The World Health Organization (WHO) has raised unspecified concerns about the manufacture of Covaxin, one of India’s home-grown COVID-19 vaccines. On April 2, the WHO said it found problems during a March inspection of the manufacturing facilities of Bharat Biotech, the maker of the vaccine. The WHO has not disclosed the nature of the problems at the Hyderabad facility in Telangana state. But it said Bharat Biotech had agreed to halt exports of Covaxin and “develop a corrective and preventive action plan.”
The WHO decision means UN procurement agencies like UNICEF countries can no longer supply the vaccine. The agency has also asked countries that have approved Covaxin to switch to other products. However, it is unclear how widely the vaccine will be used outside of India.
in the a Twitter statement posted a day before the WHO announcement, Bharat mentioned the WHO inspection but not the problems found. It announced a “temporary slowdown” in Covaxin production due to falling demand and said the company would focus on maintenance and “process and facility optimization activities.” A spokesman for Bharat Biotech tells science The company will continue to sell the vaccine in India, its largest market, where some 309 million Covaxin doses have already been managed. For some scientists, this raises questions about the oversight of vaccine production by India’s Central Drugs Standard Control Organization (CDSCO).
Covaxin is an inactivated vaccine; Its main component is killed SARS-CoV-2 particles. CDSCO granted him an expedited permit – India’s version of an emergency permit – in January 2021. before Bharat Biotech had efficacy estimates from its phase 3 trial, leading some academics to accuse the Indian government of having lax regulatory standards. A phase 3 study published in July 2021 showed that Covaxin had 77.8% efficacy in preventing symptomatic COVID-19, comparable to several vaccines approved in the United States and Europe.
Covaxin had previously encountered difficulties: After an inspection in March 2021, the Brazilian health authority (ANVISA) said it found several violations of good manufacturing practices (GMPs) – an umbrella term for measures that manufacturers must take to ensure safety, effectiveness and quality in the company’s factory. Bharat Biotech has not validated its method of inactivating SARS-CoV-2, ANVISA said, raising the possibility that the shot contained live virus and had not assured the vaccine’s sterility and efficacy. In response, Brazil temporarily suspended a plan to import 20 million doses of Covaxin; The deal fell through completely in July 2021 amid allegations of corruption and procurement irregularities.
According to a WHO spokesman, ANVISA later told the agency that Bharat Biotech had addressed the deficiencies, and in November 2021, the WHO awarded the vaccine an emergency list. Listing is a requirement for a vaccine to be made available through the COVID-19 Vaccines Global Access Facility, an effort by WHO and two other organizations to provide doses to low- and middle-income countries, and an approval stamp to help member countries decide which vaccines to use.
But when WHO inspectors visited the plant between March 14 and 21, they found several GMP deficiencies, some of which overlapped with those identified by ANVISA, according to the spokesman. The company had changed its manufacturing process after its listing, but did not communicate those changes to the CDSCO and WHO for evaluation and validation.
Hans Meerburg, a vaccine quality consultant based in the Netherlands, says manufacturers are required to notify drug regulators of any major post-approval changes because they may affect the safety, efficacy or quality of the vaccine. “If not, the product may not meet specifications, such as B. the effectiveness or the lack of active ingredients,” says Meerburg. Bharat Biotech did not respond to a question from science why it failed to submit the information.
The WHO spokesman said a preliminary risk assessment by Bharat Biotech found no indication that the benefit-risk balance of the vaccine has been altered. “The data available to the WHO shows that the vaccine is effective and there are no safety concerns,” the agency says in its Statement of April 2nd. Still, according to the spokesman, the WHO advises countries not to use the remaining doses of Covaxin.
Ocugen, Bharat Biotech’s US partner, has temporarily stopped taking it in its phase 2/3 trial in the US, as it “evaluates” the WHO statement.
For many low- and middle-income countries, Covaxin has been an easy injection to use because, unlike messenger RNA vaccines, it does not need to be stored at very low temperatures. However, a spokesman for Bharat Biotech says the WHO’s decision will have little impact outside of India as the company currently has no agreements with UN procurement agencies. The spokesman also said that Bharat Biotech stopped selling Covaxin directly to many of the 25 countries that have approved it under emergency licenses in April 2021 in India paused vaccine exports because it was battling a massive COVID-19 wave.
CDSCO has not commented on the WHO ruling. For some experts, his silence suggests that the Indian regulator is not enforcing the same quality standards as the WHO. “It worries me that CDSCO, the custodian of public health as India’s national medicines agency, has not yet issued any statements on the matter,” said Jayanthi Vuppala, an independent GMP expert based in Hyderabad. CDSCO did not respond to a question from science why it hadn’t asked Bharat Biotech to stop local sales as well.
The discrepancy between CDSCO and WHO responses needs to be addressed because it creates confusion and could fuel vaccine hesitancy, says Prashant Yadav, an expert on pharmaceutical supply chains at the Center for Global Development, a Washington, DC-based think tank. “We need more convergence of on-site inspections by WHO and national regulators,” says Yadav. “This is an important agenda…both for Indian industry’s export credibility and for protecting the health of Indian people.”