Russia through the prism of the world biopharmaceutical market

Biotechnol. J. 2007, 2 DOI 10.1002/biot.200700091 www.biotechnology-journal.com 

Review 

Russia through the prism of the world biopharmaceutical market 

Dmitrij I. Bairamashvili 1 and Mikhail L. Rabinovich 2 * 

1 Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russian Federation 

2 Bach Institute of Biochemistry, Russian Academy of Sciences, Moscow, Russian Federation 

Trends in the Russian pharmaceutical biotechnology and related fields representing the major sector 

of domestic biotech are reviewed through the prism of the world biopharmaceuticals market. 

A special emphasis is placed on biogenerics and follow-on biologics. The revival of national pharmbiotech 

is seen in close cooperation between private companies and the state, academia and industry. 

One of the first positive steps toward promoting development of domestic biopharmaceuticals 

is the Federal Program of subsidized supply of expensive pharmaceuticals (Dopolnitel’noe 

Lekarstvennoe Obespechenie). The program allows the Russian government to purchases expensive 

drugs to be provided free of cost to certain preferential categories of individuals. As an 

example, production of recombinant human insulin by the largest Russian fundamental biotechnological 

institute, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry under the trademark 

Insuran (Insulin produced by the Russian Academy of Science) is reviewed. Some prospects and 

problems of Russian biotech research related to medical area are briefly discussed. 

Keywords: Biopharmaceuticals · Russian market · Biogenerics · DLO · Insulin 

1 Introduction: Biopharmaceuticals: leaders of 

the world biotech market 

World sales of biopharmaceuticals have grown from $22.7 

billion in 2000 to $59.5 billion in 2005, demonstrating a 

most impressive annual growth rate (15–33%) compared 

to the other biotech products. The world biopharmaceutical 

market is set to almost double by 2011 [1, 2]. These accomplishments 

have been possible due primarily to the 

development of rDNA technology since the mid 70s, 

which has opened new and exciting opportunities in genetics, 

molecular biology and biotechnology. 

Correspondence: Dr. Dmitrij I. Bairamashvili, Pilot Facility, Shemyakin- 

Ovchinnikov Institute of bioorganic chemistry, RAS, Moscow, Russian 

Federation 

E-mail: bdi@kou.ibch.ru 

Abbreviations: API, active pharmaceutical ingredient; DLO, Russian abbreviation 

of the Federal Program of subsidized pharmaceutical supply; Epo, 

epoetin; GNC, Russian abbreviation of the State scientific center; GNC 

HPB, GNC for highly pure biopreparations (St Petersburg); HGH, human 

growth hormone; IBCH, Shemyakin-Ovchinnikov Institute of bioorganic 

chemistry; rHI, recombinant human insulin; (r)IFN, (recombinant) human 

interferon; VNII, Russian abbreviation of the All-Union (ALL-Russian) scientific 

research institute 

BTJ 07/07 | TD | DOI 10.1002/biot.200700091 

Received 17 May 2007 

Revised 29 May 2007 

Accepted 4 June 2007 

Improvement of transformation methods of the genetic 

apparatus of different host cells has resulted in incorporation 

of foreign genes in the genetic material of the 

bacterial, yeast, plant, insect, or mammalian host cultures. 

This has allowed cloning and expression of pharmaceutically 

important proteins on an industrial scale 

and created a new branch of pharmaceutical industry providing 

modern healthcare with principally new therapeutic 

products [3]. 

The first practical success in biopharmaceuticals 

achieved due to recombinant (r) DNA technology relates 

to molecular endocrinology, namely treatment of insulindeficient 

patients suffering from diabetes mellitus. First 

attempts of chemical synthesis of human insulin gene 

have been made by Genentech in cooperation with Eli Lilly 

by the end of 1970s [4, 5], and, as early as in 1980, recombinant 

insulin was already being tested by volunteers 

[6]. In 1982, after successful clinical trials [7], the US Food 

and Drug Administration (FDA) approved the first biotech 

drug, human insulin produced by genetically modified 

bacteria. 

GALLEY PROOF 

* Additional corresponding author: Professor Mikhail L. Rabinovich 

E-mail: mrabinovich@inbi.ras.ru or mirabi@mail.ru 

© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 1

Biotechnology 

Journal 

Insulin is the oldest medication for diabetes treatment 

and necessary for patients with type 1 diabetes, as their 

pancreas is unable to produce endogenous insulin. Although 

first successful attempt of autologous hematopoietic 

stem cell transplantation in patients suffering from insulin-dependent 

diabetes mellitus type 1 [8, 9] gives the 

patients a hope to avoid insulin injections, the need of insulin 

for the treatment of diabetes is still increasing. In addition, 

insulin is used in combination with sulfonylurea 

and biguanide to treat patients suffering from type 2 diabetes. 

There is a trend towards the greater use of insulin 

therapy to treat type 2 diabetes, which contributes to the 

market growth. According to the World Health Organization 

(WHO) estimates, more than 180 million people 

worldwide suffer from various forms of diabetes and this 

number is likely to more than double by 2030. In 2005, an 

estimated 1.1 million people died from diabetes and almost 

80% of diabetes deaths occurred in low- and middleincome 

countries. Most notably, diabetes deaths are projected 

to increase by over 80% in upper–middle-income 

countries between 2006 and 2015. Almost half of diabetes 

deaths occur in people under the age of 70 with 55% of diabetes 

deaths affecting women. WHO projects that diabetes 

deaths will increase by more than 50% in the next 

10 years if no urgent actions are taken (http://www. 

who.int/mediacentre/factsheets/fs312/en/index.html). 

Although insulins and analogues represent only 40.1% of 

the global diabetes market (worth $18.6 billion in 2005), 

they have shown the largest sales growth at 17.3% in 2005 

compared to 11.5% overall anti-diabetic market growth. 

The Top 10 leading anti-diabetic brands include four insulins 

(Lantus, Humalog, NovoLog/NovoRapid and Novolin) 

(The Global Biotech Report 2006 http://www.bioportfolio.com/cgi-bin/acatalog/info_100.html.). 

Besides recombinant insulins, other protein hormones, 

cytokines, and colony-stimulating factors (CSFs), 

modern recombinant vaccines also represent very fast 

growing sector [10]. Therapeutic monoclonal antibodies 

(mAbs) produced by the hybridoma technique are also 

quickly gaining a leading position in biopharmaceutical 

market with sales of $20 billion in 2005 [11]. Besides diabetes 

mellitus, the list of major diseases treated by modern 

biopharmaceuticals includes blood disorders, multiple 

sclerosis, various forms of cancer, some infective diseases 

like hepatitis and AIDS, as well as enzyme deficiency 

disorders, arthritis and ophthalmic disorders. A 

quarter of biopharmaceuticals sold in 2004 were for treatment 

of blood disorders. The emergence of new anticancer 

drugs such as Avastin, Herceptin and MabThera 

also contributed to the sales growth. The oncology market 

experienced a double-digit growth with an increase of 

product sales of more than 20%. The Top 8 players in the 

cancer market are represented by Roche, Johnson & 

Johnson, AstraZeneca, Novartis, Amgen, Sanofi-Aventis, 

Shering-Plough, and Eli Lilly. Cancer blockbusters include 

such biopharmaceuticals as Phase II pipeline mAb 

2 © 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 

BTJ 07/07 | TD | DOI 10.1002/biot.200700091 

Biotechnol. J. 2007, 2 

Volociximab (M200), Phase III pipeline recombinant vaccine 

BiovaxID, as well as drugs in registration: humanized 

mAb Panitumumab, recombinant vaccines Gardasil and 

Cervarix (Business Insights, http://www.bioportfolio. 

com/bioreports/Business%20Insights.htm). 

Biopharmaceuticals currently represent the strongest 

growth sector in the pharmaceutical market. Although 

the biotech sector remains a relatively small proportion of 

the total drug market (8% globally in 2004), approximately 

27% of new medicines in active development are now 

biotech products. Biopharmaceuticals have shared 12.5% 

of global prescriptions in 2004. The gap in small molecule 

drug approvals versus biological approvals is reducing 

year by year, and in 2004 the US FDA has approved 54 

new biopharmaceuticals. Of the 76 blockbuster products 

in 2004, 11 were biologics, while Humira, Rebif, Avastin 

(bevacizumab), and Erbitux (cetuximab) have attained 

blockbuster status by 2005. The launch dates and current 

sales volumes of the most important biopharmaceuticals 

are summarized in the Table 1 [12]. 

Sales of the Top 3 bioproducts of 2005 [epoetin (Epo)-α, 

recombinant human insulin (rHI), recombinant interferon 

(rIFN)-α] reached $17 billion [13]. The Top 5 selling drugs 

in 2002–2005 included Enbrel [tumor necrosis factor 

(TNF)αR-Fc fusion protein, Amgen/Wyeth], Remicade 

(anti-TNFα chimeric mAb, J&J/Shering-Plough), Rituxan/MabThera 

(anti-CD20 chimeric mAb, Roche), Eprex 

(Epo-α, Johnson & Johnson), Epogen (Epo-α, Amgen), 

and Aranesp (Epo-α variant, Amgen). The Top 20 selling 

biopharmaceutical drugs of 2005 have accounted for 69% 

of total revenues. 

According to the forecasts of the 2011 Biopharmaceuticals 

Market (http://www.bioportfolio.com/bioreports/ 

Table 1. Recombinant therapeutic proteins and monoclonal antibodies 

with sales volume more than $ 500 million (in 2002/2003) [14] 

Recombinant protein 

Sales volume 

($ million) 

Launch date 

1. Human insulin 5340 1982 (US) 

2. Human somatropin 1760 1985 (US) 

3. Interferon α 2700 1986 (US) 

4. Erythropoietin 8800 1989 (US) 

5. G-CSF (Filgrastim) 2520 1991 (US+EU) 

6. Blood factor VIII 670 1992 (US) 

7. Interferon β 2200 1993 (US) 

8. Glucocerebrosidase 740 1994 (US) 

9. Follicle-stimulating 

hormone (FSH) 

1000 1995 (EU) 

10. Blood factor VIIα 630 1996 (EU) 

GALLEY PROOF 

Monoclonal antibodies 

11. Rituximab 

(MabThera ® , Rituxan ® ) 1490 1997 (US) 

12. Infliximab (Remicade ® ) 1730 1998 (US) 

13. Palivizumab (Synagis ® ) 850 1998 (US)

Business%20Insights.htm), the US market will retain its 

world dominance for the next 5 years, whereas the share 

of both the Japanese and EU biotech world market are expected 

to fall. Enbrel (with total sales of $ 3656.7 million in 

2005 [2]) will continue to lead the world biotech market, 

while blood disorders will remain market leaders. However, 

so-called orphan diseases (tuberculosis, cholera, typhoid, 

malaria, tropical fevers, etc.) that rare in the USA, 

the EU, or Japan, but common in the third world, are also 

becoming major targets for biopharmaceuticals, owing to 

tax incentives in the USA and legislative preferences in 

the EU. In fact, three out of ten orphan disease drug approvals 

in 2004 were biopharmaceuticals. This is an indication 

of an increased focus on underdeveloped markets 

by companies that are expanding their marketing strategies. 

Emerging markets such as China, Brazil, Korea, Russia, 

and Turkey are expected to show double-digit growth 

compared to single-digit growth in US, Europe or Japan. 

Pharmaceutical sales across Brazil, Russia, India and China 

(BRIC) grew by 22.3% in 2005, with cardiovascular, 

cancer, respiratory, anti-infectives, and central nervous 

system disorders being the major sectors of the growing 

biopharmaceutical markets in the these countries. Positive 

economic growth, stabilizing political structures, 

growing patient populations and increasing direct foreign 

investment in the emerging markets of BRIC are creating 

significant opportunities for pharmaceutical companies 

to expand into these markets and maximize future revenue 

potential. 

Apart from the key multinational players in the BRIC 

markets (Sanofi-Aventis, Novartis, Novo Nordisk, Pfizer, 

GlaxoSmithKline, Janssen-Cilag, Lilly, ) and key mediumsized 

international players (Gedeon Richter, Servier, 

Menarini), each country has its own key regional players 

(see for example [2]). Most of them produce domestic biogenerics 

or so-called follow-on biologicals [14]. High current 

production costs of such biopharmaceuticals as 

mAbs and CSFs, which reflect real production difficulties, 

also restrict their marketing in the emerging economies 

and the third world. Generics are procured on a large scale 

for public healthcare systems, and are being promoted as 

an economical alternative to branded and expensive 

drugs. 

With a majority of branded blockbusters coming off 

patent, generic drug makers are expected to produce versions 

~40% cheaper compared with the original drugs. 

Improved technologies will enable more efficient production 

of biogenerics. It is expected that $ 11 billion of biopharmaceuticals 

will lose patent protection by 2007 and 

many high-revenue generating blockbuster drugs including 

Johnson & Johnson’s Procrit, Amgen’s Epogen and 

Roche’s NeoRecormon will face competitions by generic 

counterparts over the next few years. Erythropoietins and 

interferons are currently the most attractive targets for 

biogenerics and are going to face high competition. 

Generic forms of the first biological drugs are anticipated 

BTJ 07/07 | TD | DOI 10.1002/biot.200700091 

Biotechnol. J. 2007, 2 www.biotechnology-journal.com 

to capture significant market share (more than $ 12 billion 

by 2010 according to conservative estimates) [15]. China, 

India, Cuba and Israel employ relatively cheap and qualified 

manpower and are establishing their own biotech industries. 

These countries have possibilities not only to 

produce biogeneric drugs for the domestic needs but also 

export the products to other countries such as Russia. 

Therefore, these new biotech drug industries are likely to 

successfully compete with the established biopharmaceutical 

giants on both national and the international levels. 

2 Russian pharmaceutical biotechnology: 

a retrospective view 

In contrast to other emerging economies, Russia has inherited 

a developed scientific and industrial basis of the 

former USSR for the production of biopharmaceuticals. 

According to the official Soviet statistics in 1990, the 

USSR biotech industry was the second largest manufacturer 

following the USA and contributed up to 5% in the 

world biotech production. The USSR industry manufactured 

sufficient amounts of all vaccines developed at that 

time for immunization of population and prevention of 

epidemics of infectious diseases. The antibiotic industry 

created in the 50s and operating using domestic strains 

selected by All-Union (Russian) scientific research institute 

(VNII) for Antibiotics (Moscow) and All-Union Research 

and Technological Institute of Antibiotics and Enzymes 

for medicine VNITIAF (St. Petersburg) produced 

up to 3000 metric tons of the active pharmaceutical ingredient 

(API) forms; the large plants located in Kurgan, 

Saransk, Penza, Krasnoyarsk, etc. Pilot scale production of 

semi-synthetic penicillins and cephalosporins based on 

immobilized penicillin amidase was developed at the beginning 

of 80s by VNII for Antibiotics in collaboration with 

Moscow State University [16]. Biochemical plants in Kurgan, 

Sverdlovsk, Novosibirsk, etc. have produced 

cyanocobalamin (B12) and β-carotene for both medical 

and veterinary use, as well as riboxin (inosine) based on 

super-producing strains and technologies developed by 

Bach Institute of Biochemistry, VNII Genetika, VNITIAF, 

VNII for Vitamins and other research institutes. The USSR 

has covered not only its own demands but also supplied 

its satellite states with the above drugs. Enzymes for medical 

applications were produced in Berdsk (Novosibirsk 

region), and as early as the beginning of the 80s the production 

of immobilized water-soluble matrix streptokinase 

(Streptodecase) for the treatment of ophthalmic diseases 

and myocardial infarction was developed by the 

National Cardiology Research Center in collaboration 

with Moscow State University [17]. 

The USSR equipped a number of laboratories throughout 

the country, where highly qualified specialists were 

capable of creating or reproducing almost any of the ex- 

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Biotechnology 

Journal 

isting biotechnologies, including production of mAbs or 

recombinant proteins. Soviet genetic engineering has developed 

almost synchronously with that of the USA, Japan 

and the EU [18], and as early as in 1984 successful synthesis 

of human proinsulin gene was reported by the Shemyakin-Ovchinnikov 

Institute of Bioorganic Chemistry 

(IBCH) [19]. Pilot production of rIFN-α based on domestically 

engineered producer Pseudomonas sp. VG-84 and 

developed by VNII Genetika, IBCH and the Institute of Virology 

“Vector” was launched in the middle of 80s in 

Novosibirsk region [20], and already by the end of 80s, domestic 

rIFN-α was successfully tested in volunteers 

[21–23]. 

The All-Union Collection of Industrial Microorganisms 

(VKPM) possessed a number of highly efficient strains, 

that could produce major amino acids, enzymes, antigens, 

antibiotics, vitamins, etc. This formed the basis for 

construction of novel super-producers for various recombinant 

proteins. The National Center for Safety of Biologically 

Active Substances (Moscow region) has provided 

necessary biological trials for new pharmaceuticals. A developed 

network of universities, fundamental and applied 

research institutes, and project and design bureaus 

throughout the country has performed all the necessary 

stages of biopharmaceutical implementation, including 

R&D, laboratory and clinical trials, education and training 

of personnel, equipment projection, etc. More than 80% of 

equipment for the biotech industry was built by domestic 

manufacturers (http://www.biorosinfo.ru). The managing 

functions were performed by the Ministry of High School 

Education, Ministry of Medical and Microbiological Industry, 

Ministry of Healthcare, Ministry of Chemical Machine 

Building, Academy of Sciences and Academy of 

Medical Sciences. 

However, as a result of the structural disintegration 

that took place in 1992–1998, the overall biopharmaceutical 

production has reduced fourfold. The vast majority of 

domestic manufacturers traditionally focused on minor 

production increases or on reproduction of existing technologies 

to substitute imported counterparts. Efforts to 

implement new advanced technologies were minimal. 

Russian plants had obsolete equipment, and a relatively 

low technological level and did not correspond to the international 

GMP standards. In addition, they had no experience 

of aggressive marketing, unlike Western companies. 

Since the State support collapsed in 1991 and in the 

absence of models and mechanisms of venture capital 

funding of biotechnological projects, Russian manufacturers 

were no longer able to maintain connections with 

the product developers from specialized research institutes, 

who had previously visited factories on a regular 

basis to supervise and improve the manufacturing 

process. As a consequence, by the end of 90s, most of do- 

mestic pharmbiotech products were superseded by corresponding 

products of western competitors in the Russian 

market. 


BTJ 07/07 | TD | DOI 10.1002/biot.200700091 


In 2003, products of medicinal biotechnology constituted 

>70% of the Russian biotech market. However, the 

list of manufactured products was significantly shorter 

than that of the world biopharmaceuticals. As a result of 

insufficient governmental support for the basic research 

in the past 15 years, the national biotech industry primarily 

manufactured generics, with high-tech products accounting 

for only 10% of the total production. Still, antibiotics, 

vitamins, enzymes, immunology products, preparations 

derived from human donor blood, and a few genetically 

engineered products are manufactured by domestic 

companies. The domestic biopharmaceutical market was 

supplied only at the 51.3% level in 2003, of which 11.3% 

were locally manufactured (http://www.biorosinfo.ru). 

This demonstrates a potential for growth for the Russian 

pharmbiotech market. 

The list of immunological products in 2004 included 

up to 500 products■check■ manufactured by more than 

40 domestic companies (39 different vaccines, 17 anatoxins, 

23 allergens, 24 bacteriophages, 123 immunodiagnostic 

kits and 48 immunoglobulins) with total sales of 

nearly $ 1.8 billion [24]. The largest domestic manufacturers 

of immunological products have been Federal State 

Unitary Enterprise “Microgen”, private companies “Biomed”, 

“Combiotech”, “Diagnostic systems”, and others. 

In 2003, 14 state pharmaceutical plants located throughout 

Russia merged to create the state holding “Microgen” 

with the personnel of ~8000 employees, including 

~200 PhD scientists. The total sales of the holding were 

$ 160 million in 2005. The list of products manufactured 

by Microgen includes more than 400 items. One of the 

most important products, flu vaccine “Grippol” contains 

highly purified surface antigens hemagglutinin and 

neuraminidase of flu viruses type A and type B conjugated 

with water-soluble immunomodulator polyoxidonium. 

Since 1997 more than 50 million people have been vaccinated 

by Grippol (http://www.microgen.ru). 

In a related field, up to 200 immunological products 

were introduced for veterinary needs. High-quality vaccines 

and diagnostic kits against avian influenza, anthrax, 

cattle tuberculosis, epizootic aphthae and other 

diseases potentially dangerous for humans were manufactured 

by the research institute VNII of Animal Protection 

(Yuryevets, Vladimir region), Veterinary Institute 

(Khasan), Chumakov Institute of Poliomyelitis and Viral 

Encephalitis and others [24]. 

In vitro diagnostic kits constitute one of the rapidly 

growing segments of Russian biotech market, with annual 

sales of ~$ 100 million in 2003 and annual growths of 

~10% in subsequent years. Most of them are represented 

by various enzyme immunoassay and DNA diagnostic 

kits, which are manufactured by more than 40 small and 

medium-size domestic companies covering near 30% of 

national demand. The remaining 70% is imported 

(http://www.biorosinfo.ru). Leading research institutes 

(Engelhard Institute of Molecular Biology, Institute of 

GALLEY PROOF

Gene Biology, Institute of Chemical Biology and Fundamental 

Medicine of the Siberian Branch of Russian Academy 

of Sciences) are also developing modern biological 

microchips. Some of them are capable of identifying up to 

70 of the most resistant variants of tuberculosis; the most 

dangerous flu A variants including H1N1 (WSN-1933, 

Spanish flu), H7N1 (Rostock-1934), H3N2 (Victoria-1975, 

Hong Kong flu), H5N1 (avian influenza); plague; smallpox 

and anthrax. These microchips are used in more than 20 

medical centers worldwide [25]. 

Total sale of Russian genetically engineered biopharmaceuticals 

in 2000 did not exceed $ 3 million 

(http://www.bionews.ru/news/Bio.htm). Some of these 

products manufactured by Russian companies are listed 

in the Table 2 (O. A. Miroshnik, Russian market of recombinant 

preparations in 2005, www.biomedservice.ru/publish/pub48_recombinant_preparates_2005.htm; 

in Russian), 

along with their counterparts registered in the Russian 

Federation by foreign competitors. As follows from 

Table 2, although many of biogenerics could be produced 

by domestic companies, their contributions to the total 

market were very limited. The only positive example is 

domestic rIFN-α ready-to-use Viferon (http://www.viferon.ru), 

the medicine developed by Gamaleya Institute of 

Epidemiology and Microbiology. According to (www.biomedservice.ru/publish/pub48_recombinant_preparates_ 

2005.htm), Viferon was the leader of prescription-free 

drugstore sales of rIFNs in 2005. Development of new delivery 

forms of rIFN (ointment, suppositories), which can 

cure widespread sexually transmitted diseases in women, 

has played an important role in the sales growth of this 

medicine. 

3 DLO: the first step in promoting the national 

biopharmaceutical development 

Following stabilization of the economic situation in the 

beginning of the third millennium, the scientific and business 

interest for production of genetically engineered biopharmaceuticals 

in Russia has returned. The 2005-announced 

Federal Program of subsidized supply of pharmaceuticals 

(Dopolnitel’noe Lekarstvennoe Obespechenie 

or DLO in Russian abbreviation) has served as a 

promoting factor for this. Pursuant to DLO, the Russian 

government purchases drugs for free distribution to preferential 

categories of patients. DLO allowed many low-income 

patients suffering from severe diseases to receive 

most of the modern pharmaceuticals, including expensive 

drugs containing recombinant proteins or mAbs for 

the treatment of different forms of cancer, blood diseases, 

diabetes mellitus, etc. DLO gives the domestically manu- 

factured medicines an official purchase preference: 

where possible, they must constitute at least 30% of the 

supply of corresponding medicine. In the first 9 months of 

2006, DLO sales have reached $ 2 billion [26]. This has giv- 

BTJ 07/07 | TD | DOI 10.1002/biot.200700091 


en a significant boost to the Russian pharmaceutical market. 

In the fiscal year 2006, the Russian pharmaceutical 

market grew by 30% with total sales of $ 12 billion [27] 

compared with $ 8.4 billion in 2005 (12th position worldwide 

[28]). Recombinant biopharmaceuticals included in 

the Federal DLO list (http://www3.pgz.economy.gov.ru/ 

trade/view/purchase/general.html?id=101630419) are indicated 

in the Table 2 in bold characters. 

Domestic recombinant biopharmaceuticals included 

in the DLO list are represented by rHI ready-to-use forms 

Insuran ® manufactured by IBCH (http://www.insuran. 

net) and Biosulin ® (A/S Pharmstandard), EPO (Epokrin ® , 

the State Research Center of Highly Pure Biopreparations 

(GNC HPB) (http://www.hpb-spb.com), IFNα-2b (Alpharona 

® , Pharmaclon, http://www.pharmaclon.ru/ 

chemicals/alfarona_rep; and Reaferon ® , Vector-Medica, 

http://www.vector.nsc.ru), and rIFN-γ (Ingaron ® , Pharmaclon; 

http://www.pharmaclon.ru). Specificity of the DLO 

market provides manufacturers included in the DLO list 

with a real chance to take part in the contest of federal 

purchase of pharmaceuticals. In other words, these companies 

contribute to the market sales. However, as shown 

in Table 2, the list of preparations and suppliers that are 

registered in Russia but do not yet participate in DLO purchase 

is much longer. Activities of some of these companies, 

which are capable of producing their own API forms 

of recombinant biopharmaceuticals, are discussed below. 

The companies producing only ready-to-use drugs are beyond 

the scope of this review. From this point of view, the 

following companies should also be mentioned: 

– BIOCAD (http://www.biocad.ru), owner of the registered 

trademarks Genferon ® (IFNα- 2b + taurine + 

anestesine) and Leukostim ® (filgrastim). Biocad’s factory, 

equipped with German fermentors, employ 160 

people and hopes to have annual sales of $ 30 million 

within 5 years. IFN produced by company can be used 

in the form of nasal drops to treat the flu. 

– BIOTECH Ltd (http://www.biotech.spb.ru), owner of 

the trademark Ronkoleukin ® (human IL-2) and of a 

number of patents for rIFNs production. Ronkoleukin 

is being marketed outside of the DLO purchase. Its 

price is an order of magnitude lower than that of Proleukin 

(rIL-2) produced by Chiron, the Netherlands, 

and distributed in Russian Federation until 2003 by 

CSC, Italy. In contrast with Proleukin, Ronkoleukin 

causes no significant side effects. 

– BIOPROCESS Group (http://www.bioprocess.ru) and 

its subsidiary PharmaPark, manufacturer of the API 

rIFNα-2b. Ready-to-use forms are launched in 2006 

(see also Company Profile in the Forum section of this 

issue). 

– MASTERCLON A/S, manufacturer of HGH under the 

trademark Rastan ® and API filgrastim. 

– NATIONAL BIOTECHNOLOGIES (http://nbiotech.ru), 

manufacturer of API rHI. Since the beginning of 2007 

the company has also launched production of ready- 

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Journal 


BTJ 07/07 | TD | DOI 10.1002/biot.200700091 

Table 2. Recombinant biopharmaceuticals and mAbs registered in RF [28] (drugs included in the DLO list are indicated as bold characters) 

Registered trademark in RF Manufacturer Indication Remarks 

Hunan insulin and analogues (ca. 40 trademarks registered in RF) 


Actrapid NM, Mixtard 30 NM, Novo Nordisk Insulin-dependent Temporary license purchased 

Protafan NM 

Levemir (Insulin detemir) 

Novo Rapid (insulin aspart) 

(dominant supplier) diabetes mellitus in 1999 by A/S Bryntsalov A, RF 

Humulin M3, NPH, R 

Humalog (Insulin lispro) 

Lilly (dominant supplier) 

Insuman Rapid GT, Basal GT, 

Comb 25GT 

Lantus (Insulin glargin) 

Aventis (dominant supplier) 

Biosulin H, P Pharmstandard, RF 

+Marvell, India 

Gansulin P, H, 30P Dongbao, China 

Insuran R, NPH IBCH RAS, RF 

Rinsulin R A/S National Biotechnologies, Developed by A/S 

Rinsulin NPH RF since 2004 Biopreparat, RF 

License purchased by Sedico, 

Egypt www.sedico.ru 

Interferons 

Ropheron-A (rIFNα-2a) 

Pegasis (pegylated α-2b) 

Roche Hepatitis B and C, oncology 

Alpharona (rIFNα-2b) Pharmaclon, RF 

Intron A (rIFNα-2b) Shering Plough (Brinny), 

Pegintron (pegylated) Ireland 

Realderon (rIFNα-2b) Teva, Israel Distributed by SICOR, Lithuania 

Reaferon EC (rIFNα-2b) GNC Vector, First domestic rIFN (gene 

Reaferon EC-Lipint liposomal Vector-Medica, RF synthesized by IBCH and the 

Infagel ointment 

Recolin 

GNC Vector) 

Altevir liquid, (rIFNα-2b, Bioprocess subsidiary Registered since 2006 

free of HSA) Pharmapark, RF 

Viferon (rIFN-α), uvulae and Feron, RF Viral, bacterial, and Formulation by Gamaleya 

ointment, supplemented by www.viferon.com chlamydiosis in pregnancy Institute of Epidemiology and 

vitamins C and E) and newborn children, AIDS Microbiology 

Kipferon (rIFNα-2b in combination Alfarm, RF 

with human leukocyte IgM, IgA, IgG) www.alfarm.ru 

Giaferon (rIFNα-2b) A/S Vitafarma, RF 

Genferon (rIFNα-2b) Biocad, RF 

Grippferon ((rIFNα-2b, nasal form) Firn-M, RF Flu and related infections 

Ophthalmoferon 

(rIFNα-2b + dimedrol) 

Eye infections 

Gerpferon (rIFNα-2b + acyclovir + 

lidocain ointment) 

herpes 

Berofor (rIFNα-2c) Boehringer Ingelheim, Oncology, hepatitis B, Registration in RF expired 

Germany ophthalmology 

Avonex (rIFNβ-1a) Biogen B.V., the Netherlands, 

Gedeon Richter 

Multiple sclerosis 

GALLEY PROOF

BTJ 07/07 | TD | DOI 10.1002/biot.200700091 


Table 2. Continued 


Interferons 

Rebif-22 (rIFNβ-1a) Serono, Italy 

Betaferon (rIFNβ-1b) Shering AGGermany 

Imukin (rIFNγ) Boehringer Ingelheim, Hepatitis, herpes, cyto- Registration in RF expired 

Germany megalovirus, chlamydiosis, 

Ingaron (rIFNγ) Pharmaclon, RF 

http://pharmaclon.ru 

oncology, multiple sclerosis Clinical trials, 2nd stage 

Interleukins 

Betaleukin (human rIL-1β) GNC HPB, RF 

www.hpb-spb.com 

Toxic leukopenia II-IV stage 

Roncoleukin (human rIL-2) Biotech, RF Pneumonia, pleurite, acute Trials in the treatment of the 

inflammations, burns, tuber- III–IV stages head and neck 

culosis, herpes, hepatitis C, 

kidney cancer, melanoma, 

chlamydiosis 

cancer 

ARIL (rIL-1 receptor antagonist) GNC HPB, RF Preclinical trials 

Bone marrow growth factors, G-CSF 

Granocit (rec. Lenograstim) Aventis Leukopoiesis stimulation 

after chemotherapy, anemia, 

Neupogen (rec. Filgrastim, Roche transplantations of bone 

r-metHu G-CSF) marrow stem cells 

Leukomax (rec. Molgramostim, Sandoz/Shering Plough Registration in RF expired 

rHu GM-CSF) in 2003 

Leukostim (Filgrastim) Biocad, RF Since 2005 

Filgrastim (API) Masterclon, RF Since 2005 

Mielastra (Filgrastim) Lens-Pharm, RF 

API by Masterclon 

Since 2006 

Eprex (Epo-α) Janssen Cilag Anemia, hemodialysis 

Recormon (Epo-β) Roche 

Epocrin (Epo-β) GNC HPB, RF 

Erythrostim (Epo-β) Microgen, Moscow 

subsidiary, RF 

Tumor necrosis factor and other cytokines 

Refont (Fusion protein TNF-α and Pharmaclon, RF Recidivation of head and neck Temporal approval after 1st 

thymosin-α1, 10-100-fold less toxic http://pharmaclon.ru squamous cell cancer stage clinical trials 

than TNF-α) 

Hormones 

Genotropin (rec. somatropin) Pfizer Health AB HGH insufficiency, First launched HGH 

Crescormon (rHGH) Pharmacia & Upjohn hypopituitarismus 

Saizen –”- Serono, Italy 

Norditropin –”- Novo Nordisk 

Humatrop –”- Lilly 

Rastan (rHGH, API) Masterclon, RF First launched HGH in RF 

Rastan (rHGH, ready-to-use) Pharmstandart, RF 

Gonal-f (follitropin-α, FSH) Serono, Italy Stimulating ovaries to 

produce eggs 

GALLEY PROOF 


Biotechnology 

Journal 

Table 2. Continued 


BTJ 07/07 | TD | DOI 10.1002/biot.200700091 


Hormones 


Puregon (INN-follitropin-β) Organon Stimulating ovaries to 

produce eggs 

Zadaxin (peptide hormone SciClone, USA Hepatitis B,C, with pegylated Chemically synthesized 

thymosin-α1) www.zadaxin.ru. IFN-α 

Blood clothing factors 

Recombinate rec. factor VIII Baxter Int. Inc. Antihemophilic factor 

Kogenate FS –”- Bayer 

NovoSeven rec. factor VIIa Novo Nordisk 

MAbs 

Avastin (bevacizumab) Genentech/Roche Tumors, anti-neoplastic mAb 

Simulect (basiliximab) Novartis Transplantations, anti-CD25 mAb 

Resoclon anti-Rhesus 0(D) mAb Hematolog. RF Registered in 1999, in 2004 extended 

Zenapax (daclizumab) Roche Transplantations, multiple sclerosis, binds CD25 of high-affinity 

human IL2 receptor 

Remicade (infliximab) Centocor/Shering Plough Artritis, Crohn’s disease, ulcerative colitis blocks TNF-α 

MabThera (rituximab) Genentech/Roche B cell non-Hodgkin’s lymphoma, CD20 

Herceprin (trastuzumab) Disseminated breast cancer with HER2 hyperexpression 

Orthoclone (muromonab) Ortho-Pharmaceutical, US, 

Cilag, Swiss 

Transplantation, anti-CD3 of T cells mAb 

Reopro (abciximab) Centocor/Lilly Anti-aggregant thrombocyte therapy 

Enzymes 

Metalyse (tenecteplase, rec. tissue Boehringer Ingelheim, Myocardial infarction, brain insult 

plasminogen activator) Germany 

Rec. pro-urokinase: Russian Cardiology Research 

Purolase Center, RF 

Hemase Technogen, RF Ophthalmology 

Pulmozyme 

(Dornase α, rec. α-DNase) 

Genentech/Roche Mucoviscidosis 

Erisod (rec. superoxide dismutase) GNC HPB, Ophthalmology, solar and Investors needed 

Resbio, RF thermal burns, cosmetics 

Cerezyme (rec. imiglucerase) Genzyme, UK Gaucher’s disease 

Recombinant vaccines against Hepatitis B (contain rHBs-Ag) 

Engerix B GlaxoSmithKline First rec. vaccine, since 1987 

Euvac Aventis Pasteur 

HB Vac II Merck Sharp & Dohme 

Biovac-B, Wockhardt, India 

Shanvac-B Shanta, India 

HB rec. DNA-vaccine Ever Biotech, Cuba 

Rec. yeast HB vaccine Microgen, subsidiary Virion, RF 

Combiotech Combiotech, RF, http://www.combiotech.com 

GALLEY PROOF

to-use rHI forms Rinsulin ® and tries to market them 

outside of the federal DLO purchase. 

Among the aforementioned manufacturers, those of the 

governmental ownership, i.e., GNC HPB (St. Petersburg), 

IBCH RAN [Russian abbreviation of the Russian Academy 

of Science (RAS) (Moscow)], GNC Vector (Vector-Medica; 

Novosibirsk region) are using renovated industrial facilities 

created at the end of Soviet era owing to heavy state 

funding. In addition, a modern biotech complex with the 

mixed form of ownership, A/S “National Biotechnologies”, 

was built and equipped in 2003. 

In spite of an extended list of domestic manufacturers 

and some preferences for them declared by DLO, the 

structure of DLO purchases in January–June 2006 [29] 

shows an absolute domination of the key multinational 

players. The leader, Janssen-Cilag has shown a unique 

sales growth of 664% in 2006 in the DLO sector, thus increasing 

its total share to 10.33%. The Top 10 list in the 

DLO segment also includes multinational giants Roche, 

Novartis, Sanofi–Aventis and Novo Nordisk. Blockbuster 

biopharmaceuticals dominate over corresponding Russian 

biogenerics in almost all DLO top positions. Indeed, 

the Federal DLO Top 20 sales list includes Betaferon, 

Eprex, Mabtera, Lantus, and Humulin NPH, occupying 

5th, 7th, 8th, 13th, and 16th position, respectively, with 

the total market share near 6% (5.1% excluding Humulin 

NPH). Regional Top 20 lists also include Herceptin, Novo- 

Seven, and Recombinate, as well as Avastin, Remicade, 

and Cerezyme in the nomination “Novel Medicines”, 

which contribute an additional 1.3%. Taken together, recombinant 

therapeutic proteins (excluding insulins) constituted 

6.4% of the DLO market (i.e., $ 83.2 million of the 

$ 1.3 billion total DLO purchase), while pharmaceuticals 

for diabetes mellitus treatment (of which more than 90% 

of medicines in Russia are represented by insulins) contributed 

7.7% or $ 100.1 million in the first half of 2006. 

The expenses for the annual Epo-α cure supplied by 

the Western manufacturers per patient with kidney insufficiency 

are estimated to be near $ 7000; treatment of one 

patient suffering from hepatitis C with pegylated rIFN-α 

may take annually $ 4000; and for each of 100–150 thousand 

patients suffering from multiple sclerosis the annual 

cure by rIFN-β is estimated as $ 16–32 thousand. Current 

evaluations show that near 300 thousand patients suffering 

from servere diseases (hemophilia, mucoviscidosis, 

multiple sclerosis) require 40–50% of the total DLO budget, 

since every prescription for them may cost more than 

$ 400 [30]. In other words, if these categories of patients 

depend on imported recombinant biopharmaceuticals, 

they require almost the same budgetary provision as the 

rest 14 million preferential patients included in the DLO 

supply program. For this reason, according to Russian 

mass media, independent expert forecasts have estimated 

costs of DLO 2006 to be $ 2.5 billion, albeit with the 

Federal Ministry of Healthcare providing only $ 1.4 billion. 

BTJ 07/07 | TD | DOI 10.1002/biot.200700091 


Currently, federal indebtedness in the framework of DLO 

has reached $ 1.5 billion, from which only $ 0.6 billion is 

planned to be reimbursed by the Ministry. The Ministry 

suggests that the rest should be covered by the manufacturers 

participating in the DLO program and reimbursed 

later by regional insurance companies. Because of this, 

patients suffering from diabetes mellitus, multiple sclerosis, 

epilepsy, blood diseases and various forms of cancer 

receive three- to fourfold lower-than-required dosages of 

necessary medications, and in some regions (e.g., Altay) 

corresponding groups of medications were not prescribed 

at all. This demonstrates the urgency of substituting expensive 

blockbuster drugs by cheap domestic biogenerics. 

However, the practice of state purchase is accompanied 

by always delayed payment, which slows down small 

domestic manufacturers [31]. 

The Ufa subsidiary of A/S Pharmstandard developed 

and launched production of ready-to-use rHI in 2005, with 

the maximum annual capacity of 7.7 billion IU insulin. 

This would in principle fully cover the domestic needs (ca. 

7.4 billion IU calculated on the assumption of average 

0.7% population (145 million) suffering from insulin-dependent 

diabetes mellitus [32]. This minimal calculated 

demand in rHI corresponds to ca. 280 kg API rHI, assuming 

that 1 IU is equivalent to 0.0347 mg pure insulin, 

and preparation of 10 ml of the ready-to-use solution 

(100 IU/ml) requires 36–38 mg API. However, production 

of Pharmatsndard is now limited by only 5% of the existing 

capacities, since it depends on imported API rHI. 

Budgetary provisions covering all the demands of patients 

are estimated to reach $ 240 million per annum, 

whereas real domestic insulin sales by the end of 2006 

constituted $ 158 million [33], of which domestic manufacturers 

of rHI have shared only 1.9%, namely: 0.4% Biosulin 

(A/S Pharmstandard) and 1.5% Insuran (pilot facility 

of IBCH RAS). The later was the only domestic recombinant 

drug mentioned in DLO Top 10 sales lists [34], namely, 

in the nomination “Novel Medicines” in the largest federal 

district Moscow constituting 30% of the total DLO 

market. 

4 Russian recombinant insulin (Insuran): 

The path from bench to market 

Traditionally, all the patients suffering from diabetes mellitus 

were supplied in the former Soviet Union and later in 

Russia received cost-free rHI with the expenses being 

covered from the budget sources. This demand has 

formed the guaranteed national rHI market, which has 

shown 1.6-fold growth since 2000. 

Since the first recombinant insulin appearance on the 

US market, the ability to produce rHI was considered an 

indicator of the national biotech development level. The 

recommendation of WHO to have domestic production of 

rHI in all the countries with population exceeding 50 mil- 

GALLEY PROOF 


Biotechnology 

Journal 

lion has also played a stimulating role in the development 

of domestic rHI production. The first attempt at rHI production 

in the Soviet Union were undertaken during 

1987–1989. The pilot scale technology was developed and 

tested by the All-Union Institute of Antibiotics (VNIIA, 

Moscow) in cooperation with the German company Genbiotech 

GmbH (Heidelberg) and was based on the cultivation 

of the recombinant E. coli strain capable of producing 

human proinsulin linked through its N-terminal 

Met with a leader sequence [35]. However, the application 

of highly toxic BrCN seriously limited the scaling up of the 

developed process and, along with other reasons, finally 

led to the closing of this project. 

In 1996, following the Decree of President Yeltsyn “On 

the measures of the federal support of patients suffering 

from diabetes mellitus”, support for large-scale R&D on 

national rHI manufacturing was revived by the IBCH and 

the Federal Research Center GNC of Applied Microbiology 

(Obolensk, Moscow region) managed by the Federal 

holding RAO (Russian abbreviation of Russian A/S of the 

mixed state and private ownership) “Biopreparat”. The 

joint R&D program has resulted in the construction of 

highly efficient strains producing human preproinsulin 

and the lab-scale technology of API rHI [36–38]. Based on 

the obtained results, the holding “National Biotechnologies” 

(the assignee of RAO “Biopreparat”) has developed 

pilot scale API rHI production. 

The next important step in the development of Russian 

rHI from bench to market was the collaborative agreement 

signed between the Moscow Government and 

Russian Academy of Sciences represented by IBCH on 

15 May 2000. Subsequently, Major Yuri Luzhkov signed a 

corresponding directive (No 592-RM) in Moscow on 

5 June 2000, which has opened a credit line of $ 4 million 

for development of a modern biotech production facility to 

provide Moscow healthcare with high quality ready-touse 

rHI preparations. The obtained credit has allowed reconstruction 

of the existing pilot biotech facility of the 

IBCH according to GMP standards. 

Figure 1 illustrates the general principles of rHI API 

production realized in the IBCH RAS. The process is 

based on the strains E. coli JM 109 and E. coli BL 07 bearing 

recombinant plasmid pPINS 07 [36, 39]. The plasmid 

DNA harbors synthetic gene coding for a hybrid polypeptide 

containing single IgG-binding domain of S. aureus 

Protein A and human proinsulin linked by an oligopeptide 

His6GlySerArg. Insertion of tac-promoter in pPINS 07 provides 

efficient (up to 30% of the total cellular protein content) 

expression of the fusion protein following induction 

by isopropyl-β-D-thiogalactoside. 

Cultivation of the recombinant strains in the pilotscale 

3000-L bioreactor provides 1500–2000 L culture 

broth. Inclusion bodies are isolated from biomass har- 

vested by separation and passed through the French 

press. After careful washing of the precipitate for the removal 

of soluble E. coli proteins and metabolites, up to 


BTJ 07/07 | TD | DOI 10.1002/biot.200700091 

Fig. 1: rHI from proinsulin fusion protein 


35 kg of the wet inclusion bodies containing at least 13% 

of fusion protein could be obtained within one operation 

cycle. Harvested inclusion bodies are solubilized in the 

buffer solution of urea and dithiothreitol and then diluted 

and exposed to air oxygen under strong dilution to refold 

the fusion protein. 

Renatured protein is further purified by ion exchange 

chromatography and digested by trypsin and carboxypeptidase 

B in the ratio 4000:2:1(w/w) respectively 

(Fig. 2). Precipitation and further pretreatment result in 

production of raw insulin with 90% purity. After the next 

purification step, hydrophobic chromatography, the purity 

reaches 96%. The following ion exchange chromatography 

completely removes residual immunogenic contaminants. 

Finally, sterile gel filtration provides the desired 

product in pharmaceutical quality. As an alternative, 

preparative HPLC is also used [40]. The yield of dried crystalline 

zinc-insulin reaches 150 g/1000 L culture broth. 

The production capacity of the pilot facility amounts to 

10 kg API rHI annually. The facility is also equipped to 

produce ready-to-use insulin drugs: Insuran ® R and 

Insuran ® NPH. Insuran ® R soluble formulation is a rapidacting 

insulin for subcutaneous, intramuscular, and intravenous 

injections. After subcutaneous injection, effect 

develops in 30 min, with the maximal effect achieved 

within 2–4 h and a duration of 6–8 h. Insuran ® NPH (insulin-isophan, 

suspension for subcutaneous injections) is 

GALLEY PROOF


Fig. 2: Enzymatic conversion of fusion protein to rHI 

an intermediate-acting insulin formulation with the effect 

developing 1–2 h after injection, maximal effect achieved 

in 6–12 h, and duration of action 18–24 h. Both Insuran formulations 

are used for substituting therapy in diabetes 

mellitus type 1 and type 2 and are sold in the 10-mL vials 

with the specific activity 100 IU/ml. Current production 

capacities are sufficient for manufacturing 250–300 thousand 

Insuran ® vials per annum. 

The successful demonstration of API rHI production 

has stimulated potential investors for the development of 

technologies of production of other recombinant proteins 

using the IBCH pilot facility. A private investor, the Russian 

company Masterclon has supported development of 

the industrial production of recombinant human growth 

hormone (somatropin) [41, 42], granulocyte colony-stimulating 

factor (G-CSF; filgrastim) [43], and other foreign 

proteins expressed in the prokaryotic host. Production of 

somatropin, which is of great social significance, was 

based on the same principles and consisted of principally 

the same stages as rHI production (Fig. 1). In 2005, manufacturing 

of API human growth hormone (HGH) was 

launched in Russia, and, since 2007, the Russian companies 

Masterclone and Pharmstandard have launched the 

industrial production of a ready-to-use somatropin formulation 

under the trademark Rastan ® . 

The economic reliability of Russian insulin and HGH 

compared to corresponding blockbuster drugs is illustrated 

by the Table 3. For correct comparison, selling prices 

of 1g API insulin are calculated on the assumption that 

1 mL of insulin solution with specific activity of 100 IU/mL 

contains 3.6 mg API. Comparison was made for the ready- 

to-use drugs in the form of vials (5–10 mL) or cartridges for 

insulin pens (3 mL) produced by different manufacturers 

(excluding IBCH). As follows from these estimations, for 

the items 1–3, the prices of API vary from $ 400 to $ 500/g 

BTJ 07/07 | TD | DOI 10.1002/biot.200700091 

for the vials and from $ 600 to $ 700/g for cartridges, while 

the selling price of Russian insulin is below $ 400/g. For 

comparison, data for insulin analogues are also included. 

The same is also applicable to the rHGH, where the API 

for the Russian ready-to-use formulation Rastan is 30% 

cheaper than that for imported counterparts. Calculations 

based on the pilot scale facility of IBCH show that, even 

at the production scale not exceeding 10 kg per annum, 

production costs of API rHI would not exceed $ 120/g. For 

Table 3. Comparative prices of the blockbuster brands and domestic biogenerics 

(in DLO listing prices) 

Product Selling price, API cost, 

RUB* $/g 

Insulins (100 IU/mL) 

1. Actrapid HM, 1×10 mL 387.04 408.80 

Actrapid HM Penfil, 5×3 mL 875.70 616.60 

2. Insuman Rapid GT, 5×3 mL 998.89 703.35 

Insuman Rapid GT, 5×5 mL 1,003.44 423.93 

3. Humulin Regular, 1×10 mL 471.33 497.81 

Humulin Regular, 5×3 mL 974.72 686.32 

4. Insuran R, NPH 1×10 mL 350.00** 369.67 

5. Humalog 5×3 mL 1,849.79 1,302.48 

6. NovoRapid 5×3 mL 1,375.95 968.84 

7. Lantus 5×3 mL 2,153.00 1,515.98 

8. Levemir 5×3 mL 2,151.92 1,515.92 

Somatropins 

1. Sayzen, 8 mg 8,615.49 40,950.00 

2. Humatrope, 6 mg 6,207.85 39,340.00 

3. Genotropin, 5.3 mg 5,575.04 39,990.00 

4. Norditropin, 10 mg 10,238.62 38,930.00 

5. Rastan, 1.3 mg 931.70*** 27,250.00 

GALLEY PROOF 

* - 1$ = 26.3 RUB; ** - production costs; *** project price in 2007. 


Biotechnology 

Journal 

a virtual industrial scale plant capable of producing 1810 kg 

of API rHI annually, theoretical evaluations give operating 

expenses $ 42.2/g and the selling price of $ 75/g [44]. This 

demonstrates a potential of producing competitive biogenerics 

in Russia. 

Since 2004, ready-to-use Insuran formulations have 

been successfully used for the treatment of diabetes mellitus. 

Currently, ~6000 people (14% of the Moscow insulindependent 

patients) regularly use different Insuran formulations. 

With the launch of production of cartridge form 

planned for the end of 2007, the Insuran share may reach 

25% of the Moscow insulin market (45 000 patients with 

an annual demand ca. 510 million IU insulin, i.e., ~20 kg 

API or $ 16.7 million at complete saturation). Scaling up 

the created pilot facility and the developed technologies 

will allow manufacturing of effective, high-quality biopharmaceuticals 

(although biogenerics at the initial 

stage) that will have very competitive selling prices and 

successfully compete with multinational biopharmaceutical 

players for the fast-growing pharmaceutical market of 

the Russian Federation [45]. 

5 The future of biotech innovations lies with 

academia 

In the long list of tasks that have to be solved by national 

pharmaceutical biotechnology, production of highly competitive 

biogenerics and follow-on biologicsls is only the 

first step. The continued development of modern bioindustry 

and particularly its newest branches such as genetic 

and cell engineering, postgenomic technologies and 

nanobiotechnologies strongly depends on breakthroughs 

in basic research. Therefore, the next steps should include 

revival of the potential of Russian fundamental science, 

which has lost ~200 000 researchers of the most creative 

age since 1992. It would be wrong to conclude that 

basic research was not supported by Russian Government 

at all. In the past 15 years leading Russian research 

institutes have been involved in the Federal programs 

“Human genome”, “Gene diagnostics and gene therapy”, 

“Vaccine prophylaxis” and others. However, governmental 

funding spread over 57 research centers did not exceed 

3–5% of that spent, for example, in China 

(http://www.bioinfo.ru). This has partially restored the intellectual 

potential accumulated in the scientific schools 

of RAS, Russian Academy of Medical Sciences (RAMS) 

and their leading biotechnology institutes, including 

IBCH, Engelhard Institute of Molecular Biology, Pushchino 

Scientific Center, Institute of Gene Biology, Institute of 

Medico-Biological Problems, Institute of General Genetics, 

Institute of Molecular Genetics, Institute of Develop- 

mental Biology, Center of Bioengineering, Institute of 

Chemical Biology and Fundamental Medicine (Novosibirsk), 

Orekhovich NII of Biomedical Chemistry, Institute 

of Immunology, National Cardiology Research Center, Na- 


BTJ 07/07 | TD | DOI 10.1002/biot.200700091 


tional Oncology Research Center, as well as leading Russian 

high schools Lomonosov Moscow State University, St. 

Petersburg State University, Novosibirsk State University, 

Khazan State University, Sechenov Moscow Medical University, 

etc. However, the world ranking of the Russian 

fundamental science has diminished year after year due, 

in part, to poor compensations offered to Russian PhD scientists 

(monthly salaries do not exceed $ 200–300). This 

has also been a major obstacle for recruiting a new generations 

of scientists. 

In spite of the insufficient state support, some hot topics 

were successfully developed by domestic fundamental 

science mostly based on the knowledge and skills accumulated 

earlier. It is not possible to overview in one 

article all the spectrum of biopharmaceutical and related 

research carried out in Russia. Below only a few achievements 

of the national science supported by corresponding 

Russian references are given: 

– Innovative non-injected insulin delivery technology 

(insulin pills) developed as early as in the end of 90s in 

Topchiev Institute of Petrochemicals in collaboration 

with Moscow State University and Bach Institute of 

Biochemistry [46, 47], which can promote development 

and marketing of non-injecting ready-to-use formulations 

of domestic rHI; 

– Laboratory trials of a new anti-tuberculosis vaccine 

against Mycobacterium tuberculosis cytokine [48, 49], 

which is of special importance because of wide spread 

of tuberculosis in Russia; 

– Development of vaccines against the most dangerous 

infective diseases such as EBO by the GNC of Virology 

and Biotechnology “Vector” to protect the population 

from bioterrorism [50]; 

– Construction by NII of the Flu (St. Petersburg) of vaccine 

bank targeting H5N1 virus by means of reverse 

genetics to protect the population from a bird flu pandemic 

[51]; 

– Development of new rIL-based drugs [52, 53]; 

– Novel medical applications of catalytic antibodies developed 

by IBCH [54]; 

– Construction of a representative national collection of 

hybridomas [55] and development of pharmaceutical 

mAbs by Russian Oncology Research Center [56, 57]; 

– Stem cell therapy approaches [58, 59]; 

– Gene therapy approaches in the therapy of muscular 

dystrophy and other diseases [60–62]; 

– Novel delivery systems for gene therapy agents 

[63–65]; 

– New generation of polymer-conjugated vaccines by 

the Institute of Immunology in collaboration with 

Moscow State University [66]; 

– Computer design of vaccines by the Orekhovich NII of 

Biomedical Chemistry [67]; 

– New antitumor peptide drugs based on α-fetoprotein 

fragment by the Institute of Molecular Diagnostics 

[68]. 

GALLEY PROOF

The Pilot project of the Academy announced in 2007 aims 

to significantly improve the current situation by increasing 

the monthly salaries of PhD scientists to $ 800–1000. 

These researchers are expected to be highly productive 

and publish their results in leading international journals. 

The government is also making steps towards national 

science. In 2005, to promote the fundamental science focused 

on the strategic goals of modern biopharmaceuticals, 

the Federal Agency of Science and Innovations (the 

department of Russian Ministry of Science and Education) 

selected a number of projects from within the Federal 

Program of support for life sciences (http://www. 

fasi.gov.ru/fcp/technika/konkurs/ls/437/). The Agency 

guaranteed more significant funding for these projects 

compared with the projects funded by Russian Academy 

of Sciences or Russian Foundation for Basic Research 

(RFBR) (usually ≤$ 20 thousand per annum). Table 4 

demonstrates a variety of projects of real practical importance 

for biopharmacy, molecular medicine and related 

areas executed by Russian academic institutions that 

have received significant financial support of the government 

in 2005–2006. 

From this list one may conclude that Russian fundamental 

science still possesses a potential to carry out biopharmaceutical 

and molecular medicine research at the 

world level, including stem cell and gene therapy, 

nanobiotechnology approaches, postgenomic technologies, 

etc. 

6 Conclusion 

Until recently less than 50% of the Russian population had 

access to the modern pharmaceuticals for treatment of 

hypertension, cardiovascular diseases, cancer, and diabetes. 

The Russian Government is seeking to remedy this 

by establishing a system to cover the basic medical needs 

through the program of the DLO. In spite of this, muchneeded 

expensive drugs are not available in many areas. 

A number of Russian companies are capable of producing 

relatively inexpensive biogenerics of the blockbuster 

drugs for treatment of certain disorders. Unfortunately, 

the Russian regulatory process has been historically 

lengthy even for generic drugs and has resulted in the accumulation 

of an extensive pipeline of products pending 

approval. The primary task of the Russian Government in 

this situation should be acceleration of the regulatory approval 

process to facilitate delivery of generic drugs to patients. 

This, in turn, would reduce the rate of governmental 

healthcare spending and increase the demand for domestically 

produced biogenerics. 

The branded pharmaceuticals segment is also gearing 

up to meet the escalating competition from the generic 

sector. These global giants are using different approaches 

to protect their business from competition with the national 

manufacturers of biogenerics. For example, they of- 

BTJ 07/07 | TD | DOI 10.1002/biot.200700091 


fer more convenient ready-to-use forms (insulin pens, micro-needles), 

or improved variants of drugs with fewer undesirable 

side effects like Epo-α variant Aranesp, or drugs 

with improved pharmacokinetics, such as pegylated 

forms of G-CSF and IFN-α. In this strong competition 

Russian Ministry of Healthcare often plays on the site of 

the branded biopharmaceuticals, motivating this decision 

by insufficient readiness, or safety, or small production 

facilities of corresponding domestic biogenerics. In 

fact, both officials of the Ministry and the big importers 

look for and support each other. This adversely affects efforts 

of small and medium-size domestic manufacturers to 

produce comparable quality biogenerics at lower costs 

[31]. 

Moreover, Russian biogenerics and follow-on biologics 

face currently strong competition on the domestic 

market with relatively inexpensive counterparts imported 

from China and India. For example, recombinant hepatitis 

B surface antigen vaccine is produced by the domestic 

company Combiotech. However, the Russian Ministry 

of Health purchases for the National project “Zdrorovie” 

(Health) the same but more expensive vaccine from Indian 

manufacturer Shanta Biotechnics. As a result, domestic 

biopharmaceutical companies are trying to increase 

production capabilities and form strategic alliances with 

each other to tackle competition. One example was the 

formation of the above-mentioned state holding Microgen. 

Another example is the private holding A/S Pharmstandard, 

which has been formed as a result of a merger 

of pharmaceutical and related plants in Ufa, N-Novgorod, 

Tyumen, Kursk, and Tomsk. Smaller private businesses 

are also trying to combine their efforts, with an alliance 

between A/S Masterlek, A/S Masterclon and A/S Lekko 

being an example. This alliance is planning joint manufacturing 

of genetically engineered and monoclonal drugs 

based on the research and production biotechnological 

complex, which will be built in Pokrov (Vladimir region) 

by the end of next year (http://www.molva33.ru/people. 

php?cid=1113). 

Positive experience of Russian rIFN-α sales shows 

that development of non-injected and convenient readyto-use 

forms of biopharmaceuticals (nasal sprays, ointments, 

suppositories, etc.) or their formulations with reduced 

side effects that have been adapted for treatment 

of the widespread diseases in Russia may significantly increase 

the market share of domestic biogenerics compared 

with imported counterparts. However, creation of 

principally new drugs based on the achievements of 

Russian fundamental and applied science requires development 

of corresponding domestic models and mechanisms, 

since the classical strategy of a modern biopharmaceutical 

development, i.e., from universities through 

start-up companies using technopark infrastructure, venture 

capital investment, and, finally, to the large pharmaceutical 

firms, does not properly work in Russia. 

GALLEY PROOF 


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Journal 


BTJ 07/07 | TD | DOI 10.1002/biot.200700091 


Table 4. Russian biopharmaceutical and related research projects selected by the Federal Program in 2005–2006 (each project has received an annual 

budget support ranging from $ 100 000 to $ 2 million) [http://www.fasi.gov.ru/fcp/technika/konkurs/ls/437/] 

Project Institute 

Recombinant human proteins – protectants of massive blood losses Hematology Scientific Center, RAMS, Moscow 

Test systems for selection of biological agents protecting from appearance St. Petersburg University 

and development of amyloidoses of the central nervous system 

Construction of amino acid anti-aggregant oxidatively inactivating cellular Russian state medical university, Moscow 

receptors for prevention of intravessel thrombosis formation 

A universal postgenomic technology for the development of novel generation Schemyakin-Ovchinnikov Institute of Bioorganic 

of pharmaceuticals Chemistry RAS, Moscow 

Differentiated proteomics for new anti-tumor pharmaceuticals Institute of Molecular Genetics, RAS, Moscow 

Technology of high performance solid phase sorbents for medical applications Russian Cardiology Research Center, Moscow 

AIDS gene therapy by RNA-interference: development of effective Novosibirsk State University 

constructions for suppression of HIV-1 in human cells 

Construction of selective anti-tumor preparations based on microbial RNases Khazan State University 

High performance screening and synthesis of peptides and peptidomimetics, Hematology Research Center, RAMS, Moscow 

prototypes of pharmaceuticals 

Development of experimental methods for screening of ligands for target Zakusov Institute of Pharmacology, RAMS 

proteins 

Construction of immunopharmaceuticals based on humanized recombinant Schemyakin-Ovchinnikov Institute of Bioorganic 

mini-Abs■check-mAbs?■ for target effect on tumor tissues Chemistry RAS, Moscow 

Transgenic plants, producing recombinant biopharmaceutical proteins PROOF 

with Institute of cytology and genetics, RAS, Novosibirsk 

immunomodulating properties 

Recombinant polypeptides for biomedical applications Pushchino state university, Pushchino 

Markers of oxidative stress as indicators of heart diseases and efficacy of NII of physico-chemical medicine, Moscow 

their therapy 

Early diagnostics of tumors of both viral and non-viral origin Blokhin Oncology Research Center, RAMS, Moscow 

Phage display-based immunodiagnostics of the most dangerous infectious Gamaleya Institute of Epidemiology and Microbiology, 

diseases RAMS, Moscow 

New generation of conjugated polymer-antigenic and synthetic vaccines and Institute of Immunology, Moscow 

immunogens, as well as their specificity assays and quality control measures, 

and evaluation of their immunity efficacy 

New generation of vaccines and immunogens based on DNA- and genetic Institute of Immunology, Moscow 

engineering technology, and fortified vaccines, as well as measures for 

immune status evaluation 

Stem cells for regeneration of myocardial microcirculation blood flow path Russian Cardiology Research Center, Moscow 

Recovery of epithelial mesenchyme defects using stem cells Institute of Cytology, RAS, St. Petersburg 

Bone marrow stem cells for the support of heart and pancreas function Institute of Transplantology and Artificial Organs 

Tissue engineering in the regeneration of hyaline and fibrous cartilage Burdenko Institute of Neurosurgery, RAMS 

Blood supply recovery of the ischemic organs using progenitor cells carrying Engelhardt Institute of Molecular Biology, 

gene constructions regulated by oxygen level RAS, Moscow 

Isolation and cultivation of human hematopoietic and mesenchymal stem cells Cryo-Center Ltd., Moscow 

Detection of minimal residual leukosis by detection of single molecules of Institute of Protein, RAS, Pushchino 

chimeric RNA oncomarkers 

Panel of protein markers for prognoses of breast, lung, and colorectal cancer Blokhin Oncology Research Center, Moscow 

development and efficacy of their treatment 

Biosensors based on microbial cells with limited genome capacity for the Institute of Physico-Chemical Medicine, Moscow 

diagnostics pathologyGALLEY 

of human

A productive approach in the specific Russian conditions 

was an alliance between research institutes and private 

companies. One compelling example is Applied Immunology 

Institute now housing Biocad’s research team 

(http://www.biocad.ru/public/wsj.pdf). Among the recent 

alliances, cooperation between A/S Pharmstandard and 

IBCH or Bioprocess Group and GNC “Genetika” can be 

mentioned. A similar policy has recently been announced 

by the private holding “Otechestvennye lekarstva” (National 

pharmaceuticals), one of the largest domestic manufacturers 

of vitamins and antibiotics (http://www.hotlek. 

ru, see also [24]). 

In the past few years, revival of the national pharmaceutical 

industry has become both a social and an economic 

challenge. At the same time, the tendency of building 

the state capitalism has been dominating in Russia 

and spread over all branches of the national industry. The 

Russian government, following this tendency, has initiated 

establishment of the state pharmaceutical holding A/S 

“Russian Pharmaceutical Technologies” (RFT) in April 

2007 [69]. According to this incentive of the Federal Ministry 

of Industry, the merger of five plants and nine research 

institutes should be completed by the end of 2007 

and followed by a sale of 49% stocks to the private investors. 

The Ministry plans that RFT will specialize on the 

development of new drugs, as well as generics, but first of 

all biogenerics. 

According to the recommendations of WHO, all countries 

should formulate National Pharmaceutical Policies, 

and such policies have already been prepared by ~100 

countries. However, such a state policy is still absent in 

Russia [70]. The following recommendations could be 

made for Russian Pharmaceutical Policy: 

– State support of Russian manufacturers on all stages 

of both creation (research, technology development, 

clinical trials, registration procedure) and marketing of 

domestic biopharmaceutical products; 

– Legislative taxation preferences for domestic manufacturers 

of pharmaceuticals; 

– Development of the legislative basis for pre-clinical 

and clinical trials, which would be consistent with the 

international norms (GCP). The trials conducted in 

Russia may be more cost effective than in developed 

countries; 

– Publication of Russian Pharmacopoeia including sections 

related to biopharmaceuticals, 

– Essential improvement of the educational system for 

both highly qualified personnel and the technicians 

for the pharmaceutical industry, development and realization 

of the programs for re-education and retraining 

of the specialists, first of all, engineers/technologists, 

for more flexible adaptation to the requirements 

of the market of pharmaceutical vacancies; 

– Recovery of domestic production of the whole spectrum 

of feedstock and disposable materials for bio- 

BTJ 07/07 | TD | DOI 10.1002/biot.200700091 


pharmaceuticals, i.e., from fermentation broth mediums 

to chromatographic sorbents, etc.; 

– Accelerated upgrade of both analytical instruments 

and the basic equipment of the biopharmaceutical industry; 

– The state purchase order in the framework of the Federal 

programs “Health” and DLO for those domestic 

manufacturers who produce high-quality generics at 

a reduced price, on the conditions and terms of payments 

acceptable for small and medium companies; 

– Orientation of the manufacturer’s marketing on the 

real demands of Russian healthcare, including problematic 

diseases widespread in Russia; 

– Educational campaigns about domestic generics, targeting 

both healthcare professionals and consumers; 

– Gradual increase of the percentage of prescriptions 

filled by domestic biogenerics instead of respective 

branded drugs. 

These measures would favorably change the situation in 

the national biopharmacy and help Russia, with its huge 

resources and intellectual potential, to reclaim its place as 

one of the world’s leading biopharmaceutical industries. 

7 References 

[1] Grimley, J., Pharma challenged. Chem. Eng. News 2006, 84, 17–28. 

[2] Hu, X., Ma, Q., Zhang, S., Biopharmaceuticals in China. Biotechnol. 

J. 2006, 1, 1215–1224. 

[3] Johnson, I. S., The trials and tribulations of producing the first genetically 

engineered drug. Nat. Rev. Drug Discov. 2003, 2, 747–751. 

[4] Crea, R., Kraszewski, A., Hirose, T., Itakura, K., Chemical synthesis 

of genes for human insulin. Proc. Natl. Acad. Sci USA 1978, 75, 

5764–5769. 

[5] Goeddel, D. V., Kleid, D. G., Bolivar, F., Heyneker, H. L. et al., Expression 

in Escherichia coli of chemically synthesized genes for human 

insulin. Proc. Natl. Acad. Sci. USA 1979, 76, 106–110. 

[6] Miller, W. L., Baxter, J. D., Recombinant DNA—a new source of insulin. 

Diabetologia 1980, 18, 431–436. 

[7] Clark, A. J., L., Knight, G., Whiles, P. G., Keen, H. et al., Biosynthetic 

human insulin in the treatment of diabetes. A double-blind 

crossover trial in established diabetic patients. Lancet 1982, 320, 

354–357. 

[8] Voltarelli; J. C., Couri; C. E. B., Stracieri; A. B. P. L., Oliveira; M. C. et 

al., Autologous nonmyeloablative hematopoietic stem cell transplantation 

in newly diagnosed type 1 diabetes mellitus. J. Am. Med. 

Assoc. 2007, 297, 1568–1576. 

[9] Skyler, J. S., Cellular therapy for type 1 diabetes: has the time come? 

J. Am. Med. Assoc. 2007, 297, 1599–1600. 

[10] Bibby, K., Davis, J., Jones, C., Biopharmaceuticals – Moving to centre 

stage. 2003 BioPeople North American Biotechnology Industry 

and Suppliers’ Guide. IMS Global website 3–11, 2003 http://www. 

imshealth.com/vgn/images/portal/cit_40000873/43028586Bio_ 

Moving_to_Centre_Stage.pdf (30 October 2005). 

[11] Walsh, G., Biopharmaceutic benchmarks-2006. Nat. Biotechnol. 

2006, 24, 769–776. 

[12] Nightingale, P., Martin, P. The myth of the biotech revolution. Trends 

Biotechnol. 2004, 22, 564–569. 

[13] Krasilnikov, I. V., Prospects of development of recombinant pharmaceutical 

market (in Russian). Farmacevt. vestnik 2005, 16, 26 

(http://www.pharmvestnik.ru/cgi-bin/statya.pl?sid=9568). 

GALLEY PROOF 


Biotechnology 

Journal 

Dmitrij I. Bairamashvili graduated in 

1980 from the Moscow Institute of Fine 

Chemical Technology with an MSc. in 

Chemical Engineering/Technology. He 

obtained a PhD in chemistry in 1988 

from VNII of antibiotics, DSc. (D. habil.) 

in biotechnology from the Moscow 

University of Fine Chemical Technology 

in 2007. He is the author or co-author 

of more than 80 scientific articles and 

patents in the Russian Federation. After graduating and until 1990, he 

worked in research, first at the Shemyakin Institute of Bioorganic 

Chemistry on the structure and function of photoreceptor proteins and 

peptides of natural origin (until 1984), and then for 6 years as a research 

fellow at the All-Union Research Institute of Antibiotics on cyclopeptide 

antibiotics of polymyxin group. Since 1990, he has worked 

as a manager in different business structures. Since 1996, he is affiliated 

at the Institute of Bioorganic Chemistry, first as senior research fellow 

and deputy-chief of the pilot facility and currently as its chief. This 

pilot facility, which employs 80 researchers and engineers, is involved 

in the development and scaling up of various biotechnological and 

biomedical projects – starting with human recombinant insulin production. 

For this work Dr Bairamashvili was awarded in 2005 the Prize 

of the Russian Government. Dr. Bairamashvili participates in the 

preparation of sections of Pharmacopoeia of Russian Federation dealing 

with recombinant pharmaceutical proteins. 

[14] Devine, J. W, Cline, R. R, Farley, J. F., Follow-on biologics: competition 

in the biopharmaceutical marketplace. J. Am. Pharm. Assoc. 

2006, 46, 193–204. 

[15] Wick, J. Y., Zanni, G. R., Biogenerics: potential benefits and obstacles. 

Consult Pharm. 2006, 21, 208–221. 

[16] Bartoshevich, I. E., Nys, P. S., Shviadas, V. I., Navashin, S. M., Status 

and prospects in the use of biocatalysis in the synthesis of β-lactam 

antibiotics (in Russian). Antibiot. Med. Biotekhnol. 1986, 31, 98–104. 

[17] Chazov, E. I., Smirnov, V. N., Suvorova, L. A., Suvorov, A. V. et al., Effect 

of the new Soviet thrombolytic preparation streptodecase on the 

fibrinolysis system (in Russian). Kardiologiia 1981, 21, 18–21. 

[18] Ovchinnikov, Y. A., Efimov, V. A., Chakhmakhcheva, O. G., Synthesis 

of a polynucleotide corresponding to the promotor region of bacteriofage 

fd DNA. FEBS Lett. 1979, 100, 341–346. 

[19] Ovchinnikov, Y. A., Efimov, V. A., Ivanova, I. N., Synthesis of DNA 

coding for human proinsulin. Gene 1984, 31, 65–78. 

[20] Debabov, V. G., Tsygankov, Ju. D., Chistoserdov, A. Ju., Sverdlov, E. 

D., et al. Method for producing human leukocyte interferon α-2 Pat. 

SU1364343, 1988 

[21] Pokrovskii, V. I., Zmyzgova, A. V., Murzabaeva, R. T., Fomina, T. N. 

et al., Reactogenicity, toxicity and tolerance of reaferon in healthy 

volunteers (in Russian). Zh. Mikrobiol. Epidemiol. Immunobiol. 1988, 

1, 69–73. 

[22] Gabrilovich, D. I., Serebrovskaia, L. V., Murzabaeva, R. T., Semashko, 

M. I. et al., Effect of reaferon on the functional activity of peripheral 

blood lymphocytes and neutrophils of volunteers (in Russian). Zh. 

Mikrobiol. Epidemiol. Immunobiol. 1988, 3, 61–65. 

[23] Malinovskaia, V. V., Murzabaeva, R. T., Manakhova, L. S., Mironova, 

L. L., The functioning of the interferon system with different methods 

and dosages of recombinant α 2-interferon (reaferon) administration 

(in Russian). Vopr. Virusol. 1989, 34, 180–183. 


BTJ 07/07 | TD | DOI 10.1002/biot.200700091 


Mikhail L. Rabinovich graduated from 

the School of Chemistry, Lomonosov 

State University of Moscow, in 1973 

with an MSc. in Chemistry. He obtained 

his PhD in Chemistry, Kinetics 

and Catalysis in 1977. In 1987 he became 

DSc. (= Dr. habil.) in Biochemistry 

from A. N. Bach Institute of Biochemistry, 

Russian Academy of Sciences. 

Since 2000, he is Professor in 

Biotechnology from the State Attestation Committee of Russian Federation. 

From 1983 until the present time he has been affiliated at the 

A. N. Bach Institute of Biochemistry, Russian Academy of Sciences, 

and since 1998 as the Head of the Department of Environmental Biochemistry 

(http://www.inbi.ras.ru/english/labs/rabinovich-eng.html). 

For this research he was awarded the medal of the USSR State Exhibition 

of Achievements in Science and Technology in 1984 and the 

National Prize for Young Scientists in 1986. In 1988/1989, he was a 

visiting scientist at Leipzig Institute of Biotechnology, Academy of 

Sciences of GDR. From 1992 to 2003 he was a lecturing professor in 

environmental biotechnology at the Department of Ecology, Russian 

University of Peoples Friendship, Moscow. In 2004/2005, he was a 

guest professor at the Chair of Microbiology of Bayreuth University 

(Chairman: Prof. Ortwin Meyer), Germany. Dr. Rabinovich has supervised 

13 PhD and DSc. students from different countries. His field of 

expertise includes chemical enzymology, plant biopolymers, biofuels, 

fungal degradation of xenobiotics. He is the author and co-author of 

4 books, and ca. 100 reviews and research articles in refereed journals; 

in addition, he holds■check■ 14 Russian patents, is a member of the 

Advisory Board of the Biotechnology Journal (Wiley-VCH), and has 

written ■check■Recent Patents in Biotechnology (Bentham), and 

Research and Reviews in Biosciences (TSI). 

[24] Pisarev, V. V., Does Russia have a chance of implementation of modern 

biotech achievements in the medical industry? (in Russian). 

Novosti med. biotekhnol. ■year, vol? page no?■www.bionews.ru/ 

news/Bio.htm 

[25] Grigoriev, A. I., Malashenkov, D. K., The role of innovation in the development 

of life sciences (in Russian). Medbioteck-3, December, 

2006, Moscow (http://www.bioinnovation.ru/index?id=materials). 

[26] Tel’nova, E., “Toll-free” prescription has become more expensive (in 

Russian). Rossijskaya Gazeta 21.10.2006. 237, 19 (http://www.rg.ru). 

[27] Fast growth of pharmaceutical market (in Russian). Moskovskie 

apteki, 25.12.2006 (http://www.mosapteki.ru/modules/news/article.php?storyid=202). 

[28] Stepanov, V. Doctor “Brand” (in Russian). SmartMoney 04.09.2006, 

25 (25) (www.smoney.ru/article.shtml?2006/09/04/1255). 

[29] DLO: Market and patient (in Russian). Moskovskie apteki. 2006, 7–8 

(152), 7–11 (http://www.mosapteki.ru). 

[30] Konov, A. L., Biopharmaceuticals: state-of-the-art and perspectives 

(in Russian). Farmacevt. sluzhba 2006, 1, 22–29. 

[31] Kulish, D. M., Can a “biogeneric revolution” happen in Russia? (in 

Russian) Farmacevt. vestnik 2005, 16 (375), 26 (http://www.pharmvestnik.ru/cgi-bin/statya.pl?sid=9570). 

[32] Schmidt, M., Babu, K. R., Khanna , N., Marten, S. et al., Temperatureinduced 

production of recombinant human insulin in high-cell density 

cultures of recombinant Escherichia coli. J. Biotechnol. 1999, 68, 

71–83. 

GALLEY PROOF

[33] Kostina, G., Russian pancreas functions badly (in Russian). Expert 

2007, 13, 60 (http://www. expert.ru). 

[34] Vasiliev, F., Realization of the DLO Program in the first half of 2006 

(in Russian). Farmacevt. vestnik, 2006, 30 (435) (http://www.pharmvestnik.ru/cgi-bin/statya.pl?sid=11278&forprint=1). 

[35] Bairamashvili, D. I., Genetic-engineering insulin of human: successes 

and prospects (in Russian). Ross. Khim. Zh. (Zh. Ross. Khim. Obshchestva 

im. D.I.Mendeleeva) 2005, 49, 34–46. 

[36] Korobko, V. G., Boldyreva, E. F., Shingarova, L. N., Miroshnikov, A. I. 

et al., Recombinant plasmid DNA pPINS1-6 encoding fused 

polypeptide containing human proinsulin, recombinant plasmid 

DNA pPINS2-5 encoding fused polypeptide containing human 

proinsulin and strain of bacterium Escherichia coli – producer of 

fused polypeptide containing human proinsulin. Pat. RU2143493, 

1999. 

[37] Kalinin, Yu. T., Urakov, N. N., Ivanov, V. T., Stepanov, A. V. et al., 

Method of recombinant human insulin preparing. Pat. RU2141531, 

1999. 

[38] Pustoshilova, N. M., Kileva, E. V., Denisova, L. J., Shingareva, N. V. 

et al., Method of human recombinant tumor necrosis α-factor 

preparing. Pat. RU2144958, 2000. 

[39] Patrushev L. I., Bairamashvili, D. I., Miroshnikov, A. I., Bacterium Escherichia 

coli strain BL21/pPINS07(BL07) as producer of human 

proinsulin. Pat. RU2267534, 2006. 

[40] Gusarov, D., Lasman, V., Bobruskin, A., Bairamashvili, D., Pilot plant 

scale purification of the human insulin and human growth hormone 

by reversed phase HPLC and hydrophobic interaction chromatography: 

Methods comparison and qualification. Abstracts of the 5th 

HIC/RPC Bioseparation Conference, 20–23 March 2007, Interlaken, 

Switzerland., p. 68. 

[41] Vorobyov, I. I., Ponomarenko, N. A., Alexandrova, E. S., Murashev, E. 

A. et al., Highly efficient process of human growth hormone production. 

Russian Biotechnol. 2005, 5, 44–48. 

[42] Gabibov, A. G., Ponomarenko, N. A., Vorobyev, I. I., Demin, A. V. et 

al., Recombinant plasmid DNA pES1-6 encoding polypeptide somatotropin 

and strain Escherichia coli BL21(DE3)/pES1-6 as producer 

of recombinant somatotropin. Pat. RU2233879, 2004. 

[43] Gabibov, A.G., Ponomaremko, N. A., Vorobyev, I. I., Demin, A. V. et 

al., Recombinant plasmid DNA pES3-7 encoding polypeptide sequence 

of human granulocyte colony stimulating factor and strain 

Escherichia coli BL21(DE3)/pES3-7 as producer of recombinant human 

granulocyte colony stimulating factor. Pat. RU2260049, 2005. 

[44] Klyushnichenko, V., Bruch, R., Bulychev, A., Ditsch, A. et al., Feasibility 

of international technology transfer for the production of recombinant 

human insulin. Part 2. Two models for insulin manufacturing 

in Russia. BioProcess Int. 2004, 2, 46–54. 

[45] Stepanov, A. V., Rodionov, P. P., Baydus’, A. N., Astashkina, G. F., Domestic 

insulin – product of the world quality level (in Russian). Terra 

Medica Nova 2005, 1, 48–49. 

[46] Valuev, I. L., Valuev, L. I., Plate, N. A., Mechanism of action of immobilized 

insulin preparations for oral administration. Dokl. Phys. 

Chem. 1998, 360, 131–134. 

[47] Plate, N. A., Valuev, L. I., Valueva, T. A, Staroseltseva L. K. et al., Protein-containing 

polymer composition for oral administration. Pat. 

US6004583, 1999. 

[48] Mukamolova, G. V., Kaprelyants, A. S., Young, D. I., Young, M. et al., 

A bacterial cytokine. Proc. Natl. Acad. Sci. USA 1998, 95, 8916–8921. 

[49] Yeremeev, V. V., Kondratieva, T. K., Rubakova, E. I., Petrovskaya, 

S. N. et al., Proteins of the Rpf family: Immune cell reactivity and vaccination 

efficacy against tuberculosis in mice. Infect. Immun. 2003, 

71, 4789–4794. 

[50] Kudoyarova-Zubavichene, N. M., Sergeyev, N. N., Chepurnov, A. A., 

Netesov, S. V., Preparation and use of hyperimmune serum for prophylaxis 

and therapy of Ebola virus infections. J. Infect. Dis. 1999, 

179 (Suppl. 1), S218–S223. 

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[51] Kiselev, O. I., Tsybalova, L. M., Pokrovskii, V. I., Development of the 

anti-influenza H5N1 vaccines worldwide and in Russia (in Russian). 

Zh. Mikrobiol. Epidemiol. Immunobiol. 2006, 5, 28–38. 

[52] Avdeeva, Zh. I., Alpatova, I. A., Medunitsyn, N. V., Pharmaceuticals 

of cytokine system (in Russian). Citokiny i vospalenie 2002, 1, 33. 

[53] Simbirtsev, A. S., Cytokines as mediators of defence reactions of the 

organism (in Russian). Citokiny i vospalenie 2002, 1, 38–39. 

[54] Suchkov, S. V., Alekberova, Z. S., Paleyev, F. N., Naumova, T. Y. et al., 

Achievements and prospects of clinical abzymology (in Russian). 

Vestnik Ros. Akad. Med. Nauk 2005, 9, 38–43. 

[55] Baryshnikov, A. I., Sviridov, V. V., Russian collection of hybridomas 

(in Russian). Vestnik Ros. Akad. Med. Nauk 1999, 10, 30–32. 

[56] Chmutin, Y. F., Ivanov, P. K., Baryshnikov, A. Y., Monoclonal antibody-based 

design of antitumor drugs: Prerequisites and progress 


[57] Baryshnikov, A. I., Polosukhina, E. R., Monoclonal antibodies in oncology 


[58] Stadnikov, A. A., Shevliuk, N. N., Stem cells and reparative regeneration 

in mammalian postnatal ontogenesis (in Russian). Morfologiia 

(St. Petersburg, Russia), 2006, 130, 84–88. 

[59] Korochkin, L. I., Revishchin, A. V., Okhotin, V. E., Neural stem cells 

and their role in recovery processes in the nervous system. Neurosci. 

Behavioral Physiol. 2006, 36, 499–512. 

[60] Baranov, V. S., Genomics and molecular medicine. Mol. Biol. 2004, 

38, 94–99. 

[61] Shishkin, S. S., From structural to functional genomics: theoretical 

and applied aspects (in Russian). Vestnik Ros. Akad. Med. Nauk 

2002, 4, 11–16. 

[62] Baranov, V. S., Baranov, A. N., Zelenin, A. V., The current state and 

prospects of the gene therapy of duchenne muscular dystrophy 

worldwide and in Russia. Russian J. Genet. 2001, 37, 868–875. 

[63] Vlasov, V. V., Oligonucleotides as the basis of gene-targeted therapeutic 

drugs. Herald Russ. Acad. Sci. 2004, 74, 419–423. 

[64] Zhdanov, R. I., Bogdanenko, E. V., Petrov, A. I., Podobed, O. V. et al., 

Lipoplexes based on cholesterol derivatives of oligo (ethylene propylene 

imines) in gene transfer in vitro and in vivo. Dokl. Biochem. Biophys. 

2005, 401, 131–135. 

[65] Bogdanenko, E. V., Zhdanov, R. I., Sebyakin, Y. L., Zarubina, T. V. et 

al., A glycolipid containing a lactose residue: a novel agent for targeted 

DNA delivery for the purpose of genetic therapy. Dokl. 

Biochem. Biophys. 2005, 401, 145–149. 

[66] Petrov, R. V., Kabanov, V. A., Khaitov, R. M., Nekrasov, A. V. et al,. 

Conjugated polymer-subunit immunogens and vaccines. Allergy 

Clin. Immunol. Int. 2003, 15, 56–61. 

[67] Sobolev, B. N., Poroikov, V. V., Olenina, L. V., Kolesanova, E. F. et al., 

Computer-aided design of vaccines (in Russian). Biomed. Khim. 

2003, 49, 309–332. 

[68] Gorokhovets, N. V., Digtjar, A. V., Lutsenko, E. V., Lutsenko, S. V. et 

al., Antitumor peptide preparation based on α-fetoprotein fragment, 

its conjugate, pharmaceutical composition and method for treatment 

of hormone-dependent tumors. Pat. RU2285537, 2006. 

[69] Surovtsev, V., Baryshnikova, G., RFT will help to revive production of 

the most important pharmaceutical substances (in Russian). Farmacevt. 

Vestnik 2007, 12, 14 (http://www.pharmvestnik.ru/cgibin/statya.pl?sid=11977). 

[70] Pharmaceutical industry needs preferences (in Russian). 

Moskovskie apteki, 2007, 4 (http://www.mosapteki.ru/modules/ 

news/article.php?storyid=254). 

GALLEY PROOF

Russia through the prism of the world biopharmaceutical market

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