"Grab a single" new crown vaccine: global fairness and safety
China News Weekly reporter/Huo Siyi
Published in the 964th issue of China News Weekly on September 14, 2020
On August 11, 2020, Russia unexpectedly announced that the world's first new crown vaccine "Sputnik-V" has been registered for production.
Because the Russian government has not announced the vaccine's Phase I/II clinical trial data, nor has it confirmed whether the Phase III clinical trial is ongoing.
Just a day later, the local government of Paraná State in Brazil announced that it had signed a memorandum with Russia to cooperate with Russia in testing and producing "Sputnik-V" in Brazil.
In addition, Russia also revealed that it has received preliminary applications for more than 1 billion doses of the vaccine from 20 countries in Latin America, the Middle East and Asia.
As of September 8, the new crown epidemic has caused 27.33 million infections and 890,000 deaths worldwide.
Among the top ten countries with infection cases, seven are in Asia, Africa and Latin America.
Among them, India had 4.28 million confirmed cases, ranking second in the world; Brazil 4.15 million, ranking third in the world.
The top ten are followed by Peru, Colombia, South Africa, Mexico and Argentina.
The outbreaks in Brazil and India are still very pessimistic.
Since June, the number of newly diagnosed new crown cases in Brazil has been increasing every day between 20,000 and 50,000. The number of new cases in a single day at the end of July rose to 70,000. On September 6, the number of new cases in the country still exceeded 30000.
The number of new cases per day in India has risen from thousands of cases in early June. It exceeded 50,000 for the first time on July 26. Since then, the number of new cases has exceeded 80,000, setting a new record.
The panic buying of "Sputnik-V" by developing countries is actually "a last resort."
Several "star vaccines" that are already in clinical Phase III trials, such as the mRNA vaccine from Moderna in the United States and the adenovirus vaccine from Oxford University in the United Kingdom, have already been nearly "snatched up" by developed countries in Europe and the United States with billions of pre-order agreements.
The sudden appearance of "Sputnik-V", a "dark horse" that has never been filed before, is tantamount to giving developing countries a chance.
In the past two months, at the WHO's routine briefing on the new crown epidemic, Director-General Tedros Tedros has repeatedly stated that he must be vigilant against "vaccine nationalism."
Richard Hatchett, CEO of the Alliance for Epidemic Prevention and Innovation (CEPI), pointed out that the global pandemic of the epidemic crosses national borders, and it is impossible for countries to close themselves up. This problem can be solved through collective cooperation.
"We need to establish a fair global distribution system that can operate effectively after vaccine development. This system requires funding, management, and global support and collaboration." He said.
"The U.S. has the right to get the largest number of vaccines"
Currently, the United States has signed pre-purchase agreements worth more than $6 billion with many vaccine companies.
The latest order comes from Moderna. On August 11, the US government purchased 100 million doses of new crown vaccine from Moderna for US$1.5 billion. The agreement also promised that the United States could purchase an additional 400 million doses of vaccine.
In just a few weeks, the United States received 100 million doses from Johnson & Johnson, 100 million doses from Sanofi and GlaxoSmithKline, 600 million doses of mRNA vaccine jointly developed by BioNTech/Pfizer, and AstraZeneca (University of Oxford). Adenovirus vaccine authorized its supply) 300 million doses and 100 million doses of the US Novavax company.
Most agreements do not directly purchase, but provide vaccine companies with large R&D and production funds in exchange for priority access to vaccines.
For example, the White House granted Sanofi and GlaxoSmithKline a total of US$2 billion in development assistance in exchange for 100 million doses of future vaccines.
In addition, it also awarded $1.9 billion to Pfizer, $1.2 billion to AstraZeneca, and $1 billion to Johnson & Johnson.
These are all part of the US government’s “quick action”. This plan, called “New Manhattan” by Trump, aims to shorten the vaccine development cycle to 8 months by injecting large amounts of money and ensure that it will be completed in January 2021. At least 300 million doses of safe and effective vaccines are available in the United States.
The "rapid action" list almost includes most of the world's vaccine giants, such as AstraZeneca, Pfizer, Johnson & Johnson, Merck and Moderna.
By "spending money" around the world, the United States has now obtained the largest ticket to the vaccine market.
The United Kingdom recently purchased 90 million doses of the new crown vaccine from Novavax and Belgian pharmaceutical company Janssen, and pre-ordered 100 million doses of vaccine from AstraZeneca as early as May this year.
Up to now, the UK has ordered six preparatory vaccines, with a potential stock of 340 million doses.
On August 14, the EU finally reached its first pre-purchase agreement, purchasing 300 million doses of vaccine from AstraZeneca.
In the battle for vaccines, the European Union has been closely following the pace of the United States and trying to compete with the United States, but its strength is insufficient.
As the United States provided a large amount of funds to the French pharmaceutical company Sanofi as early as February, Sanofi CEO Paul Hudson said that “the United States has the right to obtain the largest number of vaccines”, but the EU reacted strongly to this and asked him to immediately Withdraw the remarks.
On July 22, shortly after the United States announced the purchase of 600 million doses of vaccines from BioNTech/Pfizer, the European Commission suddenly released news that the European Union was negotiating with a number of vaccine companies, including BioNTech/Pfizer, Sanofi, Johnson & Johnson and Moderna.
On July 31, the European Union announced the completion of preliminary negotiations with Sanofi. Although the transaction has not yet been completed, it plans to purchase 300 million doses of vaccines from Sanofi and provide them to all EU member states.
But just a few hours before the announcement in Europe, Sanofi and GSK announced that they had received US$2.1 billion in research and development funding from the United States, and pledged to provide 100 million doses of vaccine to the United States in the future.
In fact, this is the largest sum of money invested in the United States' "Rapid Action", but it is only one of them.
The total emergency fund for pre-purchasing vaccines in the EU is only 2.4 billion US dollars.
Sanofi had previously complained that the EU’s negotiation efficiency was much lower than that of the United States, and the EU’s negotiations with Pfizer and Johnson & Johnson also fell into a deadlock.
Barry Bloom, a professor of public health policy at the Harvard School of Public Health, pointed out to China News Weekly that the US government should not try to form a monopoly on the new crown vaccine. If it continues to do its own way, the US will lose the respect of the international community.
He believes that the logic should not be to get as many vaccines as you invest, but to establish an international coordination mechanism, which requires extremely complex negotiations and consultations, not just political competitions between major countries, investors, large vaccine manufacturers and the WHO The shareholders of vaccine manufacturers are also an important part of the negotiations.
"How much is left for developing countries?"
Bilateral agreements between Europe and the United States and major pharmaceutical companies have almost carved up most of the production capacity of major global vaccine companies. "How much is left for developing countries?" Sangeeta Shashikant asked.
She is the coordinator of the international organization Third World Network (TWN) and a British lawyer, mainly responsible for TWN's intellectual property projects.
TWN is mainly composed of lawyers from all over the world, committed to promoting fair access to vaccines in third world countries and solving patent issues involving vaccines.
Shashikant pointed out to China News Weekly that the problem is not only because of the wealth of Western developed countries, but also because of the extremely uneven distribution of the vaccine global industry chain. Most of the research and development and production are concentrated in Europe, North America and Southeast Asia including China. A few countries, Latin America, Africa, and most of Asia have almost no R&D and production capacity, and therefore have no right to speak and bargain at all. They can only rely on assistance from developed countries or a few bilateral transactions with small transactions.
In terms of vaccine research and development, according to WHO statistics, a total of 31 countries around the world participate in research and development, of which 22% of the research and development teams are from the United States, 11% from China, and 8% from Russia.
Among a total of 167 candidate new crown vaccines filed by the WHO, 6 have entered phase III clinical trials. There are three vaccines in China, and the other three are from the United States and the United Kingdom.
In terms of vaccine production, according to the global vaccine production capacity distribution map Vaxmap drawn by TWN, preliminary statistics show that there are 44 manufacturers in the United States and 72 manufacturers in Europe. Among them, Germany has the most with 10 manufacturers, followed by 8 in France, Belgium, Switzerland, There are 6 each in the UK and Ireland.
In China, according to statistics from the Ministry of Industry and Information Technology of the People's Republic of China, as of July 27, a total of 13 companies have successively carried out new crown vaccine production capacity construction, of which 9 have been approved to conduct clinical trials, with an estimated annual production capacity of 720 million doses.
India also has at least 11 or so vaccine manufacturers, of which the Serum Institute of India (SII) is the world's largest vaccine manufacturer.
There are 8 manufacturers in Singapore, 10 in Japan and 7 in South Korea.
Only Egypt and South Africa each have 1 vaccine manufacturer in Africa, and there are 10 in Central and South America. These are mostly small and medium-sized production capacity.
It is worth noting that Brazil, Argentina, Mexico and other developing countries with vaccine production capacity have provided multiple vaccine R&D teams with Phase III clinical trial subjects in exchange for technical support and production licenses, enabling vaccines to land in their countries. produce.
Taking Brazil as an example, it has signed technology transfer agreements with the adenovirus vaccine R&D team of Oxford University, Sinopharm and China Kexing.
Brazil was able to first produce 30 million doses of the Oxford vaccine during the trial period. After the vaccine has passed clinical acceptance, it can continue to produce another 70 million doses.
Compared with relying solely on aid and donations from developed countries, this model is seen as one of the ways that developing countries can no longer wait to die at this stage.
At an African Union meeting held at the end of June, South African President Ramaphosa called on African leaders to make vaccines produced in Africa as much as possible and work hard to expand production capacity. However, due to insufficient funds, they could only try bank financing and loans.
However, this model of "experimental fields" in exchange for technology licenses cannot break the vaccine monopoly of countries such as Europe and the United States, and some of the vaccines it obtains are far from sufficient to meet its basic needs.
Shashikant repeatedly emphasized to China News Weekly that the global pandemic of the new crown is different from previous pandemics. Due to the strong transmission capacity and high lethality of the new crown virus, experts predict that the new crown will not be like SARS, H1N1 will end soon, and the realization of herd immunity through vaccines as soon as possible is regarded as the only solution to this global pandemic.
Therefore, the biggest challenge now is how to produce such a huge amount of vaccine in a short time.
"This number is unimaginably huge, whether it is the United States or any major vaccine country, there has never been any similar experience before." She said.
Du Heng, senior program officer of the Bill and Melinda Gates Foundation, wrote an article that according to experts at Johns Hopkins University, herd immunity requires 70% to 90% of the population to be immune to the virus, according to the global population of 7.5 billion It is calculated that 5.25 billion to 6.75 billion people are required to be immunized. Considering that sometimes two doses of vaccine will be used for immunization, at least 10 billion doses of new crown vaccine are needed globally.
Based on the total global vaccine production capacity of 3.5 billion doses in 2018, this number is three times the global annual vaccine production capacity.
This means that even if all existing vaccine production lines are used to produce new crown vaccines, it will not be able to meet global demand, not to mention other conventional vaccine production cannot be abandoned.
Seth Berkley, CEO of the Global Alliance for Vaccines and Immunization (Gavi), told China News Weekly that under “vaccine nationalism”, this unprecedented vaccine gap will further aggravate the extreme uneven distribution of vaccines around the world. There are only a few countries that supply enough vaccines in their own countries, such as the United States and the United Kingdom. Even within the European Union, many wealthy countries cannot get enough vaccines, which in turn will delay the global escape from the pandemic.
He pointed out that the problems caused by the delay, in addition to the continued deepening of the epidemic in countries with insufficient vaccine access, for those countries that have cleared the epidemic, there are two main risks: 1. No one can predict whether the virus will Mutation, before all countries are protected, the risk of resurrection still exists.
2. Unlike the H1N1 outbreak in 2009, in today's deep globalization, more and more downstream supply chains have shifted to developing countries. After the global economic recession brought about by the new crown pandemic, the most affected region is the United States , Europe and China.
The United States, which pursues "vaccine nationalism", cannot be independent of its own assumptions.
Economists have reached a consensus that the economic crisis brought about by the new crown is more serious than the Great Depression of the 1930s.
Shashikant said that this is not only reflected in the huge economic losses that have already occurred, but also in the recovery cycle of the entire world from this huge disaster that will be longer than expected.
In particular, when the epidemic has not ended in most parts of the world, the rebound of the epidemic and the resumption of work in any one country or region will bring economic shocks to other countries and regions, and no one can recover their own economy alone.
In other words, even if the United States achieves herd immunity through exclusive vaccines in the short term, due to the disruption of the global supply chain, the weakening of capital flows, and the unprecedented collapse of oil demand and the collapse of oil prices caused by the pandemic, aviation, tourism, and manufacturing The industry cannot fully recover before the epidemic, and the overall macroeconomic recovery will be weak.
WHO Director-General Tan Desai pointed out that vaccine nationalism has exacerbated the new crown pandemic and has accelerated the disruption of the entire supply chain.
Vaccines developed in one country need to be placed in vials with corks produced in another country, and the high-grade glass material of these bottles must be purchased from a third country.
Therefore, sharing a limited number of vaccines on a global scale is in the national interest of each country both strategically and practically.
"We need vaccine multilateralism, not vaccine nationalism or regionalism." Berkley said.
"Even before the end of 2021,
Providing nearly 1 billion vaccines is far from enough"
"This is a global problem and requires a global solution." COVAX is currently the world's only international cooperation mechanism to promote vaccine distribution. It is jointly initiated by WHO, the Global Alliance for Vaccines and Immunization (Gavi) and the Alliance for Epidemic Prevention and Innovation (CEPI). Launched at the end of April.
In the first fundraising meeting of COVAX, Gavi CEO Seth Berkley issued the aforementioned statement.
When Seth Berkley said this, the leaders of the countries present had no objection.
But the problem is how to consider other developing countries when the domestic needs cannot be met.
This requires a clever mechanism design and a strong lead unit.
In order to attract the participation of high-income countries, COVAX has adopted a risk diversification strategy. The bottom line is that no country can be sure whether the vaccine in its hands will eventually succeed.
Due to the particularity of this new crown pandemic, vaccine development must be much faster than the normal five-year cycle.
The current international consensus is 18 months, which requires vaccine research and development, testing and production must be carried out simultaneously, which brings huge risks.
Generally, the probability of success of pre-clinical vaccines is about 7%, while for vaccines that reach clinical testing, it rises to 15% to 20%.
Therefore, most vaccine candidates may fail.
In the traditional steps, due to the development and production first, whether to establish a production line and how to expand the production capacity are all after a safe and effective vaccine has been developed.
But when multiple development steps are executed at the same time, the risk taken increases exponentially.
The cost of building a vaccine factory is between US$50 million and US$700 million.
Pfizer spent $600 million on its vaccine plant in the United States.
The Serum Institute of India estimates that it will cost US$164 million to build a new crown vaccine plant.
Johnson & Johnson is considering investing US$1 billion to build a factory.
To "make such a big bet" without knowing whether the vaccine will succeed is tantamount to "standing on the tip of a knife and dancing" for any country.
The most unfortunate result is that the investment in several vaccines all failed, and the country will face a huge risk of vaccine supply.
Therefore, unless the United States is as wealthy as the United States to invest in several vaccines, most middle- and high-income countries that only buy "one or two shots" will tremble before the dust settles.
But COVAX offers the possibility to "make multiple bets" like the US without spending too much money.
Buying vaccines is a big bet.
Due to the uncertainty of vaccines, in Berkley's view, no country can achieve 100% coverage, and no vaccine is 100% effective.
In addition, the success probability of any candidate vaccine in history is less than 10%.
"Therefore, if countries adopt a purely'me first' bilateral approach, in the end, all governments will face the risk of not having a vaccine," he said. "This is the background of the start of the COVAX project, and it is for all countries. The safest bet is to ensure that there is a sufficient dose to protect the most dangerous people."
After any country joins COVAX, it will obtain the right to use all the vaccines invested by COVAX. COVAX promises that if the vaccines invested by some countries fail, they can still obtain a successful vaccine invested by COVAX, but only about 20% of the population can be guaranteed .
Zhang Li, director of the Gavi Center for Strategic Innovation and New Investors, said vividly when explaining the COVAX mechanism in a public occasion: "It's like you are investing, and a single stock may rise or fall, but if you buy a fund, the pool is huge. There are more vaccine candidates, which is equivalent to diversifying the allocation of investment, which can reduce the risk of failure."
Another advantage is that the price of getting the vaccine is lower, in Zhang Li's words, it is "group buying."
COVAX, as a large buyer that brings together the needs of all parties, has signed purchase agreements with several large vaccine manufacturers at advantageous prices.
Under the COVAX mechanism, the main measure to ensure the fair distribution of vaccines is a financing model advocated by Gavi: Early Purchase Agreement (AMC).
When joining COVAX, there are no requirements for the ability of low- and middle-income countries to pay, but high-income countries must be responsible for their own profits and losses, and join by signing an AMC agreement. These funds will be used to purchase vaccines for 92 low- and middle-income countries.
Gavi pioneered the AMC mechanism in 2009, which was first applied to the procurement of pediatric pneumonia vaccines. In the past ten years, 225 million children in 60 low- and middle- and low-income countries have been vaccinated against pneumonia.
The list of 92 countries is determined by the Gavi Council. It mainly includes all economies with a per capita gross national income of less than US$4,000, and other economies that are eligible for the World Bank’s International Development Association (IDA). These countries also have to pay at least part of the cost .
In light of the current epidemics in various countries, COVAX's current tentative goal is to obtain at least 2 billion doses of vaccine by the end of 2021, of which 950 million doses will be provided to middle- and high-income countries pre-purchased through AMC, and another 950 million doses will be provided to low- and middle-income countries , There is an emergency buffer stock of 100 million doses to deal with emergencies.
To ensure equitable access to vaccines in low- and middle-income countries, AMC must raise at least 5.5 billion in funding, of which 2 billion in seed funding is the most urgent and must be raised within the next six months.
As of July 15, AMC has raised 600 million US dollars, but there is still a big gap between 2 billion.
Berkley told China News Weekly that at present, there are 9 vaccine candidates selected by COVAX, and the other 9 are still being evaluated.
In the confirmed list of vaccines, three vaccines are from the United States, namely Novio, Moderna and Novavax; two are from China, respectively, a recombinant protein subunit vaccine developed by China Clover Biopharmaceuticals, and a vaccine developed by the University of Hong Kong. The vaccine of the University of Hong Kong is still in the development stage and has not yet entered human testing.
Several other vaccines come from the UK, Germany and Australia.
At present, 172 countries have pledged to join COVAX and submitted letters of intent. These countries cover more than 60% of the world’s population and more than half of the G20 countries. Among them, there are 76 developed countries, including Japan, Germany and the United Kingdom.
The European Union has always stated that it is not interested in COVAX, and has also euphemistically advised EU countries not to purchase vaccines through COVAX, because there are some exclusive clauses in the EU's own purchase agreement. If EU countries join COVAX privately, "there will be legal problems."
However, on August 31, the European Union suddenly changed its tone and decided to join COVAX and provided a donation of 400 million euros, but said it would still conduct its own bilateral negotiations at the same time.
In fact, August 31 was originally the deadline to join COVAX, but now this date has been postponed to September 18, and the final date for the initial payment of participating countries has also been postponed to October 9.
The United States has clearly stated that it will not participate in COVAX, and Russia has not expressed its intention.
At the regular press conference of the Ministry of Foreign Affairs on September 2, China expressed its support for COVAX, but there is no clear response to whether it is sure to join and how much it plans to contribute.
Kate Elder, a vaccine policy expert at the international public interest organization "Doctors Without Borders", who is concerned about global health, pointed out to China News Weekly that what is worrying is that COVAX has not yet received the promise of some major vaccine countries, so it cannot change the rules of the global game. .
She remembered that more than 30 countries participated in a fund-raising meeting in early August.
These countries have raised many questions, such as who will manage the money, how it will be used, what is the screening and post-review mechanism for candidate vaccines, and what should be done if all selected vaccines fail. These questions are not received. answer.
"Many of the mechanisms of this project are not yet transparent." Elder said.
"It is necessary to break the existing intellectual property system"
In fact, COVAX has put aside the most sensitive and core intellectual property issues in vaccine distribution, and still obtains vaccines through agreements with several vaccine companies. This is essentially a bilateral agreement because COVAX as a whole is equivalent to a large Buyers.
Shashikant emphasized that this pandemic is different from previous ones. The gap between supply and demand of production capacity is very huge. It is impossible for any vaccine company to produce a vaccine that meets global demand. Therefore, it is necessary to open up and share vaccine patents so that developing countries can use their own Excavating production capacity is the most critical point in solving vaccine allocation.
Chee Yoke Ling, head of the Third World Network, told China News Weekly that during the 2009 H1N1 influenza pandemic, the United States had pre-ordered 600 million of the world’s at least 1 billion production capacity.
The United States and many European countries have pledged to donate 10% of their vaccine stocks to underdeveloped countries, but it turns out that these donated vaccines are only provided to poor countries after they have given priority to the supply of their own populations. At this moment, the pandemic has already Subside.
Several large private pharmaceutical companies in Europe and the United States have formed a monopoly on vaccines by applying for patents. These companies ostensibly claim to be "dedicated to assisting developing countries as much as they can," but in essence they are chasing commercial profits, not for global public health security.
"If this new crown pandemic is to stop repeating the same mistakes, it is necessary to break the monopoly of several major private pharmaceutical companies in Europe and the United States on vaccines, that is, to break the existing intellectual property system." She said.
The existing intellectual property system originated from the Agreement on Trade-Related Intellectual Property Rights (TRIPS) passed in 1994.
Prior to this, due to the special public product properties of drugs, it was not required to apply for patent registration in drug development and production, and all drugs were open to the world.
This model is not conducive to the enthusiasm of private companies for R&D and innovation. Therefore, under the lobbying of large pharmaceutical companies in Europe and the United States for years, TRIPS was born and introduced drug patents. It also requires that any drug production and sales must be authorized and licensed by pharmaceutical companies.
Ling suggested that when reforming the intellectual property system, we can try to refer to the traditional model before TRIPS in 1994 and make certain adjustments to achieve a better balance between public health safety and patent protection.
The international community must reach a mandatory and binding treaty through negotiation. The WHO is a good platform. Unfortunately, the WHO still avoids this sensitive issue.
Tan Desai bluntly accused vaccine nationalism, but in terms of the sharing of vaccine patents, he only said lightly that "vaccine requires public investment and public enjoyment."
An expert on international intellectual property law who did not want to be named also pointed out to China News Weekly that the key to the above-mentioned reforms lies in the revision of the law. Not only must the TRIPS be revised, the World Intellectual Property Organization (WIPO) will also convene an assembly of contracting parties to revise the patent law and promulgate A new agreement.
It is extremely difficult to complete the revision of the two laws at the same time, coordinate the interests and demands of all parties, and obtain the consent of all the contracting states.
Even after the agreement is reached, the contracting states will have to sign before it can take effect, and it will usually take at least several years to complete a set of national legislative procedures within each country.
Shashikant believes that in order to establish a brand-new intellectual property framework, it is impossible to rely on developed countries such as the United States and Europe. Developing countries must strengthen their voice and intervene more actively in this matter.
On August 3, at the TRIPS Council meeting, developing countries dominated by South Africa and developed countries dominated by the United States had a heated debate.
South Africa emphasized the need to share knowledge and technology for successful vaccines in order to achieve the widest distribution at the lowest cost.
Developed countries pointed out that intellectual property rights must be protected and enforced, and TRIPS flexibilities not related to patents can be discussed.
South African President Ramaphosa said that vaccines should be used in a fair and equitable manner worldwide, and it is time to put them into action.
This is true, as COVAX’s slogan says-“In the rapidly spreading new crown pandemic, no one can be safe unless everyone is safe.”
China News Weekly, Issue 34, 2020
Statement: The publication of "China News Weekly" manuscript is authorized in writing