COVAXIN controversy: Bharat Biotech-ICMR readying a COVID-19 vaccine in 45 days baffles reason, ignores safety concerns, says bioethicist

Four days after Bharat Biotech announced that it has successfully developed COVAXIN, a vaccine candidate for COVID-19, ICMR said that it wanted to “launch the vaccine for public health use latest by 15 August”. The vaccine was developed in collaboration with the Indian Council of Medical Research (ICMR) – National Institute of Virology (NIV), Pune. A letter, issued by the Director General of ICMR Dr Balram Bhargava, said, “This is the first indigenous vaccine being developed by India and is one of the top priority projects which is being monitored at the topmost level of the government. The vaccine is derived from a strain of SARS-CoV-2 isolated by ICMR-National Institute of Virology, Pune. ICMR and BBIL are jointly working for the preclinical as well as clinical development of this vaccine. It is envisaged to launch the vaccine for public health use latest by 15 August, 2020, after completion of all clinical trials. BBIL is working expeditiously to meet the target, however, final outcome will depend on the cooperation of all clinical trial sites involved in this project.” Bharat Biotech spokespersons have, however, refused to comment on the deadline . The announcement that India will have a possible vaccine for COVID in 45 days has baffled health experts and researchers. Dr Anant Bhan, a researcher in global health, bioethics and health policy, spoke to Firstpost about the extreme urgency of the situation. “It’s understandable for a pandemic of this scale. But we can’t compromise on the safety and the efficacy aspects. Minimum standards around safety, efficacy and quality need to be followed. Collapsing the entire process to just 45 days is unlikely, and almost impossible,” he said. Researchers usually need years to secure funding, approvals and to piece together study results to successfully launch a cure. For COVID, there are roughly 254 therapies and 110 vaccines being explored. Most health experts say a month is too short a timeline for a trial of this magnitude. The expected duration of the trial, according to the government’s official clinical trial registry, is one year and three months. In fact, seven of the 12 participating institutes are yet to receive a green-signal from independent ethics committees, Scroll reported — a prerequisite for conducting clinical trials. According to experts quoted by several reports, there is no fixed period, but the process can typically run into decades without yielding any results. “For instance, after three decades of research, the vaccine for HIV is still in phase III of clinical trials. One of the fastest-developed vaccines is the one used for mumps, which received approval in four years, after trials began in 1963,” The Indian Express reported. According to ICMR’s letter, pre-clinical development for the vaccine is still underway. Bhan raised serious doubts in the manner the ICMR and DCGI are approaching the process, which will raise questions on the efficacy of the vaccine. Bhan asked, “How can clinical trial recruitment for such a vaccine be starting on 7 July, and that vaccine be launched on 15 August? Are we pre-deciding the efficacy of a vaccine trial, which is completing in little over a month?” It is surprising how the regulator allowed such a short time period to expedite a clinical trial of this scale, Bhan said. “It could also be that they have permitted phase 1 and phase 2, and once they have the data, they have to return to the regulator for permission for phase 3. But none of this information is available for anyone to see,” he noted. Hyderabad-based Bharat Biotech, one of the seven Indian companies involved in the indigenous production of a vaccine for the novel coronavirus, received the green signal from the Central Drugs Standard Control Organisation (CDSCO) to begin human trials of ‘COVAXIN’ last week. Speaking to Firstpost, Bharat Biotech chairman and managing director Dr Krishna Ella said that the virus strain was first isolated by the NIV, Pune after it was collected by the ICMR. “This isolated strain was then used to develop a vaccine candidate at Bharat Biotech,” Ella said. On receiving the virus strain, Bharat Biotech was able to quickly layout the GMP (good manufacturing practices) protocols for the manufacture of the vaccine candidate. Bharat Biotech developed the first set of GMP batches within 40 days and upon completion, the pre-clinical trials commenced. The ICMR and BBIL have zeroed in on 12 clinical trial sites, but apart from the names of the institutes, no additional information has been made public. “Right now, there is hardly any information on what the processes for these trials are. How were the clinical trial sites mentioned in the appendix chosen? What was the criteria? What’s the eligibility? From what list were they chosen? Was this a selection done by the ICMR or by Bharat Biotech?” asked Bhan. Noting the manner in which various institutions engaged in the development of a vaccine are taking shortcuts is unprecedented, Bhan said that the “threatening tone” of the ICMR letter is also problematic. “In view of the public health emergency due to COVID-19 pandemic and the urgency to launch the vaccine, you are strictly advised to fast track all approvals related to initiation of the clinical trial and ensure that the subject enrollment is initiated no later than 7 July, 2020”, the letter, issued on 2 July, notes. “Kindly note that non-compliance will be viewed very seriously,” it added. “Otherwise non-compliance will be viewed seriously? By whom? By ICMR? Under what power?” asked Bhan. As the premier biomedical research agency of India, ICMR is expected to ensure that proper standards are met. An alum from the University of Toronto, Bhan said, “They (ICMR) have been around for many years, and have experience of running vaccine studies, so they have the experience of handling something like this, but rushing to get a vaccine without following proper protocols is not wise at this point of time. And there is not much in the public domain to allay these fears.” The timeline presented by the ICMR for the trial, which has been registered on the Clinical Trial Registry of India, also has loopholes. “Trial registered on 1 July, 2020, for phase 1 and phase 2 study and we will have efficacy data by 15 August to announce a launch for public health use?” asked Bhan. According to Bhan, having a protocol in the public domain would be ideal, where it’s for everyone to see the processes being followed and requirements that are being met. Rushing with a clinical trial in times like these “without following proper protocol is not advisable and could be counter-productive in many ways”, he explained. Ensuring adequate attention is paid to the preparations of this clinical trial is paramount, Bhan added. “Do they have infrastructure to pull off something of this scale? Do they have the adequate number of staff? Is adequate time being given,” asked Bhan, “We don’t have any studies (in the public domain) on the efficacy of the plan. We only know that there is Phase 1 and Phase 2. The trial sites have been given 5 days. ‘Get everything done by 7 July (in a letter dated 2 July) and start clinical trial participant recruitment’, the letter says. Does this mean these ‘institutions’ have to follow all due processes to enable this trial to be run within 5 days from the letter? Including ethics committee approvals? Is that not undue pressure on the institution and committees?” With extensive work for government-run public health training institutions in India and several non-government bodies in the field of health and bioethics, Bhan cautioned against such accelerated development pathway and said that even with accelerated timelines, this seems really rushed. “If found efficacious, this would be a vaccine which will be of interest to, and used in other countries not just India. And other nations, who are also researching for a cure, are watching us because while this is a major claim to make in record time, everyone is also hoping for a cure as fast as possible.” ICMR has clarified that it is adhering to global standards in developing and testing the vaccine. “Our process to develop vaccine to fight COVID-19 pandemic is as per globally accepted norms of fast tracking,”  it said in a statement released Saturday.