwide. Lyon, France: International Agency for Research on Cancer, 2010.

3 ЗЛОКАЧЕСТВЕННЫЕ НОВООБРАЗОВАНИЯ В РОССИИ В 2015 ГОДУ (ЗАБОЛЕВАЕМОСТЬ И СМЕРТНОСТЬ), под. ред. А.Д. Каприна, 2016.

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INFORMATION ABOUT TAKEDA PLANT IN YAROSLAVL, RUSSIA The construction of Takeda plant in Yaroslavl began in 2010 and was completed in September 2012; the production started in September 2013. The total investment for the period from 2010 to 2018 amounted to 98.9 million EUR, including 75 million EUR for the construction of the plant. The manufacturing unit occupies 24,000m2 and uses a warehouse of 6,000 pallet positions. The plant's capacity allows us to produce 90 million sterile ampoules and more than 3 billion tablets per year, which can satisfy the demand for a number of key products of the company in the Russian market and the CIS countries. In 2016, Takeda began deliveries of the plant’s production to the Republic of Belarus and the Republic of Uzbekistan.

At present, the company produces the following drugs: Actovegin®, coated tablets and solution for injections, Calcium-D3 Nycomed, and Cardiomagnyl. Drugs produced in Yaroslavl, in terms of quality, efficiency, and safety fully correspond to similar products produced in other European or Japanese plants of Takeda.

In 2015, Takeda Russia started a project to transfer technology of production of an innovative orphan drug NINLARO® (ixazomib) for patients with multiple myeloma in Russia. The

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production site was opened on August 1, 2018. It is planned that the plant will start production of the drug in finished dosage form in the Q4 of 2018. The total investment in the new production site amounts up to 477 million rubles. The Yaroslavl plant will be Takeda's second site for the production of NINLARO® (ixazomib) in the world. The newly created production capacities will allow to meet the unmet medical needs of patients in Russia and the EEU countries.

Takeda plant has 221 employees, the average age of the plant's personnel is 32 years. Takeda pays great attention to training of personnel and development of professional education in the Yaroslavl region. Together with the leading vocational education institutions of the Yaroslavl region, the company is implementing a project to develop and update profile training courses within the framework of the variable part of the educational program. Also, Takeda together with the Government of the Yaroslavl Region implemented a project to create an educational Center for Collective Use (CCU) on the basis of the Yaroslavl Industrial and Economic College. The established training and production base reproduces the conditions for the full cycle of the manufacturing processes of the pharmaceutical plant, that meets GMP requirements.

The Takeda plant in Yaroslavl continues to work on increasing production volumes and expanding range of its products.

In the near future, it is planned to localize the production of antidiabetic drugs in Yaroslavl.

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State Institute of Drugs and Good Practices

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AVVA RUS Invites

for Long-Term Cooperation in the Field of Contract Manufacturing AVVA RUS, a well-known Russian company, declared its intention to be involved in contract manufacturing: it is ready to help both Russian developers to enter international markets, and international companies to localize their products in Russia

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4 September 2018

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oday, the production site of AVVA RUS includes two separate buildings with facilities manufacturing non-sterile products. One of the buildings is dedicated for manufacturing beta-lactam penicillin antibiotics.

In autumn 2017, European state regulatory representative audited the quality management system at the Kirov ­facilities

State Institute of Drugs and Good Practices

Development Department of JSC AVVA RUS is engaged in contractual development and registration of drugs, including preparation of a Drug Master File in CTD format. The company offers to its clients a wide range of services from drug registration consulting, to development of certain documents of the Drug Master File, to obtaining Marketing Authorizations and approved documents for the drugs. Vast experience in development of both innovative drugs and generics enables the company to meet challenges of any complexity. The above works have resulted in registration of drugs in Russia and farabroad countries.

JSC AVVA RUS is a reliable partner of the Ministry of Industry and Trade of the Russian Federation, as evidenced by many successful government entrepots under the Federal Target Program “Development of Pharmaceutical and Medical Industry in the Russian Federation for the Period until 2020 and Further Prospects�.

Development Department specializes in pharmaceutical development of the following dosage forms: tablets; film coated tablets; dispersible tablets; delayed release tablets; capsules; suppositories; syrups; emulsions; powders/granules for oral suspension/solution; oral gels.

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EQUIPMENT To cope challenges, the central laboratory of the facility uses manufacturing and analytical equipment of the leading global providers. Analytics and Chromatography Group develops and validates analytical methods for excipients, developed dosage forms, and active pharmaceutical ingredients in accordance with cpmp/ich/381/95 на ICH requirements with subsequent application thereof for control. To enable the Analytics and Chromatography

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Group to perform the tests depending on the challenges set, it is equipped with the modern analytical instrumentation (HPLC, GLC, dissolution testers, etc.) manufactured by: Shimadzu (Japan); Waters, Agilent Technologies, Millipore (USA); Pharma Test (Germany).

HPLC devices are equipped with modern multi-channel gradient pumps, autosamplers, analytical column ovens, and various detectors. Flexible modular systems allow to develop, validate, and apply methods of different levels of complexity.

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of AVVA RUS for compliance with Good Manufacturing Practice.

In January 2018, AVVA RUS received the certificate of compliance with Good Manufacturing Practice (GMP EU) for medicines for human use, thereby confirming the top-quality standard of its products.

Thus, products manufactured at the facility of AVVA RUS may be registered in and supplied to the Russian Federation, near-abroad countries (Kazakhstan, Belarus, Georgia, Mongolia, Turkmenistan, Armenia, Uzbekistan, etc.), EU member states, and other countries participating in the Pharmaceutical Inspection Co-operation Scheme (PIC/S). Currently, medicine products manufactured by AVVA RUS are available in most CIS countries, and the registration processes for several products (including one beta-lactam antibiotic) are underway in the EU. The

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company also has a considerable experience in performing contract activities and in providing regulatory support.

The company is interested in localizing the products of foreign developers and manufacturers at its facilities, and offers mutually beneficial high-quality cooperation, including the localization of manufacturing for beta-lactam penicillin antibiotics.

State Institute of Drugs and Good Practices

AVVA RUS has been manufacturing its products for more than 20 years.

Currently, it has a portfolio of about 50 effective products, including both generics and original drugs designed by the company. In 2015, by the Order of Minpromtorg (Ministry of Industry and Trade), JSC AVVA RUS was listed among the companies exercising a significant influence on the Russian industry.

JOINT STOCK COMPANY AVVA RUS TELEPHONE/FAX: +7 (495) 956-75-54 E-MAIL: INFO@AVVA-RUS.RU

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Full-Cycle Pharmaceutical Enterprise

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State Institute of Drugs and Good Practices

Rafarma – full-cycle pharmaceutical enterprise was merged into PROTEK Group’s manufacturing segment in 2017 • Total 25 000 sq m, 5 selfcontained sites for the full-cycle manufacture of antibiotics, oncology and other products • R&D: research, development and testing laboratory, in-house experimental base at cleanroom • Manufacture of preparations in 15 dosage forms • Equipment: GLATT, Kilian, Romaco Macofar, IMA, CAM, Fedegari, Tofflon • 24 hectares are available for construction of additional manufacturing facilities

PARTNERSHIP ADVANTAGES • AVAILABILITY OF PRODUCTION FACILITIES FOR CONTRACT MANUFACTURING AND AREA FOR ADDITIONAL CONSTRUCTION • LOCAL PRODUCTION AND TECHNOLOGY TRANSFER EXPERIENCE • ATTRACTIVE PRICE-OFFER • INTEGRATED BUSINESS APPROACH: PRODUCTION, DISTRIBUTION AND PROMOTION OF MEDICINES • GUARANTEED SALES VOLUMES • MINIMIZED RISKS FOR INVESTMENTS RETURN

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склад

4

2

2 (3) / autumn 2018 1

5

PRODUCTION LINES SITE NO.1 / NONSTERILE DOSAGE FORMS TABLETS

Tablet press

S 250 SMART CLASSIC

Killian, IMA

100 000 tablets/hour

COATED TABLETS

Film coating machine

GMPC II

GLATT

45 kg

TUBES

Semiautomatic tube filling machine

С735

IMA, COMADIS

26 litres (35 tubes/min)

SUPPOSITORIES

Filling, sealing, coding and cutting machines for suppositories

BP-2 BP-3

Dott. BONAPACE

60 supp/hour

SACHET

Automatic machine for packaging heat-sealed sachets on 4 sides

OMAG С3/2

OMAG

120 packages/min

Aseptic powder filling automatic line

Romaco Macofar

9 000 vials/hour

Automatic machine for packaging heat-sealed sachets on 4 sides

Romaco Macofar

3 000 vials/hour

Romaco Macofar

9 000 vials/hour

SITE NO.2 / CEPHALOSPORINS INJECTABLE FORMULATIONS VIALS 10 ML NON-STERILE FORMULATIONS POWDERS AND SUSPENSIONS FOR CHILDREN

SITE NO.3 / CYTOSTATICS INJECTABLE FORMULATIONS VIALS 10 ML

Combined automatic line for aseptic powder & liquid filling

LIOPHYLIZAT

Vacuum freeze drying machine

LYO - 5

Tofflon

11 400 vials (10 ml)

TABLETS

Tablet press

S 250 SMART

Killian, IMA

100 000 tablets/hour

CAPSULES

Capsule filling machine

CD 40 12366

Romaco Macofar

40 000 capsules/hour

COATED TABLETS

Film coating machine

GC Smart 175 12053

GLATT

100 kg

Romaco Macofar

3500 vials/hour

NON-STERILE FORMULATIONS

SITE NO.4 / FINISHED DOSAGE FORMS INJECTABLE FORMULATIONS VIALS 10 ML

Combined automatic line for aseptic powder & liquid filling

LIOPHYLIZAT

Vacuum freeze drying machine

LYO - 5

Tofflon

11 400 vials (10 R)

TABLETS

Tablet press

S 250 SMART

Killian IMA

100 000 tablets/hour

CAPSULES

Capsule filling machine

CD 40 12366

Romaco Macofar

40 000 capsules/hour

COATED TABLETS

Film coating machine

GC Smart 175 12053

GLATT

100 kg

Romaco Macofar

3 500 vials/hour

NON-STERILE FORMULATIONS

SITE NO.5 / CYTOSTATICS VIALS 10 ML

74LIOPHYLIZAT

Combined automatic line for aseptic powder & liquid filling Vacuum freeze drying machine

LYO - 1

Tofflon

1 800 vials (10 ml) www.gmpnews.net

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State Institute of Drugs and Good Practices

CONTACTS +7 (495) 730–16–46 rafarma@rafarma.ru www.rafarma.ru Manufacturing Segment of the PROTEK Group Commercial Office bld. 7, 22/4, Kashirskoye highway, Moscow, 115201

The Production Complex of Rafarma 6 А, Dorozhnaya street, Terbuny village, Lipetsk Region, 399540 +7 (47474) 216–72

PRODUCTION CAPACITY Tablets Gelatine capsules Vials for injections Vials for suspensions

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1,330 billion 280 million 54 million 10 million

Liophylizat Sachets Semi-solid formulations API

1,35 million 18 million 7 million 220 kg

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2 (3)Â / autumn 2018 Good Manufacturing

Novo Nordisk

Insulin Full-Cycle Production Launched in Kaluga An official ceremony dedicated to the launch of Novo Nordisk insulin full-cycle production (finished insulin injection forms with original Novo Nordisk substance) was held on September 19, 2018 in Grabtsevo Industrial Park, Kaluga Region. Carsten Sondergaard, Ambassador of the Kingdom of Denmark, Anatoly Artamonov, Governor of Kaluga Region, Mike Doustdar, Executive Vice President, Novo Nordisk, representatives of the Ministry of Industry and Trade and the Ministry of Public Healthcare of the Russian Federation and representatives from non-governmental and patient organizations attended the event.

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19 September 2018 Agency for Regional Development of Kaluga Region

An innovative Novo Nordisk plant produces modern insulins unrivaled throughout Russia on full-cycle production basis. Now the production operations include the manufacturing of finished aseptic dosage forms in cartridges, assembly and packing of FlexPen® injection pens. Original substance manufactured in Denmark is used at Novo Nordisk plant in Russia. Therefore, the company

State Institute of Drugs and Good Practices

gets a status of a Russian manufacturer.

Novo Nordisk plant in Kaluga is the only plant in Russia manufacturing comprehensive portfolio of modern insulins.

By launching new shop for assembly of injection pens in Russia the Company proceeds to production of all modern insulins in pre-filled disposable FlexPen® injection pens (Levemir® FlexPen ®, NovoMix® 30 FlexPen®, NovoRapid® FlexPen®

ABOUT NOVO NORDISK A/S Novo Nordisk is a global pharmaceutical company with 95 years of innovation and leadership in diabetes care. This heritage has given us capabilities in treating other serious chronic diseases: haemophilia, growth disorders, and obesity. Headquartered in Denmark, Novo Nordisk employs approximately 43,100 people in 79 countries and markets its products in more than 170 countries. Novo Nordisk’s B shares are listed on NASDAQOMX Copenhagen (Novo-B). American Depository Receipts (ADRs) are listed on the New York Stock Exchange (NVO).

More detailed information is available at novonordisk.ru, novonordisk.com, Facebook, Twitter, LinkedIn, YouTube.

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2 (3)Â / autumn 2018 medicines). Pre-filled injection pens, for which 89% of insulin analogues accounted for in Russia, are the most common type of insulin injection worldwide.

Novo Nordisk plant in Russia is an example of successful investments in local production and modernization of the pharmaceutical industry of the Russian Federation. Novo Nordisk production facility complies with GMP standards, corporate standards, and Russian legislation in pharmaceutical production; apart from that, the advanced solutions in energy efficiency and environment protection are applied at the plant. More than 8 billion rubles was invested in the production development, some 300 jobs were created, and total production area is 13,000 square meters.

Currently, Novo Nordisk plant is the Russian manufacturer, which fully complies with local content targets, defined by completed ahead of time Pharma-2020 Strategy and currently developed Pharma-2030 Program; and it steadily continues to enhance local content in production for the benefit of Russian patients.

Anatoly Artamonov in his welcome speech reminded that the Kaluga pharmaceutical cluster was one of the major industrial clusters in the Russian Federation. It comprises more than 60 participants – these are international and Russian

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State Institute of Drugs and Good Practices

Anatoly Artamonov

pharmaceutical companies, small and medium innovation companies, leading research and education centers. More than 80% of the cluster production represent finished medicinal products.

Pharmaceutical companies of the region manufacture 154 products and several dozens of them are under development. “The main line of development consists in further localization and expansion of production facilities at already existing sites. I am confident that our joint efforts in the future will also promote implementation of innovative technologies in pharmaceutic industry, and which is far more important will enhance quality of life for people, who need modern medicines. We plan that by 2020 the volume of pharmaceutical products manufactured in Kaluga Region will not less than 10% of all-Russia production volume”, – the Governor added.

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2 (3) / autumn 2018

Carsten Sondergaard

Carsten Sondergaard, Ambassador of the Kingdom of Denmark to the Russian Federation, said: “Today’s event confirms reliability and long-term nature of business relations between Russia and Denmark. Kaluga Region is one of the regions the most favorable for business. Here, special attention is paid to advanced technologies and innovations. I am confident that the cooperation in pharmaceutical industry will continue”.

Alexei Alekhin, Director, Pharma and Medical Industry Development Department, Ministry of Industry and Trade of the Russian Federation, said: “Today, we saw one of the best production facilities. Novo Nordisk plant in Russia is an example of long-term partnership, which enhances drug safety, promotes investments in Russian economy and transfer of advanced technologies. Competencies, which are accumulated by joint efforts, have long-term and promising nature”.

Mike Doustdar, Executive Vice President, Novo Nordisk, noted when speaking at the launch ceremony of full cycle insulin production: “This year,

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State Institute of Drugs and Good Practices

Novo Nordisk Company celebrates the 95th anniversary of its creation, which took place just after revolutionary discovery of insulin by Canadian scientists in 1921. For almost one hundred years, the company scientists and researchers have been creating innovative biopharmaceutical products to treat such serious chronic disease as diabetes, which affects now more than 600 million persons. We also consider our input in ensuring higher accessibility of treatment for patients worldwide as very important. Coherent investment policy of the company in localizing hightech production in Russia fully complies with the state policy of the Russian administration in the development of pharmaceutical industry. Today, by launching full-cycle insulin production at Kaluga plant, we make one more important step to ensure that almost 5 million of Russian patients would have possibility to

Mike Doustdar

be treated with modern, effective, and accessible medicines, which enhance quality and duration of life”.

Vladimir Shipkov, Executive Director, AIPM (Association of International Pharmaceutical Manufacturers), said: “It is a pleasure to see that one of the leading global pharmaceutical companies, Novo Nordisk, continues to implement its long-term strategic investment projects in Russia, thus enhancing accessibility of modern medicines for patients. Transfer of advanced technologies to productions capacities located in Kaluga Region takes place within the framework of a localization process, and at the same time highly qualified jobs are created for the region residents. All this became possible thanks largely to the course declared by the state and oriented for innovative development of the national pharmaceutical industry. We express hope that even more efforts will be made in this development area by ensuring favorable investment climate, building strong regulatory system, and also with strict observance of investors’ intellectual property rights”.

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2 (3)Â / autumn 2018 Good Manufacturing

Full-cycle:

from Substance Manufacture to Original Drug Product Release

NEARMEDIC PHARMA Administrative building

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State Institute of Drugs and Good Practices

NEARMEDIC is a Russian pharmaceutical and biotech company founded in 1989 by a group of scientists from the N.F. Gamaleya Scientific and Research Institute for Epidemiology and Microbiology. The multi-vector development of the company has enabled it to be engaged in a wide range of activities such as creating and making new medicines (with their simultaneous introduction into medical practice), manufacturing and selling diagnostic testing systems, and supplying laboratory equipment for medical labs. In addition, a chain of NEARMEDIC clinics operates successfully in Moscow and other Russian cities.

20 September 2018

In 2015, NEARMEDIC finalized the construction of a full-cycle pharmaceutical plant (from manufacturing of a pharmaceutical substance to release of the original drug, KagocelÂŽ) in Obninsk, the Kaluga region. The pharmaceutical plant comprises a warehouse complex, a pharmaceutical substances synthesis building, a finished phar-

maceutical products building, a laboratory building, a highly flammable liquid storage building, a power-generating unit, and treatment facilities. The company is fitted with modern technological equipment manufactured by the leading foreign companies (such as Korsch, Bohle, IMA, Pfaudler, Italvacuum, Comi Condor, Stilmass, and others), as

Substance synthesis area

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CIS GMP news

2 (3)Â / autumn 2018

Aleksandr Mikhaylichenko

CEO

Perspective inventions and smart actions, based on the traditions of Russian science and production, are at the core of the NEARMEDIC style of operation.

well as by a domestic company (Artlife).

The main and auxiliary systems are characterized by a high level of automation and mechanization. The implemented SAP system allows for complete automation of the production, from ordering raw materials to releasing the finished product. The company has implemented a pharmaceutical quality system meeting the current requirements. The specialists of the quality control unit constantly monitor the internal production environment and the life cycle of the medicinal product, from incoming quality control of raw materials and materials to quality control of the finished product.

In 2016, the company successfully passed the license test for the right to manufacture pharmaceutical substances from chemical raw materials and medicinal products in the form of tablets.

In 2017, NEARMEDIC PHARMA LLC received an opinion on the production conformity to the Good Manufacturing Practice Requirements issued by the Ministry of Industry and Trade of the Russian Federation and was successfully certified for compliance with ISO 9001-2008 by the Slovak company, 3 EC. In 2017, the company also joined the Kaluga Pharmaceutical Cluster Asso-

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Pavel Petrov

Production manager

The main asset of our company is the team that was formed during the construction and launch of the plant.

Store binned warehouse, finished products warehouse, VNA truck

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ciation, which includes all leading pharmaceutical companies in the region.

The company pays significant attention to its personnel: it conducts trainings (both internal and external) on an ongoing basis, and stimulates internal employees’ promotion. The majority of NEARMEDIC PHARMA plant’s personnel lives in Obninsk and settlements in its vicinity. The company also has employees from Belarus, Ukraine, and such large Russian cities as Moscow and Saint Petersburg. The plant works day and night as its processes cannot be interrupted; therefore, 170 employees work there in four shifts.

For instance, NEARMEDIC PHARMA plant manufactures one of Russia’s most popular medicine for treatment of influenza and ARVI, – Kagocel. The company additionally inspects the medicinal products in order to confirm the high quality of production.

State Institute of Drugs and Good Practices

Sterilizing filtration of the solution

NEARMEDIC PHARMA plant Plant area – 22,000 m2 Number of employees – 170 people Production capacity – up to 100 million packages of medicinal products per year The official technological launch of NEARMEDIC PHARMA plant took place on 5 June 2015 All processes – from synthesizing process inputs to manufacturing finished pharmaceutical products – are conducted within the same production site.

In November 2016, NEARMEDIC presented the results of a post-marketing study, unique in its scale, that was conducted within the framework of "Treatment for acute respiratory virus infections and influenza in daily clinical practice" international project in conjunction with the International Society of Internal Medicine in cooperation with the Eurasian Infectious Diseases Society and I.M. Sechenov First Moscow State Medical University. 262 medical centers from Russia, Moldova, Armenia, and Georgia participated on the project and rolled in over 18,000 patients aged 18 to 93 years with a confirmed diagnosis of

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acute respiratory viral infection and influenza. The Project researchers included primary care physicians, therapists, family doctors, and general practitioners.

The study has confirmed Kagocel’s high efficacy in comprehensive treatment for influenza and ARVI in patients of different ages and severity of the disease, regardless of the time of prescription. The therapy with this drug demonstrated fast relief of all the symptoms of acute respiratory viral infection; the use of the drug allowed to reduce the number of patients with complications subject to systemic antibacterial drug treatment by 51%.

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CIS GMP news

2 (3) / autumn 2018 the requirements of such industry quality standards as ISO 13485, ISO 9001, GMP, i.e. – with all relevant current production standards, as well as to the international standard ISO 18385 specifically designed for manufactures of forensic products.

In addition, it is planned to organize production of alcohol and drug testing systems at the same facility. The technology of Dutch Diagnostics (Netherlands) will be transferred and localized for production of compact express tests providing for reliable detection of eleven groups of narcotic and alcohol substances in human

Tablet press for manufacturing of double-layer tablets

In 2015, the NEARMEDIC PHARMA plant won the Popular Vote ‘Russia’s Event of the Year 2015’ in the nomination ‘Russia’s Main Project in the Pharmaceutical Industry’, thereby adding its name to the chronicle of national achievements.

PLANS FOR THE FUTURE At the moment, the construction of a new full cycle production facility for manufacturing reagents for human genetic identification and establishment of blood relationship is being completed at the NEARMEDIC PHARMA plant.

Test sets will provide for comparison, for example, of blood traces at a terrorist act site with the information available to law enforcement authorities and identification of the offenders in a matter of hours. Genetic identification is essential in investigation of crimes and disasters.

Unfortunately, 98% of the corresponding Russian market is currently taken by foreign manufacturers. NEARMEDIC has a goal to reduce this global dependence. First of all, this is important because tests are used mainly in expert laboratories of the Ministry of Defense, the Ministry of Public Health and the Investigative Committee of the Russian Federation. The Project was supported by the Industrial Development Foundation of the Ministry of Industry and Trade. The production will comply with

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Clean pharmaceutical premises

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saliva within 10 minutes without any medical involvement.

In addition, the Obninsk site plans to produce a new original anti-tuberculosis drug. The Project is implemented together with the Swiss University, École Polytechnique Fédérale de Lausanne (EPFL). According to the world’s leading experts, this development is one of the most promising in recent decades. Manufacturing of this drug is also planned to be full cycle – from manufacturing the active pharmaceutical substance to releasing the original drug.

Furthermore, the company has a comprehensive portfolio of projects in the sphere of regeneration, for instance, a line of medical products for the standardized separation of stromal vascular fraction (SWF) "miniSTEM" from the patient's adipose tissue.

Collost and MatriFlex projects are focused on the creation of tissue native, i.e. natural matrices for guided regeneration of soft tissues and bones. All platform products can be used separately or in combination. They significantly enhance the tools of clinical research associates, increase the efficiency, and reduce the time of treatment, improve the recovery of patients with various pathologies and disorders.

State Institute of Drugs and Good Practices

Physical and chemical test laboratory

Production, packing area, blister packing area

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2 (3) / autumn 2018 Good Manufacturing

Petrovax Pharm

Has Launched Production of Grippol® Quadrivalent 6 September 2018

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ABOUT GRIPPOL® QUADRIVALENT Grippol® Quadrivalent is the first Russian 4-valent influenza vaccine; it was approved in 2018 (MA No. LP-004951 from 23.07.2018) . The vaccine protects against four influenza virus strains, i.e. two flu type A viruses (H1N1 and H3N2), and two type B viral cell lines (B/Yamagata + B/Victoria). It is the most advanced flu vaccine that employs an antigen sparing technology, and has a high preventive activity and safety.

The key benefit of the vaccine is a decrease of the body antigen load due to the use of Polyoxidonium (azoximer bromide), an adjuvant that enhances the immune response to vaccination and provides for cutting the antigen load threefold as compared to traditional technologies, i.e. for using 20 µg of hemagglutinin instead of 60 µg. This antigen sparing technology is unique; for more than 20 years, it has been used in Russia to produce vaccines that have been successfully administered within the framework of the national immunization schedules in the Russian Federation and other countries.

Only six countries manufacture quadrivalent vaccines on their own, including Australia, the USA, Canada, New Zealand, Germany, and France. Russia joined the club in 2018 with independent vaccine production capacities.

For the epidemic flu season 2018–2019, Grippol Quadrivalent will contain four viral strains as recommended by the WHO: A/Michigan/45/2015 (H1N1)pdm09-like virus;

State Institute of Drugs and Good Practices

A/Singapore/INFIMH-16-0019/2016 (H3N2)-like virus; B/Colorado/06/2017-like virus (B/Victoria/2/87 lineage); B/Phuket/3073/2013-like virus (B/Yamagata/16/88 lineage).

The WHO determines the viral strains to be included both into trivalent and quadrivalent vaccines on an annual basis. Following the WHO guidelines, the fourth viral strain being added for the epidemic flu season 2018–2019, as compared to trivalent vaccines, is B/Phuket/3073/2013-like virus (B/Yamagata/16/88 lineage).

In the epidemic flu season 2018–2019, Grippol® Quadrivalent is indicated for adults aged 18+. Presently, clinical trials of this vaccine in children are underway, as approved by the Russian Ministry of Health. The opportunity to administer the vaccine in the pediatric population in the epidemic flu season 2019–2020 will depend on the time of its complete approval by the MoH for this age group, with the appropriate amendments of the label.

Since 2012, the WHO has recommended using quadrivalent vaccines for influenza prevention. This is due to the necessity of boosting preventive action of flu vaccines and, as a result, reducing morbidity rates, economic losses, and increasing the trust for annual vaccination among the population.

According to health economics studies, in case of replacing a 3-valent vaccine for a 4-valent vaccine, the estimated number of prevented flu cases in Russia will be 265.8 thousand, with the avoided medical costs exceeding 2.5 billion rubles.

In 2018, Petrovax Pharm’s pharmaceutical complex in Moscow Region marked its 10th anniversary. The company has commemorated the event by manufacturing the first batches of Grippol®Quadrivalent, and making a presentation of the third production line for API, as well as suppository and tablet dosage forms.

Mikhail Tsyferov Chairman of the Board, Petrovax Pharm

Petrovax Pharm’s development concept is based on manufacturing patented products, and we continue sticking to the course charted. This is supported by the launch of Grippol® Quadrivalent flu vaccine that will provide for new opportunities both for the national health system in terms of influenza prevention, and the development of Russian pharmaceutical

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exports. We have marked the 10th anniversary of our manufacturing facility by another significant event – a presentation of the third production line that has been under construction since 2016. This is an investment project that will contribute to increasing the company’s lead on the Russian pharma market, boosting exports, creating contact manufacturing expansion prospects, including projects associated with phasing out imports.

Grippol® Quadrivalent, a 4-valent inactivated subunit adjuvanted vaccine, was authorized in July 2018 (Marketing Authorization No. LP-004951 of 23.07.2018). Presently, it is the most advanced flu vaccine with a high preventive activity and safety. Grippol® Quadrivalent is manufactured in Russia full-cycle starting from API production to the applicable GMP regulations; it is preservative-free and is supplied in single-shot syringes to protect against four influenza virus strains, i.e. two flu type A

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viruses (H1N1 and H3N2) and two type B viral cell lines (B/Yamagata + B/Victoria).

Alexey Bashkirov CEO, Chairman of the Board, Interros Holding Company

Petrovax Pharm has been an Interros company since 2014. For us, it is an important investment and a significant socially beneficial asset. We have come a long way over these years and may maintain that our cooperation is an effective business partnership model that has contributed to the implementation of largescale international projects, geographic footprint extension, and market launch of new products.

Ahead of the manufacturing complex’s anniversary, Petrovax Pharm has also presented an investment project for launching the third line to produce drug substances and finished dosage forms.

When implemented, the project will boost

production of APIs 2.5-fold, suppositories 4-fold, and tablets 7-fold. The new line will create more than 70 new jobs. The project investment is 1 billion rubles.

Pavel Nosyrev Vice-President for Production and Quality, Petrovax Pharm

Our manufacturing complex has been operating to the applicable GMP and ISO guidelines for 10 years, and is currently one of the most advanced high-tech biopharma facilities in Russia. We were the pioneers both in 2008 when we launched a prefilled syringe vaccine line, and in 2012 when we were issued an EU GMP certificate. We are especially proud of the international import substitution projects, i.e. localization of full-cycle manufacturing of a pneumococcal vaccine and state-of-theart thrombolytics. The company is still on the rise planning to boost production capacities to four lines, expand the storage area, and erect an office building.

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State Institute of Drugs and Good Practices

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2 (3)Â / autumn 2018 Packing and Marking

Track & Trace in Russia:

Race for Survival 24 September 2018

INTRODUCTION Russia decided to implement Track & Trace for the pharmaceutical market in February 2015 when the president Putin requested the Ministry of Health to develop a road map for deployment of the national Track & Trace system. Timelines set for all the activities related to system development, testing, and overall market implementation were a bit less than four years. By January 2019, the national Track & Trace system should have been fully up and running, recording all the drug movements that happens since product release till decommissioning.

Compared to other known examples elsewhere in the world, the Russian deadlines were seen as quite unrealistic by many industry sceptics. Why? Thousands and thousands of different market players including wholesalers, distributors, pharmacies, and hospitals of the giant country would have to adopt their business process and IT-systems to ensure they are capable of meeting regulatory expectations for coding and reporting. Significant list of governmental stakeholders was adding more complexity to the project: Ministry of Health, Federal Service on Healthcare surveillance (Roszdravnadzor), Federal Tax Service, Ministry of Industry and Trade, Federal Customs Service, not to

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mention municipalities were all busy trying to align on how the future Track & Trace system should work. The intrigue with timelines for full Track & Trace was resolved at the end of 2017 by endorsement of the 61-Federal Law amendment officially stated 1 January 2020 as the deadline, granting the Government the power to set earlier deadlines for full Track & Trace of medicinal products included to the essential drugs list.

The pilot, run by the government since 2017 to ensure Track & Trace smoothly deployed, clearly showed the two main challenges: low engagement of market players not being in rush to connect to the national Track & Trace system and premature system design.

Along the way Track & Trace system has been under continuous development and improvement. During 2017 and beginning of 2018, the industry was in close cooperation with the system operator, the Federal Tax Service, optimizing different reports. In the period between May 2017 till January 2018 eleven editions of the Track & Trace reporting guideline were published to meet industry needs. By April 2018, the pilot working group came up with even more proposals for reporting requirements, and was hoping for its early implementation when the Government puzzled all the pharma market players by publishing two orders: 791 and 792.

791-order defined that the Ministry of Industry and Trade (MIT) now becomes the main coordinator of Track and Trace system development while the state corporation Rostech will play the key role as a system developer. Another interesting detail introduced by the order was a requirement that each saleable unit bears a unique, centrally generated code, i.e. not by a product owner, containing two parts: identification code and verification code. This was a new reality! Almost two years the pharmaceutical industry has been running a pilot face a change of Track & Trace concept. Even more: a product owner will have to pay for every single code being generated for him and put it on the product.

792-order identified the product groups which will be in scope of Track & Trace starting from 1 January 2019. Medicinal products were not included, but according to 791-Order, MIT might give recommendations to the government for expansion of Track & Trace to other product groups.

It is interesting that the second version of the pilot guidelines also approved in April, on 24 April and published at the beginning of July did not contain a single word related to the new concept of Track & Trace system and new codes which should appear on product pack in the future.

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State Institute of Drugs and Good Practices

supported by

Evgeny Belov Industry expert

Mikhail Khazanchuk GMP expert

Nevertheless right after issuance of 791-Order the industry started analyzing the impact of the future Track & Trace concept. And the main newsmaker in those conversations became the company called CRPT that nominates as a Track & Trace system operator.

CRPT is a Russian acronym for the Center of Perspective Technology Development. The company was registered in July 2017, and according to the prominent business newspaper Vedomosti1 is a major investment project with a budget of about 200 billion rubles. Since CRPT service, crypto codes issuance will become obligatory for different industries, while not being for free, so the project is promised to be quite profitable. By 2024, CRPT will become responsible for all product groups, as it will be defined by the Government – including alcohol, tobacco, and drugs.

It’s worth to mention that by the time the debates around new crypto requirements began, the industry was waiting for Track & Trace deployment schedule in order to fine tune its project plans, not to start everything from scratch, and still be able to serialize both Rx and OTC products by 2020.

At the end of August, the industry learn about another important change – 1 https://www.vedomosti.ru/economics/ articles/2018/08/23/778803-usmanov-markirovki

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the Government Decree 1018, which officially nominated CPRT as a Track & Trace system operator after 1 November 2018, and prolonged the pilot till the end of 2019. Induatry still did not get any official guidance on interim Track & Trace implementation deadlines as well as official specifications for crypto coding requirements.

Anyone who has ever led a major project knows that changing a project leader in the middle of project execution quite often leads to different crises: project team might be disoriented due to lack of transition procedures from the priveous leader to the new one, important knowledge whether formalized or not can be lost, and so on and so forth, affecting project costs, time or quality of project results. If someone is dealing

with the major project scaling the whole country, thousands of wholesale organizations, manufacturing sites in the country and abroad, and besides changes in project leadership there is the need to implement in production new requirements 2D bar code which had not been originally considered by any project participant then the risk to comprise the whole project is high.

Let’s holistically assess the current situation with Russian Track & Trace and see what could be the outcome.

CRYPTO CODING According to the original and latest guidelines for Track & Trace pilot, 2D bar code consists of the following (see Table 1).

APPLICATION IDENTIFIER

DATA DEFINITION

01

GTIN

14 Digits

21

Serial number

13 alphanumeric characters

240

Commodity Code

4 Digits

10

Batch number

20 alphanumeric characters

17

Expiry date

6 Digits (YYMMDD)

FORMAT

Table 1

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2 (3) / autumn 2018

APPLICATION IDENTIFIER

DATA DEFINITION

01

GTIN

14 Digits

21

Serial number

13 alphanumeric characters

91

Identification code

4 Digits

92

Verification code

88 alphanumeric characters

240

Commodity Code

4 Digits

10

Batch number

20 alphanumeric characters

17

Expiry date

6 Digits (YYMMDD)

FORMAT

Table 2

AI (10) and AI (17) are not obligatory, according to the effective guidelines. To ensure code readability, it must be printed with resolution grade C or higher in accordance with ISO 15415 with X-dimension of module size varying between 0255 mm – 0.615 mm.

CRPT proposal for 2D barcode content, including crypto features, is as shown in Table 2.

Now according to CRPT, Commodity code is no longer obligatory, as well as batch number and expiry date.

Yet, manufacturers have already spent money to include new AI into 2D barcode, because earlier, the commodity code was represented by the authorities as a vital component for the Track & Trace system's functionality. Batch number and expiry date are normally included into 2D barcode as a standard international practice. Then it means that with crypto features, 2D barcode must be capable to encode 164 alphanumeric symbols vs 68 ones as per the current version of 2D barcode content.

2D barcode encoding capability is determined by number of columns and rows and associated amount of code modules in each column and row (See Picture 1).

Based on ISO 16022 Data Matrix barcode symbology specification and GS1 Data Matrix Guideline, a minimum barcode size to encode more than 160 symbols is 36 x 36 (modules) that can contain 228 digital symbols or 169 alphanumeric symbols. 2D barcode with the size 40 x 40 encodes 288 and 214 symbols accordingly.

Linear size of data matrix is determined by the number of modules in column and rows and the size of mod-

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ule (X-dimension). GS1 Standards recommendations for minimum, target, and maximum X-dimension of module2 are: 0,254 mm, 0,380, and 0,495 mm. Linear sizes of barcodes as a function module dimension and number of modules in column and rows represented in Table 33.

The vast majority of pharma manufacturing companies use ink jet printing technology to print variable data, including 2D barcode on secondary pack. And the main limiting factor of the installed printing equipment is the linear size of 2D barcode it can print, which is not more than 12 mm.

Test results obtained by several international manufacturing companies and shared with the authors show that acceptable print quality grade, i.e. at least grade C, can be obtained if the module size is equal to the targeted size – 0,380 mm. It means that to overcome the technological constraint, the number of symbols related to crypto components must be reduced from current 92 to 64 symbols, therefore 2D barcode will only include GTIN, serial number, and crypto components. In 2 GS1 DataMatrix Guideline, version 2.5, Table 6

Picture 1. 2D barcode structure

MATRIX SIZE

28 x 28

32 x 32

36 x 36

40 x 40

3 GS1 General Specification, release 18, Jan 2018

MODULE LINEAR X-DIMENSION, MATRIX SIZE, MM MM 0,254

7,12 x 7,12

0,380

10,64 x 10,64

0,495

13,86 x 13,86

0,254

8,13 x 8,13

0,380

12,16 x 12,16

0,495

15,84 x 15,84

0,254

9,14 x 9,14

0,380

13,68 x 13,68

0,495

17,82 x 17,82

0,254

10,16 x 10,16

0,380

15,2 x 15,2

0,495

19,8 x 19,8

ENCODING CAPABILITY NUMERIC

ALPHANUMERIC

124

91

172

127

228

169

288

214

Table 3

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that case, it would be possible to print a barcode with matrix size of 28 x 28 and the module size – 0,380 mm. However according to CRPT, the length of crypto component is defined by the Russian national standard 34.10-2012 to ensure required IT-security needed for off-line verification of product pack authenticity at points of sale (e.g. pharmacies).

Implementation of crypto coding as proposed currently will inevitably lead to upgrade of packaging equipment which can cost up to 300 000 Euros per packaging line at about 2,500 manufacturing sites in Russia and abroad. Otherwise manufacturers will face decrease in packaging line productivity, and high reject rate due to low 2D barcode printing quality.

From the very beginning when the industry learned about crypto coding, off line verification of product, authenticity was presented as the main reason for Track & Trace concept change.

It was claimed that not all pharmacies, hospitals and other entities in remote areas of the country have access to the Internet and thus there should be other means than data exchange with the Track & Trace system to verify packaging authenticity. This statement is quite vague. Nobody showed analysis

of where there is no access to the Internet, what could be potential market / patient impact etc. Not to say that conceptually, Track & Trace only works when all events with impact on product salability status are reported once happened.

Later the industry was explained that the idea to get money for Track & Trace service can be realized if the secondary pack bears crypto identifier to reliably track number of packs released to the market. Again, without comprehensive discussion, the claim can be hardly accepted. Think about European serialization model where the industry will pay for National and European databases/services functioning based on turnover and/or sales volume size depending on the country. The funding model will be realized without printing any special features on the pack besides the ones required by GS1 Specification.

Regardless the reason of why the topic appeared on CRPT agenda, and then after for the whole industry we don’t see in depth assessment of consequences the change will bring as we don’t see continuous dialogue on the topic between the industry and regulators: the last meeting of the pilot working group took place in April 2018.

State Institute of Drugs and Good Practices

TRACK & TRACE DATA REPORTING Obviously, to get centrally generated codes on the pack there should be special interfaces between manufacturers and Track & Trace database which were not considered before. Picture 2 reflects CRPT current thinking of the future reporting concept.

The idea is that a manufacturer sends sGTINs to CRPT cloud and receives back crypto codes generated based on sGTINs and then encoded to 2D barcode.

To realize this scheme, whatever IT-solution a manufacturer uses e.g.

SAP ATTP, Tracelink, or similar, IT-solution must be upgraded to ensure it’s capable to manage required data exchange and retention in addition to connection to the Track & Trace system for reporting. In reality, it means extra costs and future delays in development of Track & Track solutions.

Even if we imagine that CRPT will agree to decrease the amount of symbols in crypto components then still there is almost no time left to deploy everything what’s needed for Track & Trace functioning at the national scale

Picture 2. Track & Trace reporting model

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in accordance with the effective Track & Trace guidelines signed off by the Ministry of Health at the end of April.

We didn’t talk here about legal aspects of industry cooperation with CRPT after 1 November 2018 when CRPT becomes the official operator of the national Track & Trace system.

Future service level agreement has not been shared yet for public review, and it’s natural to expect that the document will require some adaptation based on market feedback. It will also require some time. And of course the industry expects smooth transition of all data and knowledge from Federal

Based on information shared by the authorities during different industry events, we expect implementation timelines for specific medicinal products categories will be published in October 2018. It’s also expected that Track & Trace timelines for 12 nosologies4 will be May 2019. It could be feasible if we are still in the paradigm of the effective pilot guidelines i.e. without crypto coding. However, the regulators sound quite confident promising that crypto coding requirements will be a part of the new Government Decree regardless many industry concerns. It means that after October, the whole

Considering low industry readiness and complexity of track & trace processes it’s worth to think about phased approach to full Track & Trace deployment.

Tax Services to CRPT with very minimum changes affecting all the results achieved so far.

Until now we talked about technical aspect of the proposed reporting changes. But what about system business contingency? What should the industry expect from that perspective?

And what would happen if the system is out of service for couple of hours, or more? Manufacturing sites in different parts of the world will have to stop production of lifesaving drugs. This topic has never been comprehensively reviewed and discussed with the industry.

WHAT’S NEXT? Above we provided an overview of challenges, which pharmaceutical industry faces with implementation of Track & Trace in Russia in general and specifically with respect to planned introduction of cryptography. Let us now discuss how the situation is likely to develop and what industry and regulators can do jointly to constructively deal with these challenges.

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industry will find itself in the new reality and as a consequence the pilot has to be re-started. Manufacturers will have to resolve already known technical constraints with crypto coding and thousands of wholesalers, hospitals and pharmacies will have to install specialized equipment to verify off-line authenticity of salable units and allow decommissioning.

Besides the challenges discussed above, industry involvement to Track & Trace preparatory activities is fairly low due to a lot of uncertainties with legislation and low awareness level about forthcoming. According to the latest status of registration to Track & Trace system shared with industry by the authorities as of September 2018: About 9,000 organizations are registered, including MAH and importers, out of estimated 380,000 organizations across Russia, which need to be registered. One may note that registration of organization in the state track & trace system has very little to do with actual ability and readiness of such organiza4 323-FZ On citizens health security

tion to report Track & Trace data into the state Track & Trace system.

About 1,100 medicinal products are registered, out of approximately 30, 000 medicinal products registered in Russia. It shall be noted that registration of medicinal products in the state Track & Trace system itself does not say anything about company readiness to supply particular medicinal product serialized and aggregated.

About 13 million of secondary packs out of 65,000 millions of secondary packs entering market circulation in Russia every year are registered during last 1.5 years.

Considering low industry readiness and complexity of Track & Trace processes, it’s worth to think about phased approach to full Track & Trace deployment. The industry knows quite a lot of successful examples when Track & Trace deployment started from serialization and salability verification at the point of dispense and only after reliability of implemented solutions is proved, full Track & Trace was implemented. The main reasons for such approach were to avoid serious disruption in supply chain affecting medicinal products availability on the market.

After decision to change the system operator, as defined in the Government Decree 1018 mentioned earlier and crypto coding deployment, as mentioned earlier it is now very time to consider: Reloading of the pilot working group under Roszdravnadzor supervision with appropriate representation of regulators and industry Establishment of regular working contacts between industry & CRPT via working subgroups per individual Track & Trace implementation topics, such as, for example, a) coding requirements, b) reporting requirements, c) legal and organization aspects of implementation, d) IT connection to the national Track & Trace system must be established Development of feasible requirements for Track & Trace implementation including reporting requirements, crypto coding, and approach to deployment.

The ultimate goals of the industry and regulators is to development such Track & Trace requirements and such implementation concept that all tasks set by the Government for track & trace system will be fulfilled at minimum possible cost for the industry, and with minimum risks for supply chain disruptions.

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Innovative Drug Development of the Kazan Federal University 10 September 2018

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In

the Scientific and Educational Center of Pharmaceutics of the Kazan Federal University, a portfolio of innovative drug candidates has been developed in 2010-2018. The distinctive features of these molecules are the focus on the treatment of socially significant diseases, 100% originality with the intellectual property protection in Russia and the key world markets, high manufacturability.

Several drug candidates have the potential of the best in the world in their classes. Some molecules act via unique mechanisms which have not been reported in literature so far. The industrial partner and the owner of sub-licenses for products that entered preclinical phase is JSC "Tatkhimpharmpreparaty" (Kazan, Russia). The commercialization plans for each product involve the transfer of a license for global commercialization after completion of phase I or II clinical trials,

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and the organization of production and sales in Russia and the Eurasian Economic Union countries. Industrial partners and investors are invited to collaborate on development and commercialization of this product portfolio. Below is a summary of key projects.

DRUG CANDIDATES ENTERING CLINICAL PHASE Anti-inflammatory drug. A first in class dipharmacophore prodrug molecule belonging to a group of nonsteroidal anti-inflammatory drugs (NSAIDs).

When administered orally to the body, it releases under the influence of chemical and biochemical factors two active components, pyridoxine and naproxen, which then exhibit unique synergistic effects. As a result, in all key pharmacological parameters (acute and chronic anti-inflammatory activity, analgesic activity, acute toxicity, gastric ulcerogenicity, pharmacokinetics profile), the drug significantly outperforms all the market available NSAIDs. It is planned to

complete clinical trials and start sales in Russia in 2023.

Anticancer drug based on an innovative inhibitor of ABC-transporters. The first in class innovative inhibitor of ABC efflux transporters represents a chiral supramolecular nanoconjugate of oligoether polyol nature (OEP inhibitor).

OEP inhibitor significantly potentiates the efficacy of anticancer drugs, since most of them are substrates of ABC-transports. Importantly, OEP inhibitor is highly safe after intragastric and intravenous administration to animals. A fixed-dose combination of OEP inhibitor with doxorubicin (MDR-dox) is significantly superior to unmodified doxorubicin in terms of safety and in vivo antitumor efficacy. It is planned to complete clinical trials of OEP inhibitor and MDR-dox product in 2023.

Antibacterial drug. This drug represents a structurally modified antibacterial agent of fluoroquinolone group.

Comparative preclinical studies with the best world analogues demonstrated that the modification resulted in increased antibacterial activity and improved safety. Most importantly, it also significantly decreased the ability of bacterial

State Institute of Drugs and Good Practices

pathogens to form drug resistance. It is planned to complete clinical trials and start sales in Russia in 2024.

DRUG CANDIDATES AT THE STAGE OF PRECLINICAL STUDIES Antifungal drug. After topical administration, this first in class agent inhibits the most dangerous fungal with high efficiency. In terms of efficacy and safety, it outperforms the best market available analogs. It also reduces the potential of fungal pathogens to develop drug resistance.

Antiseptic agent. A first in class drug for external use with a broad-spectrum microbicidal activity against the most common and dangerous bacterial, fungal and viral pathogens. Suppresses the potential of pathogens to develop drug resistance.

Antiepileptic drug. A first in class drug for peroral use acting via mechanisms of indirect inhibition of NMDA and activation of GABA receptors. In animal models, it effectively treats even severe epileptic seizures and demonstrates excellent level of safety after chronic administration.

Antineoplastic drug. This first in class agent has a unique mechanism of action associated with a biochemical reprogramming of malignant cells, which has not been reported in literature so far.

Drug for the treatment of diabetes complications. The mechanism of action is based on inhibition of Maillard reaction which leads to formation of advanced glycation end products. This first in class agent demonstrates potent cardio-, neuro-, nephro-, and retinoprotective activity and excellent safety profile.

Antimycobacterial drug. A structural modification of isoniazid. The modification does not impair antimycobacterial efficacy, but it reduces toxicity and suppresses the potential of M. tuberculosis pathogen to develop drug resistance.

AGENTS AT THE DISCOVERY PHASE There are up to 10 lead compounds demonstrating promising pharmacological potential in the following therapeutic areas: anticancer, antibacterial, antidiabetic, osteogenic, cardiovascular, etc.

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How Can the Russian

R&D Industry Help the Global One?

20 September 2018

P

opulation in the world is growing, life expectancy is increasing- under the influence of these worldwide factors Pharma & Biotech industry is transforming in the direction of personalized medicine based on the principle of P4 (predictive-personalized-preventive-participatory). A new patient-oriented model where treatment result is focused on the patient, is

spreading in the medicine. Limited access of patients to modern treatment technologies and high cost of treatment are hindering development of this model. Therefore, it is important to create drugs to treat previously incurable diseases or to upgrade known molecules without resorting to high-cost technologies. But large global manufacturers do not have the mobile potential to produce small

NovaMedica Innotech

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Boris Sysuev Doctor of Science, Director R&D of “NovaMedica Innotech”

batches of drugs for the treatment of orphan diseases or for targeted therapy.

In Russia, Pharma & Biotech industry is also undergoing rapid growth and transformation. Indeed, already today artificial intelligence technologies allow us to optimize research process, thus shortening time for the development of new dosage forms. As an example we can mention cooperation between the Technological Center of NovaMedica Innotech and the Skolkovo Innovation Center as part of the project for creation of drugs based on oligonucleotides that have anti-inflammatory and regenerative effects.

The current model of the pharmaceutical business in the context of R&D in Russia reflects the world trends. One of the striking examples is R&D Center of NovaMedica Innotech. It belongs to the group of CDMO (contract development and manufacturing organizations), whose task is to provide services following the “one contact” principle: pharmaceutical development, technology development, technology transfer, and manufacturing of small batches of products – both for clinical trials and for manufacturing of finished products batches (based on the GMP license).

The Center possesses a bunch of unique technologies that allow to carry out the whole cycle of pharmaceu-

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Alexandr Rudko MBA, Head of “NovaMedica Innotech”

tical development, taking into account modern international requirements.

The pipeline of the products under development includes tablets (with and without coating), prolonged-action tablets and other various modifications of tablets. Also, NovaMedica Innotechhas the competence to develop and produce soft gelatin capsules and hard gelatin capsules with different fillers.

And the availability of pellet equipment provides opportunities in terms of range of experiment in the development of new, unique dosage forms and development of individual technological solutions for complex molecules and compositions On the basis of such centers, it is advantageous to implement localization programs for manufacturing of drugs in the territory of Russia, when the center performs all set of activities related to the development and technology transfer to a local site.

Availability of modern technological and analytical equipment (Bosch, Erweka, Agilent, Shimadzu, etc.) at NovaMedica Innotech allows maintaining standards of quality and drug development (both new and within import substitution), as well as confirming the requirements of foreign pharmacopoeias.

Currently, Russia has a government decree that establishes special prefer-

ences for manufacturers of domestic drugs included into the EDL list – it is called “third-is-out rule”. According to this decree, the drug manufacturer which has no localization in Russia will not be able to offer its products in the state procurement system.

Using the potential of Russian R&D centers, it is possible to increase the amount of developments and the subsequent release of drugs for the treatment of orphan diseases. And due to the availability of manufacturing sites, the Technological Center of NovaMedica Innotech can in addition help to launch manufacturing of small batches of products in a short time. Large manufacturing sites lack flexibility and speed required for rapid changeover.

Summing up – Russian R&D centers can help foreign drugs get a "residence permit" in the territory of Russia.

Russian R&D centers work in a global context, quickly track global trends and new directions in the development and manufacturing of new drugs. We are working on the creation of new dosage forms: various kinds of tablets, capsules (solid and soft), products obtained with the help of modern technological platforms, including extrusion technology. This allows us to apply and implement innovative technologies that are in demand by global manufacturers.

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Final Report 13 September 2018   Source: achema.de Photos: Jean Luc Valentin

Higher international character, clear trends, satisfied exhibitors, but fewer visitors: these are the keywords to summarize ACHEMA 2018

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F

rom 11 to 15 June 2018, 3,737 exhibitors from 55 countries presented the latest equipment and innovative processes for the chemical, pharmaceutical and food industries on more than 132,000 m² at the world's leading trade fair for the process industry.

EXHIBITION GROUPS By far the strongest growth was recorded by the Pharmaceutical, Packaging and Storage Technology exhibition group, where two additional halls were rented due to strong demand. In view of the strong trend towards digitization and automation, it is not surprising that the "Instrumentation, Control and Automation Techniques" group was also able to grow. However, "traditional areas" such as mechanical process engineering and safety technology also occupied slightly more space, while other groups such as plant construction or laboratory technology recorded slight losses.

cals Product Group at Bosch Packaging Technology, shares this impression: "Achema has proven once again, that it is the most important international trade fair for Bosch Packaging Technology in the field of pharmaceutical and process technology. Our booth was very well attended throughout the week and we had many qualified discussions with trade visitors from all over the world".

A very eye-catching trend this year: the numerous booths where visitors could experience systems and equipment in "Augmented Reality" with the help of special glasses or even test their skills in completely virtual environments. The three focus topics were very well accepted. Numerous exhibitors presented modular solutions and intelligent components for the factory of tomorrow under the label "Flexible Production". "Biotech for Chemistry" included process development and plants from the laboratory to the fermenter that integrate biotechnological processes into the chemical industry.

"Chemical and Pharma Logistics" made

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the progressive integration of the supply chain visible and appealed to new target groups that are increasingly no longer "only" service providers but system partners of the process industry.

"We have been participating at ACHEMA for more than 60 years – and the fair is still a highlight for us. Our approach of focusing even more strongly on consulting services in solid/liquid separation has proven its worth. Many discussions revolved around possible attempts to enable us to offer the respective company a tailor-made filtration solution. In the pharmaceutical industry, the focus is shifting more and more to the modular configuration of systems for use in various applications," says Detlef Steidl, Director of Sales Filtration Technology at BHS-Sonthofen. "Compared to previous years, the number of visitors has decreased slightly. This was particularly true on the first day of the fair. At the same time, internationality continues to rise: in 2018, exhibitors and visitors from Asia in particular increasingly shaped the image of the fair.

INTERNATIONALITY Behind Germany (1,644 exhibitors / 78,909 m²), China (342 exhibitors / 5,694 m²), and Italy (307 exhibitors / 12,366 m²) showed the largest number of exhibitors, both with significant growth compared to the previous event in 2015. The number of exhibitors from India and the Russian Federation also increased, as well as from Poland, South Korea, and Turkey. The number of exhibitors from the Netherlands, Belgium, and France remained constant, while the number of exhibitors from the USA, Austria, and Great Britain declined. The proportion of exhibitors from abroad rose again to 56 %, which is higher than ever before.

ATMOSPHERE The products and technologies presented aroused great interest among the audience. "The exhibitors we talked to and we ourselves had a very successful fair," said Jürgen Nowicki, Chairman of the ACHEMA Committee and Member of the Linde Engineering Board. Uwe Harbauer, Member of the Board of Management of Bosch Packaging Technology and Head of the Pharmaceuti-

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Photo: Jean Luc Valentin

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Фото: Jean Luc Valentin

VISITORS A drawback for the organisers was the drop in visitor numbers to around 145,000, which the organisers attribute primarily to the more complex registration procedure, due to the increased security requirements for major events.

"This certainly cost a few spontaneous visitors," says Dr. Thomas Scheuring, CEO of DECHEMA Exhibitions. Nevertheless, we will analyze the numbers very diligently".

The results of the visitor and exhibitor survey, from which further information on the visitor structure can be obtained, will be available shortly.

CONGRESS The ACHEMA Congress covered the entire spectrum of chemical process technology and biotechnology. The presentations allowed insights into current research and the latest scientific results.

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On the first three days of the fair, current topics in particular were dealt with on a separate theme day: Resources, digitization and energy and climate. Above all, the digitisation topics, but also the lectures on the subject of energy, aroused particular interest. The concept of the PRAXISforums, which was introduced in 2015, was very well received; the events in the immediate neighbourhood of the halls, which are primarily intended to bring exhibitors and users together, were well attended throughout.

The two panel discussions were also very well attended. The question "Plastic-Free Europe – is a plastic-free Europe possible and sensible?” was debated controversially. The panelists agreed that plastic is indispensable and that a combined approach is needed to address the problem of plastic waste.

Of course, it is particularly efficient to avoid plastic waste wherever possible.

On the topic "Digitalization meets process Industry", experts from indus-

try and science discussed the challenges facing industry. Do companies have to change their business models in view of digitization? With regard to the right approach for the digitization of the process industry, the panelists agreed that every company should have a digital strategy that focuses on the customer.

PERSPECTIVE The next stop for the process industry is AchemAsia, which will be held for the first time in Shanghai from May 21 to 23, 2019. As the " International Expo and Innovation Forum for Sustainable Chemical Production in China", the "little sister of ACHEMA" focuses on the current trends in the process industry in China and Asia.

The next ACHEMA will take place in Frankfurt from June 14-18, 2021.

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GMP news

in Partnership with ACHEMA 2018 13 September 2018

T

his year, the informational project of the pharmaceutical industry, GMP News, not only became a media partner for the large-scale event, but also took an active part in the exhibition.

Specifically for this event, the summer issue of CIS GMP news, an English-language magazine, was pub-

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lished, describing the opportunities of the pharmaceutical markets of Russia, the CIS countries and the Eurasian Economic Union. The summer issue of this English-language magazine was published with the support of the leading pharmaceutical holding company in Russia, Pharmcontract Group, the Russian innovative full-cycle pharmaceutical

enterprise Rafarma, JSC, as well as the Czech supplier of active pharmaceutical ingredients (API), IMCoPharma.

The main topics discussed at the GMP News stand included the following: contract manufacturing of medicinal products and technological equipment for the Russian pharmaceutical manufacturing sites.

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Achema 2018, LAMSYSTEMS stand

The joint exhibition area organized by the Russian Export Center embraced twelve Russian companies. Russian participants included, for instance, private holding LAMSYSTEMS CC, PharmTechnologies LLC, and other enterprises.

At its stand, the Russian firm ROLSTECH exhibited the most recent modification of a device for labeling ampules, cartridges and vials.

"Such equipment is being used at the

best known enterprises in Russia and Belarus, including local plants of the global pharmaceutical leaders. The device is innovative in its full control of the label, including the QR and pharmaceutical codes, the quality and accuracy of applying variables and 100% quality control at the end of the process. The device has sparked much interest in specialists, and we are currently conducting focused negotiations regarding its delivery to various countries of the

world," commented Vladimir Royzman, CEO of ROLSTECH. A multi-million euro contract between Pharmasyntez OJSC and GEA for the purchase of three lines for airtight production of strong hormone medicines was signed at ACHEMA 2018.

Vikram Puniya, President of Pharmasyntez Group, noted: “When it comes to the production of hormone medicines, many critical parameters must be taken

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into account, for example, operator safety, dosing, cross-contamination, etc. GEA has offered us a high-quality solution meeting all of these requirements. We understand that reliable solutions require significant investment, but quality is the highest consideration for the pharmaceutical industry, and that's why we choose GEA." During his visit to Frankfurt, Rustam Minnikhanov, the President of the Republic of Tatarstan, visited ACHEMA 2018 exhibition. According to the President’s press service, Rustam Minnikhanov began his tour around the exhibition with the stand of the Republic of Tatarstan, which provided information about the economy of the Republic, its industrial and investment potential, The President of the Republic of Tatarstan, Rustam Minnikhanov Photo: president.tatar.ru

operate at the regional level. We were delighted to accept the invitation to the ACHEMA 2018 international exhibition, which is one of the most popular and well-known venues in the industry," emphasized the President of Tatarstan.

The ACHEMA International Exhibition was first conducted in 1920 and has since then been held every three years.

The exhibition is organized by DECHEMA Gesellschaft fĂźr Chemische and Technik und Biotechnologie e.V. The ACHEMA 2018 Exhibition and Congress once again became a showcase of technological standards and developments for the future of the pharmaceutical industry.

Pharmasyntez JSC and GEA sign contract at ACHEMA 2018

the structure of petrochemical production, and leading Tatarstan companies.

Also, the President of the Republic of Tatarstan visited the exposition of Buhler, Lodige, BASF, Festo, Linde, Siemens, and other companies.

At the meeting with German business leaders, Rustam Minnikhanov thanked for the invitation to the exhibition, noting that such events contribute to further development of business cooperation between enterprises of Tatarstan and Germany within Russian-German relations.

"We are very grateful to the governments of our countries. Despite all political disagreements, we have an excellent opportunity to conduct business and co-

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ACHEMA 2018, REATORG stand

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III All-Russia GMP Conference with International Participation in Kazan

15 September 2018

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his year, the conference was held in the hospitable Kazan – the capital city of Tatarstan. More than 1000 participants took part in the event, which became a record number of all previous years.

On August 27, during the opening ceremony, welcoming remarks addressed to the participants came from the office of the President of the Republic of Tatarstan, the Ministry of Health of the Russian Federation, the Federal Service for Surveillance in Healthcare, the National Center for Standardization and Health of the Russian Ministry of Health, and the Eurasian Economic Commission.

Viktor Yevtukhov, State Secretary – Deputy Minister of Industry and Trade of the Russian Federation addressed the participants and guests of the conference, "Today, more than a thousand participants gathered for the event. We see that interest in the area grows heavily with every year, and this un-

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derlines its importance. It is important that the All-Russia GMP conference this year has significantly expanded its agenda, providing more opportunities for discussions, negotiations and obtaining expertise on the market. I am confident that the conference will add to the development and further strengthening of Russian pharmaceutical manufacturers."

DRIVERS OF THE RUSSIAN PHARMACEUTICAL MARKET A plenary session dedicated to the 'Drivers of pharmaceutical market growth. Global View' came up first on the business agenda of the III All-Russia GMP conference with international participation Russia and the World. Management of the

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pharmaceutical market growth potential.

The moderator of the discussion, Vladimir Shipkov, Executive Director of the Association of International Pharmaceutical Manufacturers (AIPM), referred to measures offered by the Chinese government in support of their pharmaceutical industry. They include – among others – attractive market environment and a shorter wait time for registration of innovative pharmaceutical products most wanted in the healthcare system and already registered in the ICH region, i.e. no more than three months for orphan drugs, and six months – for non-orphan ones.

Valentina Kosenko, Deputy Head of the Federal Service for Surveillance in Healthcare talked about legislative measures in Russia used for active development of pharmaceuticals. For example, the risk-based approach in drug circulation lifts the burden off bonafide participants on the pharmaceuti-

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cal market, and helps identify those who are reluctant to follow government regulations.

Aleksey Alekhin, Head of the Department of Pharmaceutical and Medical Industry Development of the Russian Ministry of Industry and Trade took part in the session. He identified a number of drivers that have impact on the pharmaceutical market, i.e. interaction between key players of the pharmaceutical market, protection of intellectual property, and growing exports. Regulatory standards remain the main driver, "One of the regulatory reforms to be implemented by the Russian Health Ministry is the introduction of a conditional registration system. This will allow carrying out extended clinical trials immediately at the time of introducing medicines to patients or their commercial sales. The Russian Ministry of Industry and Trade has actively supported pharmaceutical manufacture within the frameworks of the government program."

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Business representatives from NovaMedika, Novartis, and the General Director of GeroPharm Group, Petr Rodionov, shared their views on what exactly can make a difference for the growing pharmaceutical market. "Looking at the basic drivers and influencing factors in the industry, we are certain that regulatory norms provide the foundation on which the industry develops. Without the standards, supporting measures would be less effective".

Examples of support at the regional level were sounded in the reports of the Minister of Industry and Trade of the Republic of Tatarstan, Albert Karimov, and Deputy Head of the Moscow Department for Science, Industrial Policy, and Entrepreneurship, Kristina Volkonitskaya.

BUSINESS MEETS GOVERNMENT On Day One – during the panel discussion devoted to the Pharmaceutical industry of the Future. Government and business perspectives. – the participants touched on the most urgent issues including interaction of key players in the pharmaceutical market. The panel was honored by offi-

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cials from the Russian Ministry of Industry and Trade, the Russian Health Ministry, the State Institute of Drugs and Good Practices; and business circles from BIOCAD, Nanolek, Teva, GEROFARM, MSD, Merck Biopharma Russia & CIS, as well as a representative of Pharmaceutical Innovations (Association of Pharmaceutical Companies). The audience shared their understanding of what the industry should be like in ten years.

The Ministry of Industry and Trade is actively working on Pharma-2030 Strategy, and the conference has become another tool to fine-tune this document of utmost importance for Russian pharmaceutical industry.

"On behalf of the Russian Ministry of Industry and Trade, I would like to thank all those who took part in drafting the strategy. We held a series of meetings and developed a unanimous position of all stakeholders, highlighted the milestones that should be followed in the Development Strategy for pharmaceutical industry. I would like to draw your attention to the fact that since we are in charge of evolving production competencies through 2030, the whole document is about industry. And there no doubt that as an industry we need to rely on market laws," said Alexey Alekhin, Head of the Department of Pharmaceutical and Medical Industry Development of the

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Ministry of Industry and Trade of the Russian Federation.

Education and human resources simply could not be left out of the discussed issues. Leaders of the prominent academic institutions, i.e. the St. Petersburg State Chemical and Pharmaceutical University, the Kazan Federal University, the Scientific Centre for Expert Evaluation of Medicinal Products shared their professional expertise in that respect. Personnel training now requires additional investments that universities and colleges cannot always accommodate. Challenges of globalization and digitalization of economy, growing appeal of IT technologies make education in the industry impossible without modeling systems.

The delegates called on Strategy authors to pay attention to success stories of foreign product localization. Representatives of foreign companies – Merck Biopharma Russia & CIS and Teva – shared their insights on making Russian market a priority for investments.

"The Strategy should be aimed at finding solutions to secure an innovative breakthrough for Russian pharmaceutical industry. Russia should become a country where innovations from all over the world are striving – it concerns molecules that are already being developed in the Russian Federation and

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those that are designed abroad; sooner or later they will find the way to the Russian market most probably through the localization mechanism," said Andrey Kolesnikov, TEVA CEO for GR and Market Access in Russia and Eurasia.

Effective interaction between all market participants is the key to the development not only of the pharmaceutical industry, but also of the country’s economy as a whole. Defining clear goals and objectives for the next ten years will now set priorities in the training of export and production specialists. As the session moderator – Dmitry Chagin, Chairman of the Board of the EAEU Pharmaceutical Manufacturing Association – expressed hope and confidence to hear Russian businesses at the largest international conferences sharing success stories of localizing their products in foreign countries.

NEW GMP TRENDS IN THE EAEU REGULATORY SYSTEM On Day Two of the III All-Russia GMP conference, Elena Denisova, Deputy Head of the Department of Pharmaceutical and Medical Industry Development of the Russian Ministry of

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Industry and Trade, moderated a panel discussion dedicated to New GMP trends in the EAEU regulatory system .

In meetings with their international peers, the delegates reviewed a number of issues including new trends in the technical regulation of the EAEU good manufacturing practices, common pharmaceutical market, rules and procedures of GMP inspections in line with the EAEU guidelines, and current inspection standards.

Valery Koreshkov, Member of the EEC Board (Minister) for Technical Regulation, spoke about legal foundations of GMP regulation in the Eurasian Economic Union. The commission is currently developing a large block of the 3rd level documents covering all key aspects of GMP inspections.

"A GMP compliance certificate is an essential part of the registration dossier. The GMP rules have been developed based on international experience, and European guidelines, in particular."

Dmitriy Rozhdestvenskiy, Head of the Coordination Department for drugs and medical devices circulation of the EEC Department of Technical Regulation and Accreditation, drew the audience’s attention to different types of inspections that must be considered and correctly interpreted to shape up

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proper marketing tactics, "The first thing that comes to mind, in addition to the existing routine and random inspections, they can be divided by team composition into single-auditor and team inspections."

Professor Natalya Pyatigorskaya, Head of the Industrial Pharmacy Department of the Sechenov First Moscow State Medical University, Member of the Council for Pharmaceutical Competence, Ph.D., expanded on EAEU regulatory requirements for certification of qualified persons in pharmaceutical manufacture. According to Professor Pyatigorskaya, the certification procedure includes verification of required education, relevant training and work experience of qualified persons in line with the EAEU procedure and GMP rules of the Union, regulating QP job portfolio. Based on the findings, a respective EAEU regulating authority certifies the QP indicating pharmaceutical manufacturing activities for which the QP was certified.

GDP inspections results for the past years came from Yelena Stepkina, Head of the Administration for Implementation and Development of Good Pharmaceutical Practices and International Standards of the National Center for Expertise of drugs, medical devices and medical equipment of the Kazakhstan Ministry of Health and Social Development. The de-

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nial rate of GDP inspection results is going down compared to last year's figures. Yelena mentioned some defects leading to deviations: improper storage, lack of evidence of equipment qualification, inadequate documentation, and others.

Nurylbek Asylbekov, Deputy Chair of the Pharmaceutical Committee of the Kazakhstan Health Ministry shared GMPinspections experience. Among major defects, he noted lack of validation of critical processes, lack of qualification of technological equipment, insufficient information provided in the registration dossier, and contamination in cleanrooms.

Chinara Mambetalieva, Head of the Quality Assessment of Drugs and Medical Products, Department of Medicines and Medical Devices, Kyrgyzstan Health Ministry, told the audience about legal framework governing the establishment of Pharmaceutical Inspectorate in the Kyrgyz Republic. As provided for in the General Quality Requirements of EAEU Pharmaceutical Inspectorates (Decision No. 82 of the EEC Council dated November 03, 2016) the Statute of the Department of Good Practices and Quality System of the Pharmaceutical Inspectorate are currently in the works. It will include policies, quality manual, SOPs, records and reports, training for the pharmaceutical inspectors. Among upcoming trends, Chinara mentioned

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effective interaction with inspectors of the EAEU regulatory authorities in the area of pharmaceutical circulation and eventual integration into the Pharmaceutical Inspection Cooperation Scheme (PIC/S).

That did not exhausted the discussion. Participants and speakers reviewed the regulatory system in detail during master classes scheduled for the following day, the Day of Best Practices. Practical master classes of leading industry experts on current issues of pharmaceutical manufacture: GMP inspection, data integrity, qualified persons, and production regulation (radiopharmaceuticals case study).

"Last year, we noted genuine interest that QC/QA experts demonstrated in our practical sessions. Most participants preferred to attend the GMP inspection class: delegates with great interest and involvement took part in our event where we navigated the audience through the most difficult situations that our inspectors encountered. This year we plan to increase the site to accommodate all comers; also we will have no simultaneauos sessions so that our guests are able to visit all scheduled master classes," – said Natalia Chadova, Head of the Administration for Pharmaceutical Products Inspection and Evaluation of the State Institute of Drugs and Good Practices.

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INTERNATIONAL IMPACT OF THE III ALLRUSSIA GMP CONFERENCE The program book described Day Two as the day of international activities. Russia is part of the global pharmaceutical market. Interaction between countries, common market, international experience in GMP, GDP, GEP, labeling of pharmaceuticals made their way into the conference agenda.

Vladislav Shestakov, Director of the State Institute of Drugs and Good Practices started the day with highlighting main discussion topics such as: distinctions of pharmaceutical legislation and GMP regulation in different countries, regulatory convergence of GMP inspections and procedures, impact of global regulatory approaches on development of drugs, and opportunities for country-to-country interaction.

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An important goal of the event was to harmonize the GMP rules and make efforts towards mutual recognition in the international community. This year more than ten foreign regulators took part in the conference, including Japan, the U.S., Cuba, Mexico, Bulgaria, Croatia, Kazakhstan, Kyrgyzstan, and others.

"GMP harmonization and mutual recognition – as we know – are quite a job to do. In this regard, today the ability to integrate effectively into crosscountry associations is at the forefront. Day Two of the conference mostly covered the said issues," said Vladislav Shestakov.

Pharmaceutical company Akrikhin organized an expert discussion of the issues of smart use of resources and country-to-country cooperation in GMP area as well as mutual recognition. Elena Popova, Director for Regulatory Policy in Healthcare Sector, Association of International Pharmaceutical Manufacturers (AIPM) moderated the session.

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Within the framework of the session, the participants discussed the role of the European Medical Agency in GMP inspection and quality assurance; current issues of drug quality evaluation throughout its life cycle; reviewed Russian and international requirements; specifics of pharmaceutical legislation and GMP regulation in different countries; approaches to GMP inspections in different regulatory jurisdictions (the EU vs the U.S.), etc.

For example, Isabela Majich – Head of the Croatian Inspectorate (HALMED) – talked about practical outcomes of the MRA of GMP inspections signed between the United States and the European Union. She noted that ‘capability’ of the Inspectorate does not mean adhering to the inspection order and production control identical to those of the US FDA. She cited some assessment criteria of inspectorate’s preparedness: legal and regulatory power to conduct inspections in accordance with the GMP rules, experience of ethical resolution of conflicts of interest, experience of evaluation and mitigation of risks, employment of inspectors with relevant qualifications, work experience, skills and knowledge necessary to identify manufacturing malfunctions that pose potential risks to patients, and tools available for protection of public from harm of low-quality pharmaceuticals.

Stephan Rönninger – Amgen’s Director for Quality and External Relations – drew attention to the existing state of affairs in GMP inspections. There have been a lot of changes and improvements: innovation and best practices have drowned out of the traditional industries, the volume of foreign inspections increased significantly compared to 2010, new laws and regulations came into force. There is almost no interruption in pharmaceutical supplies.

Bogdan Kirilov – Executive Director of the Bulgarian Drug Agency – noted that successes of the Russian GMP Inspectorate and the Russian pharmaceutical industry would have been impossible without their cooperation based on two principles – professionalism and enthusiasm.

At the end of the session, Anna Arutyunova – Quality Director of Valenta Pharm – presented on the company’s tactics for compliance with quality standards, "Quality policy exists in our company since its foundation. Because it is aimed at the company’s strategic goals, we have been carrying out production activities for many years in accordance with GMP standards. One of the fundamentals of our company’s quality policy is ongoing improvement, therefore, we

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extended the standards of good practices to cover not only the manufacture, but also many other aspects: i.e. preclinical and clinical GLP/GCP trials, pharmaceutical QbD developments, QPPV pharmacovigilance, etc. One of the tactical moves in the process of improvement was the launch of a high-tech research and production complex, where all processes are implemented in accordance with the best world quality standards. This means to demonstrate efforts Valenta Pharm takes to follow international standards and apply the best world’s practices throughout the life cycle of innovative and other drugs – from their development, research and registration to production and subsequent monitoring.

We readily embrace advanced technologies, digitalization of technological processes, and the newest standards in personnel development, procedures, and infrastructure. I can say with confidence that quality assurance should be a strategic goal of all responsible manufacturers who value their reputation, aim at development, and seek to improve life quality of their fellow citizens."

Tatarstan’s pharmaceutical industry attracts investments into the region – that was the motto for presentation of the Republic’s investment, scientific, and educational capacity for pharmaceutical and biopharmaceutical companies that plan to localize in Russia, organize contract manufacturing or joint development of innovative drugs.

“Significance of the conference for each of us and for pharmaceutical industry in general is obvious. It is necessary for knowledge transfer, sharing information on main GMP trends in the pharmaceutical market. Compliance with GMP standards is an important development strategy for Russian pharmaceutical industry. New markets and increased exports of domestic products will remain out of reach without strict compliance with international quality standards. The conference this year substantially expanded its business agenda, there has been more opportunities for discussions and negotiations between experts and pharmaceutical market professionals. The conference revealed Tatarstan’s potential. The Republic has created a unique investment climate. Scientific and technical capacity for the successful development of the pharmaceutical industry, universities, high tech laboratories – all are concentrated here“, – commented Timur Khanannov, CEO of TatKhimPharmPreparaty JSC. International experience in implementation of labelling of medicines for human use was also part of the internation-

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al day discussions. Experts exchanged opinions on mandatory labeling in Russia, reviewed international regulators’ take on introduction of pharmaceuticals traceability systems, and the current state of affairs in Russia.

Joseph Traple – Head of the Global Technologies Division of Takeda Pharmaceuticals International – spoke about international experience in implementing labeling and came to the following conclusion, ‘It is necessary to demand that suppliers stick to standardized solutions using software that complies with the GAMP5 standard, as well as GMP regulatory requirements.’

Andrey Akhantyev – Head of Economic Security, GEROPHARM – noted that his company supports pharmaceutical labeling in all seriousness, "We fully support the project introducing labeling and monitoring of drugs circulation, because we believe that this will completely clear the pharmaceutical market of adulterated and falsified products. We have equipped our production lines with the necessary equipment and software, and we have repeatedly tested the entire supply chain. At the present time – however – it is extremely important to agree on clear, transparent, and consistent rules – especially for those participants who are yet to join the project.

A majority of pharmaceutical manufacturers fear that uncalled for and unjustified cryptographic protection (with codes generated and sold by a monopolistic private company) as well as absence of clear regulations will slow down the project and fail Federal law 61 introducing mandatory labeling. It may also increase risks associated with rejected products, exports of drugs, dependence on an outsourced crypto codes, transfer of a hefty array of commercial data to a private company with vague obligations, and grave liabilities to stakeholders in pharmaceutical industry and the government."

Overview of GEP trends. EAEU ISPE discussion rounded up the international agenda. The discussed issues included technical regulation and standardization of manufacturing guidelines and rules, interaction between professionals in the pharmaceutical industry, high tech API production, and Pharma 4.0.

BEST PRACTICES DAY August 29 was the final day of the III All-Russia GMP conference with international participation. The venue was

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zoned into master classes. Leading experts covered current issues of pharmaceutical manufacture. The organizers took a serious approach to preparation and had collected requests from industry professionals for discussion topics beforehand.

Liliya Titova, Executive Director of the Union of Professional Pharmaceutical Organizations noted that the entire conference was very practical, which distinguished it from other similar events, and allowed participants to get specific skills that are hard to find in professional literature. According to her, the third day – the day of the master classes – is the best day of the conference.

Sanofi Russia supported the master class on GMP-inspection that marked the beginning of the busy schedule day. Natalia Chadova – Head of the Administration for Pharmaceutical Products Inspection and Evaluation of the State Institute of Drugs and Good Practices of the Russian Ministry of Industry and Trade moderated the event.

The participants discussed inspection of drug manufacture, management of GMP inspections, as well as differences between GMP inspectorates in different countries. Elena Denisova, Deputy Head of Department of Pharmaceutical and Medical Industry Development of the Russian Ministry of Industry and Trade noted: "Our inspectorate needs assistance in its first steps, the Russian pharmacopoeia – however – does not need to be adjusted to others. The first Russian pharmacopoeia appeared at the age of Catherine the Great, that is, in the mid-18th century, so the history of our pharmacopoeia is very rich; we have experience no less than other countries. We say yes to harmonization, but no to mimicking."

Olga Maklakova, Quality Director Akrihin Staraya Kupavna raised the issue of GMP inspections from the manufacturer’s point of view. In her speech, she touched upon the GMP inspection of Russian manufacturers by the EAEU procedures, "I think it is in the applicants’ best interests to submit registration dossiers according to the EAEU rules, and we are all pressed for time prior to the inspection. Therefore, QA should be proactive in registration, supportive of the company’s intent to receive EAEU certificates, and take concerted and timely actions."

At the end of the master class, the results of the survey conducted by the organizers prior to the conference were summed up to identify areas of the industry and, in particular, GMP inspections, which should be improved according to manufacturers and experts.

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Manufacturing regulation of certain pharmaceuticals groups (radiopharmaceuticals, blood products, etc) were at the center of discussion among pharmaceutical industry professionals at a master class supported by Pharmimex.

Experts, including foreign inspectors, raised the following questions: licensing of nuclear medicine facilities, production of API’s for RPh’s, and requirements for new RPh’s development.

Natalia Aladysheva, Deputy Head of the Division for Pharmaceutical Licensing and Inspections of the Russian Ministry of Industry and Trade, moderated the class. She established a successful dialogue between representatives of the state inspectorates and drug manufacturers.

Igor Falkovsky, Head of the Department of Good Engineering Practices of the State Institute of Drugs and Good Practices moderated the third day’s master class on data integrity. It brought together representatives of international companies responsible for compliance. At the master class, Gilda D’Incerti, PQE General Director presented a Data Integrity Guide for the industry, which was developed in cooperation with the The State Institute of Drugs and Good Practices.

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SUMMARY Sixty companies supported the III All-Russia GMP conference with international participation in 2018. Valenta Pharm was the general partner, while Gedeon Richter and TatKhimPharmPreparaty were strategic partners. Many pharmaceutical manufacturers supported both the conference, and specific sessions. For example, Amgen partnered in the session dedicated to Modern regulatory system. New trends and interaction modes, as well as the closing ceremony.

The event aroused great interest in the media: about 40 accredited outlets, more than 15 information partners, including industrial and federal ones. The conference was also supported by professional organizations such as the Russian Association of Pharmacy Networks, the Association of Russian Pharmaceutical Manufacturers, the Moscow Pharmaceutical Society and the Union of Professional Pharmaceutical Organizations.

Full halls at each session and each master class have proven the relevance and significance of the conference, which means that in one year from now experts of pharmaceutical industry will convene again at the GMP conference.

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2 (3) / autumn 2018 Exibition, Forums, Conferences

Russia's BIOTECHMED Conference – an International Hit

12 September 2018

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ore than 1400 delegates from 17 countries took part in Russia’s top conference focusing on biotechnologies and pharmaceutical industry. More that 300 companies from all over the world took part in the exposition and business programme, which included 19 open panels and two closed meetings with 210 participating speakers.

The forum’s exhibition consisted of 22 booths, while 33 partner companies presented state-of-the-art biomedical technologies. The programme also included press conferences of key participants of the plenary session, the Russian Export Center (REC); the presentation of the physiotherapeutic equipment for arterial blood pressure correction by Schwabe. "Startup-rally-2018" biomedical projects contest

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final was the closing event for BIOTECHMED 2018.

"BIOTECHMED is not only a space helping to establish a dialogue between the industry players, but also an exhibition site allowing to demonstrate the recent developments in pharmaceutical and medical industries, Russia's Minister of Industry and Trade Denis Manturov said. – The forum mainly focuses on biotechnologies that have been actively entering medical services for mass market. They change the image of medicine and form radical competitive advantages globally.

For example, active introduction of advanced information technologies into medical sphere can fit into the category, as well as personal medicine development, post-genomic technologies, etc.", he added.

During his speech at the forum's plenary session that was dedicated to the national project on healthcare, Russia's Deputy Minister of Health Yevgeniy Kamkin noted: "One of the strategic targets of the development of the Russian Federation is to boost life expectancy to 78 years by 2024 and to 80 years by 2030. In accordance with the national targets the country's Ministry of Health has developed "Healthcare" National Project passport, which includes eight federal projects".

BIOTECHMED has been actively developing, and has seen the number of its visitors doubling during the three years of its existence. The event is traditionally held with the support from the Ministry of Health of the Russian Federation, the Ministry of Industry and Trade of the Russian Federation, Rostec State Corporation, Krasnodar Territory Administration. Russian Export Center is the general partner, JSC National Immunobiological Company is the strategic partner of the forum.

"We think that the level of attention to the forum, the number of delegates present at the venue, and the number of federal and regional media covering the event show that biomedical technologies industry in Russia has truly been gaining

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­ omentum. To accomplish "Healthcare" National m Project purposes and tasks, we should pay more attention to early-stage diagnosis. The whole medical industry focuses on that. Most medical devices and medications that were presented at BIOTECHMED 2018 are also mostly designed for early-stage diagnosis and preventive treatment", said Olga Piven, BIOTECHMED director, while summarizing the forum results.

"Project workshops were held in June as part of the Russian Export Center, where the support measures plan was drawn up. These measures will become a part of the national project to support exports and will allow us to achieve the targets mentioned by the Russian President Vladimir Putin in his May decrees. Let me remind you that according to these decrees the pharmaceutical products export is to reach $2.8 billion by 2024, while medical devices export is to double. The main problem of Russia's pharmaceutical industry is the complexity and high costs of testing abroad to obtain international certificates, which allow shipping the products abroad.

We are preparing a set of measures which will let the companies to use the finance support measures with utmost effectiveness to fulfill these tests", said Irina Kashirina, REC Head of the medical and pharmaceutical industry export support project during the press conference.

"Preventive treatment is the key to longevity and the new paradigm of the country's healthcare. Today the priorities obviously drift from curing the illness to its prevention, health care activities. The AVR051 device for arterial blood pressure correction we

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presented at BIOTECHMED is one of the results of our work targeted to boost life expectancy in Russia.

As of today we have already reached agreements on exporting the device, including a Malaysian partner and stipulating the introduction to South-East Asia and China markets", said Ivan Ozhgikhin, Schwabe Deputy CEO, during the new device presentation.

Among partners of the forum are Russian Venture Company; BIOCAD biotechnology company; Prospective Technologies Development Center; Techmash; Schwabe; National Center of Informatization; Takeda Russia; JSC Pharmasyntez; Pharmaclon; Siemens Helthineers; MSD; State Research Institute of Highly Pure Biopreparations, Russia's FMBA; IRVIN 2 LLC; Diaprocess LLC; JSC POZiS; Geropharm.

RUSSIAN EXPORT CENTER ACTED AS BIOTECHMED 2018 GENERAL PARTNER Russia's key biomedical technologies forum BIOTECHMED 2018 was held in Gelendzhik on September, 9-11 with the Russian Export Center acting as the general partner of the event.

Medical services and devices export was one of BIOTECHMED 2018 key topics. During the forum, its participants discussed the questions of Russia's pharmaceutical, biotechnological, medical, and cosmetics industry enterprises development and realization of their potential.

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REC, being the state-owned development institution, acted as an expert during the forum's programme, occupied a separate pavilion at the exhibition, and hosted a press conference. The Center specialists shared the information on the existing export cycle, entrepreneurial activities in exports, and external economic activity.

According to the Edict of the President of the Russian Federation Vladimir Putin, the Russian enterprises should double the non-resource non-energy export volumes during the next six years. During the Forum, REC organized a series of events and meetings dedicated to the questions of the Russian medicine and medical services export.

On September, 10 Irina Kashirina, REC Head of the medical and pharmaceutical industry export support project, spoke during the panel "Export cooperation development in biotechnology and biomedicine". The participants discussed export development measures in the context of cooperation among Russia's Minpromtorg, REC and the manufacturers, taking into account successful cases.

Irina Kashirina also took part in the panel "The strategy of Russia's cosmetics industry development".

The session included discussion of R&D competences development, as well as export potential of Russia's cosmetics industry.

BIOTECHMED forum also included a press conference with Irina Kashirina. The press conference touched upon the plan on Russia's medical and pharmaceutical industry export support measures that

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are to enter the national project "International cooperation and exports" and will allow reaching the targeted indicators designated by Russia's President Vladimir Putin.

"Russia's pharmaceutical industry main problem is complexity and high costs of testing on foreign markets in order to obtain international certificates which would allow exporting the products. We are now preparing a set of norms that will allow the companies to more effectively use the financial support measures to pass these tests", said Irina Kashirina.

REC occupied a separate pavilion at the exhibition, which acted as a venue for talks and meetings between foreign buyers and exhibitors.

"I'm sure that hosting such forums like BIOTECHMED with REC acting as the general partner will also help to raise interest in our country – it is critical to openly discuss with all the stakeholders the future development of this direction, which is crucial for the economy", said Andrey Slepnev, REC General Director while summarizing the forum results.

More than 1,500 experts from 52 regions and more than 300 companies took part in BIOTECHMED 2017 forum. JSC National Immunobiological Company; JSC Schwabe; LLC NCI; JSC POZiS; JSC Pharmasintez; Skolkovo Foundation; OOO MERK; ­ ZAO BIOCAD; Russian Helicopters; NP ­Biotechnology of the Future; Novaya Meditsina LLC (DOC +); Marathon Pharma; Konversiya NPO; NIPK Elektron; NPP Pharmaclon; ChemRar; ELTA Company and GRPZ became BIOTECHMED forum partners.

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About GMP news

In

autumn of 2010, the first edition of the “GMP news” industry magazine was published. The print edition was created to spread the information about international standards for manufacturing medicinal products in Russia and CIS countries. Thanks to “GMP news”, professionals and specialists are up to date with everything regarding the pharmaceutical market. Among the main topics is modernization of pharmaceutical productions in accordance with GMP, development and launch of new medicinal products into production, changes in regulatory rules and standards introduced not only to pharmaceutical market of CIS, but international markets as well.

“CIS GMP news” – an English language publication – was created to show readers the modernization and the development of pharmaceutical industry of Russia, EAEU, and CIS countries in general. Special attention is given to localization of pharmaceutical industry, technology transfer, contract manufacturing in order to give the professional community from different parts of the world a chance to cooperate in scientific research, and business.

To learn more about “GMP news” project, go to gmpnews.net/about

Media Partnership

M

edia partnership is one of the ways you can cooperate with “CIS GMP news”. We offer media partnership to everybody interested – organizations, learning centers, conferences, exhibitions, magazines, newspapers, internet portals, and other mass media.

We also extend our partnership to pharmaceutical industry specialists and experts, who are going to be able to publish topical articles on manufacturing of medicinal products on the pages of our publication. Companies are invited to share the details about their work as well.

Today, our project is comprised of internet news portals GMPnews.Net (in English) and GMPnews.Ru (in Russian), and print publication – magazines «Новости GMP» in Russian, and “CIS GMP news” in English. This allows us to spread the information of our partners quickly and efficiently! In addition, an every day newsletter with fresh publications is sent out to our subscribers, is broadcasted in news aggregators and social networks.

We are always happy to work with you on mutually agreeable terms!

Contact email: editor@gmpnews.net

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