Li Yao, a reporter from Economic Observer Network, reported on the evening of July 22nd that Changchun Changsheng Biotechnology Co., Ltd. (hereinafter referred to as "Changsheng Bio") illegally produced freeze-dried rabies vaccine for human use, saying that it had been found out that the enterprise had fabricated production records and product inspection records and changed the process parameters and equipment at will.
The person in charge said that this is the second time in a year that the company has been found to have quality problems in product production. In June last year, 5438+ 10, the former US Food and Drug Administration found that the titer of 1 batch of DTP vaccine produced by this enterprise was unqualified, and the product is still being discontinued.
In China, vaccines and other products are distributed in batches. Why are unqualified vaccines still on the market under such strict supervision?
Six vaccines and two stopped using.
On the evening of July 22nd, the person in charge of the State Administration of Pharmaceutical Products reported that Changsheng Bio's behavior of fabricating production records and product inspection records and changing process parameters and equipment without authorization seriously violated the relevant provisions of the Drug Administration Law of People's Republic of China (PRC) and the good manufacturing practice. The State Administration of Pharmaceutical Products has ordered enterprises to stop production, withdraw drug GMP certificates and recall unused rabies vaccines. The State Administration of Pharmaceutical Products, together with Jilin Provincial Bureau, has filed an investigation on enterprises, and those suspected of committing crimes have been transferred to public security organs for criminal responsibility.
Also on July 22nd, on the afternoon of July 22nd, Changsheng Bio issued an announcement in response to the inquiry letter from Shenzhen Stock Exchange, saying: Although the freeze-dried rabies vaccine for human use and DTP combined vaccine have been discontinued, the varicella vaccine is still on sale, and the company has obtained the drug registration approval, new drug certificate and GMP certificate of tetravalent influenza virus split vaccine, which are in normal production and operation. In 20 17, the company realized the sales income of varicella vaccine of 572 million yuan, accounting for 37% of the company's operating income in 20 17. As of the disclosure date of this announcement, only the company and other two companies have obtained the production license of tetravalent influenza virus split vaccine, and the market competition pattern is good.
There are six kinds of vaccines for immortals, two of which have been discontinued. Its early products include 6 freeze-dried live attenuated varicella vaccine, freeze-dried human rabies vaccine (Vero cells), freeze-dried live attenuated hepatitis A vaccine, split influenza vaccine, cell-free DTP combined vaccine and ACYW 135 meningococcal polysaccharide vaccine. The two products that have been stopped because of quality problems are cell-free DTP combined vaccine and freeze-dried rabies vaccine for human use (Vero cells).
The absorption of acellular DTP combined vaccine occurred on 20 17 1 1.3. The former US Food and Drug Administration issued the "Introduction on the Disposal of Products with Unqualified DTP Vaccine Titers", saying that it recently received a report from the Central Inspection Institute and detected Changchun Changsheng Biotechnology Co., Ltd. and Wuhan Biological Products Research Institute Co., Ltd. in the drug sampling inspection. The titers of two batches of DTP vaccines produced by the company did not meet the standard requirements. As early as 2065438+2007 65438+29 10, the State Food and Drug Administration and the National Health and Family Planning Commission organized experts to make judgments and issued notices to relevant provinces and cities, requiring all localities to do a good job in the disposal of unqualified vaccines: First, order enterprises to find out the flow direction; Second, stop using unqualified products immediately; The third is to order vaccine manufacturers to report the factory inspection results of two batches of unqualified vaccines, re-examine the retained samples, and carefully find out the reasons for unqualified titer; The fourth is to send an investigation team to investigate the two enterprises and check the compliance of the on-site production system; Fifth, all samples of DTP vaccines produced by the two companies within the validity period are taken for inspection, and the inspection conclusion takes 6-8 weeks.
On July 5, 20 18, the State Pharmaceutical Products Supervision and Administration issued another announcement, claiming that there were serious violations of the good manufacturing practice (drug GMP) in the production process of freeze-dried rabies vaccine for human use, and instructed the US Food and Drug Administration in Jilin to withdraw the GMP certificate related to longevity.
On July 8, 2065438, the US Food and Drug Administration in Jilin issued a penalty decision, which made it clear that the batch number of the adsorbed acellular DTP vaccine produced by Changsheng Bio was 201605014-01,and the remaining adsorbed acellular DTP vaccines were1. At the same time, it was fined 2.584 million yuan for three times the value of illegally produced drugs, and the total amount of fines and confiscations was 3.4429 million yuan. At this time, nine months have passed since the notification from the National Bureau, and the falsification of rabies vaccine production records is also fermenting.
As of the close of July 20, Changsheng Bio has been down for five consecutive days, and its market value has evaporated by nearly 10 billion yuan. It closed at 14.50 yuan/share on Friday, with more than 550,000 sales orders topping the list.
Regarding the DTP vaccine incident, Changsheng Biological Company announced that in 20 16 and 20 17, the DTP vaccine revenue was about 37 million yuan and 30 million yuan respectively. They accounted for 3.62% and 65,438+0.95% of the company's operating income in that year respectively. In view of the relatively small proportion of DTP combined vaccine in the company's total sales revenue, the suspension of production has no significant impact on the company's production and operation.
Changsheng Bio also said that at present, the company's DTP production workshop has stopped production, and the company is actively studying DTP component vaccines and multi-vaccines based on them. According to the current situation, disease control institutions in some areas have temporarily stopped using other vaccine products of the company.
With the announcement of the State Pharmaceutical Administration on July 15, the freeze-dried rabies vaccine for human use has also been discontinued. The recall of this product is expected to reduce the company's operating income by about 200 million yuan in the first half of 20 18 and its net profit by about1400,000 yuan. The discontinuation of freeze-dried human rabies vaccine (vero cells) will have a great impact on the company's production and operation. It is estimated that the operating income will decrease by about 540 million yuan in the second half of 20 18. Under the quality storm of rabies vaccine and DTP vaccine, whether the other four vaccines can support the future of immortals may still be tested.
Affected by the rabies vaccine incident, Changsheng Bio has issued an announcement to revise the performance forecast for the first half of 20 18. It is estimated that the change range of net profit attributable to shareholders of listed companies during the period of 20 18+0-6 is 2 10/00,000 yuan to 3 10/00,000 yuan, and the change range is revised to -20%.
The more serious reality for longevity organisms is that according to the current drug administration law, those who produce and sell inferior drugs will be confiscated of their illegally produced and sold drugs and illegal income, and will be fined for more than one time and less than three times the value of their illegally produced and sold drugs. If the circumstances are serious, it shall be ordered to stop production, suspend business for rectification or revoke the drug approval certificate, and revoke the Pharmaceutical Production License, Pharmaceutical Trading License or Pharmaceutical Preparation License of Medical Institutions; If a crime is constituted, criminal responsibility shall be investigated according to law. At the same time, if enterprises or other units produce and sell counterfeit drugs and produce and sell inferior drugs in serious circumstances, the directly responsible person in charge and other directly responsible personnel shall not engage in drug production and business activities within ten years.
Why are there still unqualified vaccines after the batch is issued?
According to a report by the Food and Drug Administration on the 22nd, all the products that have been marketed by Changsheng Bio have passed the statutory inspection, and no quality problems have been found. In order to further confirm the effectiveness of vaccines that have been marketed, National Medical Products Administration has begun to conduct laboratory evaluation on product samples retained by enterprises.
The announcement of Changsheng Bio on the 22nd also indicated that all the rabies vaccine products listed by the company passed the self-inspection and the quality met the national registration standards. According to the Management Measures for Batch Issuance of Biological Products, the products of the company can only be listed after obtaining the batch issuance certificate of biological products issued by China Food and Drug Inspection and Research Institute.
What does this mean?
On the current batch issuance system of vaccines and blood products in China. Specifically, according to the requirements of China's "Drug Administration Law" and other laws and regulations, vaccine manufacturers must carry out all project tests on the safety and effectiveness of each batch of vaccines on the market. After passing the self-inspection, the enterprise applies for the batch issuance of vaccines, and the provincial food and drug administrations organize sampling in the pharmaceutical factory within 5 working days, seal the samples, and then send them to the Central Inspection Institute or other provincial drug inspection institutions with the right to batch issuance.
On May 24 this year, the reporter of Economic Observer Network learned that the staff of the inspection and acceptance hall of the Chinese Academy of Sciences will open the box at the scene to check whether the materials and samples are complete and whether the vaccine samples are transported in cold chain. After acceptance, part of the samples will be sent to the main inspection department for inspection of related projects, and the other part will be kept in a special low-temperature sample warehouse for use in case of quality problems of vaccines.
Then, why are there still unqualified vaccines in each batch?
A spokesman for the Food and Drug Administration said in a previous introduction on the disposal of products with unqualified DTP vaccine titer indicators that the China People's Procuratorate conducted safety indicators inspection on batches of vaccines submitted for approval by enterprises, and randomly selected 5% titer effectiveness indicators for inspection according to international practice. After inspection and recording, the safety indicators of the two batches of vaccines meet the standards, and the titer and effectiveness indicators are not within the scope of sampling inspection.
The spokesman pointed out that the titer of two batches of DTP vaccine was unqualified, which may affect the immune protection effect, but it has no effect on human safety.
It is worth noting that batches of unqualified biological products will not enter the market, but will be directly destroyed, while biological products with "criminal records" in the past will be treated more strictly. According to the Measures for the Administration of Batch Issuance of Biological Products, China will inspect all the biological products that were ordered to stop production in the past due to violation of relevant laws and regulations and were approved to resume production according to the registration standards, and only after at least three batches of products have passed the continuous production can some projects be inspected.
The quality of domestic vaccines should not be demonized.
The fermentation of longevity biological vaccine has caused many problems, such as "turning over vaccine books" has become a hot word in Weibo. A consumer called 1233 1 to ask whether he had been vaccinated with domestic rabies vaccine three years ago, whether he could find out the specific batch number, and whether he was worried about the subsequent onset. Concerns about the quality of longevity biological products are rising to the question of the whole domestic vaccine.
Is the quality of domestic vaccines really unbearable?
During an interview with the Institute of American Food and Drug Administration in China, the reporter from Economic Observer Network learned that China is one of the few countries in the world that can solve all the planned immunization vaccines by itself. Domestic vaccines account for more than 95% of the actual vaccination in China. At present, there are 45 vaccine production enterprises in China, which can produce 63 kinds of vaccines and prevent 34 kinds of infectious diseases, with an annual production capacity of over 6,543.8 billion doses.
Vaccines listed in China, whether domestic or imported, must be strictly in accordance with the requirements of the State Drug Administration and undergo strict pre-marketing clinical research before they are allowed to be listed. Enterprise production must also meet the requirements of Good Manufacturing Practices (GMP).
In 20 17 years, China * * * distributed about 7120,000 doses of vaccines, and 20 varieties of Class I vaccines were distributed on the market, with about 56 10/0,000 doses, accounting for 78.79% of the vaccines on the market; There are 34 kinds of second-class vaccines, about 1.5 1 100 million people (there are both recombinant hepatitis B vaccine, inactivated hepatitis A vaccine and other first-class vaccines, so the statistics of varieties are repeated); According to the origin, there are about 694 million domestic vaccines and only 0./kloc-0. 80 million imported vaccines.
Shen Qi, director of the Institute of Biological Products of the Chinese Academy of Sciences, said that China has established a supervision system covering the whole life cycle of vaccines, with a relatively complete vaccine supervision system, legal system and standard management, a scientific and rigorous vaccine registration and approval system, the implementation of good manufacturing practice (Pharmaceutical GMP) which is in line with the international advanced level, and strict quality management standards for pharmaceutical operations. All vaccines on the market are subject to the management of national batch issuance, and a monitoring and reporting system for abnormal reactions to vaccination has been established.
According to official data, since 1978, it has been 40 years since China responded to the request of the World Health Organization to implement immunization programs on a global scale. In the past 40 years, the national vaccine-preventable diseases have fallen to the lowest level in history. China has established an immune barrier with domestic vaccines, effectively controlling the spread of vaccine-preventable diseases.
In 2000, China was confirmed polio-free; After universal hepatitis B vaccination for newborns, the HBsAg carrying rate of children under 5 years old decreased from 9.67% in 1992 to 0.32% in 20 14 years, and the HBsAg carrying rate ratio decreased by 97%. The number of measles cases in 20 17 was less than 6,000, and the highest year (1959) was over 9 million. No diphtheria cases were reported after 2006, and the highest year (1960) was 15000 cases. There were less than 200 cases of meningitis in 20 17, and 3.04 million cases were reported in the highest year (1967). In 20 17 years, there were only more than 1,000 cases of Japanese encephalitis 1000, and nearly 200,000 cases of Japanese encephalitis were reported in the highest year (197 1). In 20 17 years, there were reported cases of pertussis 10000 cases, and the highest year (1973) was more than 2.2 million cases.
In terms of international accreditation, WHO has conducted two in-depth independent evaluations of vaccine production supervision in China in the past six years, and the results of both evaluations show that the supervision system in China has reached WHO standards.
In 20 13, live attenuated Japanese encephalitis vaccine, a subsidiary company of China Bio, became the first vaccine pre-certified by WHO in China. Subsequently, on 20 15 and 20 17, the influenza vaccine produced by Hualan Bio, the inactivated hepatitis A vaccine produced by Beijing Kexing Bio-products Co., Ltd. and the live attenuated oral polio vaccine produced by China Bio-North Bio-Research Co., Ltd. also passed WHO pre-certification and were listed in WHO.
People in the pharmaceutical industry believe that the product quality of many enterprises has approached or reached international standards, and the illegal behavior of individual enterprises should not rise to demonize the whole domestic vaccine. Being able to find the production fraud behind qualified products, on the other hand, shows that the sensitivity of the supervision system is improving.