The Drug Controller General of India (DCGI approved two vaccines for restrictive emergency usage in India on 3, January -- Oxford-AstraZeneca's Covishield which is produced in India by Serum Institute of India (SII), and Bharat Biotech's Covaxin which is developed in collaboration with National Institute of Virology (NIV) and Indian Council of Medical Research (ICMR).
This comes after an expert panel of the drug regulator, Subject Expert Committee (SEC) gave its nod on 1, January for the two vaccine's emergency use authorization (EUA). Covishield is developed in India with a master seed from Oxford-AstraZeneca, Covaxin is derived from a strain of SARS-CoV-2 virus, isolated at NIV in Pune. Both vaccines will be administered in two doses, 3-12 weeks apart and can be transported and stored at normal refrigeration temperatures.
The approval of the Bharat Biotech's Covaxin, which is still undergoing phase-3 clinical trials, has raised serious questions. The DCGI said Covaxin was approved in public interest with abundant precaution in “clinical trial mode”, to have more options of vaccines in India, especially in the light of new mutant strains of the virus. The clinical trial ongoing within the country by the firm will continue.
Prime Minister Narendra Modi called the approval of Covaxin as a "game-changer". Union health minister Dr Harsh Vardhan said it was a “Monitored Approval” and that the “clinical trial mode” would mean that all vaccine recipients will be tracked as if they are in a trial.
But what is a “clinical trial mode”? "I have no clue," said Gagandeep Kang, renowned microbiology professor at Christian Medical College, Vellore. "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", he added.
Health watchdog All India Drug Action Network said it was "shocked" at the Covaxin approval. Opposition parties are also questioning the speed and the manner the 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 a vaccine and how is it developed.
A vaccine uses our body’s natural defences to build resistance to specific infections by training our immune system to create antibodies, just as it does when it’s exposed to a disease. However, because vaccines contain only dead or weakened forms of the germs they do not put us at the risk of the disease's complications. The immune system remembers the disease and if you are then exposed to the germ in the future, the immune system can quickly destroy it.
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 like preclinical trials, safety trials, efficiency trials, regulatory review before getting approval for distribution, which usually takes years. But due to the enormity of the Covid-19 pandemic, the regulatory framework has been relaxed.
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. Everyone is in agreement that Covaxin is still in Phase III trial, the main objection of the critics is that it has got approval in great haste.
ICMR transferred the strain NIV had isolated to Biotech Bharat on 9, 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 in 50 days the company claims to 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 ‘ordinary’ mice can’t get infected with the novel coronavirus. These mice need to be shipped from the US, Europe or China. Could Bharat Biotech have gone ahead with the human trials phase at such a short time?
Covaxin Phase III efficacy trial was initiated in India on 25,800 volunteers on 6, November 2020. In a 22, December statement, Covaxin said it had recruited 13,000 volunteers, about half its target for trials. Now, the regulator says that till date, 22,500 participants have been vaccinated across the country and the vaccine has been found to be safe but didn’t provide further details.
But trials 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.
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' have created more confusion.
In my view, the DCGI should have given more time to Bharat Biotech to complete its Phase III trial. Approving the vaccine before trials were complete is a matter of concern irrespective of how safe or effective the vaccine eventually turns out to be. The government's decision not to release data on the vaccine's efficacy for peer review is something I am really concerned about. The government needs to be more transparent about the authorization process because the success of the Covid-19 vaccine programme depends on public trust.
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 one of using an inactivated virus and there is every reason to believe the vaccine will work. But I think we should start with Covishield which has already started the rollout in the UK and let Bharat Biotech finish its Phase III trial. Let the firm continue its clinical trial, get additional efficacy data and monitor its trial participants for long-term protection and safety.