New Delhi: On Sunday, the country’s drug regulator announced that the vaccine candidates of Bharat Biotech (BB) and Serum Institute of India have been granted permission for ‘restricted’ emergency use. With BB touting its candidate – Covaxin – as India’s first ‘indigenous’ vaccine, there has been considerable interest in it, though the Hyderabad-based pharmaceutical company has not been very forthcoming about safety and efficacy data.
The involvement of the Indian Council of Medical Research (ICMR) and the National Institute of Virology (NIV) in developing the vaccine, along with the government’s haste to push out an ‘Indian vaccine’, have also caused some consternation regarding the vaccine candidate.
From the time BB received permission to conduct clinical trials in late June, until Covaxin received the Drugs Controller General of India (DCGI)’s nod on January 1, The Wire Science is compiling the information that you need to know about the company during the pandemic.
BB receives the nod for clinical trial
On June 29, the company became the first in India to get the nod for human clinical trials.
The DGCI’s Central Drugs Standard Control Organisation (CDSCO) granted permission to initiate phase 1 and 2 human clinical trials of Covaxin after BB submitted results generated from pre-clinical studies, demonstrating safety and immune response.
The pre-clinical study process was expedited through the national regulatory protocols and the vaccine was developed in collaboration with the ICMR and NIV.
How indigenous is the vaccine?
While BB has from the beginning touted the vaccine as indigenous, Prem Anand Murugan raised some questions about this claim in his piece for The Wire Science.
The company received the strain that the NIV had isolated from the ICMR on May 9. It received the nod to conduct human clinical trials on June 29.
In those 50 days, the company should have “developed the inactivated vaccine, conducted preclinical animal trials (with mice and hamsters, according to the company), and sent its reports to be evaluated and approved by DCGI”, Murugan wrote. This process usually takes three months.
On May 20, BB announced a collaboration with the Pennsylvania-based Jefferson Vaccine Centre (JVC), which had earlier announced a promising vaccine candidate named Coravax.
“…based on what we already know, there appears to be room for the possibility that Covaxin is Coravax by another name – and by another viral strain. And even if the vaccine is wholly indigenous, the timelines for the animal trials don’t line up.”
It was only in September that the company uploaded a preprint paper, showing that it had indeed conducted pre-clinical trials and animal challenge studies. The paper revealed that time animal trials began on June 6, which means that by the time Covaxin received DCGI’s nod for human trials, the immunization of animals hadn’t finished.
ICMR director’s letter causes uproar
On July 2, ICMR director general Balram Bhargava caused an uproar when he asked 12 hospitals and research centres to begin enrolling participants for the clinical trial no later than July 7 and to have the vaccine ready for “public health use” by August 15. He also warned the institutes that if they do not comply with his directives, their non-compliance “will be viewed very seriously”.
Writing for The Wire Science, Vasudevan Mukunth expressed fears that politics was driving science, adding:
“This [hastened time frame] was by all standards less a rapid vaccine development process and more an improper one. Many observers quickly raised multiple questions about whether such a trial could even be considered legitimate.”
Questions about institutions chosen to conduct trials
In another piece for The Wire Science, Aakash Sethi and Gayatri Laha doubted the abilities of the 12 institutions which Bhargava asked to expedite Covaxin’s human trials, apart from a number of other questions that needed to be asked.
They found that the phase 1 trial hadn’t received the ethics committees’ approvals at some of the institutes that were to participate. At many others, the ethics committee had been registered for the first time just then – and so lacked the expertise to assess such an important trial. Some did not even have such committees at all.
“…four of the six sites that have received approval from their respective ethics committees – Gillurkar Hospital, Jeevan Rekha Hospital, Prakhar Hospital and Rana Hospital – are small private hospitals that are neither research centres nor attached with any medical college.”
‘Candidate is safe’
After BB received permission to conduct late-stage trials for its candidate, the company’s executive director Sai Prasad said in late October that Covaxin was found to be “safe without any major adverse events in the first two stages of the trials involving about 1,000 people”. Though the company did not make this data public, Prasad told news agency Reuters that more than 90% of the participants in the first two stages developed antibodies against the novel coronavirus.
Company says it expects 60% efficiency
On November 21, BB said its COVID-19 vaccine candidate is expected to have an efficiency of around 60%. It also announced that the vaccine will be rolled out around June 2021 for distribution, after securing all the necessary approvals. Scientists were wary of these claims, as Covaxin’s phase 3 clinical trials were yet to be concluded at the time. At this stage too, BB had not released the results for its phase 1 and 2 trials. It released a pre-print paper in late December, which said phase 2 results found the vaccine candidate to be safe.
Haryana home minister’s infection raises questions
Haryana home minister Anil Vij’s public admission that he was infected with COVID-19 raised more tricky questions about BB’s phase 3 trials.
Vij announced on December 5 that he had tested positive for COVID-19, advising those who had been in contact with him to get tested. Two weeks earlier, BB had administered an injection to Vij as part of ongoing trials for Covaxin.
But because the trials were blinded, no one ought to have known at the time if Vij had actually received a dose of Covaxin or the placebo.
Experts slam ‘misleading advisory’
In late December, the company released a document to address queries raised by volunteers for Covaxin trials, as it was running short of volunteers for its ongoing phase-3 trials. Public health experts criticised the advisory, saying it “misguides” principal investigators and participants and highlighted the risk associated with misleading.
“The document clearly has troubled language. The whole purpose of a phase 3 study is to establish efficacy. This document presupposes efficacy but on what basis?” Anant Bhan, a researcher on global health, health policy and bioethics, told The Print.
“They are assuming that their vaccine is already good enough. How can sponsors assume it?” editor of the Indian Journal of Medical Ethics Amar Jesani also said. According to Jesani, by saying that the vaccine can be given now rather than later on, the company had violated the “cardinal principle” of clinical equipoise or a medical research ethic which requires researchers to be uncertain about the effectiveness of different interventions offered in a trial.
Many questions even after DCGI nod
On January 3, a day after the subject expert committee of the CDSCO recommended giving restricted emergency use authorisation for Covaxin, the DCGI gave its nod for the vaccine candidate. However, many questions still remain unanswered.
The DCGI’s statement said that BB’s application was accepted “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”.
This raised many questions, including whether the people who would receive Covaxin would be treated as being part of a clinical trial, or if Covaxin is part of a “back-up plan”, or if the nod for BB’s candidate was hastened in light of the more infectious strain identified in the UK and if so, why?