Vaccine is a substance that stimulates the immune system to produce protective antibodies after it is usually injected or taken orally. It is generally believed that vaccination is the most economical and effective public health intervention measure to prevent and control infectious diseases. Under normal circumstances, the average cycle of a vaccine from research and development to approval for marketing is 10 years. Against the background that the epidemic situation in COVID-19 has affected areas and the population breadth has never happened in a hundred years, about 200 kinds of vaccines have been developed in different countries, and a number of vaccines have been approved by the regulatory authorities to enter clinical trials. Based on the differences in technical and economic capabilities, the research and development of vaccines in COVID-19 is highly concentrated in a few countries. Just like other vaccines, the antigen of COVID-19 vaccine should be well matched with the prevalent virus to have the expected preventive effect. However, the urgency of controlling the epidemic situation in COVID-19 makes it inevitable that the vaccine successfully developed in a few countries will be used internationally. Of course, this is also a good opportunity for enterprises with research and development capabilities and related countries to show their strength and responsibility. However, in the western multinational pharmaceutical companies that have dominated the global vaccine supply for a long time and the governments that control them, why is the transnational application of COVID-19 vaccine after its successful development not a key topic? How can China’s self-developed COVID-19 vaccine become an international public product?
The first question involves many factors. However, there is no reason to judge a country’s lack of awareness of global health public goods by not voluntarily indicating that its approved COVID-19 vaccine is open to countries or society that cannot develop it by itself. Just like ordinary new drugs, the process of vaccine application includes six links: research and development, registration and approval, production, storage and transportation, and finally vaccination. Internationally, the pharmaceutical industry is the most extensive and strict field of intellectual property protection. Unlike other products, it covers all links from raw materials to production, storage and transportation. How to recover the high development and sales costs? Therefore, the use of vaccines is affected by the economic level, which is exclusive and does not meet the basic definition of public goods. This is one of the sources of accessibility problems faced by countries with insufficient R&D and production capacity in newly developed vaccines (both in terms of output and price).
Closely related to the adaptability and reactivity of the vaccine is its safety. For the producers concerned, because the recipients have no symptoms or symptoms are not obvious, the possible side effects caused by vaccination are traced back to both scientific issues and legal and economic responsibilities.
In the history of world immunization, "Carter incident" is a classic case. In 1955, the polio produced by Cutter Laboratories in California, USA, had an accident. Of the 120,000 children vaccinated with the vaccine, 40,000 were sick, 56 of them suffered from paralytic polio, and finally 113 were paralyzed for life and 5 died. The protracted litigation that accompanied the illness caused huge civil compensation for Carter, a pharmaceutical company established in 1897, was acquired by German Bell Company in 1974. It was not until 1986 that the National Child Vaccine Injury Act was passed by the US Congress that it could provide a solution to the persistent doctor-patient dispute. The incident also led other vaccine companies to reduce or even stop vaccine production.
Different countries have different medical and legal systems, and the dispute over joint and several liability will inevitably become a difficult problem that affects the reputation of pharmaceutical companies and even countries. Therefore, there is a lack of connection between vaccine producing countries and vaccine using countries in terms of medical policies such as examination and approval, supervision and medical dispute resolution, and legislation and law enforcement are within the scope of national sovereignty. These are the realities that vaccine-related enterprises must face in judging safety risks. Historically, vaccine production was an incidental undertaking of commonly used drug manufacturers. With the passage of time, vaccines have become the products specialized by very few enterprises, and the strict degree of national examination and approval has been continuously improved. This is also the reason why the global high-quality vaccines are highly concentrated in a few enterprises and countries in a few countries with high industrialization, and the newly developed vaccines are treated on the principle of self-production and self-use. The transnational trade of vaccines has gradually formed a path dependence between different countries based on the safety, economy and legality of vaccines.
As part of global health governance efforts, the World Health Organization (WHO) established the vaccine pre-certification system in 1987. Its main purpose is to ensure that vaccines purchased by United Nations agencies (UNICEF, UNICEF, etc.) as intermediaries and supplied to low-income countries meet the guidance of WHO Expert Committee on Standardization of Biological Products on vaccines and the bidding requirements of United Nations agencies in terms of safety, effectiveness and quality, meet the requirements of national immunization plan and are suitable for current immunization procedures. The secondary purpose is to replace the other regulatory functions of vaccine recipient countries except for marketing license registration and post-marketing supervision, and to serve as a quality reference for countries that directly purchase vaccines, and to ensure adequate vaccine supply bases by seeking candidates and additional suppliers.
This pre-certification partly adapts to the complex reality of public health in international relations. After all, ensuring and promoting residents’ health is first and foremost the responsibility of the state, and any country’s contribution to other countries’ health governance is limited. In addition, especially in the field of epidemics, one of the essentials of cooperation between countries is mutual protection. The accessibility of vaccines and generic drugs should be balanced with the economic sustainability of their development and trade. One way for UNICEF and other institutions to play their role is to promote the use of vaccines in developing countries through collective procurement from manufacturers in developed countries and seek international assistance to reduce unit prices.
COVID-19 vaccine will be a new product in the existing international vaccine market and will join the existing circulation channels. The World Vaccine Market Report 2019 released by WHO divides the world circulation of vaccines into five channels. First, international organizations such as UNICEF jointly purchase from suppliers such as the Global Alliance for Vaccines and Immunization (GAVI), and then sell them in low-income countries with price reduction and exemption. Second, UNICEF/GAVI jointly sell to middle-income countries. Third, the Pan American Health Organization (PAHO) purchases vaccines and sells them to member countries through its rolling fund. Fourth, vaccines in some middle-income countries are mainly produced and used by themselves, supplemented by GAVI and others. Fifth, in high-income countries, their vaccines are generally produced for their own use. China, Indian, Indonesian and other middle-income countries are in the fourth category, and they have a working relationship with GAVI and other supply mechanisms.
On the one hand, the supply of the world vaccine market has been tight for a long time, and many countries are highly dependent on specific manufacturers or manufacturers’ alliances as procurement sources. On the other hand, the real monopoly of vaccine supply is rare. According to WHO’s vaccine market description, 68% of vaccines are provided by more than four manufacturers, while 37% of vaccines have three or more pre-certified suppliers.
The improvement of vaccine availability in developing countries is partly due to the Developing Country Vaccine Manufacturers Network (DCVMN) established in 2000. The alliance is a kind of recognition of technology and management ability. Apart from promoting the international certification of vaccines in developing countries, its members have the opportunity to obtain authorized production of patented vaccines and imitation production of generic vaccines. Under the background of COVID-19 epidemic, DCVMN issued an appeal, expecting its production capacity to have the opportunity to participate in the production of approved vaccines, so as to improve the availability of vaccines in countries unable to conduct independent research.
No matter how the vaccine flows, in addition to the affordability of the price, the advance purchase agreement between the purchaser and the supplier, the vaccine transportation (especially the cold chain) and the matching of vaccination implementation capacity also affect the progress and stability of vaccine supply and marketing.
It is worth noting that even in the poorest countries, the vaccine supply has the participation of manufacturers from developed countries. GAVI covers more than 50% of the poorest countries in the world.
In other words, the global vaccine circulation has the inertia of its market operation mechanism. The international trade of vaccines is also characterized by regionalization on a continental basis. America and Europe mainly rely on local vaccine manufacturers, while Southeast Asia relies almost exclusively on India’s vaccine supply.
For China, it is of positive significance to characterize the self-developed COVID-19 vaccine as an international public health product in the current global health and development governance dynamics. But in the international vaccine market, this is only an active position. The overseas use of China’s self-developed COVID-19 vaccine must deal with the superposition effect of multiple complex factors that China still faces in the outward flow of medical and health products. Specifically, at least three factors should be considered.
First, the safety and effectiveness of China’s new vaccine must be internationally recognized.It is a necessary but not sufficient prerequisite for a vaccine developed by a middle-income country like China to get a ticket to the world vaccine market. In 2011 and 2014, China passed the evaluation of WHO’s national vaccine supervision system twice. By July 2019, four vaccine products had passed the WHO’s vaccine pre-certification, entered the international procurement list and sold to more than a dozen countries and regions. At present, there are more than 20 vaccine products in China that are or intend to apply for WHO vaccine product pre-certification. According to the work plan, in 2021, China will welcome a new round of WHO’s evaluation of national vaccine supervision system, and be tested by WHO with its latest global benchmark evaluation tool, so as to build China’s vaccine quality management system with higher requirements.
At the same time, we should also see that there is no linear equivalent relationship between the "safety" of a COVID-19 vaccine at the hard technical level and the "reassurance" of patients and potential patients. In many developed countries and some developing countries, the campaign of refusing vaccines or even radical anti-vaccine has a long history and is spreading. New vaccines and new vaccine producers/suppliers must face the test of overseas medical sociology. This often requires a process.
In response, Chinese entities, especially vaccine research and development institutions, include the effective participation of potential users (institutions, rather than countries or governments in a broad sense) in the process of vaccine development as a necessary part of selling self-developed vaccines for China. This participation includes the implementation of clinical trials on people abroad under the condition of matching technical and social conditions. In addition, the field technical training of vaccine storage, logistics and vaccination is also necessary.
The basic management unit of the international health system is still the country. Through the docking between domestic and foreign vaccine regulatory agencies, it is an essential way to obtain the approval and certification of COVID-19 vaccines approved by the relevant national authorities in the experimental stage and in the future in China. This step cannot be omitted because of WHO’s pre-certification.
Second, handle every step of China’s entry into the international COVID-19 vaccine market in a low-key and pragmatic manner.China must realize that the statement that "the world medicine bottle is in China’s hands" has emerged in recent years, regardless of its truthfulness, it already has a strong political and policy market abroad. At the same time, between countries capable of producing COVID-19 vaccine, drugs and medical devices are high-tech, influenced by exclusive competitive initiative.
The overseas use of China’s self-developed COVID-19 vaccine should be led by China’s vaccine research and development, storage and transportation and implementation entities. Based on China’s vaccine market practitioners, it is fully qualified to refer to the rules of GAVI and DCVMN, and set up the COVID-19 vaccine overseas use alliance composed of China vaccine entities, so as to improve the competitiveness through collective action.
The third is to choose a multilateral platform in the promotion strategy and avoid using bilateral arrangements.The basic situation of the existing global vaccine market cannot be shaken. Make full use of the existing multilateral platforms in the field of vaccines, such as GAVI,DCVM, CEPI (Coalition for Epidemiological Preparedness Innovations) and other vaccine R&D and production mechanisms, and WHO, UNICEF and other vaccine circulation policy mechanisms. Relevant entities in China have decades of experience in participating in these mechanisms at different levels.
Another reason why a multilateral platform is a must is that it is conducive to sharing experiences and risks among suppliers.
Fourth, in terms of product pricing, China’s self-developed COVID-19 vaccine should be defined as "not-for-profit" rather than "no profit" or below cost.Not for profit has fulfilled the policy promise of China COVID-19 vaccine as a global public product.
The cost of drug R&D and production in different countries and societies and the permitted profit margins are not automatically comparable. But in terms of cost calculation methods, China and foreign countries should be on the same platform.
Fifth, adhere to the contract as the blueprint for overseas sales.The contract needs to include the following points:
1. The number of vaccines purchased or sold (pre-sold) is the basic point to protect the interests of Chinese enterprises and is also an international practice; In fact, the same country has the freedom to purchase from different national supply sources.
2. Legal arrangement of production authorization, in which the effective protection of intellectual property rights is one of the key points, and the other key point is to cooperate closely with WHO, GAVI, CEPI, DCVM and national regulatory agencies to handle the minimum technical threshold requirements of overseas entities participating in production and sales.
3. Incorporate (potential) buyers’ investment in vaccine production in China into the arrangement options, and handle the contradiction between aid dependence and debt trap.
4. Exemption of side effects of vaccination and dispute resolution mechanism.
In addition, in the process of promotion, political and diplomatic needs should only play an auxiliary role, not a leading role. It should be dominated by vaccine companies, which will also help to enhance China’s voice in the international vaccine field.
To sum up, for China, if you want to see the self-developed vaccine become a public product, you must pay attention to two key points:
First, the road map for the construction of China vaccine circulation with countries that have expressed procurement initiatives; China’s focus should not be on vaccine supply or the amount of aid.
Second, how to deal with the possible side effects and its dispute settlement path should be included in the contract in advance.
In addition, it must be noted that transnational health industry has its own product chain, industrial chain and value chain, and is also restricted by the change of international political and economic relations.
China’s road to developing COVID-19 vaccine as an international public good should be oriented by specific needs, issues and contracts. And these aspects of work need solid work in every link to make progress. It is a meaningful and relatively simple step to identify the self-developed COVID-19 vaccine as a global public health product, and hard work is needed to make it a reality.
(The author Cha Daojiong is a professor at Peking University Institute of International Relations and School of South-South Cooperation and Development of Peking University. This article is a summary of the author’s speech at the seminar on China’s participation in global public health governance organized by China International Development Knowledge Center. The author thanks Professor Cui Fuqiang from Peking University School of Public Health and Ms. Qiao Jianrong from WHO Beijing Office for their contributions to the revision of the article. )
