Brief Report Medical Trends and Achievements in Iran

Fereidoun Mahboudi 1*, Haleh Hamedifar 2, and Hamideh Aghajani 3

1. Biotechnology Research Center, Pasteur Institute of Iran, Tehran Iran 2. CinnaGen Co, Tehran, Iran 3. Aryogen Co, Karaj, Iran

Abstract A healthcare system has been the most important priority for all governments worldwide. Biotechnology products have affected the promotion of over the last thirty years. During the last several decades, Iran has achieved significant success in extending healthcare to the rural areas and in reducing the rates of infant mortality and increasing population growth. Bio- medical technology as a converging technology is considered a helpful tool to fulfill the Iranian healthcare missions. The number of biotechnology products has reached 148 in 2012. The total sales have increased to 98 billion USD with- out considering vaccines and plasma derived proteins in 2012. Iran is one of * Corresponding author: the leading countries in the Middle East and North Africa in the area of Medi- Fereidoun Mahboudi, Ph.D., Biotechnology Research Cen- cal biotechnology. The number of biotechnology launched in Iran is Downloaded from http://www.ajmb.org ter, Pasteur Institute of Iran, 13 products until 2012. More than 15 products are in pipelines now. Manufac- Tehran, Iran turers are expecting to receive the market release for more than 8 products Tel: +98 21 66953311 by the end of 2012. Considering this information, Iran will lead the biotechnol- Fax: +98 21 66465132 ogy products especially in area of biosimilars in Asia after India in next three E-mail: [email protected] years. The present review will discuss leading policy, decision makers’ role, Received: 5 Aug 2012 human resource developing system and industry development in medical bio- Accepted: 30 Aug 2012 technology. Avicenna J Med Biotech 2012; 4(4): 200-205

Keywords: Biopharmaceutics, Human resources, Iran, Medical biotechnology

Introduction "Biotechnology" was defined in 1919 by Karl ing organisms to the diagnosis or treatment of Ereky, a Hungarian engineer, to describe a disease. methods and techniques which produce sub- Modern Biotechnology or Molecular bio- stances from row materials with the aid of technology was shaped in the early 1970 by living organisms (1). A standard definition of the means of heterologous cloning in E.coli (3). biotechnology was achieved in the Conven- The first biopharmaceutical products, recom- tion on Biological Diversity (1992) – "any binant insulin and recombinant human growth technological application that uses biological hormone, were launched to the world market systems, living organisms or derivatives there in 1980’s (4). In this decade, more than 10 bio- of, to make or modify products and processes pharmaceutical products were approved by for specific use" (2). This definition was agreed the regulatory offices in the United States and by 168 member nations, and also accepted by European countries (4). From then, new and the Food and Agriculture Organization of the more affective vaccines, drugs and diagnostic United Nations (FAO) and the World Health tools have been developed by medical bio- Organization (WHO) (2). According to this def- technology for cancer, autoimmune disease, inition, medical biotechnology is applied liv and infectious diseases such as tuberculosis,

20020 Copyright © 2012, Avicenna Journal of Medical Biotechnology. All rights reserved. Vol. 4, No. 4, October-December 2012 20 Mahboudi F, et al malaria and HIV/AIDS. Figure 1 shows the Regenerative . In recent years, Iran new biopharmaceutical drugs approved by has registered achievements in this field for FDA since 1982 (5). Biopharmaceutical ap- more than 12 products (7). In this review, the provals are expected to further increase in the leading policy for developing biotechnology, coming years, with many applications pend- educational system and industries frontiers in ing or expected, including new classes of Iran will be explored. products, e.g., gene therapies, stem and other (5) Policy cellular therapies, and cancer vaccines . Due The advancement of biotechnology as a to its promising products, medical biotech- successful industry, confronts many challeng- nology is described as “technology of hope”. es related to research and development, crea- Therapeutic biotechnological products and tion of investment capital, technology transfer vaccines that are currently being marketed and technology absorption, patentability and have an annual market value of 98 billion intellectual property, affordability in pricing, USD, and benefiting over a hundred million (6) regulatory issues and public confidence. Cen- people worldwide . There are hundreds tral to this are two key factors: affordability more of these products in clinical develop- and accessibility to the products of biotech- ment. Medical biotechnology can deliver the nology. Policies that foster a balance between next wave of technological change that can be sustaining innovation and facilitating technol- as radical or even more pervasive than what ogy diffusion need to be put in place. The brought about by other technology like In- Ministry of Science, Research and Technolo- Downloaded from http://www.ajmb.org formation Technology. Employment genera- gy (MRS), The Ministry of Health and Medi- tion, intellectual wealth creation, expanding cal Education, Deputy of Research and tech- entrepreneurial opportunities, augmenting in- nology of Presidency, and Center for Cooper- dustrial growth are a few of the compelling ation of science and innovation of Presidency factors that warrant a focused approach this serves as the coordinating body for science technology. Therefore, Biotechnology is a and technology policy making. powerful and enabling technology for a coun- The priorities of medical biotechnology in- try like Iran which can revolutionize health- volve molecular detection of infectious and care and pharmaceutical industry. genetic diseases, production of recombinant The Iranian biotechnology sector has, over medicines and vaccines, and the last two decades, taken shape through a are defined by National Medical Biotechnolo- number of scattered and sporadic academic gy Network and National and industrial initiatives. Trends of medical network. Based on these activities, different biotechnology in Iran are in the fields of bio- committees and working groups are assigned pharmaceutical, Diagnosis, Cell Therapy, and for these tasks. The most active task groups for policy making and priority setting are as follow:

- Biotechnology Committee under the super- vision of Science and Technology Deputy of Presidency: The major tasks of this committee is setting policy and priority setting for re- search and development and grant the applied research and investment grant for biotechnol- ogy startup companies. - Biotechnology Board for Medical Biotech- nology at Ministry of Health and Medical Ed- ucation: The task of this Board is helping to Figure 1. FDA approved biopharmaceutics 1982-2010 (5) set up postgraduate studies and curriculum

Avicenna Journal of Medical Biotechnology, Vol. 4, No. 4, October-December 2012 201 Medical Biotechnology Trends and Achievements in Iran

development in Medical Universities and re- growth rates and research achievements in the search centers. world. Meanwhile, majority of the young stu-

- Biotechnology Committee at Environmental dents voluntarily were fighting and they were Department. in front line of the battles. In addition to the - Center for Cooperation of science, Technol- war, a high number of senior immi- ogy and Innovation of Presidential office: grated to the Western countries in this period. The task of this center is to help for financial By the end of the war, research institutes had support and facilitate the rules and regulations access to more scientific environments and that help start up companies to get into the money resources to develop new technologies market. like biotechnology. Nowadays, more than 15 - High Tech Department at Ministry of Indus- biotechnology research centers and depart- try: This is an organization for supporting the ments are operating in Medical Universities. financial status for production specially works The first Iranian National Center for Bio- such as Venture capitalist at the governmental technology and Genetic Engineering (NCB level, in addition, to subsidize some portion of GE) was established in 1989 under the super- the Banking loans. vision of the Ministry of Science, Research - National Medical Biotech Network: This and Technology (MRST). Plant, animal, med- network tries to bring the scientists together to ical and marine, industrial and environmental work for a specific project at national level in are in the scope of NCBGE.

areas of biopharmacutics and mega projects Aims of this center are defined as research Downloaded from http://www.ajmb.org and also, to help increase national capacity activities in the field of advanced molecular building for centers and scientists. Priority and biotechnology, promoting applied setting and scientific advice are two major and basic research in science and technology. duties of this network. Pasteur Institute of Iran, as the second bio- - National Molecular Medicine Network: This technology research center, started to work in network tries to bring the scientists together to this area in 1992. The first biotech and mo- work for a specific project at national level in lecular biology departments started with 15 areas of human and genetic disor- Ph.D., candidates in Pasteur institute. Pasteur ders, and mega projects. Also, helps to in- medical biotechnology department has fo- crease national capacity building for centers cused on recombinant production of different and scientists especially to establish national proteins used as biopharmaceutics, vaccine gene banks for different disorders. candidates or diagnostic kit components.

- Eastern Mediterranean Health Genomics and In collaboration with International Center Biotechnology Network, and Regional Net- for Biotechnology and genetic Engineering of work: This network was established in 2005 Cuba, the production facility for Hepatitis to bring the scientists of this region together. vaccine and three recombinant pharmaceuti- More than 8 countries are members of this cal proteins, Erythropoietin, Interferon alpha, network including Egypt, Pakistan, Oman, and Streptokinase was built. To assess the an- Bahrain, Iran, Morocco, Tunisia, Saudi Ara- alytical characteristics of these recombinant bia, and Syria. proteins a protein chemistry unit was estab-

Human resource and education lished in 1999. Further to recombinant phar- Iran was involved with the imposed war maceutics, a new drug discovery group has from the Iraqi government for 8 years, 1980- been recently established in Medical Biotech- 1988. While most of the Iranian research cen- nology department to design and develop tar- ters and scientists were busy with problem get based anti-infective compounds including raised during the war specially the chemical new antifungal and also anticancer agents. weapon that was used by the Iraqis, bio- The other important biotechnology institute is science and biotechnology had the highest Razi, a vaccine and serum research institute.

20220 Avicenna Journal of Medical Biotechnology, Vol. 4, No. 4, October-December 2012 Mahboudi F, et al

It is one of the oldest and most important ap- 1. Iranian Society for Biotechnology (ISB), plied research and development organization established 1997, 600 members, four branches in Iran. Razi produces over 2.5 billion doses in different provinces of 55 different biological products, including 2. Iranian Genetic Society (IGS), established human and veterinary vaccines and also diag- 2001, 500 Members nostic antigens, at an annual value of about 3. Iranian Biosafety Society (IBS), established 100 million USD. It has 28 different depart- 2003, 150 members ments and 1250 staff, including 133 scientists. 4. Bioethics Society in Science and Technol-

Graduate programs for basic medical sci- ogy (ESST), established 2004 industry. ences related to biotechnology issues includ- Iran has a fairly well-developed pharma- ing immunology, , , mo ceutical industry compared to others in the lecular biology and chemical engineering developing world. Iran has also been success- were launched at state universities. At the ful in extending healthcare to the entire popu- moment, with not more than 1700, the num- lation. Its origins date back about 80 years ber of senior researchers (with Ph.D.) seems ago to the establishment of the Razi Vaccine to be very limited in the field of medical bio- Production Research Institute in 1925 and the technology, But, for Iran to build a competi- Pasteur Institute in 1920. Both institutes be- tive biopharmaceutical industry, it should in- gan by producing vaccines through traditional crease the resources (human as well as finan- biotechnology methods, first for veterinary cial) devoted to the field by several folds to applications and subsequently for human use. Downloaded from http://www.ajmb.org build a critical mass of research and develop- Pharmaceutical companies in Iran can be di- ment activities. Table 1 shows the most im- vided into two groups. One group develops portant research centers and universities. the cell line and produce active raw materials In addition to the above, there are several in their facilities. There are 5 companies that NGO’s involved in biotechnology human re- can be categorized into this group. source organization. These NGO’s are re- The second group started their operations sponsible to develop the Iranian science- by licensing the products and processes from matrix: the Transnational Corporations (TNCs) and

Table 1. Universities and research centers involved in training of medical biotechnology

Centers and universities Graduate programs NCBGE and medical biotechnology Pasteur Institute of Iran Basic medical sciences and biotechnology Tehran University of Medical Sciences Biopharmaceutic and basic medical sciences Mashhad University of Medical Sciences Biopharmaceutic and basic medical sciences Gorgan University of Medical Sciences Molecular Medicine Zanjan University of Medical Sciences Molecular medicine Hamadan University of Medical Sciences Molecular medicine and biotechnology Shiraz University of Medical Sciences Basic medical sciences Semnan University of Medical Sciences Medical Biotechnology Sharif University Chemical engineering Tehran University Chemical engineering Tabriz University of Medical Sciences Molecular Medicine and basic medical sciences Shahid Beheshti University of Medical Sciences Molecular Medicine and basic medical sciences Royan Research Centers Medical biology and biotechnology Avacinna Research Centers Molecular Medicine and biotechnology Tarbiat Modares University Genetic and medical biotechnology, chemical engineering, process development Azad Islamic University Genetic and medical biotechnology

Avicenna Journal of Medical Biotechnology, Vol. 4, No. 4, October-December 2012 203 Medical Biotechnology Trends and Achievements in Iran

manufacturing them locally. The operations nant medicine for orphan drugs take most of mainly involved importing the raw material the health care cost for all government. Iran (bulk drugs) and formulating them locally. has started to market its products outside its Since 1980, more than 148 recombinant bi- borders. Interferon beta 1a is one of the most opharmaceuticals have received approval and expensive recombinant medicines in biophar- launched worldwide. Supporting the local maceutics. Iranian brand for this medicine, manufacturing, biosimilar regulations have CinnoVex, has been launched in three coun- been approved in the Ministry of Health and tries with annual sale of close to 18 million Medical Education in Iran. More than 12 USD. Among the firms that are most active in products have been approved and more than the biotechnology industry are: Razi Vaccine 15 are in the pipeline to be approved in the and Serum Production Research Institute and next three years for recombinant proteins and the Pasteur Institute of Iran. Both institutes monoclonal antibodies. Table 2 shows the list are publicly founded. The rest of the compa-

Table 2. List of biopharmaceuticals that have received approval from MOH as biosimilar

Products Name of company 1 IFN alpha Pasteur Institute of Iran, Poyesh Daro 2 G-CSF Poyesh Daro 3 EPO alpha Pasteur Institute of Iran, Poyesh Daro, Notarkib

4 IFN beta 1a (CinnoVex) CinnaGen, Downloaded from http://www.ajmb.org 5 IFN beta 1a (ReciGen) CinnaGen 6 Epo beta CinnaGen, Zahravi 7 PTH CinnaGen 8 Buscerlin CinnaGen 9 Interferon beta 1b Zist daro Danesh 10 Interferon gamma NoTarkib 11 Peg-Interferon alpha Poyesh Daro 12 Antihaemophilic factor VII AryoGen 13 HBS (Vaccine) Pasteur Institute

of biopharmaceutical products in Iran. More Table 3. List of biopharmaceutical products in different than 15 recombinant pharmaceutical products phase of development

are in the pipelines. It is expected to be re- Year expected Products leased to the market in the next two to three to be launched years. Considering these products, Iran will 1 FSH 2012 be one of the biggest biosimilar producers in 2 PEG-G-CSF 2012 the world and will lead the countries in Asia 3 Human Growth Hormone 2013 in a numbers of products. Table 3 shows the 4 Herceptin 2012 number of biopharmaceutical products that 5 Enbrel 2012 are in different phase of development. 6 Rituximab 2012 There are also other companies involved in 7 Cetuximab 2013 licensing biotechnology products. They are 8 VIII 2012 producing recombinant protein under the li- 9 LH 2013 cense using active raw materials as imported 10 Streptokinase 2012 materials. Human Growth hormones and insu- 11 t-PA 2013 12 Darbopoetin 2013 lin are two major ones. 13 IL-2 2013 Biopharmaceutical products are among the 14 Infleximab 2013 most expensive medicines available in the 15 Rabies Vaccine 2013 market. Monoclonal antibodies and recombi-

20420 Avicenna Journal of Medical Biotechnology, Vol. 4, No. 4, October-December 2012 Mahboudi F, et al nies are private investments. rules and regulations that help to facilitate the In order to build up a solid biopharmaceuti- production life cycle in the country are well cal industry, a "big push" is needed by the defined. The only item that is needed is exe- government through the provision of substan- cution of the laws and regulations. Implemen- tial research funding in the national research tation of the both long and short term plans institutes and the provision of seed and ven- surely will put Iran in the first position in this ture capital funding to start-up firms. This technology in the region, third in Asia and 12 would stimulate entrepreneurship among the in the world. In some cases like biosimilar, it scientists. In some of developing countries is noted that Iran can move to the first posi- such as India, the government-owned com- tion in Asia and even in the world by launch- mercial banks have started their own venture ing more than 27 products by 2013. The total capital operations. Iranian banks should be local market value will be close to 800 mil- encouraged to do likewise. lion USD with potential world-wide market value expected to be up to 2 billion USD an- Conclusion nually. In terms of human resources, more Medical biotechnology is rapidly expand- than 3000 university graduates, with various ing world-wide and biotechnology-based di- degrees: BS, MS, Pharm. D., MD and Ph.D. agnostics, vaccines and drugs offer very high will be hired and more that 9000 indirect jobs added-value productions. Iran could enter will be created for the university graduates. profitably in this field, initially with generic Downloaded from http://www.ajmb.org products, since many important patents for Conflict of Interest such products have expired or are about to Authors declare no conflict of interest. expire, and, conceivably, later, with novel products and processes more specific for the References country and the region. 1. Fári MG, Kralovánszky UP. The founding father of Advanced biotechnologies can offer inter- biotechnology: Károly (Karl) Ereky. Int J Hortic Sci 2006;12(1):9-12 esting opportunities for the economic devel- opment of Iran, considering that biotechnolo- 2. Young FE. Biotechnology: the view from the FDA. Health Matrix 1986;4(3):10-15. gy-based applications are not demanding in terms of capital investment or in requirements 3. http://www.fao.org/biotech/fao-statement-on-bio- technology/en/ [Online]. for raw materials, whereas they rely essential- ly on the availability of well-trained scientists 4. 4, Rader RA. Paucity of biopharma approvals raises and technicians. Iran can thus draw advantage alarm, lower numbers, novelty, and economic im- pact indicate problems. GEN 2008. from its appreciable human capital in differ- ent scientific fields. 5. Rader RA. FDA biopharmaceutical product ap- In order to build up the biopharmaceutical provals and trends. Biotechnology Information sector, or the whole biotechnology sector for Institute, www.biopharma.com/approvals_2011 .html. that matter, the government will need to adopt strategies of technology missions and techno- 6. Sasson A. Medical biotechnology: achievements, prospects and preception. Tokyo, New York, Paris: logical roadmaps with clear long-term and United Nations University press; 2006. short-term objectives and plans. Iran has es- tablished the long and short term plans for 7. Samadikuchaksaraei A, Mousavizadeh K. High- tech biomedical research: lessons from Iran's this sector. All the requirements, including experience. BioMed Eng OnLine 2008;7(17):1-6. human resources, capital investment, and

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