Selection Of Key Technologies For Research And Development Of Medical Countermeasures For Major Emerging Infectious Diseases

Over the past three decades,there have been multiple major infectious disease epidemics classified by WHO as “public health emergency of international concern”,including the SARS epidemic in 2003,the H1N1 Influenza A epidemic in 2009,the poliomyelitis epidemic in 2014,the Ebola epidemic in West Africa in 2014,the Zika epidemic in Brazil in 2016,the Ebola epidemic in Congo in 2018,and the Corona Virus Disease 2019(COVID-19)epidemic in 2019,especially the COVID-19 epidemic,which has resulted in an unprecedented health crisis for human society.Consequently,the major infectious disease epidemic has become an outstanding public health problem for humankind.In the prevention and control of major infectious disease epidemic,the research and development(R&D)of the medical countermeasures(MCMs)such as vaccines,neutralizing antibodies and small molecule drugs is of particular importance.The development rate and efficiency of the MCMs play a key role in epidemic prevention and control,and the key technologies which support the R&D of these products is the embodiment of the fundamental capabilities in scientific research response.In the context of limited social resources and fierce international competition,the grasp and foresight of technology trends play a very important role in scientific and technological resources management.Thus,taking the COVID-19 as an example,this study investigated the selection of key technologies for MCMs R&D,aiming at strengthening the judgment on the development direction of relevant cutting-edge technologies and implementing forward-looking layout,as well as improving the effectiveness of scientific research management decision and resource allocation,which is of great significance for strengthening the technological reserve for responding to major emerging infectious disease epidemics.In this study,we mainly used the methods such as case study,literature survey,expert consultation,SWOT analysis,matrix analysis,and qualitative analysis combined with quantitative analysis.With the aid of these methods,we discussed the theoretical basis and important concepts related to the study;analyzed and evaluated the R&D progress of the MCMs such as COVID-19 vaccines,neutralizing antibodies and small molecule drugs,screened key technologies from the products that have been on the market and have entered their clinical research stages,built a list of key technologies based on literature research and expert consultation;established a key technology evaluation index system,carried out a study on key technology selection with this index system,obtained the priority of scientific research breakthroughs and reserved technologies development under emergency conditions;and finally put forward the development strategy for key technology by evaluating the internal and external factors faced by the development of the key technologies for vaccines,neutralizing antibodies and small molecule drugs R&D,divided the key technologies into four categories with matrix analysis,and put forward development proposals for each category.The main contents and conclusions of this study are as follows:1.Concept definition and theoretical researchThe concepts involved in the study were surveyed and analyzed,including public health emergency,emergency management,emergency scientific breakthrough,MCMs,core technology in key fields,key technology and key technology for the MCMs,etc.,and thus the “key technology for the MCMs R&D for major emerging infectious disease”was analyzed.This technology,the application purpose of which is to satisfy the development needs of the MCMs for emergency prevention and control in our country now and in the future,has become a core technology as well as a bottleneck technology for promoting and accelerating the MCMs R&D,and a strategic technology leading future development.Meanwhile,by taking the COVID-19 as an example,the contents of emergency scientific and technological breakthroughs were teased out,and the core role and particularity of the MCMs in emergency scientific and technological breakthroughs were elaborated.In view of the importance and particularity of the MCMs R&D,this study compared the disadvantages of the MCMs R&D technology management between China and the United States.It is found that,China lacks the forward-looking layout and sustainment of the technological reserve for the MCMs,so it is necessary to determine the R&D direction and priority fields scientifically.Finally,the basic idea of how to carry out the study on the selection of key technologies was put forward so as to lay a theoretical foundation for follow-up study.2.Construction of the list of key technologies for COVID-19 MCMs R&DUtilizing the authoritative drug development database “Adis Insight” as the main information source,based on the R&D status of the typical target products for the COVID-19 that have been on the market and have entered their clinical research stages,the vaccines,neutralizing antibodies and small molecule drugs were divided into different technological subfields,and the key technologies involved were screened.On this basis,the core key technologies and cutting-edge technologies involved in each technological subfield were extracted by means of literature survey.By integrating the key technologies extracted by both approaches,a preliminary “List of Alternative Technology” was developed.Then the “List of Alternative Technology” was further supplemented and improved in three aspects as follows by the means of the combination of questionnaires and expert interviews:(1)merging the key technologies with similar principles;(2)removing the key technologies that are not part of the rate-limiting component of product R&D under emergency conditions;(3)adding the key technologies not included in the list to form a scientific and complete “List of Key Technology” eventually.The technology list in vaccine field includes nine technological subfields,a total of 30 key technologies.The technology list in neutralizing antibody field includes six technological subfields,a total of 27 key technologies and the technology list in small molecule drugs field includes three technological subfields,a total of 13 key technologies.3.Selection of key technologies for COVID-19 MCMs R&DFirst,the key technology evaluation index system was established,included five aspects such as expert familiarity,significance,urgency,innovation and feasibility,involving nine indices.Then,with this technology evaluation index system,we selected key technologies for the MCMs R&D,and prioritized scientific research breakthrough and reserved technology development under emergency conditions.The key technologies for vaccines R&D with high comprehensive priority include: antigen construction technology,non-replicating viral vector vaccines,inhalation administration technology,etc.The key technologies for neutralizing antibodies R&D with high comprehensive priority include: antibody quality control technology,large-scale separation and purification technology,large-scale culture technology,etc.The key technologies for small molecule drugs R&D with high comprehensive priority include:target structure-based repurposing technology,ligand structure-based repurposing technology,knowledge map-based repurposing technology,etc.4.Development strategy of key technologies of MCMs R&D based on COVID-19Based on SWOT analysis,the advantages and disadvantages,the opportunities and challenges of key technology development were discussed,the key technology development strategy was put forward,and the key technologies were divided into four categories as follows with the aid of matrix analysis by utilizing the realizability and priority of technology as the classification criteria: “priority development”;“supportive development”;“encouraging development” and “concern development”,and development proposals were presented for each category.The development strategies presented for vaccines field are as follows: promoting the self-dependent innovation in vaccines technology;paying attention to the close integration of industry,university,and research;raising our capacity for rapid R&D and production of vaccines and improving emergency vaccines supply system;creating new and better ways for the scientific supervision over vaccines R&D.The key technologies within “priority development” category include nine technologies such as antigen construction technology.The key technologies within “supportive development”category include eight technologies such as nanovaccine technology.The key technologies within “encouraging development” category include seven technologies such as the expression and construction technology for VLP(Virus-Like Particle).The key technologies within “concern development” category include seven technologies such as pathogen gene attenuation technology.The development strategies presented for neutralizing antibody field are as follows:promoting the breakthrough in core technologies in key fields of neutralizing antibody drugs R&D and building a technical platform for rapid R&D and industrialization of antibody drugs;fostering advantages in international competition and promoting higherstandard integration into global innovation network and industrial system.The key technologies within “priority development” category include seven technologies such as bispecific antibody technology.The key technologies within “supportive development”category include nine technologies such as humanized antibody technology.The key technologies within “encouraging development” category include eight technologies such as broad-spectrum neutralizing antibody.The key technologies within “concern development” category include eight technologies such as DNA-encoded monoclonal antibody.The development strategies presented for small molecule drugs field are as follows:strengthening study on small molecule drugs biological mechanism;promoting the application of the drug design technology represented by artificial intelligence in the R&D of small molecule drugs;improving the policy environment to encourage innovation;boosting international drug administration cooperation.The key technologies within “priority development” category include three technologies such as target structure-based repurposing technology.The key technologies within “supportive development” category include two technologies such as knowledge map-based repurposing technology.The key technologies within “encouraging development”category include four technologies such as artificial intelligence-based drug design.The key technologies within “concern development” category include four technologies such as fragment-based drug discovery technology.The main innovations in this paper are as follows:(1)Based on the special requirements for the safety and effectiveness of the MCMs used in major emerging infectious disease,the key technologies are extracted and screened from the R&D of the crucial MCMs such as vaccines,neutralizing antibodies and small molecule drugs,thus the list of key technology for R&D is built,which has a strong guiding significance and practical value in further scientific evaluation and strategic reserve of relevant key technologies.(2)According to the urgent needs for scientific and technological breakthroughs in emerging infectious disease epidemic,the development priorities of key technologies for vaccines,neutralizing antibodies and small molecule drugs R&D under emergency conditions is presented,underpinning the R&D resource allocation and assistant decision more effectively.