Conditional Approval for Serum, Bharat Bio COVID-19 Vaccines In India Amid Uproar
Source : 'Scrip Intelligence'
In a move indicative of the unusual times that the world finds itself in due to COVID-19, India granted conditional accelerated approvals to two vaccines, one of them still in Phase III clinical trials and the other seemingly lacking efficacy data from Indian studies.
Both Serum Institute of India Pvt. Ltd. and Bharat Biotech, whose vaccines got approved, have presented safety data from earlier phases of trials to the regulator, Drugs Controller General of India (DCGI). Also, there are precedents of drugs being approved while still in clinical trials.
Since 2009, the US Food and Drug Administration has issued several emergency use authorizations (EUAs) for drugs, devices and diagnostics based on the best available evidence for prevailing public health crises, for example for HIV, anthrax, avian flu (H1N1), MERS-CoV, Ebola and Zika.
Similar procedures were recently followed in India as well for hydroxychloroquine, remdesivir, favipavir and itolizumab. However, the nod caused a furore in Indian media, more so as they go against a statement by DCGI that an emergency use authorization (EUA) would not be granted to COVID-19 vaccines till they complete clinical trials.
AstraZeneca PLC
/University of Oxford partner Serum Institute of India (SII) submitted efficacy data from the Oxford/AZ studies conducted outside India, along with Phase III immunogenicity data from 100 Indian subjects out of the 400 in the immunogenicity cohort and 1200 in the safety cohort. It has been directed to provide safety, immunogenicity and efficacy data from local and international trials for every 15 days up to two months and post that, every month till completion of Phase III trials.
Bharat Biotech’s COVID-19 vaccine, Covaxin, began Phase III trials in November and hasn’t completed vaccination of candidates to reach the stated target of 26,000 subjects. In an unprecedented move, the approval for Covaxin was given “in clinical trial mode.”
Covaxin has been in the spotlight as it is the first indigenous vaccine simultaneously developed with COVID-19 vaccines around the globe. Not only have expectations around its success been high, there has been considerable right-wing support as well.
After the DCGI’s Subject Expert Committee (SEC) recommended approval for Covishield on 1 January while deferring a decision on Covaxin, a tweet by Subramanian Swamy, a long-time member of the ruling Bharatiya Janata Party read: “I am shocked to learn the Bharat Biotech a swadeshi (local) company has already done trials on 13,000 persons in Phase III. The Angrez (English) vaccine has been tested only on 1200 persons. Yet the Angrez has got the contract and swadeshi in the ditch”. The SEC recommended approval the next day.
“One can argue that these are extraordinary times and therefore need extraordinary measures. In the case of SII, it seems like the regulator is relying heavily on the results of the Oxford-AZ study and is able to give the benefit of the doubt to SII. Of course, SII will have to continue the study and table the results in due course. One would have expected the regulator to wait until then, but there is also the clamor to begin vaccinating people as early as possible, given that vaccination drives have begun in the US and UK,” Salil Kallianpur, former executive vice-president at GlaxoSmithKline plc in India, who now runs a digital health consultancy, told Scrip.
Murali Neelakantan, former global general counsel for Cipla and currently a lawyer at private legal firm Amicus, told Scrip 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. 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,” he said.
At best, the Phase II/III trial done in India may be described as a ‘bio-equivalence’ 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.
“I think the approval to Bharat Biotech 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 Scrip.
Neelakantan declined to comment on the potential reasons behind the approvals 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 that ‘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, the health ministry has asserted that the approval to Covaxin is strategic to vaccine security and repeatedly pointed out that Covaxin will be used outside of clinical trials only if required, with people who are administered the vaccine monitored as is done in trials.
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 against potential mutant strains in a dynamic pandemic situation.”
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 that the vaccine is more likely to work against newer strains like the UK variant.
India anticipates that the SARS-CoV-2 mutant strain that surfaced in UK might cause COVID-19 to spread more rapidly as it is reported to be more infectious. However, the scientific community has pointed out there is no data to support such claims. Vice-chair of the board of Coalition for Epidemic Preparedness (CEPI) Dr Gagandeep Kang has also said as much.
Meanwhile, Zydus Cadila announced it will soon start Phase III clinical trials of it plasmid DNA candidate, ZyCoV-D, after having received permission from 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 study of the vaccine ZyCoV-D was carried out in over 1,000 healthy adult volunteers as part of the dose escalation, multi-centric, randomized, double-blind, placebo-controlled study.
The trial has been reviewed by an independent Data Safety Monitoring Board and results submitted to Central Drugs Standard Control Organization regularly for the update on safety outcome.
By Vibha Ravi