Industrialization Project of Recombinant Human Growth Hormone Multi-Dosage Achievement

Industrialization Project of Recombinant Human Growth Hormone Multi-Dosage Achievement of Changchun City

 

1. Introduction to the Project

1.1 Project Background

1.1.1 Product Introduction

Growth hormone is the only medicine suitable for under size treatment of children. It has been recorded in Pharmacopoeia of many countries, and entered hospitals of more than 60 countries. Till now, it has had a history of 30 years. Recombinant human growth hormone is a kind of protein consisting of 191 amino acid residues, or 192 amino acid residues with N-terminal the methionine. It can be added with appropriate amount of excipient or stabilizer. The content of recombinant human growth hormone e should be 90.0% -110.0% of the labeled amount. It has the role of adjusting the endocrine system, activating and the maintaining the normal working of the immune system. Since the introduction of recombinant human growth hormone in the 1980s, with the continuous expansion of its field of application and medication patient population, the world renowned R & D institutions and pharmaceutical companies began looking for new selling points in a new dosage form. At present, they are conducting R & D of long-acting formulations, but the long-acting growth hormone is still a blank so far in the field of international pharmaceutical. In the country, there are a total of four pharmaceutical factories conducting research and development on recombinant human growth hormone, but the species of most manufacturers are single, only launching freeze-dried powder dosage used for undersize. The development of other new formulation just begins, thus the level is low. The research and development team of this project has the most complete variety in the development of recombinant human growth hormone, and progress is far ahead. Besides launching the first freeze-dried powder for children dwarf in China, it has launched water injection type for burned recombinant human growth hormone and for children dwarf in 2001 and 2005. The research and development of long-acting growth hormone has been completed. This project seeks to industrialize the results of the multi-dosage recombinant human growth hormone. It adopts international leading polyethylene glycol coupling, amorphous protein stabilization technology and process to obtain long-acting human growth hormone, approval of pre-canned growth hormone production, completes the construction of the production line and passes GMP certification, and implements the industrialized production of multi-dosage recombinant human growth hormone products.

1.1.2 Market Prospects

Growth hormone is a protein secreted by the pituitary gland; it can promote the growth of all other tissues except for the nerve tissue, and promote the body compound anabolism and protein synthesis. Recombinant human growth hormone uses genetic engineering technology. It has significant function for improving the body's metabolism, stimulating protein synthesis, and promoting the growth and development of the entire body functions. The product is used for treatment of short stature and deficiency of children growth hormone. It is widely recognized by doctors and patients.

Currently, more than 60 countries around the world have listed recombinant human growth hormone into the range of medical insurance. Each year in the world, more than 300,000 people use recombinant human growth hormone. The annual growth rate of compounding of recombinant human growth hormone on the global market is as high as 24.4% in 2005-2010. In 2011, the sales volume of recombinant human growth hormone in the world reached 9.754 billion U.S. dollars. The global leaders of human growth hormone market include Pfizer, Novo Nordisk, Eli Lilly Company, Roche / Genentech and Serono Company etc. It is estimated that the growth hormone used for children or adolescent growth disorders, for adult growth hormone deficiency, and for AIDS-related weight loss accounts for about 1/3 respectively.

In China, the market potential of recombinant human growth hormone is also huge. In the domestic market, the incidence rate of children's various growth and development disease is high, including short stature incidence rate of 1%, with about nearly 1 million patients having short stature, and the potential market is 4 billion yuan per year. Only more than 30,000 children and more than 70,000 burn patients use medicine, accounting for 5%. A large blank market is yet to be developed. It needs the society, doctors, schools, and other ways to carry on product knowledge propaganda. Especially through attacking various counterfeits that have no treatment effect, patients will recognize growth hormone and accept medication treatment. In 2008, recombinant human growth hormone, as the only effective drug for the treatment of growth hormone deficiency that leads to short stature, smoothly entered the national children's health insurance directory. Another unlimited potential market of growth hormone is the anti-aging effect. After people enter the age of 35, growth hormone secretion is reduced, and medicine proves that growth hormone deficiency and aging shows a positive correlation. The earliest application of it is for patients after pituitary operation. The effects of improving the quality of life have been confirmed; it does not cause tumor recurrence, is safe and effective, and widely welcomed by the high-end consumers in the world. Growth hormone is the leading product of the globe in anti-aging field: the estimated current market value is $ 3 billion, and is rapidly growing; with the improvement of economic level, more and more attention is paid to the quality of life. At present, it has not yet been fully accepted by mainstream medicine, but depending on civilian force and consumers, it will grow quickly. In addition, after domestic recombinant human growth hormone products enter the market, the price has a considerable advantage, and the market will rapidly expand. The market size of domestic recombinant human growth hormone will develop from 530 million yuan in 2008 to 1.1 billion in 2012, with the compound annual growth rate of up to 32.8%. It is expected that in 2015, the sales volume of domestic recombinant human growth hormone will reach 1.8 billion yuan, thus product market prospects area broad. According to the current market situation, the experts predict, recombinant human growth hormone will keep a rapid development momentum at least for 20 years. Therefore, the project has broad market prospects.

1.1.3 Technical Analysis

This project seeks to industrialize the results of the multi-dosage recombinant human growth hormone. It adopts international leading polyethylene glycol coupling, amorphous protein stabilization technology and process to obtain long-acting human growth hormone, approval of pre-canned growth hormone production, completes the construction of the production line and passes GMP certification, and implements the industrialized production of multi-dosage recombinant human growth hormone products. All the technologies used in the project are independently researched by the research institutions in the park, with independent intellectual right, without technological risk problem.

1.1.4 Advantageous Conditions of Project Construction

（1）Policy conditions

Changchun High-tech Zone owns "one academy, four institutes and four universities”, that is, Changchun Branch of Chinese Academy of Sciences, Jilin University, Northeast Normal University, Changchun University of Science and Technology, Changchun University of Technology, Optics Institute, Applied Chemistry Institute, Biology Institute, and Geography Institute. It establishes “technology innovation strategic alliance”, adopts government investment pulling, diversified investment, market-oriented operation, enterprise management mode. The joint construction area is seven square kilometers. ChangchunNortheastTechnologyInnovationCenter, with a total investment of 17.2 billion yuan, will mainly construct incubator area, research and education area, commercial and residential supporting area etc. three major functional areas. Changchun Hi-tech Zone gathers 14 full-time colleges such as JilinUniversity, Changchun University of Science and Technology, 39 research institutes such as the CAS Changchun Institute of Optics, 29 national key laboratories, and 76 above the city level enterprise technical centers. The institutions involving biological and pharmaceutical industries are: Changchun Biological Products Institute, College of Chemistry of Jilin University, College of Pharmacy of Jilin University, Changchun Chinese Medicine Hospital, and Jilin Province TCM and Chinese Medicine Institute etc.12 science and technology institutions, 13 key provincial and ministerial labs in the field of medicine, 5 professional national testing organization laboratories in the field of medicine, and 10 above the city level enterprise technical centers of pharmaceutical companies. It is the most concentrated area of JilinProvince in the aspect of science and education resources, and research and development institutions.

（3）Human resource advantage

ChangchunCity is a famous cultural city of China. The per capita number of college students in Changchun ranks the 6^th in the country. Changchun High-tech Zone has total human resources of about 90,000 people, including high-end creative talents of 30000, accounting for more than 60% of the city; more than 2,400 doctors, masters, and 1,000 overseas returnees, as well as 242 people who lead the founding of corporations, 21 academicians, 23 experts that obtain the subsidy of talent development fund of the provincial government, accounting for 62.5% of the city's total. A team of high-level personnel that covers all fields, with reasonable echelon, good quality, convergence of old and new, and can meet the development needs of innovative enterprises has been formed. Around the strategic emerging industries and high-end services, within five years, it will introduce 30 overseas high-end and leading talents, introduce and cultivate 200 high-level innovative talents that will start business, 300 senior management personnel, and 1000 highly skilled personnel. By 2015, the total amount of human resources in the region will reach 145,000 people, and over 100 start enterprises led by high-level personnel, and that have an important support and leading role in regional development will be cultivated.

In addition, in order to ensure the sustainability of human resources, since 2011, with creating “Changbai Intelligence Valley” that takes gathering talents as the goal, Changchun High-tech Zone starts the construction of “talent special zone”, focuses on the four plans of “gathering of overseas high-end leading talent, introduction of high-level creative talents, enhancement of senior management personnel, and growth of highly skilled personnel”. Each year, it will allocate 100 million yuan to support innovation and entrepreneurship. A batch of industrial leading talent and senior management personnel has been gathered. It has obvious talent advantage.

（4）Industrial cluster advantage

In the context of a new round of development strategy, to better develop bio-pharmaceutical industry, Changchun High-tech Zone plans Changchun Northeast Biological and Medical Science and TechnologyIndustrial Park in the Changchun northeast core area. The park covers an area of ​​6 square kilometers, and stage one construction will cover 3 square kilometers. It will focus on the construction of bio-industry, pharmaceutical industry and irradiation industry etc. three bases. The High-tech Zone will provide great policy support for the first phase of settled projects. In 2011, the pharmaceutical enterprises above designated size in Changchun High-tech Zone realized output value of 3.8 billion yuan, profits of 310 million yuan; the total industrial output value accounted for 1.3% of the zone. According to statistics in late 2011, the High-Tech Zone currently has 176 biological and pharmaceutical enterprises, including 127 pharmaceutical enterprises (including genetic engineering drugs), 49 biotech companies (including bio-medicine).  Of the 127 pharmaceutical companies, there are 19 pharmaceutical class manufacturing enterprise. (including two genetic engineering enterprises, seven modern Chinese medicine enterprises, ten western medicine or chemical drug enterprises); 14 medical equipment production enterprises, five medical accessory material production enterprises, 24 pharmaceutical R & D enterprises and 65 pharmaceutical services sales enterprises. Of the 49 bio-pharmaceutical enterprises, there are seven biological pharmaceutical enterprises, and four biological agriculture enterprises (including biological food); 34 R & D enterprises, and four distribution services enterprises. In the whole zone, the existing bio-pharmaceutical companies produce over 600 varieties, including four class one new drugs such as hepatitis A vaccine, interleukin, 11 class two new drugs such as human growth hormone, interferon and 17 protected Chinese medicine type such as Weilexin. The industrial cluster advantage is obvious.

（5）Platform advantage

 Changchun High-tech Zone exerts the advantage of R & D and innovation, promotes industrial agglomeration, strives to improve the international competitiveness of the bio-pharmaceutical industry, drives the regional industrial structure optimization and upgrading, and constructs nine public platforms. First: experimental animal breeding and experimental center; second: test center of genetically engineered drugs; third: technology center of biological enzyme engineering; fourth: vaccine research and development engineering center; fifth: drugs screen center; sixth: research center of Chinese medicine formulations; seventh: food and drug inspection and information consulting service center; eighth: public platform for Chinese medicine pretreatment; ninth: irradiation and sterilization device center. The construction of the nine platforms will play a crucial role for improving the biological and pharmaceutical industrial chains, and is conducive for enterprises to settle in the zone and invest in factories. In addition, the High-tech Zone also sets up specialized departments and Industry Bureau to serve related businesses and projects. Thus it has outstanding platform advantage.

（6）Advantage of infrastructure

Since 2009, The High-Tech Zone has invested accumulated 30 billion yuan in development and construction, newly built 190km roads. In the south district and Changchun northeast core area of 86 km², the supporting facilities are complete, creating a miracle in urban construction. Within 30 km² of the highway in south district, the infrastructure supporting facilities are all in place, basically realizing "eleven connections and one leveling" (water connection, electricity connection, road connection, communications, gas,  internet, radio and television, heating, post, drainage and sewage on construction site, and site leveling), reaching the first class standard in China. Around the goal of building green, ecological and livable modern city, it will accelerate greening, landscaping, lighting and other environmental constructions. The landscape characteristics, with the natural scenery of ChangbaiMountain as main body, combined with Suzhou garden style, integrating greening, landscaping, lighting and sculpture has formed.

The supporting infrastructure is excellent. The Changchun High-tech Zone Changchun northeast core area is the forefront for ChangchunCity to integrate into the Chang-Ji-Tu. The planning and construction of the core area takes industrial development as the main line, takes technology innovation and high-end service as supplement, and will be constructed according to international metropolis standard. In order to improve the living quality of residents in the core area, the core area has a total of two world-class parks, of which the BeihuWetlandPark has been opened. The Longfor, CESL-based real estate projects have started construction. In the aspect of transportation lines, the bus line leading to Changchun Station has been opened. In the subway project under the planning of ChangchunCity, the number 7 subway line will pass through Changchun northeast core area. Thus the supporting infrastructure is excellent.

1.2 Content and Scale of Project Construction

1.2.1 Product Scheme and Scale

The project plans to newly purchase equipment of 50 sets (units), with annual production of 20 million pieces of water injections.

1.2.2 Construction content

The project covers an area of 20,000 square meters, including 18,000 square meters of construction area. The main buildings include R & D building, production workshop etc.

1.3 Total Investment and Funds Raising of the Project

1.3.1 Total Investment（detailed in table 1）

Total investment of the project is 120 million yuan, including construction investment of 60 million yuan, interest incurred in construction period of 3.9 million yuan, and working capital of 56.1 million yuan.

 Table 1      List of Total Investments of Project     Unit: 10,000 yuan

Note: the “10,000 yuan” in the table is RMB.

1.4 Financial Analysis and Social Evaluation

1.4.1 Major Financial Indexes 

In normal year of this project, it will realize operating income of 1 billion yuan, profit of 100 million yuan, financial internal rate of return of total investment of 31%, payback period (after tax) of all investment of 3.25 years, and profit rate of investment of 70.84%.

 Table 2   List of Major Indexes for Financial Benefits Forecast  

Note: the “10,000 yuan” in the table is RMB.

1.4.2 Social Evaluation

In China, the incidence rate of children's growth and development disease is high, of which the dwarf incidence accounts for about 1% of the population, with almost 1 million people with short stature. The implementation of this project not only has good economic benefits, but also makes a great contribution to the healthy growth of our children, thus it has great social benefits. In addition, due to the huge investment of the project, the implementation of the project will bring a lot of employment opportunities for the local place, thus making some contribution to the stability of the region.

1.5 Cooperative Ways of the Project

Joint venture cooperation.

1.6 What to be Invested by Foreign Party

Capital.

1.7 Construction Site of the Project

The Changchun Northeast Core Area of Changchun High-Tech Development Zone

1.8 The On-going Condition of Project

Project cooperation plan has been compiled.

2. Introduction to Partner

2.1 Basic Conditions

Name: Administrative Committee of Changchun National High-Tech Industrial Development Zone

Address: 3333 of Silicon Valley Street, Changchun City

Legal representative: Sun Yaming

2.2 Overview

Changchun High-Tech Industrial Development Zone is the first batched of state-level high-tech industrial development zone approved by the State Council in 1991. It is the first development zone in JilinProvince, and the first state-level development zone. It is located in the southwest of ChangchunCity, known as "City of Science and Technology", “CulturalCity", with a total area of ​​78.6 square kilometers.

Changchun High-tech Zone has created a BiomedicalPark, Modernized Science and Technology Industrial Park of Traditional Chinese Medicine, PhotovoltaicTechnologyIndustrial Park, Automotive Research and DevelopmentPark, ChangchunSoftwarePark, and New Material Industrial Park etc. The development pattern of multi-parks in one zone has formed. The Biomedical Park and Modernized Science and Technology Industrial Park of Traditional Chinese Medicine is settled by 110 pharmaceutical enterprises, and 13 enterprises have output value of over 100 million yuan, with over 400 varieties, and more than 150 research projects. There are many biopharmaceutical companies, and a large number of biological vaccines and genetically engineered products account for a considerable share of the domestic and foreign markets. Of the 10 genetically engineered drugs approved by the city, 6 are from the High-tech Zone. Of the 26 kinds of vaccine products with production capacity in ChangchunCity, 24 kinds are from the High-tech Zone. The zone has Asia's largest vaccine and cytokine production base. The production capacity of interferon suppositories ranks the first in the country. The sales of attenuated hepatitis A vaccine account for more than 40% of the domestic market. Interleukins, human growth hormone and other biological drugs are sold in the domestic and foreign markets. AIDS vaccine developed by enterprises in the region enters the clinical research first. The Modernized Science and Technology Industrial Park of Traditional Chinese Medicine, as the main park of the National Modernization of Traditional Chinese Medicine Industry (Jilin) base, has been settled by Jilin Tian Pharmaceutical, Xiuzheng Pharmaceutical and Chenguang Pharmaceutical etc., which produce 21 varieties of national protected Chinese medicine.

In 2010, the total revenue and total industrial output value of Changchun High-tech Development Zone had exceeded 200 billion yuan, realizing 239.6 billion yuan, 237.4 billion yuan respectively, which is 1.8 times that of 2008, of which: the disposable financial resources exceeded 9 billion yuan, 25 times of 2008. Changchun High-tech Zone will create two trillion yuan economic uplift belt around “five industrial parks” of advanced equipment manufacturing, biological medicine, new materials, and new energy etc. It will accelerate the construction of Changchun Northeast Technology Innovation Center, Business Center, production means logistics center of science and technology, as well as sports and leisure center in the south district of Changchun High-Tech Zone, and construct high-end service area; it will also pay close attention to professional investment attraction, and begin targeted investment attraction around the cultural and creative industrial park in the south district of Changchun High-Tech Zone, Comprehensive Technological Enterprise Incubator in the north district, Olympic Park, as well as Cultural Tourism Industrial Park. It will strive to introduce three Fortune 500 companies and ten 10 central enterprises.

Sun Yaming, director of the Administrative Committee, male, born in August 1957, Han, member of the Chinese Communist Party, postgraduate degree from the Provincial Party School, was member of the standing committee of Changchun Lvyuan Party Committee, secretary of Commission for Discipline Inspection, member of the standing committee of Lvyuan District Committee, director of the Organization Department, deputy secretary and mayor of Lvyuan District Committee, secretary of Kuancheng District Committee. Currently, he is assistant mayor of ChangchunCity, director (Vice municipal level of ChangchunCity) of the administrative committee of Changchun Hi-tech Industrial Development Zone. On July 22, 2011, the 13^th session of the Standing Committee of NPC of Changchun held the 28^th meeting. On the meeting, Sun Yaming was appointed vice mayor of ChangchunCity.

2.3 Contact Method

Contact person of project undertaker: Li Tiangang

Tel：13578712560

Fax: 86-431-85542548

E-mail：lee-66666@163.com

Website: http://www.chida.gov.cn/

 

Contact person of city (prefecture) of project：Lou Huimin

Tel：0431-82715338  13943008496

Fax：0431-82715338

E-mail：cc82715338@126.com

Website：www.ccmbc.com