The World Health Organization (WHO) has raised unspecified concerns over the manufacture of Covaxin, one of India’s COVID-19 vaccines. On April 2, the WHO said it found problems during a March inspection of the production facilities of Bharat Biotech, the producer of the vaccine. The WHO did not reveal the nature of the problems at the factory, located in Hyderabad, Telangana state. But he said Bharat Biotech had agreed to halt Covaxin exports and was “developing a corrective and preventive action plan”.

The WHO decision means that UN procurement agencies such as UNICEF can no longer provide the vaccine to countries. The agency has also asked countries that have licensed Covaxin to switch to other products. However, the extent of the vaccine’s use outside India is unclear.

In a statement on Twitter posted 1 day before the WHO announcement, Bharat mentioned the WHO inspection, but not the issues identified. He announced a “temporary slowdown” in Covaxin production due to lower demand and said the company would focus on maintenance and “process and plant optimization activities”. A Bharat Biotech spokesperson recounts Science the company will continue to sell the vaccine in India, its largest market, where some 309 million doses of Covaxin have already been administered. For some scientists, this raises questions about the oversight of vaccine production by India’s drugs regulator, the Central Drugs Standard Control Organization (CDSCO).

Covaxin is an inactivated vaccine; its main ingredient is killed SARS-CoV-2 particles. CDSCO gave it expedited approval — India’s version of an emergency use authorization — in January 2021, before Bharat Biotech had efficacy estimates from its Phase 3 trial, which led some scientists to accuse the Indian government of lax regulatory standards. A phase 3 trial published in July 2021 showed Covaxin to be 77.8% effective in preventing symptomatic COVID-19, comparable to several vaccines approved in the United States and Europe.

Covaxin has run into problems before: following an inspection in March 2021, the Brazilian Health Regulatory Agency (ANVISA) said it found several violations of Good Manufacturing Practices (GMP) – an umbrella term for steps that manufacturers must take to ensure safety, efficiency and quality — at the company’s plant. Bharat Biotech has not validated its method for inactivating SARS-CoV-2, ANVISA said, raising the possibility that the vaccine contains live virus, and has not ensured the sterility and potency of the vaccine. 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 irregularities in public procurement.

According to a WHO spokesperson, ANVISA later told the agency that Bharat Biotech had corrected the shortcomings, and in November 2021 the WHO assigned the vaccine an emergency use list. Listing is a prerequisite for a vaccine to be provided through the Global COVID-19 Vaccine Access Mechanism, an effort by WHO and two other organizations to provide doses to low- and low-income countries. intermediary, and a seal of approval that helps member countries decide which vaccines to deploy.

But when WHO inspectors visited the factory between March 14 and 21, they found several GMP deficiencies, some of which overlapped with those identified by ANVISA, according to the spokesperson. The company had changed its manufacturing process after listing but had not communicated these changes to 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 changes after approval, as they may impact safety, l efficacy or quality of the vaccine. “Otherwise, the product may not meet specifications, such as potency or no active ingredient,” Meerburg says. Bharat Biotech did not respond to a question from Science why he failed to provide the information.

The WHO spokesperson said a preliminary risk assessment by Bharat Biotech showed no indication that the risk-benefit ratio of the vaccine had changed. “Data, available to WHO, indicate that the vaccine is effective and there are no safety concerns,” the agency said in its April 2 statement. Still, the spokesperson says, WHO advises countries not to use leftover doses of Covaxin.

Ocugen, Bharat Biotech’s US partner, has temporarily suspended dosing in its Phase 2/3 trial in the US as it “evaluates” the WHO statement.

For many low- and middle-income countries, Covaxin was an easy-to-deploy vaccine because, unlike messenger RNA vaccines, it does not require ultra-low temperature storage. But a spokesperson for Bharat Biotech says the WHO decision will have little impact outside India as the company currently has no agreement with UN procurement agencies. The spokesperson also said that Bharat Biotech stopped selling Covaxin directly to many of the 25 countries that authorized it under emergency licenses when, in April 2021, India suspended vaccine exports because that she was battling a massive wave of COVID-19.

The CDSCO remained silent on the WHO verdict. For some experts, his silence suggests that the Indian regulator does not apply the same quality standards as the WHO. “It worries me that CDSCO, the guardian of public health as India’s national medicines regulator, has yet to issue any statement on this matter,” said Jayanthi Vuppala, an independent GMP expert based in Hyderabad. CDSCO did not respond to a question from Science why he didn’t ask Bharat Biotech to stop local sales as well.

The discrepancy between CDSCO and WHO responses needs to be addressed as it creates confusion and could foster vaccine hesitancy, says Prashant Yadav, a pharmaceutical supply chain expert at the Center for Global Development, a group think tank based in Washington, DC. convergence on site inspections by WHO and national regulatory authorities,” says Yadav. “This is an important program…both for the export credibility of Indian industry and for the protection of the health of the Indian people.”