India Grants Controversial Conditional Approvals To Serum, Bharat COVID-19 Vaccines

Source : 'The Pink Sheet'

In a move indicative of the unusual times the world finds itself in due to COVID-19, India has granted conditional accelerated approvals to two vaccines, one for which Phase III trial recruitment is still not complete and the other which seemingly lacks efficacy data from Indian studies.

Both Serum Institute of India Pvt. Ltd. and Bharat Biotech, whose vaccines have been approved for “restricted use in emergency situation,” had presented safety and immunogenicity data from earlier phases of trials to the national regulator, the Drugs Controller General of India (DCGI).

There are precedents of products being approved outside India while they were still in clinical trials. The US Food and Drug Administration, for example, has issued several emergency use authorizations (EUAs) for drugs, devices and diagnostics for prevailing public health crises, for example HIV, anthrax, avian flu (H1N1), MERS-CoV, Ebola and Zika.

However, when accelerated approvals were recently granted in India for hydroxychloroquine, remdesivir, favipavir and itolizumab as treatments for COVID-19 patients, there was an outcry among civil society and patient groups over the limited data that was relied on in most cases. ()

The furor is greater this time as the nods are for vaccines which will be used to immunize healthy individuals and as they go against a statement by the DCGI that an EUA would not be granted to any COVID-19 vaccine until its completes clinical trials.

Murali Neelakantan, former global general counsel for major Indian pharma company Cipla Limited and currently a lawyer at private legal firm Amicus, told the Pink Sheet there is insufficient proof of efficacy for Serum Institute and Bharat Biotech’s vaccines for an accelerated approval to be granted. ()

The Serum Institute vaccine is not the same vaccine that has been approved overseas although it may “be claimed to be similar," he said. "There is therefore a clear requirement for the vaccine to have full clinical trial in India. Efficacy has not been claimed in the trials done by SII in India.” 

At best, the Phase II/III study in India may be described as a "bioequivalence" study, which is insufficient for approval of a new vaccine. There are specific provisions for circumstances where bioequivalence studies are sufficient for approval and the SII vaccine does not meet those conditions, he added.

Given that the Indian government plans to roll out its immunization program soon, it is expected to use Covishield for the initial phase of vaccination. Form-23, issued to Serum granting permission for manufacture of formulation for sale or for distribution, clearly states that its vaccine can only be supplied for immunization programs.

Going back to Bharat Biotech, experts believe the approval for the firm's vaccine is based on the need for a contingency plan and to reduce dependence on Serum Institute alone. "Competition will optimize prices, increase availability and provide choice to consumers,” Kallianpur told the Pink Sheet. 

Neelakantan declined to comment on the potential reasons behind this approval, saying: “The letter of the law requires proof of efficacy which can only be determined in Phase III clinical trials. This is yet to be done. There is therefore no provision in the law that allows such approval to be granted. Since it has not been possible for me to identify the provisions of law pursuant to which the vaccines have been approved, I am in no position to speculate on the reasons for the approvals to be granted.”

Another expert said “One cannot rule out the possibility of pressure on the regulator to approve a vaccine that promotes the ‘Make in India’ narrative that the current government is passionate about.”

However, Kallianpur warned these vaccines can prove dangerous if not studied adequately. “An approval without any evidence is quite a brazen thing to do and one prays that it works out for the people or it can break down public confidence in the vaccination drive that is such a necessity in these days.”

Meanwhile, India's health ministry has asserted that the approval of Covaxin is strategic to vaccine security and repeatedly pointed out that it will be used outside of clinical trials only if required, with people who are administered the vaccine monitored, as is done in such studies.

Dr Harsh Vardhan, Minister of Health and Family Welfare, tweeted “For those spreading rumours, let it be known that EUA for Covaxin is differently conditional – in clinical trial mode. All Covaxin recipients to be tracked, monitored as if they’re in trial...This approval ensures India has an additional vaccine shield in its arsenal esp [especially] against potential mutant strains in a dynamic pandemic situation.”

India anticipates that the SARS-CoV-2 mutant strain that surfaced in the UK might cause COVID-19 to spread more rapidly, as it is reported to be more infectious.

Bharat Biotech chairman and managing director Krishna Ella has said Covaxin can “deal with virus mutations,” with Dr Vardhan affirming this in a tweet which said the vaccine is more likely to work against newer strains like the UK variant.

However, the scientific community has pointed out there are no data to support such claims. The vice-chair of the board of Coalition for Epidemic Preparedness (CEPI), Dr Gagandeep Kang, has also said as much.

In addition, Zydus Cadila has announced it will soon start Phase III clinical trials of its plasmid DNA vaccine candidate, ZyCoV-D, after having received permission from the DCGI.

The company plans to recruit nearly 30,000 volunteers for this phase after ZyCoV-D was found to be safe, well tolerated and immunogenic in the adaptive Phase I/II clinical trials, it added.

The Phase II portion was carried out in over 1,000 healthy adult volunteers as part of the dose-escalation, multi-center, randomized, double-blind and placebo-controlled study.

The trial has been reviewed by an independent data safety monitoring board and the results submitted regularly to India's Central Drugs Standard Control Organization for updates on safety outcomes.

By Vibha Ravi