On 3rd January 2021, Drug Controller General of India (DGCI)’s approval of two Covid vaccines for restrictive emergency usage in INDIA, has created a lot of controversary. The decision to approve Bharat Biotech Covid-19 vaccine (Covaxin), which is still undergoing phase-3 clinical trials, has raised serious questions, writes Dr Kafeel Khan.

As we entered into a new year with continuing coronavirus threat there was good news as on 3rd January, 2021. Drug Controller General of India (DGCI) approval of two vaccines for restrictive emergency usage in INDIA, spells hope in these dire times. The first one is Oxford-AstraZeneca’s Covishield which is produced in India by Serum Institute of India (SII) and the second one by Bharat Biotech in collaboration with the National Institute of Virology (NIV) and Indian Council of Medical Research (ICMR) Covaxin.

This comes after an expert panel of the drug regulator, the Subject Expert Committee (SEC) gave its recommendation on 1st January 2021, for the emergency use authorization (EUA). While Covishield developed in India with a master seed from Oxford-AstraZeneca’s, COVAXIN derived from a strain of SARS-CoV-2 virus, isolated at NIV, Pune, India. Both vaccines will be administered in two doses 3-12 weeks apart and can be transported and stored at normal refrigeration temperatures.

Approval of the Bharat Biotech Covid-19 vaccine Covaxin, which is still undergoing phase-3 clinical trials, has raised serious questions. The DCGI said Covaxin was approved in the 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.

Honorable Prime Minister Narendra Modi touted the approval as a “game-changer”.

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Dr. Harsh Vardhan, Minister of Health and Family Welfare, said the Covaxin approval is a “Monitored Approval” and that the “clinical trial mode” would mean that all vaccine recipients will be tracked as if they’re in a trial.

When asked what the “clinical trial mode” means, Gagandeep Kang, a microbiology professor at Christian Medical College, Vellore reacted

“I have no clue. I have never seen anything like this before. I’m completely unaware of any data that suggests that Covaxin has any efficacy against any strain of Covid-19, let alone special efficacy against the variant (UK) strain.”

Health watchdog –All India Drug Action Network said it was “shocked”. Opposition parties are also questioning the speed and the manner approval was given. The decision to approve an incompletely studied vaccine, even under an accelerated process, raises more questions than answers.

To answer this let us first understand what is an Vaccine?

The vaccine uses your body’s natural defenses to build resistance to specific infections by training your immune system to create antibodies, just as it does when it’s exposed to a disease. However, because vaccines contain only killed or weakened forms of germs they do not cause the disease or put you at risk of its complications. The immune system remembers the disease and If you are then exposed to the germ in the future, your immune system can quickly destroy it before you become unwell.

While Covishield is based on the virus’s genetic instructions for building the spike protein using double-stranded DNA added to another virus (adenovirus), COVAXIN is an inactivated vaccine (a vaccine that uses the dead virus).

Vaccine development has to go through different phases which usually takes years but due to Covid-19 enormous effects on health and social -regulatory framework have been relaxed –

Now let’s try to answer  — For me ‘Clinical trial mode” is similar to Phase III trial where the efficacy of the vaccine is tested on consented volunteers. If an experimental vaccine is given to people, there should be informed consent explaining the potential risks and benefits of the vaccine and post-vaccination follow-up. In case there is any serious adverse reaction, the recipient may also be eligible for compensation. Critics and Government are on the same page that Covaxin is still on Phase III trial but the question is why so hurry?

Since the beginning, Covaxin speed has raised so many unanswered questions. ICMR transferred the strain NIV had isolated to Biotech Bharat on 9th May 2020. It takes at least three months to do animal trials to establish safety. The company published its results on June 29, 2020. So there were only 50 days in between, during which time the company should have developed the inactivated vaccine, conducted preclinical animal trials (with mice and hamsters), and sent its reports to be evaluated and approved by DCGI.

A related issue is that animal trials for COVID-19 can only be conducted with hACE2 transgenic mice, as ‘normal’ mice can’t get infected with the novel coronavirus. These mice need to be shipped from the US, Europe, or China.

These issues, therefore, raised initial concerns about whether Bharat Biotech could have proceeded to the human-trials phase of vaccine development within only 50 days of receiving the inactivated virus from NIV?

ICMR’s Dr. Balram Bhargava has earlier created a similar uproar when he wrote a letter to Bharat Biotech in early August 2020 writing, “It is envisaged to launch the vaccine for public health use latest by 15th August 2020 after completion of all clinical trials.” 

Covaxin Phase III efficacy trial was initiated in India on 25,800 volunteers on November 6, 2020. In a December 22 statement, Covaxin said it had recruited 13,000, or half of its target for these trials. Now the regulator says that to date, 22,500 participants have been vaccinated across the country and the vaccine is safe but didn’t provide further details. It can’t happen so fast as the vaccine needs two shots 3-12 weeks apart, the volunteers need to be tracked and tested until enough of them have contracted Covid-19 to allow the vaccine’s efficacy to be analyzed. 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.

The Indian Council of Medical Research (ICMR), said Covaxin has the potential to mount a resistance against new mutants of SARS-CoV-2. No data has been shared by the regulator or the company to support this claim. Words like – ” Likely “, Restricted use ” “Backup Plan ” has created more confusion.

In my view, DGCI should have given more time to Bharat Biotech to complete its Phase III trial. It should not be seen as an unsurprising push in the wake of 26th January, Republic Day announcements at the cost of common citizens. Approving the vaccine before trials were complete, was a matter of concern irrespective of how safe or effective the vaccine eventually turned out to be. The government’s decision not to release data on the vaccine’s efficacy for peer review is something I am concerned about. The government needs to be more transparent about the authorization process because the success of the Covid-19 vaccine program depends on public trust. It should not lead to vaccine-hesitancy as already India is struggling with anti-vaccine, anti-scientific views.

Bharat Biotech is a reputed drug manufacturer that delivers four billion doses around the world for infections like rotavirus, hepatitis, Zika, Japanese encephalitis, and others. The method they have chosen is a very old and tested method of using an inactivated virus and have high hopes because of its proposed mechanism of action. Let us start with Covishield which has already started in the UK and let Bharat Biotech finish its Phase III trial.

Clinical trial / Safety and additional efficacy data continue to be collected–participants will continue to be monitored for long-term protection and safety.

Do remember “A vaccine will complement the other tools we have, not replace them ” Contact tracing, testing more and more people, isolation, the quarantine will need to continue. We had to continue to follow distancing norms, mask-wearing and hand hygiene practices.

• Dr Kafeel Khan is a Doctor in Department of Pediatrics, BRD Medical College, Gorakhpur, U.P