Explained: Why conditional approval for Bharat Biotech’s Covaxin is raising questions

The Drug Controller General of India (DCGI) on January 3 granted permission for restricted emergency use of the AstraZeneca-Oxford University and Bharat Biotech Covid-19 vaccines. The approval was based on the recommendations of the Subject Expert Committee (SEC), which reviewed the data on safety and immunogenicity of the two vaccines.

Approval of the Bharat Biotech Covid-19 vaccine Covaxin, which is still undergoing phase-3 clinical trials, has raised some questions. Bharat Biotech has developed Covaxin in collaboration with the Indian Council of Medical Research (ICMR) and National Institute of Virology (NIV), Pune, from where they received the virus seed strains.

What is the data that the SEC/regulator relied on for the Covaxin approval?
The DCGI said Bharat Biotech has generated safety and immunogenicity data in various animal species such as mice, rats, rabbits, Syrian hamsters, and also conducted challenge studies on non-human primates (Rhesus macaques).

The regulator added that the Phase I and Phase II clinical trials were conducted on approximately 800 subjects and the results have demonstrated that the vaccine is safe and provides a robust immune response. The Phase III efficacy trial was initiated in India on 25,800 volunteers and till date, 22,500 participants have been vaccinated across the country and the vaccine has been found to be safe as per the data available till date. To be sure, there is no clarity on whether there is data from phase-3 to meet the criteria for an interim analysis on the vaccine’s efficacy

What is the justification being made for the approval?
The DCGI said Covaxin was approved in public interest as an abundant precaution, in “clinical trial mode”, to have more options for vaccinations, especially in cases of infection by mutant strains. The clinical trial ongoing within the country by the firm will continue. Dr Harsh Vardhan, Minister of Health and Family Welfare, said the Covaxin approval is a “Monitored Approval” with strict follow-ups and a rolling review.

 What is “clinical trial mode”?The regulator has said that the approval is in “clinical trial mode” but there isn’t any clarity from the DCGI on this front. If an experimental vaccine is given to people, there should be informed consent explaining the potential risks and benefits of the vaccine, post-vaccination follow-up and in case there is any serious adverse reaction the recipient may become eligible for compensation. Oversight and ethics committees will also come into the picture. Dr Randeep Guleria, Director, All India Institute of Medical Sciences (AIIMS), told News18 that any person who develops side-effects after being administered Covaxin will be eligible for compensation. An official statement from the DCGI is needed to clear the air on this.

Does Covaxin provide protection against mutant SARS-CoV-2 strains?
The Indian Council of Medical Research (ICMR), which has collaborated with Bharat Biotech for the vaccine, said Covaxin has the potential to mount resistance against new mutants of SARS-CoV-2. The whole virion-inactivated vaccine, in theory, is likely to be effective against mutating strains compared to vaccines targeting spike proteins.

Bharat Biotech said Covaxin has shown long-term persistence of immune responses to multiple viral proteins, as opposed to only the spike protein, and has demonstrated a broad-spectrum neutralising capability with heterologous SARS-CoV2 strains, thus potentially reducing or eliminating escape mutants. No data has been shared by the regulator or the company to support this claim.