n mid-July, Changchun Changsheng Bio-tech Co of Northeast China’s Jilin Province, a major vaccine producer listed on the Shenzhen Stock Exchange, came under fire after investigators found it had forged records for human rabies vaccines and supplied ineffective DPT (diphtheria, whooping cough and tetanus) vaccines to the domestic market – vaccines used as part of the nationwide mandatory inoculation of babies and children.
A public outcry followed the revelations, which went viral on social media and once again placed the dubious safety of vaccines throughout China in the spotlight. Both Chinese President Xi Jinping and Premier Li Keqiang expressed concern over the issue, urged regulators to investigate and said the truth should be disclosed in a timely manner and the perpetrators punished “severely.”
Shortly after, the police bureau in Changchun, Jilin, launched an investigation that resulted in numerous arrests of top company officials. Then another major vaccine producer, Wuhan Institute of Biological Products Co Ltd was also found to have produced substandard DPT vaccines.
It was not a routine inspection but a tip-off from an ex-Changsheng employee that revealed irregularities in the company’s vaccine production, prompting China’s drug watchdog, the State Drug Administration (SDA), to carry out a spot check on July 15th. The inspection found the company had fabricated production records for freeze-dried rabies vaccines for human use, the SDA said. Since the process used to make rabies vaccines violated manufacturing standards, the SDA revoked Changsheng’s Good Manufacturing Practice (GMP) license to produce the vaccine.
The company has since been under investigation by the China Securities Regulatory Commission for violating rules and for irregularities in information disclosure. Under pressure, Changsheng recalled its rabies vaccines and apologized to the public for the incident, telling investors that it might be delisted. Changsheng’s stock price plummeted by more than half its value since mid-July.
The issue escalated when a few days later, the public learned that the SDA’s sampling inspections in October 2017 had also found a batch of DPT vaccines produced by Changsheng did not meet potency standards, and production was suspended. It was only on July 20 that the Jilin Food and Drug Administration finally fined Changsheng 3.44 million yuan (US$ 0.5m) for its misconduct. Evidence of the production records, their whereabouts and whether these substandard vaccines had been recalled was still unclear.
The SDA announced on July 22 that 252,600 doses of Changsheng’s ineffective DPT vaccines – which inoculate children against diphtheria, whooping cough and tetanus – were all sold to China’s eastern province of Shandong. According to SDA experts, the substandard DPT vaccine could make people more vulnerable to the diseases, but it was unlikely to directly threaten people’s health.
According to the latest press release from Shandong Provincial Center for Disease Control and Prevention, a total of 215,184 children in eight cities inside Shandong had been given the substandard DPT vaccines. The SDA said a plan to reinoculate those affected children was worked out in February this year. However, this was not publicly released.
Changsheng chairwoman and majority shareholder Gao Junfang did not answer repeated calls from NewsChina on July 23. Around 11am a police car was seen driving into the company. An employee in the Changsheng sales department told NewsChina a vaccine recall had been undertaken to meet the drug authority’s investigation. “The authorities required a recall of all of Changsheng’s vaccine products after the recent event, not just the problematic ones,” the source said.
“Once the GMP certificate was revoked, the company could no longer conduct any production or sales activities,” said Zhao Nan, a health columnist with five years’ experience in the vaccine industry.“The company was ordered to recall all its products for testing, and even if they were found to be up to standard, they had to be destroyed.”
The vaccine scandal fueled widespread public anger, particularly after the previous DPT case was disclosed. The nine-month gap between the drug authority’s investigation into the sale of a quarter of a million doses of vaccine and the public being told about it was a source of particular ire. Furthermore, Changsheng failed to mention it in its 2017 annual report.
After the disclosure, another ineffective batch of DPT vaccines surfaced – this one from Wuhan Institute of Biological Products Co Ltd in Hubei Province – which was discovered in November 2017. According to the SDA, spot checks in November 2017 found that due to a temporary failure of the packaging equipment, 400,520 doses produced by the company failed to meet quality standards.
These recent disclosures were interpreted by the public as more examples of fabricated vaccines, which have been a long-running issue in China. There were calls on Weibo, China’s twitter equivalent, to boycott domestic vaccines.
Industry insiders were concerned about whether the final investigation would give the public, and in particular the children who had taken substandard vaccines, a clear explanation. “From a scientific perspective, it needs to be clarified whether the vaccines were effective–and whether re-inoculation was required, and if so by how many doses,” said Tao Lina, an industry insider and vaccine expert.
According to the China Securities Journal, a paper, the Changsheng spot check conducted by the State drug regulator in 2017 was the result of a tip-off from a company employee who reported that there were problems with substandard containers during the vaccine cell fermenting process. Wang Yuedan from Peking University Health Science Center told NewsChina: “Once the container standard is changed, the conditions for culturing cells are changed, and the amount of antigen might not meet the standard.” SDA staff did not respond to detailed questions from NewsChina, only saying, “the investigation is on-going and yet to be announced officially.”
Mao Qun’an, the National Health Commission’s disease control chief, said on July 17 that those who had not yet finished taking the whole course of Changsheng rabies vaccines could choose a rabies vaccine from another company instead. But for those who have taken the whole course, no authority could give advice on what to do.
“The greatest fear is that there will be public distrust of vaccines in general,” Zhao added. It was important that people did not blame vaccines themselves, which are extremely important to preventing the spread of disease. “However, the scandal and fermenting public fury towards it may result in serious distrust of the domestic immunization program, and if people start to shun vaccinations the consequences could be disastrous.”
In a statement on August 3, the World Health Organization’s (WHO) China office expressed concern over improper practices by Chinese vaccine manufacturers and encouraged Chinese citizens to“consider this event in the context of the importance of immunization as a public health intervention, and the achievements over several decades of China’s successful, life-saving immunization program.”
“There are many Chinese people alive today who would not be, if not for immunization. While the events at Changchun Changsheng Life Sciences Ltd should never have happened, the fact that the anomalies [of the DPT vaccine] were detected by the regulators–and responded to quickly and robustly once so – shows that the regulatory authority’s system of checks and balances to protect population health is working,” added the WHO in the statement, which did not mention the fact that a whistleblower had revealed the anomalies with the rabies vaccine.
Part of a Pattern
Inside China, private drug companies have boomed and since the GMP certificates began being promoted by the State drug regulator, domestic drug companies have started to go global. Before 2005, imported vaccines dominated the Chinese market. It was in 2006 that Liaoning Chengda Biotechnology Co., Ltd became the first domestic producer for rabies vaccines for human use. The authorities adopted compulsory tests and rectification processes for each batch of vaccine that entered the market.
Despite the regulations, numerous scandals over fake vaccines have erupted since then. In late 2016, a case of fake rabies vaccines in Heilongjiang Province was uncovered. In February 2009, 11 batches of freeze-dried rabies vaccines for human use produced in 2008 by Liaoning Dalian Jingang Andi Biotech Co Ltd were found by the authorities to have illegal additives of nucleic acid, a material which could enhance the vaccine’s potency if the effective content of the vaccine is lower than the standards. According to Tao Lina, adding nucleic acid, a practice not approved in China, could lower production costs by one-third. In December 2009, a total of seven batches of more than 210,000 doses of rabies vaccine for human use by Jiangsu Yanshen Biotech Co Ltd and Hebei Fuer Drug Co Ltd were found to not meet national potency standards. Later on, according to Jiangsu Provincial Food and Drug Administration and the local public security department, Jiangsu Yanshen had broken the law by using inferior materials, fabricating records, and evading supervision. Their substandard vaccine products were sold to more than 21 of China’s provinces.
These fabricated rabies vaccines claimed lives, like the five-year-old boy who was bitten by a dog in a rural village in Guangxi Zhuang Autonomous Region in December 2009. He died three weeks later, despite being administered a rabies vaccine at a local health center. Investigations revealed a total of 13 township level health centers and 20 village level health centers had purchased vaccines through illegal market channels. More than 1,000 doses of ineffective rabies vaccines were confiscated. Eight people were ultimately sentenced to prison.
In March 2016, police in Shandong Province discovered 22 types of illegal vaccines – including those for influenza, hepatitis B and rabies – with a market value of more than 570 million yuan (US$83.44 million), which were sent unrefrigerated to more than 20 provincial regions, including Anhui, Beijing and Fujian. Since then, the circulation of vaccines has gained the attention of regulators who have imposed stricter rules on local government procurement procedures, and improved monitoring of what is called the “cold chain” for vaccine transportation.
Experts interviewed by NewsChina claimed there was little difference between the quality of domestically produced vaccines and imports. According to the 2017 Annual Review of Biological Product Issuing in China, released by the National Institutes for Food and Drug Control, seven batches of rabies vaccines for human use failed to meet domestic standards, with one batch produced by a domestic company, and the rest imported from other countries. The report found “this indicates the issuing processes could effectively prohibit substandard vaccine products to enter the domestic market.”
“Addressing this recent vaccine scandal issue, the authorities should disclose the investigation results in a timely manner and punish any crimes,” sad Tao Lina, adding that the best way to rebuild trust was transparency and real action from the government.
Changsheng’s transgressions could date back as early as 2014. In August, investigators told the Xinhua News Agency the company began to violate rules on vaccine production and national drug standards as early as April of that year. In addition to the earlier disclosure, investigators found another substandard batch of 247,200 doses of DPT produced by Changsheng. On August 7, the SDA issued nationwide free re-inoculation procedures to local provincial governments for those who had taken half the course of Changsheng’s rabies vaccines – saying they could substitute the rest of the course with a different brand. As of August 9, there was no further information on the investigation or handling of the Changsheng executive personnel.
Then on August 16, a meeting of the Standing Committee of the Political Bureau of the Central Committee of the Communist Party of China presided over by President Xi Jinping heard reports of the investigation and announced punishments for the officials involved. Vice governor of Jilin Province, Jin Yuhui, who was responsible for the food and drug administration in the province, was removed from his post. In total, around 40 government officials, including seven at and above the provincial level, have been held accountable. Three senior officials were ordered to resign, including Bi Jingquan, head of the former State Food and Drug Administration, former Jilin vice governor Li Jinxiu, and Changchun Mayor Liu Changlong.
The National Health Commission also told the public it would arrange follow-up vaccinations for those who had received the substandard shots.