HONG KONG – India’s conditional approval on Jan. 3 of a COVID-19 vaccine developed domestically by Bharat Biotech International Ltd. but still in phase III trials has sparked concerns about its safety. The Drugs Controller General of India (DCGI) gave emergency authorization to the product, Covaxin, along with the Astrazeneca plc and Oxford University vaccine Covishield. The DCGI said the conditional approval granting “restricted use in emergency situation” for Covaxin was done in “clinical trial mode” to account for the fact that the shot is still being tested. But the rush to approve it has created controversy and confusion.

“We are extremely alarmed and shocked because it signifies the grant of regulatory approval without any efficacy data,” Malini Aisola, co-convener of the All India Drug Action Network, told BioWorld. While the phase III trials remain underway, it is too early for data to meet the criterion for an interim analysis, she said.

The only human data available on safety and immunogenicity of Covaxin so far is on 755 participants in the phase I and II trials, she noted. Moving ahead with the product’s use now amounts “to rolling out an untested and unproven vaccine to the public, which raises concerns. Moreover, it's a violation of the criteria in the draft regulatory guidelines for development of COVID-19 vaccines published by CDSCO on Sept. 21, 2020,” she said.

Clinical trial mode

Aisola is not the only one who has expressed concerns about whether the rollout may be premature.

“Covaxin has a nicely laid out trial plan. But the licensure has come before the studies have been completed, essentially approving a vaccine without the final clinical efficacy data. That I do not understand,” Gagandeep Kang, vice-chair on the board of the Coalition for Epidemic Preparedness Innovations and a professor in the Department of Gastrointestinal Sciences at the Christian Medical College in India, told BioWorld.

Kang was also confused by the “clinical trial mode” aspect of the Covaxin approval, which she says has not been seen before. According to India’s Minister of Health and Family Welfare, Science and Technology, and Earth Sciences, this condition means that all recipients of Bharat Biotech’s vaccine would be track and monitored as if they are in a trial.

“I’m not sure what this ‘clinical trial mode’ means. Does this mean that the government will be backing a study or is it permission for a company to do a clinical trial? If it’s the latter, why isn’t it just trial approval for a single-arm study then?” said Kang.

Aisola has similar concerns. “We would like to know if the individuals who get vaccinated will get detailed information about the vaccine candidate, such as the lack of efficacy data for the vaccine and that it is still in phase III, if informed consent will be taken and if the vaccinated individuals would get the benefit of provisions in the law that apply to clinical trial participants such as compensation for adverse events, ethics committee oversight, etc.,” she said.

Even Bharat Biotech appears to be in the dark about what the approval actually means. Bharat’s Chairman and Managing Director Krishna Ella asked reporters during a virtual press conference Monday to give the company “some time to understand the whole thing”.

Ella did say that the approval in clinical trial mode means that the company will not need a placebo but “it is open label, where we keep vaccinating people.” He also underscored the fact that the company has deep experience producing vaccines that are distributed to 123 countries and asked for “one week’s time” to distribute data.

Even with the lack of data available for Bharat Biotech’s candidate, the DCGI Venugopal Somani has said that both approved vaccines are “110% safe.”

Covaxin is an inactivated two dose SARS-CoV2 vaccine, manufactured in a Vero cell manufacturing platform. Bharat says the platform has a track record of more than 300 million doses. The company makes its monovalent vaccines for rotavirus gastroenteritis, Rotavac and Rotavac 5D, on a similar Vero cell platform.

Extending trust

Despite the scepticism and confusion, Covaxin and the government’s decision do have some supporters.

“If the manufacturers have confidence to produce and invest in millions in inventory, we too should trust them,” Rajiv Nath, the managing director of Hindustan Syringes & Medical Devices and forum coordinator of the Association of Indian Medical Device Industry, told BioWorld.

“The manufacturers and regulatory experts have the raw data on the phase III trial so far and, based on this, have decided to give a limited restricted usage approval with strict individual monitoring controls as would be under a clinical trial. Considering the pandemic situation, the government of India and its regulatory body, in its discretionary wisdom, has taken this decision or could have waited till March or April for full closure of the clinical trial report with more evidence of efficacy data,” he said.