Vaccine consistency evaluation is coming! May the tragedy of "longevity vaccine" cease to exist

On the eve of Christmas Eve in 2019, the State Drug Administration issued the technical guidelines for the clinical comparability study of preventive vaccines (see the annex to the end of the policy) Looking forward to the stars, looking forward to the moon, you are finally born As a parent of school-age children, it's hard to forget that dark and obscure time "The long life vaccine case" was exposed The article "the king of vaccines" in the friend circle described that "the problem vaccine entered 250000 children's bodies", which affected my heart I frequently went to the community health center to check the vaccine brand, find the drug traceability code, and repeatedly verified and compared, but I couldn't let go of the suspended heart In the name of life, "I pray to God, your grace, to forgive my sin on this day" is the lyrics of Jay Chou's song of supporting justice in the name of the father, which is the helpless portrayal of all parents "The long-term vaccine case" eventually became the annual hot spot of that year, breaking the eyeball, refreshing the lower limit, and making countless parents and babies live in fear Experts from the medical department of Peking University summed up the ineffective vaccine injection into two words - killing! All public events will attract the attention of our country After all, we want to live a warm, safe and dignified life Premier Li Keqiang made a comment on the vaccine incident: we must give the people of the whole country a clear account! People's Daily: investigation of Changsheng case! The latest notice from the State Food and drug administration came On August 6 of that year, the investigation team of the State Council announced the progress of investigation on the illegal production of rabies vaccine by Jilin Changchun Changsheng company According to the investigation team, Changchun Changsheng company has seriously violated the relevant provisions of the drug production quality management specifications and the national drug standards in the production of rabies vaccine since April 2014 Some batches were mixed with expired stock solution, the date and batch number were not filled in, and some batches were later marked with the production date All batches of vaccine were recalled The person in charge of the enterprise, the enterprises involved in the case and the relevant officials are all punished to varying degrees The accountability of officials was the first to bear the brunt The ministerial officials were removed The director of drug administration resigned On August 16, 2018, the Standing Committee of the Political Bureau of the CPC Central Committee held a meeting on August 16, 2018 The total number of accountability personnel was 42 Of the seven ministerial cadres, four were dismissed, one was put on file, and two were subject to in-depth inspection It was agreed that Jin Yuhui (deputy governor of Jilin Province, in charge of food and drug supervision in Jilin Province since April 2017) would be removed from his post, Li Jinxiu (vice chairman of CPPCC Jilin Province, vice governor of food and drug supervision in Jilin Province from December 2015 to April 2017) would be ordered to resign, and Liu Changlong (mayor of Changchun City, acting mayor of Changchun City in September 2016, from October 2016 to now) would be required He served as mayor of Changchun City and Bi Jingquan (secretary of the Party group and deputy director of the State Administration of market supervision, and former director of the State Administration of food and Drug Administration from February 2015 to March 2018) resigned Behind this series of actions is the country's high attention to the field of vaccines and the determination to make great efforts to rectify Only blocking from all aspects can effectively prevent the recurrence of the "longevity vaccine case" In accordance with the relevant provisions of the jurisdiction of administrative penalties, the State Drug Administration and Jilin food and drug administration respectively imposed a number of administrative penalties on Changchun Changsheng company The State Drug Administration revokes the drug approval certificate of rabies vaccine (gyzz s20120016) of Changchun Changsheng company; revokes the batch issuance certificate of biological products involved in the case, and imposes a fine of 12.03 million yuan The food and Drug Administration of Jilin Province revoked its drug production license, confiscated 1.89 billion yuan of illegally produced vaccine and illegal income, imposed a fine of 7.21 billion yuan three times the value of illegally produced and sold goods, and confiscated 9.1 billion yuan in total On November 8, 2019, the website of Shenzhen Stock Exchange released the announcement of Changsheng Biotechnology Co., Ltd on bankruptcy and liquidation of its wholly-owned subsidiary, declaring the bankruptcy of Changchun Changsheng Biotechnology Co., Ltd On November 27, 2019, shares of Changsheng biological Co., Ltd were delisted So far, with the demise of Changsheng Biotechnology Co., Ltd., the Changsheng vaccine case has really been completed, but countless parents who can't end the pain of heart, is the future vaccine safe? How to manage vaccines in the United States? The world's top pharmaceutical companies attach great importance to vaccine production, especially Pfizer Pharma, MSD, Sanofi and GSK, the world's leading pharmaceutical companies, all produce vaccines In particular, Pfizer's vaccine line showed outstanding performance According to the financial statements of the first three quarters of Pfizer, its contribution to the field was nearly $4.8 billion, slightly down from the same period last year, but it still did not affect its becoming a heavy bomb of Pfizer, accounting for nearly 11% of the total sales of Pfizer At the same time, it has become the king of global vaccines with absolute advantages Peier is used for active immunization of infants and young children to prevent invasive diseases (including bacteremic pneumonia, meningitis, septicemia and bacteremia) caused by pneumococcal serotypes 1, 3, 4, 5, 6a, 6b, 7F, 9V, 14, 18C, 19A, 19F and 23F Streptococcus pneumoniae is the most common cause of invasive diseases as well as pneumonia and upper respiratory tract infection 2010acip recommends: 13 valent pneumococcal conjugate vaccine and 23 valent pneumococcal polysaccharide vaccine to prevent pneumococcal disease in infants and children In the United States, the approval of vaccine research and development is similar to that of drugs to ensure the effectiveness and safety of vaccines In the United States, FDA's Center for biological product evaluation and research is responsible for supervising vaccines in the United States Clinical development of vaccines follows the same path as drugs and other biological agents Pre marketing (pre license) vaccine clinical trials are usually conducted in three stages, which is the same as the steps of any drug or biological product If clinical trials show a safety risk, FDA may request additional data or discontinue the study After the successful phase III clinical research, the vaccine production facilities can be pre inspected by submitting the application for biological preparation license After FDA reviews the application for a new indication, the applicant and FDA may submit their findings to the FDA's Advisory Committee on vaccines and related biological products for advice on the safety and effectiveness of the vaccine for the proposed indication After the approval of the vaccine and production process, FDA will continue to monitor the production of the vaccine to ensure the continued safety of the vaccine As soon as it enters the market, many vaccines will be studied in phase 4 At the same time, the vaccine adverse event reporting system was launched to monitor the safety of vaccine clinical application at any time The consistency evaluation gave birth to the results and made the imported vaccine reduce the price The consistency evaluation of domestic vaccine quality improvement started in 2016, confused in 2018 and scheduled to 2019 On February 29, 2016, Bi Jingquan, then director of the State Food and drug administration, said that the main body of the consistency evaluation was the enterprise The enterprise should take the initiative to look for product reference preparations, conduct research and clinical trials according to the prescribed methods The government should coordinate the confirmation, evaluation methods, application and evaluation of product reference preparations as a whole, and give guidance to this work The consistency evaluation policy is coming out, and all enterprises are looking forward to it On December 6, 2018, the first batch of drugs of 4 + 7 national centralized purchase was announced, which shocked the industry In 2019, with the negotiation and access of medical insurance, the achievement and expansion of national centralized procurement, pharmaceutical enterprises have a common understanding that national centralized procurement will become the norm, and the era of eliminating fake drugs and reserving the real will come The result will be to continue to ensure that the quality level of China's generic drugs is consistent with that of the imported original drugs, and the price will be greatly reduced, which is scheduled for 2019 With the promotion of generic drug consistency evaluation, the country further standardized the field of vaccine for prevention Promote clinical trials of vaccines and improve the level of clinical research and development, ensure similar safety and effectiveness of similar vaccines when they are registered on the market, and guide the clinical research and development and evaluation of non innovative vaccines The evaluation document standardizes the evaluation of vaccine consistency from five aspects: pre clinical trial considerations, general considerations of clinical trial design, statistical considerations of clinical trial design, data management and quality assurance, and evaluation of clinical trial results In the circulation link, the State Council decided to revise the 2016 version of the regulations on the administration of vaccine circulation and vaccination as follows: first, Article 10 should be revised as: "the procurement of vaccines should be conducted through the provincial public resources trading platform." 2、 Article 15 is revised to read: "the second type of vaccine shall be centrally purchased by the provincial disease prevention and control institutions on the provincial public resource trading platform, and then purchased by the county-level disease prevention and control institutions from vaccine manufacturers and supplied to vaccination units in their respective administrative regions "Vaccine manufacturers shall directly distribute the second type of vaccine to county-level disease prevention and control institutions, or entrust enterprises with cold chain storage and transportation conditions for distribution Enterprises accepting consignment for distribution of the second category vaccine shall not entrust for distribution The management of vaccines from process, production to circulation will gradually become an in-depth part of China's medical reform Let's see the near future China's vaccines can reach the international advanced level In the process of medical reform, the emphasis on innovation will promote more vaccine enterprises to develop "freiber" for the benefit of Chinese patients We hope that the living environment can be safe and peaceful, as described in the Tao Te Ching: "neighbors meet, the voice of chickens and dogs is heard, and people do not communicate with each other until old age and death." Annex: technical guidelines for clinical comparability of vaccines for prevention In order to further standardize the clinical trials of preventive vaccines (hereinafter referred to as vaccines) and improve the level of clinical research and development, ensure the similar safety and effectiveness of similar vaccines when they are registered on the market, and guide the clinical research and development and evaluation of non innovative vaccines, the guiding principles are hereby formulated The non innovative vaccines mentioned in these guidelines refer to the vaccines that have already been listed in China and are comparable with the same vaccines that have been listed in terms of quality, safety and effectiveness This guideline is applicable to non innovative vaccines that use immunogenic alternative endpoints for effectiveness evaluation For vaccines involving changes in prescription and production process, if it is necessary to further evaluate the feasibility of changes through clinical comparability study, please refer to the guidelines The clinical trial of vaccine shall strictly abide by the drug administration law of the people's Republic of China, the vaccine administration law of the people's Republic of China, and implement the relevant provisions of the drug registration administration measures, in accordance with the GCP, the guiding principles for the quality management of clinical trial of vaccine, the technical guiding principles for clinical trial of vaccine, and the vaccine for prevention Guidelines for grading standards of adverse events in clinical trials This guiding principle only represents the current view and understanding, and will be revised and improved with the deepening of research and understanding 2、 Pre clinical trial considerations for non innovative vaccines, the effectiveness and safety of clinical use of the same vaccines should be fully evaluated in the R & D project Generally, we should first carry out the pharmaceutical and non clinical comparative study between the candidate vaccine (or trial vaccine) and the same vaccine (or control vaccine) which has been put on the market The comparative data combined with the clinical trial results are used to evaluate the comparability of the two vaccines Acceptability limits of key quality standard items of marketed vaccines (such as antigen content / titer, virus titer, product and process related miscellaneous)