Professor Tan was featured on the cover of the May issue of “Shanghai Biomedical Science and Technology Industry Newsletter”, which published a story about Professor Tan

Full text of the reproduction.

BioEngine: Technology Service Drives Culture Media Localization and Accelerates the Development of Domestic Antibody and Vaccine Industry

"It is difficult to succeed without persistence, and it is important to think deeply when deciding to do each thing, and to do it without rebellion." This is the motto of the academic leader of the State Key Laboratory of Bioreactor Engineering - Professor Tan Wensong. In the "Bioengineering Forum" held by East China University of Science and Technology on May 25, 2016, Prof. Tan emphasized the word "persistence" again. His team is the first and only one in China to specialize in this field in 1986. Now, relying on this elite team, BioEngine will accelerate the development of biopharmaceutical industries such as antibodies and vaccines in Shanghai and even in China through innovative R&D and services of key technologies for antibody and vaccine biomanufacturing, and drive the customization and localization of personalized culture media.

An independent innovation company that faces difficulties and moves forward bravely

In December 2014, Prof. Tan's elite team and East China University of Science and Technology (Shanghai Huali Investment Management Center) jointly funded the establishment of Shanghai BioEngine Sci-Tech Co., Ltd. (short for BioEngine). In the second year of its establishment, Bechtel Biotech was awarded the special development fund of Shanghai Zhangjiang National Innovation Demonstration Zone in 2015 for the construction of a pilot plant (Phase I) for the application service platform of antibody and vaccine biomanufacturing technology and the localization of raw materials and equipment, and the pilot production capacity of personalized serum-free culture medium reached 6 million liters per year. In March 2016, BioEngine received the first round of investment from Shanghai Science & Technology Investment Co., Ltd.

The efficient production of antibody drugs through animal cell expression systems and animal cell mass culture technology has been the core topic of biopharmaceutical technology since the 1990s. The previous National High Technology Research and Development Program (referred to as the "863" program) mainly tracked foreign high technology, making genetic engineering drugs, vaccines, and gene therapy fields become the theme, but China's recombinant protein drugs and antibody drugs based on animal cell expression system industry started late, and the number of products is also small, and the proportion of the overall biopharmaceutical. However, China's recombinant protein drugs and antibody drug industries based on animal cell expression systems started late, and the number of products is small, and they do not account for a high proportion of the overall biopharmaceutical industry. Nowadays, antibody engineering has become a hot spot for precision medicine, and pharmaceutical giants have laid out the field, but these drugs are still mainly dependent on imports and are expensive. To solve this imbalance in development, it is impossible to do without the technology of large-scale and efficient culture of animal cells. The Ministry of Industry and Information Technology of the People's Republic of China pointed out in the Guide to the Development of Key Common Technologies for Industry (the Guide) issued in 2015 that key common technologies for the industry have become bottlenecks that restrict the healthy and sustainable development of China's industry and enhance the core competitiveness of the industry. Among the key common technologies listed in the Guide, the pharmaceutical industry is involved in four directions, one of which is the key technology of large-scale and efficient animal cell culture and protein purification that Professor Tan has been engaged in for a long time. With the completion of the biotechnology R&D service platform and the pilot production line of customized culture media, it will put an end to the weak R&D and industrialization technology of viral vaccines and antibody drugs in China and the market pattern that high-end culture media are monopolized by foreign investors, and significantly improve the technical level of industrialized production in these fields and the competitiveness of domestic and foreign markets.

The only team in China that has mastered animal cell culture and reactor design

To the elite in the field of biopharmaceuticals, the name Wensong Tan is not unfamiliar. As an important part of the State Key Laboratory of Bioreactor Engineering of East China University of Science and Technology and Shanghai Collaborative Innovation Center of Biofabrication Technology, the team has completed more than 30 national "863" program projects, national key science and technology research projects, and the "Major New Drug Creation" project. The team has undertaken and completed more than 30 national "863" program projects, national key science and technology research projects, national science and technology major special projects, national science and technology support program key projects, national natural science fund, key fund of the Ministry of Education and Shanghai science and technology development fund, etc. The team has established the critical technology development and application of the animal cell culture process and its application for the efficient industrial production of animal cell expressed drugs (antibody, recombinant protein, virus vaccine). We have accumulated rich experience in the basic research and application development of large-scale, high-density, serum-free culture technology and bioreactor engineering for animal cells. It has become the only unit in China that can develop and optimize the animal cell culture process and personalized culture medium and microcarrier design and development as well as bioreactor design and development at the same time.

With his passion for cell research, Prof. Tan has stayed away from academic fickleness and fame and has not left his career to change his profession. Prof. Tan has received funding from many talent programs, including the Ministry of Education's Cross-Century Excellent Talent Training Program, the Outstanding Young Teacher Grant Program, the Shanghai Shuguang Program, and the Shanghai Qixing Program. Currently, Prof. Tan is also the platform leader and academic leader of the State Key Laboratory of Bioreactor Engineering of East China University of Science and Technology, a unit of the Shanghai Biomedical Industry Technology Innovation Service Platform, the team leader of Shanghai Collaborative Innovation Center of Biofabrication Technology, the director of Zhangjiang Institute of Modern Biotechnology of East China University of Science and Technology, the deputy director of the editorial board of Journal of Chemical Engineering in Colleges and Universities, the deputy director of Journal of He is a member of the editorialboard of Journal of Bioscience and Bioengineering, a member of the organizing committee of Cell Culture Engineering International Conference, a member of the international organizing committee of JAACT International Conference in Japan, and an expert in technology foresight in critical areas of science and technology development in Shanghai. So far, Prof. Tan has published more than 250 academic papers at home and abroad and obtained 29 Chinese invention patents.

High-quality technical services help enterprises turn losses into profits

At the beginning of its establishment, BioEngine signed technical service contracts with three well-known domestic vaccine manufacturers and protein drug pharmaceutical companies. In just over a year, BioEngine has achieved a turnover of more than 10 million RMB, which is rare among start-ups.

In providing technical service solutions to one of the animal vaccine manufacturers, BioEngine established the first international industrialized production process of avian influenza vaccine in serum-free single-cell suspension culture through key technical innovation, realizing the efficient industrialized production of influenza virus vaccine. The new process has obvious technical and cost advantages and can avoid environmental pollution to the greatest extent. The application of a bioreactor for large-scale serum-free suspension culture of animal cells for the production of avian influenza vaccine is a major technological innovation that has enabled this company, which had been losing money for a long time, to greatly increase its production capacity in a short period while turning a loss into a profit, and has also enabled BioEngine to gain good recognition and trust among its customers.

The antibody and virus vaccine industry is seeing opportunities for faster development

Animal cell expression system and its large-scale culture technology is the most important production system and core technology for biotechnology drugs and biologics industry at this stage and a long period in the future, and its products include various antibodies, recombinant proteins, human and poultry virus vaccines, etc. Both varieties and global market share have exceeded 75% of the biological drug industry. In particular, the rapid development of the antibody-drug industry in recent decades has made the use of mammalian cell expression systems to express and produce biotechnology drugs a deserved mainstream in the development of the biopharmaceutical industry today.

Among them, antibody drugs have been the fastest-growing class of biotechnology drugs in recent years, with global antibody drug sales exceeding the $90 billion mark in 2015. However, China's antibody drug industry started late, with sales of less than $6 billion in 2015.

The viral vaccine industry is mainly divided into two fields: human vaccines and animal vaccines. In 2012 global market for human vaccines reached 18 billion euros, while in China, with a population of 1.3 billion (about 20% of the global population), the market size in 2009 was only 9 billion RMB. At the same time, China's animal epidemic prevention system is relatively weak, but in recent years the country has implemented a compulsory immunization system so that the market size of China's veterinary vaccines from 2000 to 2013 reached a compound annual growth rate of more than 23%.

In the above-mentioned biopharmaceutical industry, product development and production, serum-free medium, and animal cell suspension culture technology have been industrialized and applied in enterprises in developed countries in Europe and the United States, thus substantially improving the capacity and production efficiency of these drugs. Domestic biopharmaceutical companies not only started late, most of them still have not mastered the core technology of animal cell culture - the formulation of culture medium and its optimization technology methods, so the formulation and product supply are dependent on foreign professional culture medium companies. China's 95% of animal cell culture medium is purchased from the United States Life Technology, SAFC, and Thermo Fisher three companies, which are not only expensive but also difficult to implement process optimization and effective regulation of product quality. Thus, the development and large-scale production of serum-free and personalized cell culture media with independent intellectual property rights is an important guarantee to reduce the production cost of biopharmaceutical products, improve market competitiveness and ensure product quality.

Nationalized pilot platform to turn the situation around

In such an industrial environment, BioEngine has made a breakthrough in key technologies such as high-density culture of animal cells, serum-free and protein-free medium design and development, bioreactor optimization and scale-up, and product quality optimization and control, and designed and built the first domestic production line with reactor scale of thousand upgrades, cell density of ten million levels, and fusion protein expression of grams per liter. Its product's high expression of the flow-plus culture process and the separation and purification of antibody fusion protein sialic acid content and biological activity and other indicators are equal to or exceed the requirements of the original drug quality standards, reaching international advanced level, thus breaking the situation of China in the antibody-drug and virus vaccine industry key technology and supporting industry monopoly by foreign enterprises. The antibody fusion protein drug produced by this process has been approved by the State Food and Drug Administration for drug registration and the GMP Certificate issued by the State Food and Drug Administration and has been officially marketed and sold.

Prof. Wensong Tan said that his team will continue to focus on the major needs of the national development of recombinant proteins, antibodies, and viral vaccines and other biopharmaceutical industries, dedicate to the innovative research and development of key technologies and application services, strive to realize the localization of raw materials such as serum-free medium, microcarriers, separation and purification media and equipment such as bioreactors and separation and purification equipment, and promote the construction of a standardized system, to enhance the international competitiveness of China's antibody and viral vaccine industries. global competitiveness of China's antibody and virus vaccine industry and seize the world's high point of biotechnology drugs!