What Exactly is a Backup Vaccine? Five Questions About Covaxin Nod

Covaxin approval: Several questions are being asked about the efficacy of the vaccine and a rush to approve it.

(Photo: The Quint)

Covaxin's approval should have been a moment of great pride, after all it is backed by the biggest names in the scientific community in India – including the Indian Council of Medical Research (ICMR) and National Institute of Virology (NIV). Instead, the approval has raised more serious questions about the vaccine’s efficacy and the way the permissions have been pushed through.

Covaxin may well prove to be India’s robust response to a raging pandemic, but why the hurry?

What Studies/Data Led the SEC to Recommend Covaxin?

Where’s the data? And why is it not shared in public? These are some of the questions experts are asking, and asking legitimately.

The DCGI said that the Subject Expert Committee (SEC) of the CDSCO relied on safety and immunogenicity data submitted by Bharat Biotech in various animal species such as mice, rats, rabbits, Syrian hamster, and also conducted challenge studies on non-human primates (Rhesus macaques) and hamsters.

They also relied on Phase I and Phase II clinical trials that were conducted in around 800 subjects. All this data presumably demonstrated that the vaccine is safe and provides a robust immune response.

Bharat Biotech has shared this data publicly only in pre prints, with no peer review conducted.

There’s a bigger problem. None of the above data is enough to indicate efficacy of a vaccine that can only be established via larger phase 3 trials. Bharat Biotech is still recruiting for phase 3 trials of Covaxin, that are ongoing.

Speaking with The Quint, Prof Shahid Jameel, virologist and director of Trivedi School of BioSciences, Ashoka University, says, “The two key requirements for approval of any vaccine are safety and efficacy in a population. Phase 3 trials are designed to be representative of the population. Even though inactivated viral vaccines have a long track record of being safe and efficacious, technically that is not yet proven for Covaxin. As an outsider, it is hard for me to say what weighed on the minds of SEC members and DCGI to grant this EUA.”

Dr Jameel warns that clear and effective communication would be required to mitigate growing vaccine hesitancy in India. Especially in light of this approval.

If Efficacy and Safety is Not Established, Why a Rush to Approve Vaccine?

The exact text of the DCGI approval is long and convoluted, and some experts say they just don’t know what it means.

This is how the approval reads, “grant of permission for restricted use in emergency situation in public interest as an abundant precaution, in clinical trial mode, to have more options for vaccinations, especially in case of infection by mutant strains.”

Complicated much? Dr Gagandeep Kang, a leading virologist and vice chair, CEPI, in an interview to Times of India, summed up what a lot of scientists are really thinking, "I am completely confused. I have no clue."

The more simple question is this: If phase 3 trials are the only way to establish efficacy, why not just wait for the trials to get over, collect the data, establish efficacy and then give proper legible approvals?

Bharat Biotech has struggled to recruit volunteers. After weeks of challenges, the firm said that they've recruited 22,500 of the 26,000 volunteers required.

While Covishield’s bridge trials are also still ongoing in India, they've submitted data from global trials that indicate 70.4 percent efficacy of the vaccine.

Both Moderna and Pfizer were granted EUA only once they had met all criteria, with phase 3 trials showing efficacies around 95 percent.

What Exactly is a Backup Vaccine?

In an interview with The Quint, Dr Randeep Guleria, director, AIIMS, said Covaxin’s approval was a backup vaccine in case of a virus surge. Covishield will remain India’s go-to vaccine till Bharat Biotech completes phase 3 trials and proves efficacy.

Dr Balram Bhargava, chairperson for ICMR, gave a similar defence.

A day after outpouring criticism, Bharat Biotech Founder Dr Krishna Ella on Monday, 4 January, strongly defended Covaxin’s emergency use authorisation approval, saying, “It’s a vaccine. It’s not a backup.” He further rubbished the term, urging “people to be responsible before making such statements.”

But to Dr Bhargava, Dr Guleria and the Health Minister, our question is simple. What is a backup vaccine? Either the vaccine is efficacious or it isn’t. And if its efficacy is under question, presumably because of which it remains a backup, why would you deploy it during a surge?

Would it not defeat the purpose? Isn’t it prudent to give vaccines to avoid a possible surge, and not wade in with inconclusive vaccine when people’s lives are at risk?

Adar Poonawalla, CEO of Serum Institute, the manufacturer of Covishield in India, said in an NDTV interview, “There are only three vaccines in the world that have proven efficacy... it's Pfizer, Moderna and Oxford-AstraZeneca, these are the only three vaccines which have been proven to work. Everything else has been proven to be safe, just like water. But the efficacy to know how well a vaccine works, 70 percent, 90 percent, 80 percent, has only been proven in these three vaccines.”

From all indications Covaxin will prove to be a robust vaccine against the novel coronavirus, but so far it’s safe not efficacious.

What Does 'Clinical Trial Mode' Really Mean?

Dr Harsh Vardhan, Union Health Minister, said that we should ignore the rumours, and the approval for Covaxin was in 'clinical trial mode.' All those who receive the vaccine will be tracked, their data collected and if there is an adverse event, they will be treated by the government.

But here's a question. The clinical trials are already ongoing. Nearly 22,500 volunteers have received the first jab. These trials are happening under a robust clinical trial design that is double blind and randomised. Science is being followed, with all safety precautions in place.

Why experiment on the public? Why not just wait a month or two?

How Do We Know it Works Better on UK Mutant Variant or other Mutations?

We don't. Even though the UK variant and a possible surge because of the UK variant, is being used to defend the approval. Read the words again, "public interest as an abundant precaution... especially in case of infection by mutant strains."

Both Dr Guleria and Dr Bhargava said that inactivated vaccines are known to work well on mutant strains. Bharat Biotech Chairman and Managing Director Krishna Ella had also said that the protein components of inactive Covaxin will take care of mutations.

But we just don't have any data, any study to back this claim.

Again, Covaxin may well work against the UK variant, we just don't know yet. And to rush approvals based on conjecture is not scientific.