A letter sent by Dr Balram Bhargava, the Director General of the Indian Council of Medical Research (ICMR), on July 2 to 12 institutes with a “strict advise” to fast track all approvals relating to the initiation of clinical trials of a vaccine by the Hyderabad-based Bharat Biotech International Limited (BBIL) has raised eyebrows. The apparent reason for the advice was that the vaccine had to be launched by August 15. That there was something more than science behind the directive became clear as the letter also pointed out that the development of the “first indigenous vaccine in India was one of the top priority projects being monitored at the top most level of the government.”
Both BBIL and ICMR were working for the pre-clinical and clinical development of the vaccine, which had been derived from a strain of SARS COV- 2 isolated by the National Institute of Virology at Pune.
Among the 12 institutes identified as sites for clinical was the All India Institute of Medical Sciences, Delhi. In an official communication, Dr. Bhargava has informed him that the ICMR had partnered with BBIL to fast-track indigenous trials of the COVID – 19 vaccine (BBV152 Covid Vaccine). Also written in bold letters in his communication was that “non-compliance would be viewed very strongly”. He wrote that the project had to be treated as one of “high priority” and that the “given timelines” must be met “without a lapse”.
Balram Bhargava’s lettter also said that while BBIL was “working expeditiously to meet the target” the outcome would depend much on “the co-operation of all clinical sites for the project”. Interestingly, it was on the day the letter was sent that the 12 institutes were informed that they had been selected as trial sites. There was some initial speculation that the letter might be fake but Frontline confirmed from an ICMR source that the plan was to launch the vaccine by August 15 and that there was pressure to fast track processes.
“Clinical trial sites cannot fast track approvals. Approvals can only come from authorised regulatory agencies or agency for approval after ethical clearances are obtained through the necessary local processes. The intention could be a signal to regulatory agencies to fast track since no one can influence the regulatory agency directly,” said an eminent virologist.
He also said that “fixing a date to launch an untested product will certainly raise eyebrows and earn India a bad name in scientific circles. Everyone trusts the Indian vaccine industry. It is against national interest to tarnish the image of science and technology, biotechnology here,” he told Frontline.
The details of the trials and studies of the vaccine to be developed as given in the Clinical Trials Registry were interesting. It appeared that regulatory clearance for the trials was obtained from the Drug Controller General of India on June 29, 2020
and the study was registered on July 1, 2020 with the words “registered prospectively” written in parentheses. The study was titled “Whole-Virion Inactivated SARS COV – 2 Vaccine (BBV 152) in healthy volunteers”. The registry details showed that ethical committees of eight out of the 12 trial site institutes selected had still not given their approval for the trials. They were under “review”. Perhaps this is what Dr. Bhargava had meant by ‘fast tracking’ in his letter bordering on intimidation.
The trials were to be done on “virologically confirmed COVID-19 patients”. The time points mentioned for both primary and secondary outcomes of phase 1 and phase 2 of the trials stretched anywhere between seven days to 194 days, during which the subjects would be checked for serious adverse events, immunogenicity, and so on. The dictionary definition of a “time point” was the point before the participant started receiving the experimental treatment. Going by the “time points” given in the registry, the August 15 deadline would be impossible to meet.
As many as 1125 volunteers were to be enrolled for the trials and date for the first enrollments was given as July 13. The “estimated duration of trial” given in the registry was “1 year, 3 months”. As for the slot on “recruitment status”, it was written “not yet recruiting.”
Dr Satyajit Rath, who retired from the National Institute of Immunology and presently is an Adjunct Faculty with the Indian Institute of Science Education and Research, Pune, told Frontline that it was impossible that the launch could happen on August 15 as phase three trials involving a large number of people had not yet been registered. He said that normally phase one and phase two trials for vaccine development “gave themselves” anywhere between one to two years. But what was more shocking and depressing was the letter written by the ICMR Director-General to those institutes, he said. “What is his locus standi to do so I wonder? Do these institutes come under the ICMR? These are all independent institutes and the ICMR’s own guidelines insist on the independence of ethics committees. My worry is not about the technical process involved or the trials themselves but more about a senior most functionary of the government of India attempting to bring about coercive pressure. I can understand the hurry in the context of the pandemic and committees can be asked to expedite. But the question also is whether licensing of a vaccine can be done if regulatory processes are cut short,” he said. He told Frontline that “institutions cannot fast track approval”. He was surprised that the Director-General’s letter was dated July 2 wherein the institutes were instructed that subject enrollment had to be done not later than July 7. “All this shows that we can be quite cavalier about due processes at the highest levels,” he said.
It would be of great significance if a vaccine for COVID-19 was indeed launched on August 15. But not many were clearly amused by the tenor of Dr. Bhar letter of July 2 which seemed less to do with science or vaccine development and more to do with the politics of nationalism is the order of the day. In this mileu, August 15 does not seem to be an innocuous deadline.