China has taken a shortcut in the global sprint to develop and deliver vaccines for the novel coronavirus. Sinopharm, the state-owned company developing two of China’s leading vaccine candidates, told China National Radio on Monday that it has already vaccinated hundreds of thousands of Chinese citizens — even though the company’s phase 3 clinical trials have not yet concluded.
Individuals received one of two Sinopharm vaccines in development in an emergency use program launched by the Chinese government in late July, which also authorized a third vaccine, CoronaVac, developed by the privately owned drugmaker Sinovac Biotech. Under Chinese vaccine law, such authorization is allowed within a certain scope and time frame during a health emergency. China’s top vaccine official mentioned front-line medical workers and customs officials when he first announced the program, implying these high-risk groups had been prioritized to receive the still-experimental vaccines.
Phase 3 clinical trials, which look at the efficacy of a vaccine candidate at preventing a virus from spreading in a community, for the three Chinese vaccines had just begun overseas when they were approved for emergency use domestically. In July, Sinopharm initiated phase 3 trials for its two vaccine candidates in the United Arab Emirates; one of the vaccines also began trials in Morocco and Peru in August, according to the New York Times vaccine tracker. Sinovac launched CoronaVac’s phase 3 trials in July in Brazil, followed by Indonesia the following month. (The trials are being conducted outside of China because the vaccines’ protectiveness can be better evaluated in regions where Covid-19 transmission is high.)
China and Russia are the only countries that have provisionally greenlit vaccines that have yet to be deemed safe and effective through phase 3 trials.
In the US, the Centers for Disease Control and Prevention has told states to prepare to distribute vaccines to high-risk groups by the end of October or early November, stirring concerns that the vaccine approval process may be politicized ahead of the 2020 election. However, nine leading vaccine developers pledged to not submit their vaccines for approval until data from phase 3 trials shows that they meet predetermined safety and efficacy thresholds. No Chinese companies signed the pledge.
So far, China has not reported any serious issues with its emergency vaccine program. But vaccine experts told Vox that skipping or shortening phase 3 trials is risky and could subject citizens to an ineffective or unsafe vaccine. The risks are even higher in China, where vaccine producers have a history of scandals and the media is largely unable to play a watchdog role because of state control.
Although transmission has reportedly been very low in China since February, controlling local hot spots is still a priority for the government, said Yanzhong Huang, a professor of global health at Seton Hall and author of Toxic Politics, an examination of China’s environmental health crisis. “They have this strong incentive to develop vaccines to show Chinese high-tech capacity, and also [to] give people the sense of national pride,” Huang added.
Here’s what we know about how China’s emergency vaccine program is playing out so far.
China’s stealth emergency use vaccine program, explained
In the crowd of pharmaceutical companies that have jumped into the vaccine effort, Chinese companies got a swift and aggressive start. Of the 211 vaccines in development worldwide as of September 11, nine vaccines are in phase 3 trials, and four of the nine are from Chinese companies.
These trials allow scientists to determine the vaccines’ efficacy and identify side effects that may not have appeared in phase 1 or phase 2 trials.
But rather than waiting for trial results, the Chinese government started allowing certain workers to be vaccinated on a separate track.
The emergency program was only made public in late August during a carefully orchestrated segment on China’s vaccine development that aired on the country’s state-run television station CCTV. The program had been approved by the State Council on June 24 and was officially launched on July 22, Zheng Zhongwei, the leader of China’s vaccine program, explained on air.
Zheng said the program applies only to certain groups of people, pointing to medical workers treating Covid-19 and other illnesses, customs officials, food market workers, transportation workers, and some service industry personnel. The emergency use program is regulated through nine plans covering medical consent, the monitoring of side effects, and compensation, Zheng said.
The extent of the program had remained under wraps until early September, when new information revealed that participation had not been as limited as the government initially suggested. Sinopharm disclosed that hundreds of thousands of people have received their vaccines as part of the program. The CEO of Sinovac, the other vaccine maker involved, said 90 percent of the company’s employees and their family members — up to 3,000 people — have taken the vaccine voluntarily, Reuters reported. To justify the vaccine’s emergency use, the CEO explained it would help ensure the company’s workers could continue to produce vaccines.
The protocol for who, exactly, gets to receive the vaccine under the emergency program remains unclear. “That is still pretty much shrouded in mystery,” said Huang.
Outside of this official emergency program, the Chinese military in late June authorized the use of a vaccine candidate created by CanSino Biologics for military personnel. Separately, workers of state-owned companies traveling overseas were also allowed to take one of the two Sinopharm vaccines in June.
The risks of circumventing phase 3 trials
After China’s initial outbreak peaked in February, the government swiftly brought the spread under control, reporting zero local cases by mid-March. Since then, new hot spots have emerged in regions such as Beijing and Xinjiang. In Xinjiang, where over a million Uighurs and other ethnic minorities have been put in detention over the past three years, the Chinese government has imposed a strict lockdown to rein in the spread, and some residents have reported being forced to drink Chinese traditional medicine.
Outside of these hot spots, transmission in China has remained very limited since March.
“The irony is that in China, at the moment infection rates are really very low,” said John Moore, an immunologist at Weill Cornell Medical College. “They are actually in a situation where they could afford to wait for the outcome of ongoing phase 3 trials, understand the safety and efficacy properly, without compromising their population.”
With occasional clusters of domestic transmission and imported cases, China still has an incentive to roll out a vaccine. However, introducing a vaccine prematurely comes with serious risks. Phase 3 trials require a large group of people, in part so that rarer side effects not discovered in earlier trials can be identified. Vaccinating hundreds of thousands of people before phase 3 trials conclude means those people could be harmed by any of these potential side effects. The World Health Organization recently emphasized that phase 3 trials are essential to evaluate the safety and efficacy of Covid-19 vaccine candidates.
“One needs to carefully conduct clinical trials of adequate size with adequate time for follow-up, look at both efficacy and safety, and those data have to be very carefully reviewed before you start giving the vaccine to people outside of a carefully designed clinical trial,” said Daniel Salmon, director of the Institute for Vaccine Safety at Johns Hopkins.
So far, Sinopharm reports that no one who has received its vaccines through the emergency program has experienced obvious adverse effects, and none have been infected with Covid-19. Interim results from the company’s phase 1 and 2 trials of the vaccine developed by subsidiary Wuhan Institute of Biological Products showed low rates of adverse effects. Sinopharm has yet to publish results from the phase 1 and 2 trials of its other vaccine, developed by the Beijing Institute of Biological Products.
Sinovac hasn’t published a peer-reviewed study of its phase 1 and 2 data, either, but it reported no severe side effects in those trials, and the company’s CEO told Reuters that the rate of adverse reaction has so far been very low across all the inoculated people.
When China first began allowing workers traveling overseas to get vaccinated, a couple of Chinese academics and a pharmaceutical executive expressed concerns about the practicality and ethics of the decision, as reported by the New York Times. But Huang said he hasn’t seen explicit criticism of the emergency use program from Chinese scientists.
Will Chinese vaccine makers be held accountable if safety issues with the Covid-19 vaccines arise?
The recent history of Sinopharm and Sinovac raises questions about their ability to produce safe vaccines. In 2018, the Wuhan Institute of Biological Products — the subsidiary company of Sinopharm Group that is developing one of its vaccines — was found to have sold more than 400,000 faulty diphtheria, whooping cough, and tetanus vaccines in two Chinese provinces.
The company was fined and nine employees were punished. Production at their factories restarted later that year following inspections, and China’s National Institutes for Food and Drug Control pledged to redouble supervision of the vaccine industry.
Sinovac also has a checkered past. The company was charged with bribing a Chinese official in charge of drug approval from 2002 to 2014, the New York Times reported.
Huang said this history does “not bode well for the quality of the Covid vaccines,” especially in the “rush to develop a vaccine without even following the typical protocols.”
China’s chokehold on the media may also inhibit accountability for any issues with the emergency use program. Huang pointed to the government’s strict media censorship, which could block reports about side effects or bad reactions to the vaccine.
China’s vaccine program is proceeding on two separate tracks
More Chinese people will likely be eligible for the emergency use program in the coming months, per Zheng Zhongwei’s CCTV interview. “In order to prevent the disease spread in the fall and winter, we are considering a moderate expansion in the program,” Zheng said. “The purpose would be to first build an immunity barrier among special groups in the population.”
Airline industry workers in China have already been notified that they will soon be given the vaccine on a voluntary basis, Reuters reported last week.
China’s vaccine development has been a source of national pride on social media, Seton Hall’s Huang said, and deals for Chinese vaccine shipments are already being offered to China’s allies. But if “there [are] reports suggesting that the vaccine is not effective, or could cause severe or adverse reactions,” Huang said, “that is going to tarnish the reputation of the Chinese vaccines.”
Lili Pike is a science, health, and environmental reporting (SHERP) master’s student at NYU and a freelance journalist with a focus on China.