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The development of new N7H9 vaccine was stopped even before the period of clinical tests. By now， no vaccine enterprises in China have got the permission to stage the clinical test. Whether the vaccine can be produced massively depends on the epidemic situation.
“The development of vaccine industry in China is far behind the one in foreign countries.” The top five vaccine enterprises in the foreign countries take 80% of the global market while in China， 10 of the 33 vaccine enterprises are state-owned enterprises with others being small private companies. China National Biotech Group， the largest vaccine producer in China， has the global market share only equal to 10% of GlaxoSmithKline.
As the N7H9 epidemic situation gets worse， the battle for the research of N7H9 vaccine silently started after China’s Spring Festival.
On February 7， Shanghai Public Health Clinical Center passed the news that Shanghai Research Institute for New and Reappearing Epidemic Disease， an organization under the Center， has already developed a new N7H9 vaccine through genetic engineering.
Before that， several big vaccine enterprises， led by the Ministry of Science and Technologies， have already finished the pre-clinic research of the vaccine and they have submitted the applications for clinical tests since January 2014.
However， compared with foreign biomedicine companies， Chinese R&D institutions and vaccine enterprises are acting in quite a low profile. As of the start of N7H9 cases in China in April 2013， many vaccine enterprises in the U.S. and Canada started to develop the vaccine through various new technologies. They have made several breakthroughs already and the fastest company is now preparing for the secondphase clinical tests.
These show that the bird flu spread in China is going to be the hotbed for an international competition. In this battlefield without gunfire， the “local force” rising from provinces/cities of China， the “national force” that walks step-by-step as ordered and the fastmoving “foreign forces” are going to wrestle with each other， showing the“technological preparation” for the epidemic situation of different countries.
“Local Forces” Hard to Win the Market
“I will no longer answer the call I don’t know. These are all the requests of interviews from the media，” said Prof. Xu Jianqing at Shanghai Research Institute for New and Reappearing Epidemic Disease. Prof. Xu is the leader of a 40-people team that started the development of N7H9 vaccine with genetic technologies. Actually， the Shanghai Public Health Clinical Center is not a backbone force of the vaccine development in China. It is not one of these key research institutions led by the Ministry of Science and Technologies in the R&D of H7N9 vaccine. Right now the “national forces”consist of National Institutes for Food and Drug Control， Chinese National Influenza Center， China National Biotech Group， Hualan Bio and Sinovac Biotech Ltd.
This Shanghai-based institute entered the public vision totally accidentally. One week before the Spring Festival， Shanghai TV recorded a TV program about the cure and diagnosis of H7N9， in which Prof. Xu was invited to have a talk about the development of H7N9 vaccine. Half a month later， this program was suddenly broadcast. The outsiders did not know that the Shanghai team was also studying into the H7N9 vaccine until now.
Prof. Xu returned from the U.S. and devoted himself to the research of HIV vaccine. After the first case of H7N9 case in Shanghai， Prof. Xu was appointed the leader of the team and he chose the genetic resort.
“The traditional inactivated vaccine guaranteed the security through killing virus. The genetic engineering separates the genes that activate the immune system and attaches them to another safe vaccine vector，” Prof. Xu. This guarantees the safety and avoids the link of inactivation to keep the protein structure from being influenced and ensure the validity of vaccine.
However， it is still far from the massive production of H7N9 genetic vaccine and the clinical use.
As Prof. Xu said， it might take 10 months to finish the clinical research while the clinical test might cost six years. Apart from the restraints of the research expense， the biggest hurdle is how to turn the new technologies into the products launched into the market.
The director of a vaccine enterprise in China said that there are matured technologies to produce hepatitis B vaccine with genetic engineering， but it is a new trial to put it into the development of flu vaccine. If this kind of H7N9 vaccine is given the permission for production， new production lines and factories need to be established and need to be accredited by the new Good Manufacturing Practice. It will cost a lot of time and money， which can hardly trigger the interest of big vaccine enterprises and is hard for the emerging enterprises to afford.
By now， no governmental departments， institutions or enterprises have shown the will to cooperate with Shanghai Public Health Clinical Center. That means the development of H7N9 genetic vaccine might be stopped before the start of clinical test. “Foreign Forces” Take the Lead
The genetic engineering is also a tool for foreign companies to develop the H7N9 vaccine， but the situation is quite different from that in China.
On March 31， 2013， the Chinese Center for Disease Control and Prevention announced the epidemic situation of H7N9 and shared the genetic sequences of the virus with the world. After one month， Greffex， a biotech company in the U.S.， announced that it had developed the first promising H7N9 vaccine through adenovirus vector. One day after that， another U.S. company Protein Science also declared the completion of the development of new gem carriers， which are the core substances to create H7N9 vaccine.
At that time， the Chinese researchers did not regard those rightly. They thought that the two enterprises just finished the basic virus structuring. But soon there are enterprises beginning to do real research.
On June 13， 2013， Canada-based Medicago made use of a patented tech- nology named virus-like particles in the development of the H7N9 virus. It was the first company to publish the results of pre-clinical tests on animals. Five months later， Novavax， a biomedicine company based in Maryland， also used the virus-like particles to finish the first clinical tests of H7N9 vaccine， covering 284 test subjects.
“It is really very fast to finish the first-phase clinical test in such a short while，” said Prof. Xu Jianqing. In comparison， no Chinese enterprises or institutions have been allowed to start the clinical tests by now.
Apart from the amazing speed， the output of U.S. enterprises is very stunning as well. The computer model showed that the vaccine producers can produce the first group of H7N9 vaccines 12 weeks after the outbreak of H7N9 influenza and the output can be increased to 50 million dosages in four months， or 100 million in six months.
In the U.S.， venture investors are very interested in the small biotech companies like Greffex and Protein Sciences. There are 30-40 thousand companies of this kind in this country. The big companies usually get these new technologies through acquiring small companies， and they usually get the orders from the government.
Novavax， for example， has its development of H7N9 vaccine started with the support of Biomedical Advance Research and Development Authority （BARDA）， which is a governmentsponsored organization to deal with the emergent public health problems.
BARDA and Novavax signed a three-year contract with the value of US$9.7 billion， as well as the purpose of re-organizing the flu vaccine and producing adequate vaccines for the influenza pandemic. The H7N9 vaccine was just a side product of the cooperation.
“This is a necessary result caused by the government-led and market-oriented system，” said Prof. Xu Jianqing.
“National Forces” Having Stepby-Step Progress
Compared with the international peers， Chinese enterprises seem to be too quiet and calm.
The traditional method of developing influenza vaccine is to inject the screened strain into the fertilized egg and extract the massively multiplied viruses. These viruses are going to be injected into human’s body after being inactivated to force the immune system to produce antibodies against the influenza virus. The process usually takes several months. The “national forces” finally used this method after consideration.
Several experts think that the government-selected enterprises all turn to the traditional method， making the technological route too simple.
After looking through the files， Prof. Xu Jianqing and his team found that a test in Holland in 2003 found that the inactivated virus-based vaccine against H7N3 failed to activate the immune protection response. This might mean that the traditional inactivation technologies might not work for the H7-serial influenza viruses.
For this， a director of a company joining in the research of H7N9 vaccine said that the animal tests show good effect of the vaccine， which is said to be between swine flu vaccine and H5N1 vaccine.
In spite of this， insiders of some enterprises chosen to be a part of the national forces secretly joked that the expenses they gained were only enough to buy chick embryo. Sometimes the governmental departments get the sup- plies but refuse to pay the money. By now， there are some funds unpaid for the swine flu vaccines purchased by the government in 2009.
In addition， the “national forces”still follow the prescribed order in developing the vaccine. The Health and Family Planning Commission of China set a period of “six to eight months”while the Ministry of Science and Technologies wanted it to be done in seven months. The application of Hualan Bio for the clinical test of its H7N9 vaccine was accepted on January 3， 2014 and now being examined by the State Administration of Drugs while Sinovac Biotech’s application was accepted one day before the Spring Festival. The current epidemic situation of H7N9 still features the bird-to-man infection. So the State Administration of Food and Drugs will not turn on the green light in accordance with The Special Procedures for Approving Drugs.
“It is easy to see the apparent gap between the levels of vaccine development in China and foreign countries，”said Prof. Hu Yinlian with China National School of Administration. In foreign countries， the vaccine market is highly centralized as the top five vaccine enterprises take 80% of the global market. Their products are mostly the combined vaccines and they have already begun to use the genetic technologies to develop new products. In comparison， the Chinese vaccine market is scatters and does not have a strong leader， which is to be blamed for the current chaos.
“For the strategic products like vaccine that concern the national security， the government should support the national forces while endorsing the technological innovation and increasing the investment，” said Hu Yinlian.
After handling the outside chaos（mostly requests of interviews）， Prof. Xu decided to continue his research. His next goal is to develop a broadspectrum influenza vaccine， which might be effective for the H1， H3 and H5 viruses. Meanwhile， he will continue the study into the antibodies to cure the H7N9.
“If we can get the governmental support in the future and the market system is set up， the job of turning R&D results to products might be given to others，” said Prof. Xu.
“The development of vaccine industry in China is far behind the one in foreign countries.” The top five vaccine enterprises in the foreign countries take 80% of the global market while in China， 10 of the 33 vaccine enterprises are state-owned enterprises with others being small private companies. China National Biotech Group， the largest vaccine producer in China， has the global market share only equal to 10% of GlaxoSmithKline.
As the N7H9 epidemic situation gets worse， the battle for the research of N7H9 vaccine silently started after China’s Spring Festival.
On February 7， Shanghai Public Health Clinical Center passed the news that Shanghai Research Institute for New and Reappearing Epidemic Disease， an organization under the Center， has already developed a new N7H9 vaccine through genetic engineering.
Before that， several big vaccine enterprises， led by the Ministry of Science and Technologies， have already finished the pre-clinic research of the vaccine and they have submitted the applications for clinical tests since January 2014.
However， compared with foreign biomedicine companies， Chinese R&D institutions and vaccine enterprises are acting in quite a low profile. As of the start of N7H9 cases in China in April 2013， many vaccine enterprises in the U.S. and Canada started to develop the vaccine through various new technologies. They have made several breakthroughs already and the fastest company is now preparing for the secondphase clinical tests.
These show that the bird flu spread in China is going to be the hotbed for an international competition. In this battlefield without gunfire， the “local force” rising from provinces/cities of China， the “national force” that walks step-by-step as ordered and the fastmoving “foreign forces” are going to wrestle with each other， showing the“technological preparation” for the epidemic situation of different countries.
“Local Forces” Hard to Win the Market
“I will no longer answer the call I don’t know. These are all the requests of interviews from the media，” said Prof. Xu Jianqing at Shanghai Research Institute for New and Reappearing Epidemic Disease. Prof. Xu is the leader of a 40-people team that started the development of N7H9 vaccine with genetic technologies. Actually， the Shanghai Public Health Clinical Center is not a backbone force of the vaccine development in China. It is not one of these key research institutions led by the Ministry of Science and Technologies in the R&D of H7N9 vaccine. Right now the “national forces”consist of National Institutes for Food and Drug Control， Chinese National Influenza Center， China National Biotech Group， Hualan Bio and Sinovac Biotech Ltd.
This Shanghai-based institute entered the public vision totally accidentally. One week before the Spring Festival， Shanghai TV recorded a TV program about the cure and diagnosis of H7N9， in which Prof. Xu was invited to have a talk about the development of H7N9 vaccine. Half a month later， this program was suddenly broadcast. The outsiders did not know that the Shanghai team was also studying into the H7N9 vaccine until now.
Prof. Xu returned from the U.S. and devoted himself to the research of HIV vaccine. After the first case of H7N9 case in Shanghai， Prof. Xu was appointed the leader of the team and he chose the genetic resort.
“The traditional inactivated vaccine guaranteed the security through killing virus. The genetic engineering separates the genes that activate the immune system and attaches them to another safe vaccine vector，” Prof. Xu. This guarantees the safety and avoids the link of inactivation to keep the protein structure from being influenced and ensure the validity of vaccine.
However， it is still far from the massive production of H7N9 genetic vaccine and the clinical use.
As Prof. Xu said， it might take 10 months to finish the clinical research while the clinical test might cost six years. Apart from the restraints of the research expense， the biggest hurdle is how to turn the new technologies into the products launched into the market.
The director of a vaccine enterprise in China said that there are matured technologies to produce hepatitis B vaccine with genetic engineering， but it is a new trial to put it into the development of flu vaccine. If this kind of H7N9 vaccine is given the permission for production， new production lines and factories need to be established and need to be accredited by the new Good Manufacturing Practice. It will cost a lot of time and money， which can hardly trigger the interest of big vaccine enterprises and is hard for the emerging enterprises to afford.
By now， no governmental departments， institutions or enterprises have shown the will to cooperate with Shanghai Public Health Clinical Center. That means the development of H7N9 genetic vaccine might be stopped before the start of clinical test. “Foreign Forces” Take the Lead
The genetic engineering is also a tool for foreign companies to develop the H7N9 vaccine， but the situation is quite different from that in China.
On March 31， 2013， the Chinese Center for Disease Control and Prevention announced the epidemic situation of H7N9 and shared the genetic sequences of the virus with the world. After one month， Greffex， a biotech company in the U.S.， announced that it had developed the first promising H7N9 vaccine through adenovirus vector. One day after that， another U.S. company Protein Science also declared the completion of the development of new gem carriers， which are the core substances to create H7N9 vaccine.
At that time， the Chinese researchers did not regard those rightly. They thought that the two enterprises just finished the basic virus structuring. But soon there are enterprises beginning to do real research.
On June 13， 2013， Canada-based Medicago made use of a patented tech- nology named virus-like particles in the development of the H7N9 virus. It was the first company to publish the results of pre-clinical tests on animals. Five months later， Novavax， a biomedicine company based in Maryland， also used the virus-like particles to finish the first clinical tests of H7N9 vaccine， covering 284 test subjects.
“It is really very fast to finish the first-phase clinical test in such a short while，” said Prof. Xu Jianqing. In comparison， no Chinese enterprises or institutions have been allowed to start the clinical tests by now.
Apart from the amazing speed， the output of U.S. enterprises is very stunning as well. The computer model showed that the vaccine producers can produce the first group of H7N9 vaccines 12 weeks after the outbreak of H7N9 influenza and the output can be increased to 50 million dosages in four months， or 100 million in six months.
In the U.S.， venture investors are very interested in the small biotech companies like Greffex and Protein Sciences. There are 30-40 thousand companies of this kind in this country. The big companies usually get these new technologies through acquiring small companies， and they usually get the orders from the government.
Novavax， for example， has its development of H7N9 vaccine started with the support of Biomedical Advance Research and Development Authority （BARDA）， which is a governmentsponsored organization to deal with the emergent public health problems.
BARDA and Novavax signed a three-year contract with the value of US$9.7 billion， as well as the purpose of re-organizing the flu vaccine and producing adequate vaccines for the influenza pandemic. The H7N9 vaccine was just a side product of the cooperation.
“This is a necessary result caused by the government-led and market-oriented system，” said Prof. Xu Jianqing.
“National Forces” Having Stepby-Step Progress
Compared with the international peers， Chinese enterprises seem to be too quiet and calm.
The traditional method of developing influenza vaccine is to inject the screened strain into the fertilized egg and extract the massively multiplied viruses. These viruses are going to be injected into human’s body after being inactivated to force the immune system to produce antibodies against the influenza virus. The process usually takes several months. The “national forces” finally used this method after consideration.
Several experts think that the government-selected enterprises all turn to the traditional method， making the technological route too simple.
After looking through the files， Prof. Xu Jianqing and his team found that a test in Holland in 2003 found that the inactivated virus-based vaccine against H7N3 failed to activate the immune protection response. This might mean that the traditional inactivation technologies might not work for the H7-serial influenza viruses.
For this， a director of a company joining in the research of H7N9 vaccine said that the animal tests show good effect of the vaccine， which is said to be between swine flu vaccine and H5N1 vaccine.
In spite of this， insiders of some enterprises chosen to be a part of the national forces secretly joked that the expenses they gained were only enough to buy chick embryo. Sometimes the governmental departments get the sup- plies but refuse to pay the money. By now， there are some funds unpaid for the swine flu vaccines purchased by the government in 2009.
In addition， the “national forces”still follow the prescribed order in developing the vaccine. The Health and Family Planning Commission of China set a period of “six to eight months”while the Ministry of Science and Technologies wanted it to be done in seven months. The application of Hualan Bio for the clinical test of its H7N9 vaccine was accepted on January 3， 2014 and now being examined by the State Administration of Drugs while Sinovac Biotech’s application was accepted one day before the Spring Festival. The current epidemic situation of H7N9 still features the bird-to-man infection. So the State Administration of Food and Drugs will not turn on the green light in accordance with The Special Procedures for Approving Drugs.
“It is easy to see the apparent gap between the levels of vaccine development in China and foreign countries，”said Prof. Hu Yinlian with China National School of Administration. In foreign countries， the vaccine market is highly centralized as the top five vaccine enterprises take 80% of the global market. Their products are mostly the combined vaccines and they have already begun to use the genetic technologies to develop new products. In comparison， the Chinese vaccine market is scatters and does not have a strong leader， which is to be blamed for the current chaos.
“For the strategic products like vaccine that concern the national security， the government should support the national forces while endorsing the technological innovation and increasing the investment，” said Hu Yinlian.
After handling the outside chaos（mostly requests of interviews）， Prof. Xu decided to continue his research. His next goal is to develop a broadspectrum influenza vaccine， which might be effective for the H1， H3 and H5 viruses. Meanwhile， he will continue the study into the antibodies to cure the H7N9.
“If we can get the governmental support in the future and the market system is set up， the job of turning R&D results to products might be given to others，” said Prof. Xu.