"The amount of batch issuance this year is already quite large. You see, there are more than two months left, and now it has exceeded the entire year last year." Zhang Min, an insider of a domestic flu vaccine manufacturer, told the reporter of "Daily Economic News" on the phone.

Reporter of the Economic Business: Jin Zhe Tang Hui Editor of the Economic Business: Zhang Haini

"The amount of batch issuance this year has been quite large. You see, there are more than two months left (by the end of the year), but now it has exceeded the entire year last year." Zhang Min (pseudonym), an insider of a domestic influenza vaccine manufacturer, told the reporter of the "Daily Economic News" on the phone.

From November to March of the following year, it is the epidemic season for the flu. This year, coupled with the impact of the new crown pneumonia epidemic, people are more cautious and hope to get the flu vaccine as soon as possible. Although many people choose to receive the vaccination time one or two months earlier than usual, they find that the flu vaccine that few people are interested in in the past is so difficult to get, and some even go back to their hometown to get the flu vaccine.

Many people think that the reason for the difficulty in getting the flu vaccine is insufficient supply. In fact, according to data from Bohai Securities, the number of influenza vaccines approved and issued by the CPPCC from July to September this year reached 33.3596 million, while the level for the whole year last year was 30.7842 million. However, since the domestic vaccination rate of influenza vaccines has remained at 2% to 3% all year round, in the face of sudden explosion in demand, the current output naturally cannot withstand it. In this case, while working overtime to produce vaccines, the influenza vaccine manufacturer is sent to the CPR Institute for approval and issuance, it also calls on the public to be vaccinated rationally and not to crowd.

Map: Tang Hui

Residents' health awareness has increased, and their vaccination intention has increased significantly

Starting from November every year, my country enters the influenza epidemic season, which is also considered the most suitable time for influenza vaccination. But this year, due to the COVID-19 epidemic, many people hope to get the flu vaccine as soon as possible.

On the National Day holiday, Ms. Jiang, who works in Shenzhen, took her children back to her hometown in Taixing, Jiangsu. One of the itineraries was to get vaccinated. She originally wanted to vaccinate her child with influenza in Shenzhen, but she made an appointment several times but didn't make an appointment. After returning to her hometown, she went to two epidemic prevention stations and all adults and children were vaccinated.

"There are quite a lot of people getting influenza vaccines in their hometown during the National Day. A relative lives in Suzhou and also got the vaccine in their hometown." Ms. Jiang told reporters. The reporter searched for relevant information on social platforms and found that compared with big cities, the supply of influenza vaccines at the first-level areas of some counties is not that tight, and going to these places to get vaccinated is regarded as a shortcut by some parents.

Compared with Ms. Jiang, Ms. Su, who lives in Tianfu New District, Chengdu, is more lucky. On October 10, the teacher in the public kindergarten where her child is located counted the list of unified voluntary and self-paid influenza vaccinations, "basically all the children in the workplace have signed up." Ms. Su said. At the same time, she signed up for the "Second Baby" who is over 1 year old. "I don't know if I can call them together. I will register first to occupy the place. Some parents have registered their children's grandmothers."

In many mother groups, everyone is sharing the influenza vaccine appointments at different epidemic prevention stations. Some netizens joked that it takes a quicker time to make an appointment for flu vaccine this year, which is comparable to grab tickets to the "Idol" concert. Why are flu vaccines in short supply? Sichuan Provincial Center for Disease Control and Prevention Director and chief physician Qi Qi believes that there are two main reasons:

First, the people's willingness to vaccinate has increased significantly. In the past three years, the average number of influenza vaccination doses in Sichuan Province has been around 940,000. Affected by the new crown epidemic this year, the demand for influenza vaccines in the province has increased significantly, and the total number of influenza vaccines reported by cities (prefectures) is 6.26 million, an increase of nearly 6 times.

Second, the supply of influenza vaccines cannot meet the demand. According to the supply plan reported by 11 influenza vaccine manufacturers, Sichuan Province plans to supply 4.555 million influenza vaccines this year. 11 influenza vaccine manufacturers can only meet 74.1% of the total supply in 2020 due to production capacity reasons by the end of October.

Qiqi said that antibodies with protective levels can usually be produced in the body 2 to 4 weeks after receiving the influenza vaccine. After 6 to 8 months, the antibody titer begins to decay, which means that the protective effect can last for 6 to 8 months. Because the peak of influenza begins in November, it is recommended that the flu vaccination is best completed by the end of October.

Many people are doubting that if fails to be vaccinated in time before the end of October, should we still get the flu vaccine? reporter consulted Dr. Huang, attending physician of Hainan Provincial Center for Disease Control and Prevention as a patient. She said: “If you fail to get vaccinated before the flu season, considering the burden of disease and complications caused by influenza infection, it is still recommended to get vaccinated throughout the flu epidemic."

South China A staff member of the Center for Disease Control and Prevention who did not want to be named told reporters that according to previous years' experience, the supply from October to January of the following year will increase, and it is recommended to be vaccinated in batches.

Specifically for the selection of influenza vaccines, Dr. Huang said that it is recommended to get a 4-valent vaccine. If you are short of the 3-valent vaccine, you should get a 3-valent vaccine, so as not to miss the vaccination time due to waiting and not to be protected in time.

In addition, Qi Qi reminded that developing a healthy lifestyle and improving your own immunity and resistance is also one of the effective ways to resist the influenza virus.

September 27, a vaccination site in Chengdu. Photo source: reporter Tang Hui, photographed by Meijing reporter

production cycle for four or five months, with an effective period of only one year

Human influenza viruses are divided into three types: A, B and C. Each type includes dozens of subtypes. The virus strain of each subtype will undergo large or small changes due to antigen mutation. At present, it is believed that vaccination is one of the most effective ways to prevent large-scale outbreaks of influenza.

Because influenza vaccines are seasonal and viruses are prone to mutating, they have special production processes and requirements. On February 28 this year, in Geneva, Switzerland, after a four-day meeting on global influenza virus epidemiology, etiology and vaccine serology analysis, The World Health Organization released the recommended components of the northern hemisphere influenza vaccine from 2020 to 2021. This recommendation and scientific basis are conveyed to regulatory agencies and global vaccine manufacturers.

vaccine manufacturers determine the type and scale of vaccine production after obtaining the influenza vaccine components. From this, it can be estimated that the true production time of influenza vaccines is usually after March of each year. After 4 to 5 months of production cycle, the vaccine that passes the self-inspection can only be launched after the CSIU completed the completion of the issuance of the CSIU, and then transported to the CDC centers of various provinces and cities, and then allocated to the vaccination institutions.

Therefore, influenza vaccines are not ordinary products that can be ordered. Under such a market process, the first batch of influenza vaccines will be issued at the earliest in August, and usually enter the stage of increasing volume after September. This year, due to the new crown pneumonia epidemic, many manufacturers have prepared in advance, and the influenza vaccine is on the market.

According to the Beijing Daily, on July 14, the influenza vaccine produced by the Shanghai Institute of Biological Products (hereinafter referred to as Shanghai Institute) won the first batch of influenza vaccines in China in 2020. The batch issuance certificate of product batch is nearly a month earlier than in previous years.

"Daily Economic News" reporter found that the batch issuance volume as of October 14 has exceeded the total batch issuance volume in any year in the past five years, but the supply of influenza vaccines by vaccination institutions is still quite tight at present.

Since enterprises have accelerated production progress and the batch issuance volume has also increased, why is influenza vaccine still "hard to find a shot"?

First of all, the vaccines that can be put on the market cannot meet people's sudden explosion of vaccination needs.

In the past many years, although experts have been constantly calling for vaccination to be the most effective way to prevent influenza in the world, the national influenza vaccination rate has remained at 2% year-on-year. After an overseas pharmaceutical company conducted an investigation into 2,160 residents in seven cities including Beijing, Shanghai, and Guangzhou in the early years, it pointed out that lack of attention to influenza, belief that getting influenza vaccine is too troublesome, and concerns about the insecurity of getting influenza vaccine are the three main reasons that affect China's influenza vaccination.

But this year, people have a strong desire to get flu vaccines. Although there is currently no accurate data to count how many people are queuing up to get influenza vaccines in various places, the reporter learned through phone, WeChat and other means that many places in the north and south have crowded appointments at epidemic prevention stations, even in the southern regions where the temperature is still at 30℃.

Beijing Kexing Bioproducts Co., Ltd. (hereinafter referred to as Beijing Kexing) Relevant persons said in an interview with the Daily Economic News that the total amount of influenza vaccines is not large, and the production cycle is still very long. It is completely unrealistic to want to be vaccinated in advance, so at the beginning, there will inevitably be a shortage of supply and demand, and vaccination will produce a run effect. The more you say that the seedlings are short of seedlings, the more you will be short of seedlings. Moreover, the epidemic trend of influenza in my country varies greatly from north to south. Excessive early vaccination in southern provinces affects the effectiveness of vaccines and the enthusiasm for later vaccination, and will also affect the supply of vaccines in the northern region.

Secondly, companies cannot accurately estimate how big the flu vaccine market was back then.

In previous years, October and November were the peak periods of influenza vaccination every year, and some places also had supply in short supply. But when the peak period passes, 20% of the vaccines have to be scrapped after the period. Feng Zijian, deputy director of of the Chinese Center for Disease Control and Prevention, previously said that in the past few years, the vaccination rate of influenza vaccine in China has not been high, about 2%, far lower than the vaccination rate of 60% to 70% in developed countries in Europe and the United States. About 26 million influenza vaccines are produced each year, and about 6 million will be destroyed due to their expiration. More than 10 years have passed, and the Chinese people’s emphasis on influenza vaccines has not improved much until the arrival of the new crown epidemic. For enterprises, influenza vaccines are non-immune planning vaccines, resulting in inaccurate demand forecasts. Therefore, relatively conservative strategies are generally adopted and they dare not produce in large quantities.

The aforementioned person from Beijing Sinovac said that for enterprises, capacity construction will inevitably be considered based on market demand or potential market demand. Because influenza vaccine production is seasonal, the workshop is idle and not produced in normal years. Unless the market has stable demand, it is possible to consider expanding production capacity. Otherwise, the idle cost is too high to build such a large workshop and recruit so many people.

Influenza vaccination notice page. Photo source: Meike reporter Tang Hui, photographed by

This year, the batch issuance volume has exceeded the whole year of last year. Enterprises are working overtime to produce

From few people to the current "hot cake", influenza vaccine has become the most popular vaccine variety second only to the new crown vaccine. In order to alleviate the contradiction between supply and demand, production companies have to work overtime to promote more vaccines to be launched as soon as possible.

"Daily Economic News" reporter learned that the main influenza vaccines that have been launched in the world include inactivated vaccines , live attenuated vaccines and subunit vaccines. Among them, the inactivated vaccine has trivalent and tetravalent, which are injections; the live attenuated vaccine is a nasal spray influenza vaccine, which does not require injection, only 0.1 ml is sprayed in each of the two nostrils. Judging from the batch issuance of influenza vaccines in 2019, trivalent influenza vaccines account for about 70%, and quadrivalent influenza vaccines account for about 30%.

There are 11 influenza vaccine manufacturers in my country, namely Hualan Biological, Sanofi Pasteur, Changchun Institute, Beijing Kexing, Guoguang Biotech, Jiangsu Jindik, Changchun Baike, Dalian Yalifeng, Zhongyi Anke, Wuhan Institute and Shanghai Institute.

Image source: China Center for Disease Control and Prevention's "Technical Guidelines for the Prevention of Influenza Vaccine (2020~2021)" Screenshot

Before 2018, only trivalent influenza vaccines were listed in my country, and nearly 20 manufacturers were produced. In 2018, the quadrivalent influenza vaccine of Changsheng Bio and Hualan Bio were approved for marketing. However, in July 2018, after Changsheng Biosciences stopped production due to the vaccine incident, Hualan Biosciences became the only company in China to produce quadrivalent influenza vaccines. With its first-mover advantage, the quadrivalent influenza vaccine has become Hualan Bio's moat. In 2019, Hualan Bio was approved to issue 12.93 million doses of trivalent and quadrivalent influenza vaccines, accounting for 42% of the total influenza vaccine approvals in that year, of which quadrivalent influenza vaccines accounted for 86.9% of the same varieties in the country. Changchun Institute's market share is 19.9%, all of which are trivalent influenza vaccines, while Sanofi Pasteur's market share is 18.6%.

In 2019 and 2020, the quadrivalent vaccines of Jiangsu Jindik, Changchun Institute and Wuhan Institute were successively approved, and domestic influenza vaccines gradually transitioned from trivalent to tetravalent. Data from the of the of the test institute showed that as of the end of September, 15.134 million quadrivalent influenza vaccine produced by four enterprises had been issued, exceeding the 9.71 million meter-valent influenza vaccines for the whole year last year.

As expected by the outside world, the total volume of influenza vaccine batch issuance this year will also exceed previous years. Zhang Hui, deputy director of the China Food and Drug Inspection Institute, said at the 2020 (37th) National Pharmaceutical Industry Information Annual Conference on on August 30 that more than 30 million influenza vaccines have been issued so far this year, and by the time the flu season arrives next month, it is estimated that it will reach 50 million.

However, now that the flu vaccine is hard to find, can this gap be filled? Zhang Min said it was almost difficult. Because the mainstream influenza vaccine production now adopts the chicken embryo culture process, to use special eggs that have been incubated for about 10 days after fertilization, you must book with the farm in advance.If we start producing a new flu vaccine now, it will take about 4 months from production to batch issuance. It will be next spring until it is launched.

Hualan Bio's secretary Xie Junmin recently said that based on the shortage of influenza vaccines in various places this year, the company is working overtime to produce influenza vaccines to meet the current shortage of influenza vaccines in various places. It is predicted that the production of trivalent influenza vaccines will be nearly 3 million, and the production of quadrivalent influenza vaccines will increase from the planned 16 million to 20 million. On October 12, a reporter from "Daily Economic News" called Hualan Biology to raise an interview request. The staff said that the company has been very busy recently and has no time to accept interviews.

However, Hualan Bio did not disclose the revenue of influenza vaccines separately. The subsidiary Hualan Bio Vaccine Co., Ltd.'s revenue in 2019 was 1.049 billion yuan, a year-on-year increase of 30.68%, and a net profit of 375 million yuan, a year-on-year increase of 38.92%. In the first half of 2020, its vaccine business revenue was -5.79 million yuan, a year-on-year decrease of 148.37%. In the secondary market, Hualan Bio has attracted much attention recently due to the concept of influenza vaccine, reaching a maximum of 65 yuan per share on October 13.

reporter noticed that although Hualan Bio currently has more than 60% of the market share of the quadrivalent influenza vaccine, Hualan Bio will usher in many strong opponents in the near future. According to the Dingxiangyuan Insight database, there are currently 6 companies in the third phase of clinical trials, and the approval of the market will be concentrated within 5 years. Among them, the quadrivalent influenza vaccines of competitors such as Shanghai Institute, Zhifei Longcoma, Sanofi Pasteur, and Liaoning Chengda may shake Hualan Bio's first position after it is launched.

Among them, the Baike Bionasal Spray Influenza vaccine, a subsidiary of Changchun High-tech, was first issued in August. On September 27, Changchun Hi-Tech stated on the interactive platform that according to relevant batch issuance data, the number of 1.25 million of the 100-gram bioinfluenza vaccines that have been issued by the batch issuance is about 1.25 million.

At the same time, an important reason why the influenza vaccine has attracted capital attention is that the current penetration rate of influenza vaccine in my country is only 2.2%, and the room for growth is still very huge. From 2016 to 2017, the vaccination rate of the elderly aged 65 and above in the United States, the United Kingdom, and Australia was 65% to 73%, and the vaccination rate of the elderly aged 60 and above in Mexico and Brazil 60 and above has exceeded 80%, while the average annual vaccination rate of influenza vaccine in my country is 1% to 3%.

The paper published by Feng Luzhao and Li Zhongjie of the Infectious Disease Management Office of the Chinese Center for Disease Control and Prevention in 2019 mentioned that compared with countries with higher vaccination rates, influenza vaccines belong to the second category of vaccines in my country, and the financing channels are single. my country's behavioral research shows that the general public has a very low awareness of influenza vaccination, with 61% of people having little or no knowledge of flu, while the proportion of people in Mexico or the United States is only 17%. At the same time, there is also a lack of management and incentive mechanisms for medical institutions and medical personnel.

They believe that policy changes can increase vaccination coverage by 5% to 10% in the short term. Maintaining high vaccination coverage levels is the result of long-term efforts by all stakeholders to improve. The health administrative departments and relevant management departments continue to actively lead and advocate policies: establish a multi-channel financing mechanism, comprehensively carry out free vaccination projects for high-risk groups such as the elderly and medical personnel, and gradually and plan to achieve free vaccination for the whole population; establish a long-term government-enterprise supply and demand dialogue mechanism, pre-order mechanism, multi-party cooperation mechanism, and build a communication platform between vaccine approval-supervision-using departments and influenza vaccine companies.

According to securities companies' estimates, the current market size of influenza vaccines is about 2 billion yuan, with 5 times growth space in the next few years, with a penetration rate increased to 10%, and the market size can reach 10 billion.

In the view of relevant people from Beijing Kexing, given that the domestic flu vaccine has been approved for the pre-issuance of fewer approvals, appointment methods (phone/digitalization) should be considered, and people including medical staff, the elderly, and children should be given priority, followed by healthy adults. In addition, in combination with the domestic influenza vaccine batch issuance system, the batch issuance information and progress should be shared with the public to let the public understand that influenza vaccines are not "supervision is tight" but are in a state of "not yet completed the batch issuance".

He also suggested that, first, the CPR has approved the simultaneous issuance of influenza vaccine manufacturers, but the overall progress cannot meet domestic demand. We should consider simplifying procedures under the premise of strict control procedures, reducing the batch issuance cycle, and improving the pace of vaccine supply; second, in response to the insufficient supply in various places, whether vaccines can be coordinated in cities/districts as units on the premise of ensuring the traceability of cold chains at the same time to avoid waste; third, according to the requirements of the Vaccine Law, vaccination points will be set up in units (such as tertiary hospitals, pharmacies, etc.) except for community health service centers, township health centers, private hospitals, etc. (such as tertiary hospitals, pharmacies, etc.) to vaccinate specific groups (such as adults) to alleviate the pressure of front-line vaccination; fourth, for vaccines that cannot be vaccinated within one month before the epidemic season or cannot be vaccinated as planned, they will be donated to charities (such as welfare homes) for vaccination to avoid waste and protect more lives.

In early January this year, the deputy director of Guangdong Maternal and Child Health Hospital Chen Yunbin submitted a "Suggestions on solving the problem of difficulty in seeking medical treatment for children during peak flu." He told the reporter of "Daily Economic News" that Guangdong had entered the peak period of influenza at that time, and there were many clustered flu epidemics in schools across the province, causing many classes to be suspended. At the same time, pediatric patients are facing the problem of difficulty in seeking medical treatment. Due to the significant increase in pediatric cases during the flu season, it is difficult to register for pediatrics in all parts of the province. The waiting time for queuing for medical treatment is often 3 hours, and some hospitals even queue for emergency treatment is as long as 5 hours.

On September 27, a vaccination site in Chengdu. Photo source: Photo by Tang Hui, reporter of Meike

Chen Yunbin pointed out that both the World Health Organization and the China Center for Disease Control and Prevention clearly stated that influenza vaccination has good effects on preventing influenza. In order to provide good disease prevention to infants and children, local governments should continue to invest in expanding national immunization programs. "Since there may be two peaks of influenza epidemics in our (Guangdong) province every year (winter, spring and summer), students in school are at high risk for influenza infection and are prone to clustered influenza epidemics and need to be vaccinated with influenza. Therefore, it is recommended that students in school be given free flu vaccination every year in all parts of the province." Chen Yunbin mentioned.