DCGI approval to Bharat Biotech’s Covaxin has experts divided: Here’s why

Days after the United Kingdom approved the Oxford University-AstraZeneca COVID-19 vaccine, the government of India has granted ‘restricted use in emergency situation’ approval to two COVID-19 vaccines in India. The Drugs Controller General of India (DCGI) Dr VG Somani announced on Sunday that the union government will permit the emergency usage of both the vaccines — Serum Institute’s Oxford vaccine ‘Covishield’ and Bharat Biotech’s ‘Covaxin’ — under certain conditions. 

In a press briefing on Sunday, the DCGI said that Serum Institute of India (SII) which developed the Covishield vaccine with a technology transfer from AstraZeneca-Oxford University, had submitted data on safety, immunogenicity and efficacy of the vaccine trial conducted on 23,745 participants in their overseas study. The DCGI added that the vaccine’s efficacy was found to be 70.42%. “Further, M/s Serum was granted permission to conduct Phase-II/III clinical trial on 1,600 participants within the country. The firm also submitted the interim safety and immunogenicity data generated from this trial and the data was found comparable with the data from the overseas clinical studies,” the statement said, adding that the ongoing clinical trials of the vaccine in India will continue.  

Similarly, the DCGI also granted permission for ‘restricted use in emergency situation’ to Covaxin, developed by Bharat Biotech, in collaboration with ICMR and NIV, Pune. The permission for this vaccine has been accorded in larger public interest in order to have more options for vaccinations, especially in case of infection by mutant strains of the coronavirus, the DCGI said. However, phase 3 trials of the vaccine are still underway.

“Phase I and Phase II clinical trials were conducted in 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 in 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,” the CDSCO statement said. 

What does ‘restricted use in emergency situation’ mean?

Dr Jacob John, a virologist and former professor at Christian Medical College, Vellore, told TNM that ‘Emergency Use Authorisation’ (EUA) is the permission given to officers to administer a product that is not licensed yet. “This unusual step is taken when the product is reasonably safe and the probability of clinical protective efficacy is high. The terms ‘restricted’ and ‘emergency’ denote nothing but EUA,” he said. Adding that the CDSCO has used a Subject Expert Committee (SEC) to evaluate the need for such approval at this point in time and the promise of safety and efficacy, Dr John said that vaccines with ‘restricted use in emergency situation’ approval will not be allowed to be sold by the company in the market. 

“That needs registration (licensure), which normally requires sufficient data through Phase 3 trial,” he explained. It essentially means that citizens cannot claim this vaccine as their right. 

While SII’s Covishield has been received approval for emergency use, Bharat Biotech’s Covaxin has been approved for emergency use in a ‘clinical trial mode.’

What is clinical trial mode?

Another issue that experts have noted that the country’s drug regulator’s approval to Covaxin is for a ‘clinical trial mode’ in the larger public interest, in order to have more options, now that mutant variants of the coronavirus have also emerged. As per Dr Randeep Guleria, the Director of the All India Institute of Medical Sciences (AIIMS), administering a vaccine on clinical trial mode means that the recipient will be treated at par with a clinical trial participant and all that applies to a volunteer in a clinical trial will apply to the recipient of the vaccine, like safety requirement, monitoring and compensation in case of an adverse reaction. 

Concerns around clinical trial data

While the news of DCGI approval for Covishield brought in cheers at large, the approval for Covaxin, developed indigenously, has raised eyebrows among experts in relation to the clinical trial data and the overall efficacy of the vaccine. 

According to reports, the Subject Expert Committee (SEC) of the Central Drug Standard Control Organisation (CDSCO) had requested Covaxin’s developers Bharat Biotech to submit the data of the clinical trials conducted with the vaccine and expedite the recruitment of volunteers for its third phase of trials. The company submitted interim efficacy data from the first two phases and the immunogenicity data that was published in a non-peer-reviewed journal. However, phase 3 trials are still going on, and Bharat Biotech is reportedly yet to submit any result or data of the third phase of its clinical trials. 

Dr Gagandeep Kang, who has spent 20 years researching and developing vaccines and 30 years in the study of infectious diseases, said in an interview to CNBC-TV18 that her first reaction on hearing the news on Sunday was of “utter confusion.” She was surprised that Covaxin was granted approval despite there being no public data available.

“My first reaction is one of utter confusion. I thought I knew the processes by which vaccines are generally approved and I can kind of understand the basis on which Covishield receiving emergency use authorisation. But I have absolutely no understanding of the data that informed the decision to give exactly the same approval for the Covaxin vaccine. Yesterday, we heard the report from the Subject Expert Committee, which seemed to distinguish between the two vaccines Covishield and Covaxin. And yet, today the media statement issued by DCGI treats both vaccines exactly the same and says that both of them are for use in emergency situations (sic),” she said, pointing out the contradictory stance taken by the SEC and the DCGI.  

She also pointed out that DCGI’s statement pictures Covaxin as a backup option against the mutant strain of the virus, on account of larger public interest. However, she added that there is no data to support the same. ”I am completely unaware of any data that states that Covaxin has any efficacy of any strain of SARS-CoV2, let alone special efficacy against the variant strain. This is hypothetical at best and in the absence of knowing whether a vaccine is efficacious against any SARS-CoV2 strain, I think it would be quite a stretch to say that it should work against the UK variant,” she explained. 

Anant Bhan, a global health researcher, told TNM that the lack of transparency around the approval provided to Covaxin is disturbing. "The main issue is of safety and immunogenicity. The understanding was that the approval even for emergency use would be based on either a foreign regulator giving permission and then the local bridging data being available or analysis of local efficacy data. The efficacy data of Covaxin is not public and the recruitment for trial subjects for Phase 3 has been going on in recent weeks," he explained. 

The conditions around this like be it the clinical trial mode or the regulatory monitoring are not very clear, he added. "I would have liked to see more data and transparency around this. We don't know who the SEC members are, we don't know on what basis they made these decisions, what were the questions asked and what were the responses provided etc. So that's what is the troubling element," he said, adding that it is important to ensure transparency and communication in the public interest. 

‘Generated excellent safety data,’ says Bharat Biotech

Meanwhile, Bharat Biotech in a statement said it has generated excellent safety data with robust immune responses to multiple viral proteins that persist and their goal is to provide global access to populations that need it the most.

“The approval of Covaxin for emergency use is a giant leap for innovation and novel product development in India,” Krishna Ella, Chairman and Managing Director of the Hyderabad-based pharmaceutical firm said in a statement. "While this vaccine addresses an unmet medical need during this pandemic, our goal is to provide global access to populations that need it the most. Covaxin has generated excellent safety data with robust immune responses to multiple viral proteins that persist," he said.

Covaxin has been evaluated in approximately 1,000 subjects in Phase I and Phase II clinical trials, with promising safety and immunogenicity results, with acceptance in international peer-reviewed scientific journals, Ella said.