Hopes are rising that Chinese Covid-19 vaccines may be among the first to receive regulatory approval, but analysts say hurdles remain before China becomes a key player in the global market, even if it produces a successful vaccine.
Three Chinese vaccines are now leading the race, with the privately-owned Sinovac and state-owned China National Pharmaceutical Group (Sinopharm) both expecting interim data from their last stages of clinical trials by the end of this year.
In a press conference last Tuesday, Wang Tao, chief review officer of China’s regulator the National Medical Products Administration, said the approval process would be expedited when there was enough data to prove safety and efficacy, as well as evidence that manufacturing capabilities could meet quality standards.
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Zhang Yuntao, vice-president of the China National Biotec Group, part of Sinopharm, said earlier that preparations for “conditional approval” assessment had already begun for its two vaccines that, once granted, would permit them to be administered on the general Chinese public.
But, ahead of any interim data being made available, hundreds of thousands have already been jabbed with experimental Covid-19 vaccines, after China granted controversial emergency use licensing (EUL) to the three front runners, with many people paying from their own pockets or having their employers meet the cost.
In contrast, the US Food and Drug Administration has tightened its EUL requirements in response to rising pressure not to be seen to rush approvals to meet US president Donald Trump’s wish for a vaccine ahead of the November election. Under the new requirements, Pfizer said the interim data from its Phase 3 clinical trial was expected to be postponed to the third week of November, while Moderna also said its interim data would not be available until next month.
Trials for two other contenders – under development by Oxford/AstraZeneca and Johnson and Johnson – resumed last Friday after they were paused because of unexplained illnesses reported by some participants.
Chinese vaccines may gain inroads overseas before they win conditional approval in China, via EULs granted by other national regulators. Last month, a Sinopharm experimental vaccine became the first Chinese Covid-19 candidate to receive an overseas EUL, from the United Arab Emirates which approved it for its frontline health workers.
Other countries are also considering giving EULs to Chinese vaccines. Achmad Yurianto, director general of Disease Prevention and Control at Indonesia’s health ministry, has said his country plans to procure 18 million doses from China’s Sinovac, Sinopharm and CanSino, and could grant an EUL as early as November.
A source close to one of these companies said some developing countries had approached Chinese embassies to relay their interest in procuring vaccines for EUL. “These countries are usually those without vaccine production capacity,” he said, declining to be named because the Chinese government had banned vaccine developers from speaking to the media without approval.
However, individual regulators will still have to assess the data ahead of a final decision, even if China is willing to provide the vaccines. Indonesia, for example, sent a team to China on October 15 to inspect production sites of the three producers – Sinovac, Sinopharm and CanSino – that will supply vaccines, Penny Lukito, head of the country’s Food and Drink Administration said in a statement on October 16.
Countries also face domestic pressure about using Chinese vaccines, with Brazil flip-flopping last week before its regulator on Friday finally approved the import of 6 million doses of the CoronaVac vaccine produced by Sinovac for its national immunisation programme.
The World Health Organization (WHO) is holding pre-assessment meetings with Chinese vaccine developers after inviting expressions of interest from companies wishing to apply for a WHO EUL, but experts said the agency would first require efficacy data from Phase 3 clinical trials.
The Covid-19 pandemic could be a game changer for China’s vaccine industry, which has long focused on the domestic market, even though it is one of the world’s largest suppliers, producing 700 million doses of existing vaccines annually – about 20 per cent of global vaccine production.
Jennifer Huang Bouey, a senior policy researcher at the Rand Corporation, said most of China’s 5,300 to 7,000 vaccine producers were small and the market fragmented. “They aim at government contracts to provide cheap but basic coverage … it is driven by the size of the population rather than the competitiveness of the companies,” she said.
“There are only four Chinese pharmaceuticals that went through the World Health Organization prequalification procedures and to (have their vaccines) on the UN procurement list. That is mainly because Chinese manufacturers were not incentivised to get into the world market and, by their nature, vaccines are not high profit products.”
WHO prequalification for a vaccine means it has met the agency’s high regulatory requirements and is recommended for procurement by UN agencies and WHO member states.
According to the WHO, Southeast Asia is the largest export market for Chinese vaccines, which made up only 2.37 per cent of vaccine procurement in these countries in 2018. In the same year, China supplied 0.9 per cent of vaccines in the eastern Mediterranean region, which includes the Middle East and North Africa, 0.42 per cent in Europe, and 0.62 per cent in the western Pacific region, encompassing part of Asia, the Polynesian islands, and Australia.
US and European pharmaceutical giants are the largest vaccine suppliers in the West, while India is the largest supplier to Southeast Asia, Africa and Middle Eastern countries.
Beijing has promised to provide Covid-19 vaccines to several dozen developing countries, following President Xi Jinping’s pledge in May to make its vaccines a global public good. After months of hesitation, China finally agreed to join Covax, the vaccine distribution mechanism led by the Bill Gates-backed alliance Gavi, the Coalition for Epidemic Preparedness Innovations (CEPI), and WHO.
Experts said the move would boost international confidence in Chinese vaccines and incorporate China’s vaccine industry into the world’s supply chain in the long term.
“The beauty for China contributing to Covax is that the vaccines have to be WHO pre-qualified, which commits the Chinese companies to a standard that is actually over the international [good manufacturing practice] standard that China follows,” said Jerome Kim, director general of the International Vaccine Institute founded by the United Nations.
“So asking them (Chinese firms) to ramp up production and participate in global mechanisms is a good opportunity for CEPI and Gavi to really begin to incorporate Chinese capacity into the global vaccine supply chain,” he said.
So far, the Chinese front runners in Phase 3 clinical trials have not been included in the Covax vaccine portfolio, but both China and Gavi have indicated that more Chinese vaccines may be added to the portfolio.
“If you have several major global health institutions – the WHO, CEPI, Gavi – all accepting the Chinese-made vaccines, procuring them and, for WHO, pre-qualifying them, it actually legitimises the Chinese-made vaccines,” said Yanzhong Huang, a senior fellow for global health at the Council on Foreign Relations.
“That could also be used to serve as a rebuttal [to criticism] that the Chinese vaccines are not safe or not effective, so it would help China to promote and market its vaccine internationally.”
The Chinese vaccine industry has been marred by scandals in the past but analysts said these had mostly involved small producers regulated by local authorities. In contrast, the Covid-19 candidates are developed by China’s best vaccine producers and receive more stringent scrutiny.
“I think the Covid-19 vaccines are quite different from the vaccines we heard in causing these scandals,” Bouey said. “For Covid vaccines, given the high stakes, they would be regulated by the central government … In terms of game players, it will be a different player so I am more assured with these high-stake products versus the routine vaccines.”
Sinopharm and Sinovac both have other vaccines pre-qualified by the WHO. A subsidiary of Sinopharm was the first to receive WHO prequalification for Japanese encephalitis vaccines after years of support from several UN agencies to help it meet the standard. “They know what the WHO wants,” Kim said, adding that China was supplying 80 per cent of the Japanese encephalitis vaccines in Asia.
China will be under huge pressure to produce enough doses to meet its domestic demand while also fulfilling its pledges to so many countries. Zheng Zhongwei, a National Health Commission official, said on Thursday that China’s capacity had been ramped up to produce 610 million doses by the end of the year. China said in late September that its capacity is set to further increase to 1 billion doses in 2021.
Sinovac said it aimed to be able to produce 100 million doses by the end of this year and plans to expand its capacity to 300 million doses. Sinopharm plans to more than triple its annual capacity, from nearly 300 million doses to 1 billion by early next year.
A fourth Chinese candidate – an adenovirus vector vaccine developed by CanSino – has been approved for military personnel but not civilians. It is planning to produce 200 million doses a year at a new facility. However, the first two stages of clinical trials found it triggered a less robust immune response while having stronger side effects.
International technology transfers could also increase manufacturing capacity. Sinovac is teaming up with Indonesia’s Bio Farma and Brazil’s Butantan Institute to produce vaccines if they are approved. The former also has a WHO pre-qualified vaccine of its own.
For the Chinese market, Shenzhen Kangtai Biological Products will produce AstraZeneca’s potential Covid-19 vaccines in China, while Pfizer and BioNTech have an agreement with Fosun Pharma in China on material transfer of their advanced mRNA vaccine.
Even with approvals, Chinese vaccines are unlikely to be sold in developed countries like the US, Japan and EU members, which have different sets of more stringent requirements. There is also a mistrust of China-made vaccines fuelled by rising tensions and Western scepticism about China’s early handling of the coronavirus outbreak.
Experts warned that China should be aware of the risks when exporting large quantities of vaccine. Any adverse event – whether caused directly by Chinese vaccines or not, would cause a serious backlash, they warned. Problems with transport, storage, or with administering the vaccine – even a recipient’s underlying condition unrelated to the jab – can lead to mishaps.
There is an added layer of complexity for the preferred Chinese approach to development of a Covid-19 vaccine, the only country to pin its hopes on the use of inactivated viruses, a technique used in numerous older vaccines but largely shunned in most new development work.
The three Chinese front runners are inactivated vaccines which, while easier to produce because of established manufacturing facilities, carry higher safety requirements as they involve the handling of live viruses.
“If there is any problem, that would be adding to the negative image for China. The risks are very high, I don’t know if Chinese companies and the government realise the degree of negative forces out there,” Bouey said.
China’s officials have repeatedly said its vaccines are safe, with no adverse events after the hundreds of thousands of doses delivered under China’s own EUL. But experts said the assurances did little to shore up international confidence ahead of any concrete data from the Phase 3 clinical trials.
“With large-scale use of a vaccine before a Phase 3 trial it is much more difficult to assess safety and efficacy. I think confidence in a vaccine will be gained by conducting a large Phase 3 trial, and without this, there is likely to be continuing uncertainty about both safety and efficacy,” said Peter Smith, professor of tropical epidemiology at the London School of Hygiene and Tropical Medicine.
Michael Kinch, director of the Centre for Research Innovation in Biotechnology and Drug Discovery at Washington University in St Louis, said a WHO EUL alone would not be enough as many countries would be unlikely to recognise it unless the transparency issue was addressed.
“Were the Chinese vaccine industry to be successful and sufficiently transparent, it would certainly be a shot in the arm – pardon the pun – for the Chinese pharmaceutical industry. Yet this will not be automatic,” he said. “The only way that credibility will be established is through complete transparency.”
Additional reporting by Simone McCarthy
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