India Approves 2 Vaccines For ‘Restricted Emergency Use’ Ahead of Phase 3 Trial Data
Medicines & Vaccines 04/01/2021 •
Dr VG Somani, Drugs Controller General of India (DCGI), has said that two COVID vaccines have been approved for emergency use. He refused to take questions from the press following the announcement, however.

Delhi – India’s chief drug regulator approved two COVID-19 vaccines for “restricted emergency use” in the country on Sunday, opening the doors for a mass vaccination campaign against COVID to begin in one of the world’s largest countries, and a lower middle-income country at that.

However, some watchdog groups said that the review process leading up to the government’s approval had lacked transparency – and in the case case of one locally-developed vaccine, Phase 3 trials had not been completed.

The approved vaccines include the AstraZeneca-Oxford vaccine, to be manufactured at large scale in India by the Serum Institute, and an indigenous vaccine developed by India’s Council for Medical Research, and to be produced by the Hyderabad company Bharat Biotech.

While the AstraZeneca vaccine was also approved last week in the United Kingdom, Indian government approval of the Bharat Biotech vaccine came before Phase 3 trials had even been completed, prompting criticism over a lack of efficacy data.  The fact that Bharat Biotech has not completed its Phase 3 trials, means that India will now join the ranks of China and Russia as the only countries to have approved vaccines without Phase 3 clinical trial data.

The Drugs Controller General of India (DCGI), Dr VG Somani, said that the drug regulatory body approved the vaccines after “adequate examination”. Approval of the two vaccines was recommended by an expert committee of doctors who examined data from the clinical trials.

The Indian government plans to first immunise 30 million healthcare workers. In this first phase, the government also plans to immunise about 270 million people above the age of 50, and those younger with comorbidities. The vaccine will be given free of cost as promised by India’s Health Minister, Dr Harsh Vardhan.

While the Serum Institute vaccine was granted permission for restricted use in emergency situations “subject to certain regulatory conditions”, the Bharat Biotech vaccine was approved “as abundant precaution, in clinical trial mode.” The Bharat Biotech vaccine was developed the Indian Council for Medical Research, a government research body.

No Phase 3 Trial Data

While the AstraZeneca approval relied upon Phase 3 data gathered abroad, India’s Serum Institute has not yet submitted complete data from the AstraZeneca trials being conducted in India, critics also said. Scientists and other experts questioned the meaning of the approval of the Bharat Biotech vaccine while still in “clinical trial mode”. They warned that a hasty approval process could stoke vaccine hesitancy or even fuel anti-vaccine sentiments.

Phase 3 trials are usually double-blinded, with one arm of the trial participants receiving the vaccine, and the other arm getting a placebo. In case of the COVID-19 vaccine trials, the two arms are compared to see which group had participants that did not suffer from COVID-19. The extent of protection provided in the vaccine group determines its efficacy.

In terms of the AstraZeneca vaccine, the DCGI relied on the safety, efficacy and immunogenicity (the ability to induce immune responses) data generated on 23,745 adult participants from the UK and Brazil which showed vaccine efficacy of 70.42%, the govenrment statement said. The efficacy results were published in The Lancet earlier in December. The Serum Institute in India is still conducting a bridge trial with 1,600 participants in India.

In case of the Bharat Biotech vaccine, the company’s founder Krishna Ella said in a press conference on Monday that the company will be able to submit phase 3 trial data by March 2021.  Under the government authorization, members of the public being administered the vaccine will be tracked and monitored as if they are in a trial. However, critics said that ethically, that could be problematic, insofar as a placebo arm for the trial could not realistically be maintained:

“Once the vaccine has been authorised, it’s unethical to continue Phase 3 and give placebo to participants. You cannot continue clinical trials,” said Dr Amar Jesani, an independent researcher and bioethicist pointed out.

According to the DCGI, Bharat Biotech’s Phase 3 trial has already recruited 22,500 participants so far and was “found to be safe” – although it provided no further details. Other media reports, meanwhile, contradicted that statement, saying that not enough volunteers had even been registered for Phase 3 trials of the vaccine.

The controversy quickly took on political tones as some leaders from opposition parties also questioned the local vaccine’s approval ahead of the completion of Phase 3 trials.

An Indian government official retorted meanwhile, that the opposition’s comments were “disgraceful” and an attempt to politicise the vaccine approvals.

Opaque Approval Process – Indian Watchdog Group Calls for Vaccine Transparency

AstraZeneca’s India trial has already been a subject of controversy.  In October 2020, a trial participant from Chennai, in southern India, sent a legal notice to Serum Institute seeking Rs 5 crores (or approximately US$ 684,000) as compensation, claiming he had suffered serious neurological impairment following one dose of the vaccine.

Serum Institute threatened to counter-sue the trial participant calling the allegations in the notice “malicious and misconceived”, and it was subsequently reported that the adverse event was not vaccine-related.

Dr Jesani flagged that while the trial stopped after a serious adverse event was reported in the UK, the same did not happen in India. That and other issues related to a reproted lack of transparency have stirred debates in the media about about the way in which the local arm of the AstraZeneca trial was conducted and monitored.

And while the US Food and Drug Administration (FDA) live-streamed the 8 hour proceedings that led to the emergency authorization of the Pfizer-BioNTech vaccine, the process in India has been comparatively opaque. The government has provided no criteria by which the vaccines were reviewed. Only a few lines of text described the meeting held to approve the vaccines.

Although DCGI Dr Somani’s statement was published live, he also refused to take any questions from the press.

The All India Drug Action Network (AIDAN), a public health watchdog, demanded that authorities provide more information on the process that had led to the clearances of the two vaccines for restricted emergency use.

“We are baffled to understand what scientific logic has motivated the top experts in the SEC to approve this vaccine posthaste,” it said in a statement.

The statement further demanded the drug controller clarify the legal provisions under which the two vaccines were approved, and asked the regulator to share the “detailed rationale for the decision along with disclosure of the data, evidence and information” reviewed by the expert panel and drug controller.

“There is a stronger case for transparency in the pandemic because of the accelerated process of vaccine regulatory approval. Globally a norm has set in with vaccine companies sharing trial data even through publications and pre-prints in the interest of public disclosure. We have unfortunately not made enough progress in India on the transparency front,” said Malini Aisola, co-convenor of AlDAN.

Image Credits: Flickr – Trinity Care Foundation.

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