药品监管科学推动中国新冠病毒疫苗研发概述
Review on Drug Regulatory Science Promoting COVID-19 Vaccine Development in China
监管科学是一门综合应用自然科学、社会科学和人文科学，开发新工具、新标准和新方法，以评估受监管产品的安全性、有效性、质量和性能的学科。监管科学研究的根本目的是为行政决策提供技术支撑。在甲型H1N1流感、严重急性呼吸综合征（SARS）和中东呼吸综合征（MERS）等传染病大流行期间，监管科学研究有力支持了抗病毒药物和疫苗的研发。特别在新型冠状病毒（简称新冠病毒）肺炎（COVID-19）疫情大流行期间，药品监管科学支持下的疫苗研发在疫情防控中发挥了重要作用。本文总结了中国疫苗产业、新冠病毒疫苗研发以及疫苗监管科学发展的总体概况。此外，本文重点从国家规划、法律法规、技术指南、质量控制和疫苗上市后监管等方面，回顾和分析了监管科学研究为推动中国新冠病毒疫苗研发所发挥的重要作用。本文为当前大流行阶段以及后疫情时代的疫苗研发策略制定提供参考，并为将来如何更好地应对新发和再发传染病提供借鉴和指导。
Regulatory science is a discipline that uses comprehensive methods of natural science, social science, and humanities to provide support for administrative decision-making through the development of new tools, standards, and approaches to assess the safety, efficacy, quality, and performance of regulated products. During the pandemics induced by infectious diseases, such as H1N1 flu, severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome (MERS), regulatory science strongly supported the development of drugs and vaccines to respond to the viruses. In particular, with the support of research on drug regulatory science, vaccines have played a major role in the prevention and control of coronavirus disease 2019 (COVID-19). This review summarizes the overall state of the vaccine industry, research and development (R&D) of COVID-19 vaccines in China, and the general state of regulatory science and supervision for vaccines in China. Further, this review highlights how regulatory science has promoted the R&D of Chinese COVID-19 vaccines, with analyses from the aspects of national-level planning, relevant laws and regulations, technical guidelines, quality control platforms, and post-marketing supervision. Ultimately, this review provides a reference for the formulation of a vaccine development strategy in response to the current pandemic and the field of vaccine development in the post-pandemic era, as well as guidance on how to better respond to emerging and recurring infectious diseases that may occur in the future.
| Manufacturer | Vaccine candidate | Platform | Decision date |
|---|---|---|---|
| BioNTech/Pfizer | BNT162b2 | Nucleoside modified mRNA | 31 Dec 2020 |
| AstraZeneca | ChAdOx1_nCoV-19 (AZD1222) | Recombinant ChAdOx1 vectored vaccine encoding the spike protein antigen of the SARS-CoV-2 | 16 Apr 2021 |
| Janssen | Ad26.COV2.S | Recombinant, replication incompetent adenovirus type 26 (Ad26) vectored vaccine encoding the SARS-CoV-2 spike protein | 12 Mar 2021 |
| Moderna | mRNA-1273 | mRNA-based vaccine encapsulated in lipid nanoparticle | 30 Apr 2021 |
| Sinopharm (Beijing) | BBIBP-CorV | Inactivated, produced in Vero cells | 7 May 2021 |
| Sinovac Biotech Co. Ltd. | CoronaVac | Inactivated, produced in Vero cells | 1 Jun 2021 |
| Vaccine platform | Vaccine | Doses | Schedule | Route | Developers | Status |
|---|---|---|---|---|---|---|
| Inactivated vaccine | BBIBP-CorV | 2 | Day 0 + 21 | IM | Sinopharm (Beijing) + China National Biotec Group Co., Ltd. + Beijing Institute of Biological Products Co., Ltd. | Conditional approved |
| CoronaVac | 2 | Day 0 + 14 | IM | Sinovac Biotech Co. Ltd. | Conditional approved | |
| COVILO | 2 | Day 0 + 21 | IM | Sinopharm (Wuhan) + China National Biotec Group Co., Ltd. + Wuhan Institute of Biological Products Co., Ltd. | Conditional approved | |
| KCONVAC | 2 | Day 0 + 28 | IM | Shenzhen Kangtai Biological Products Co., Ltd. | Emergency use | |
| Inactivated vaccine (Vero cells) | 2 | Day 0 + 28 | IM | Institute of Medical Biology, Chinese Academy of Medical Sciences | Emergency use | |
| Protein subunit | ZF2001 | 3 | Day 0 + 28 + 56 | IM | Anhui Zhifei Longcom Biopharmaceutical Co., Ltd. + Institute of Microbiology, Chinese Academy of Sciences | Emergency use |
| Recombinant vaccine (sf9) | 2 | Day 0 + 28 | IM | West China Hospital, Sichuan University | Phase 3 | |
| SCB-2019 | 2 | Day 0 + 21 | IM | Clover Biopharmaceuticals Inc. + GlaxoSmithKline plc. + Dynavax Technologies Corporation | Phase 3 | |
| SCTV01C targeting VOCs | 1 | Day 0 | IM | SinoCellTech Ltd. | Phase 2/3 | |
| Recombinant vaccine | 3 | Day 0 + 28 + 56 | IM | Academy of Military Medical Sciences, Academy of Military Sciences + Zongyianke Biotechnology Co., Ltd. + Liaoning Maokangyuan Biotechnology Co., Ltd. | Phase 2 | |
| Recombinant vaccine (V-01) | 2 | Day 0 + 21 | IM | Guangdong Provincial Center for Disease Control and Prevention + Gaozhou Center for Disease Control and Prevention | Phase 2 | |
| Recombinant vaccine (Chinese Hamster Ovary cell) | 2 | Day 0 As a booster | IM | National Vaccine and Serum Institute, China + Beijing Zhong Sheng Heng Yi Pharmaceutical Technology Co., Ltd. + Lanzhou Institute of Biological Products Co., Ltd. | Phase 1/2 | |
| 202-CoV | 2 | Day 0 + 28 | IM | Shanghai Zerun Biotechnology Co., Ltd. + Walvax Biotechnology Co., Ltd. + CEPI | Phase 1 | |
| ReCOV | 2 | Day 0 + 21 | IM | Jiangsu Rec-Biotechnology Co., Ltd. | Phase 1 | |
| PIKA-adjuvanted vaccine | 2 | Day 0 + 7 | IM | Yisheng Biopharma Co., Ltd. | Phase 1 | |
| Viral vector | Ad5-nCoV | 1 | Day 0 | IM | CanSino Biologics Inc. + Beijing Institute of Biotechnology | Conditional approved |
| DelNS1-2019-nCoV-RBD-OPT1 | 2 | Day 0 + 28 | IN | University of Hong Kong + Xiamen University + Beijing Wantai Biological Pharmacy Enterprise Co., Ltd. | Phase 3 | |
| Viral vector + antigen-presenting cell | Covid-19/aAPC vaccine | 3 | Day 0 + 14 + 28 | SC | Shenzhen Geno-Immune Medical Institute | Phase 1 |
| mRNA | ARCoV | 2 | Day 0 + 14 or Day 0 + 28 | IM | Academy of Military Sciences + Walvax Biotechnology Co., Ltd. + Suzhou Abogen Biosciences Co., Ltd. | Phase 3 |
| mRNA vaccine | 2 | TBD | IM | Shanghai East Hospital + Stemirna Therapeutics Ltd. | Phase 1 | |
| mRNA vaccine | 2 | TBD | IM | Zhuhai Lifanda Biotechnology Co., Ltd. | Phase 1 | |
| DNA | INO-4800 | 2 | Day 0 + 28 | ID + electroporation | Inovio Pharmaceuticals Inc. + International Vaccine Institute + Advaccine (Suzhou) Biopharmaceuticals Co., Ltd. | Phase 3 |
| SARS-CoV-2 DNA vaccine | 2 | Day 0 + 21 | IM + electroporation | The University of Hong Kong | Phase 1 |
| [1] |
Liang X, Wu Z. Implementation of EPI for 30 years to protect hundreds of millions of people’s health. Chin J Prev Med 2008;42:4–6. |
| [2] |
Zheng J, Zhou Y, Wang H, Liang X. The role of the China Experts Advisory Committee on Immunization Program. Vaccine 2010;28(Suppl 1):A84–7. |
| [3] |
Cohen J, Enserink M. Infectious diseases. As swine flu circles globe, scientists grapple with basic questions. Science 2009;324(5927):572–3. |
| [4] |
Li JS, Dong XG, Qin M, Xie ZP, Gao HC, Yang JY, et al. Outbreak of febrile illness caused by coxsackievirus A4 in a nursery school in Beijing, China. Virol J 2015;12(1):92. |
| [5] |
Meng XD, Tong Y, Wei ZN, Wang L, Mai JY, Wu Y, et al. Epidemical and etiological study on hand, foot and mouth disease following EV-A71 vaccination in Xiangyang, China. Sci Rep 2020;10(1):20909. |
| [6] |
Wang L, Wang Y, Jin S, Wu Z, Chin DP, Koplan JP, et al. Emergence and control of infectious diseases in China. Lancet 2008;372(9649):1598–605. |
| [7] |
Li H. The major achievements of biological products in China. Chin Med J 2000;113(10):942–7. |
| [8] |
Economic Daily. Domestic vaccines account for more than 95% of the country’s actual vaccination [Internet]. Beijing: Economic Daily; 2018 Jun 7 [cited 2021 Dec 12]. Available from: http://news.cctv.com/2018/06/07/ ARTIIuehDvxFl4UACvwtljiy180607.shtml. Chinese. |
| [9] |
World Health Organization. China enters the global vaccine market [Internet]. Geneva: World Health Organization; 2014 Aug 10 [cited 2021 Dec 12]. Available from: http://www.who.int/bulletin/volumes/92/9/14-020914.pdf. |
| [10] |
China Center for Food and Drug International Exchange. The vaccine produced in China passed the World Health Organization pre-certification for the first time [Internet]. Beijing: China Center for Food and Drug International Exchange; 2013 Oct 14 [cited 2021 Dec 12]. Available from: https://www. ccfdie.org/cn/yjxx/yphzp/webinfo/2013/10/1481297438038593.htm. Chinese. |
| [11] |
World Health Organization. WHO lists additional COVID-19 vaccine for emergency use and issues interim policy recommendations [Internet]. Geneva: World Health Organization; 2021 May 7 [cited 2021 Dec 12]. Available from: https://www.who.int/news/item/07-05-2021-who-lists-additional-covid -19-vaccine-for-emergency-use-and-issues-interim-policy-recommendations. |
| [12] |
World Health Organization. WHO validates Sinovac COVID-19 vaccine for emergency use and issues interim policy recommendations [Internet]. Geneva: World Health Organization; 2021 Jun 1 [cited 2021 Dec 12]. Available from: https://www.who.int/news/item/01-06-2021-who-validates-sinovac-covid-19- vaccine-for-emergency-use-and-issues-interim-policy-recommendations. |
| [13] |
World Health Organization. WHO coronavirus (COVID-19) dashboard [Internet]. Geneva: World Health Organization; [cited 2021 Dec 3]. Available from: https://covid19.who.int/. |
| [14] |
World Health Organization. COVID-19 vaccine tracker and landscape [Internet]. Geneva: World Health Organization; 2022 Jan 4 [cited 2022 Nov 30]. Available from: https://www.who.int/publications/m/item/draftlandscape-of-covid-19-candidate-vaccines. |
| [15] |
Staff. COVID-19 vaccines: global authorizations [Internet]. Staff; [updated 2021 Dec 3; cited 2021 Dec 3]. Available from: https:// www.coronavirustoday.com/covid-19-vaccines. |
| [16] |
Data OWi. COVID-19 vaccine doses administered [Internet]. Data OWi; [updated 2022 Jan 6; cited 2022 Nov 30]. Available from: https:// ourworldindata.org/grapher/cumulative-covid-vaccinations. |
| [17] |
He Q, Mao Q, Zhang J, Bian L, Gao F, Wang J, et al. COVID-19 vaccines: current understanding on immunogenicity, safety, and further considerations. Front Immunol 2021;12:669339. |
| [18] |
World Health Organization. The COVID-19 vaccines within WHO EUL/PQ evaluation process [Internet]. Geneva: World Health Organization; 2021 Oct 20 [cited 2021 Dec 29]. Available from: https://extranet.who.int/pqweb/sites/ default/files/documents/Status_COVID_VAX_20Oct2021.pdf. |
| [19] |
Elmgren L, Li X, Wilson C, Ball R, Wang J, Cichutek K, et al. A global regulatory science agenda for vaccines. Vaccine 2013;31(Suppl 2):B163–75. |
| [20] |
Wu J, Xu F, Lu L, Lu M, Miao L, Gao T, et al. Safety and effectiveness of a 2009 H1N1 vaccine in Beijing. N Engl J Med 2010;363(25):2416–23. |
| [21] |
Zhu F, Xu W, Xia J, Liang Z, Liu Y, Zhang X, et al. Efficacy, safety, and immunogenicity of an enterovirus 71 vaccine in China. N Engl J Med 2014;370 (9):818–28. |
| [22] |
Li R, Liu L, Mo Z, Wang X, Xia J, Liang Z, et al. An inactivated enterovirus 71 vaccine in healthy children. N Engl J Med 2014;370(9):829–37. |
| [23] |
The National People’s Congress of the People’s Republic of China. Vaccine Administration Law of the People’s Republic of China [Internet]. Beijing: The National People’s Congress of the People’s Republic of China; 2019 Jun 29 [cited 2021 Dec 29]. Available from: npc.gov.cn/englishnpc/c23934/202012/ 0b1fd779c29e49bd99eb0e65b66aa783.shtml. Chinese. |
| [24] |
The National People’s Congress of the People’s Republic of China. Drug Administration Law of the People’s Republic of China [Internet]. Beijing: The National People’s Congress of the People’s Republic of China; 2019 Aug 26 [cited 2021 Dec 29]. Available from: http://www.npc.gov.cn/englishnpc/ c23934/202012/3c19c24f9ca04d1ba0678c6f8f8a4a8a.shtml. Chinese. |
| [25] |
World Health Organization. Criteria for COVID-19 vaccine prioritization [Internet]. Geneva: World Health Organization; 2020 May 17 [cited 2021 Dec 12]. Available from: https://www.who.int/publications/m/item/criteriafor-covid-19-vaccine-prioritization. |
| [26] |
State Administration for Market Regulation. The management of lot release of biological products [Internet]. Beijing: State Administration for Market Regulation; 2020 Dec 11 [cited 2021 Dec 29]. Available from: https://gkml. samr.gov.cn/nsjg/fgs/202012/t20201221_324542.html. Chinese. |
| [27] |
Center for Drug Evaluation, NMPA. Technical guidelines on research and development of COVID-19 prophylactic vaccines (trial edition) [Internet]. Beijing: Center for Drug Evaluation, NMPA; 2020 Aug 14 [cited 2021 Dec 12]. Available from: https://www.cde.org.cn/main/news/viewInfoCommon/ 4cbbbe5b191c1110c4b73bbca35b3e0c. Chinese. |
| [28] |
Center for Drug Evaluation, NMPA. Technical guidelines on pharmaceutical research of COVID-19 prophylactic mRNA vaccines (trial edition) [Internet]. Beijing: Center for Drug Evaluation, NMPA; 2020 Aug 14 [cited 2021 Dec 12]. Available from: https://www.cde.org.cn/main/news/viewInfoCommon/ 4cbbbe5b191c1110c4b73bbca35b3e0c. Chinese. |
| [29] |
Center for Drug Evaluation, NMPA. Technical points for non-clinical studies and evaluation of prophylactic COVID-19 vaccines (trial edition) [Internet]. Beijing: Center for Drug Evaluation, NMPA; 2020 Aug 14 [cited 2021 Dec 12]. Available from: https://www.cde.org.cn/main/news/viewInfoCommon/4cbbbe5b191c111 0c4b73bbca35b3e0c. Chinese. |
| [30] |
Center for Drug Evaluation, NMPA. The technical guidelines on clinical research of COVID-19 prophylactic vaccines (trial edition) [Internet]. Beijing: Center for Drug Evaluation, NMPA; 2020 Aug 14 [cited 2021 Dec 12]. Available from: https:// www.cde.org.cn/main/news/viewInfoCommon/4cbbbe5b191c1110c4b73bbca 35b3e0c. Chinese. |
| [31] |
Center for Drug Evaluation, NMPA. Technical guidelines on clinical evaluation of COVID-19 prophylactic vaccines (trial edition) [Internet]. Beijing: Center for Drug Evaluation, NMPA; 2020 Aug 14 [cited 2021 Dec 12]. Available from: https://www.cde.org.cn/main/news/viewInfoCommon/4cbbbe5b191c1110c 4b73bbca35b3e0c. Chinese. |
| [32] |
Sun SH, Chen Q, Gu HJ, Yang G, Wang YX, Huang XY, et al. A mouse model of SARS-CoV-2 infection and pathogenesis. Cell Host Microbe 2020;28(1):124– 33.e4. |
| [33] |
Bao L, Deng W, Huang B, Gao H, Liu J, Ren L, et al. The pathogenicity of SARSCoV-2 in hACE2 transgenic mice. Nature 2020;583(7818):830–3. |
| [34] |
Lu S, Zhao Y, Yu W, Yang Y, Gao J, Wang J, et al. Comparison of nonhuman primates identified the suitable model for COVID-19. Signal Transduct Target Ther 2020;5(1):157. |
| [35] |
Shan C, Yao YF, Yang XL, Zhou YW, Gao G, Peng Y, et al. Infection with novel coronavirus (SARS-CoV-2) causes pneumonia in Rhesus macaques. Cell Res 2020;30(8):670–7. |
| [36] |
Deng W, Bao L, Liu J, Xiao C, Liu J, Xue J, et al. Primary exposure to SARS-CoV-2 protects against reinfection in rhesus macaques. Science 2020;369 (6505):818–23. |
| [37] |
Jiao L, Li H, Xu J, Yang M, Ma C, Li J, et al. The gastrointestinal tract is an alternative route for SARS-CoV-2 infection in a nonhuman primate model. Gastroenterology 2021;160(5):1647–61. |
| [38] |
Nie J, Li Q, Wu J, Zhao C, Hao H, Liu H, et al. Establishment and validation of a pseudovirus neutralization assay for SARS-CoV-2. Emerg Microbes Infect 2020;9(1):680–6. |
| [39] |
National Institutes for Food and Drug Control. Catalogue of national standards and reference products for in vitro diagnostic reagents. Beijing: National Institutes for Food and Drug Control; 2020 Sep 24 [2021 Dec 12]. Available from: https://www.nifdc.org.cn/nifdc/bshff/bzhwzh/bzwztzgg/ 202009240827391048.html. Chinese. |
| [40] |
Mao Q, Xu M, He Q, Li C, Meng S, Wang Y, et al. COVID-19 vaccines: progress and understanding on quality control and evaluation. Signal Transduct Target Ther 2021;6(1):199. |
| [41] |
Nie J, Li Q, Wu J, Zhao C, Hao H, Liu H, et al. Quantification of SARS-CoV-2 neutralizing antibody by a pseudotyped virus-based assay. Nat Protoc 2020;15:3699–715. |
| [42] |
Li Q, Wu J, Nie J, Zhang L, Hao H, Liu S, et al. The impact of mutations in SARS-CoV-2 spike on viral infectivity and antigenicity. Cell 2020;182:1284– 94.e9. |
| [43] |
Li Q, Nie J, Wu J, Zhang L, Ding R, Wang H, et al. SARS-CoV-2 501Y.V2 variants lack higher infectivity but do have immune escape. Cell 2021;184:2362–71.e9. |
| [44] |
Wu J, Zhang L, Zhang Y, Wang H, Ding R, Nie J, et al. The antigenicity of epidemic SARS-CoV-2 variants in the United Kingdom. Front Immunol 2021;12:687869. |
| [45] |
Zhang L, Cui Z, Li Q, Wang B, Yu Y, Wu J, et al. Ten emerging SARS-CoV-2 spike variants exhibit variable infectivity, animal tropism, and antibody neutralization. Commun Biol 2021;4:1196. |
()
/
| 〈 |
|
〉 |
PDF
(939KB)
