On the night of July 2, a few WhatsApp groups comprising medical professionals and health activists went abuzz with a letter written by Dr Balram Bhargava, director general, ICMR. The letter was addressed to principal investigators of 12 institutes that had been picked to conduct the phase one and phase 2 trials for Covaxin, the indigenous vaccine that is being jointly developed jointly by ICMR and Hyderabad-based Bharat Biotech. The letter asked them to “fast-track” these trials by recruiting human participants “no later than July 7, 2020”, since the plan was to ready the vaccine for public health use by “August 15, 2020”. “Non-compliance” would be viewed seriously, the letter stated, and asked the principal investigators to take the call for recruitment seriously.
Given the tone and tenor of the letter, as well as the unrealistic deadline—if accomplished, India would be the first in the world to have developed a COVID vaccine—it generated enough controversy among medical professionals, some of whom wondered about the veracity of the letter, too. On July 3, however, the ICMR comfirmed that the letter was indeed genuine. Several questions were raised about how could research be shrunk in such a short time frame, and what that meant for the safety of the vaccine.
Vaccine development, experts say, takes anywhere from 10-15 years, beginning with elaborate tests for safety and immunogenicity of the shot on animals, and subsequently, on human participants. Human trials—the ones that the letter has asked trial sites to hasten—take several months, even years, as researchers begin with small groups of people on whom safety and immunogenicity is tested in the first two phases, and moving on to larger groups of people in phase three. “If they are planning to give three doses of the vaccine, each dose has to be spaced by at least a month. So, that makes it straight three months from the day you give the first dose, that too, the day after the last participant is recruited. The recruitment itself would take time, so the August 15 deadline is just plain ridiculous,” said Dr Jacob Puliyel, a Delhi-based paediatrician and former member of the National Technical Advisory Group on Immunization. After having administered the vaccine, the researchers need to look for the antibodies that are developed. “All antibodies that may develop as a result though may not be protective. Protection from a vaccine develops due to a multitude of factors,” said Puliyel. In dengue, for example, the antibodies that were generated after the dengue vaccine was given, actually ended up being harmful.
So, we will know if the vaccine is useful only when people get exposed to natural disease, Puliyel said. "One has to assess whether those vaccinated have less disease than those who have not received the vaccine. If the vaccine is protective, then it may be licensed. Even after the vaccine is licenced the manufacturer has to monitor for rare adverse events which may not have manifested when the smaller clinical trials were taking place. The adverse events for the dengue vaccine were noticed only after the vaccine had been licenced and large numbers were given the vaccine. There can be no short cuts without compromising safety," he said. There's also a need for transparency. “In the case of the Indian Rotavirus vaccine, the manufacturer has till date not released the data for adverse events,” Puliyel pointed out.
The Indian Academy of Science, too, criticised the deadline; in a scathing letter, the scientsists' body, that includes many who are engaged in vaccine development, said that while administrative approvals can be expedited, the scientific processes of experimentation and data collection have a natural time spanthat can not be hastened without compromising standards of scientific rigour. “For example, immune responses usually take several weeks to develop and relevant data should not be collected earlier. Data collected in one phase should be adequately analysed before the next phase can be initiated,”the letter, signed by Dr Partha P. Majumder, president, IASc stated. If data collected from any phase is shows that the vaccine is not adequately safe, then the next phase can not be initiated and the vaccine candidate has to be discarded, the letter reads.
A day after several such experts questioned the ICMR's move to hasten the trials, the research body released a clarification. Even as it deftly skirted the August 15 deadline from the previous letter, the ICMR defended the letter stating that the letter was meant to cut “unnecessary red-tape” and “speed up” recruitments of human participants without bypassing any necessary process. The idea, it said, was to “insulate the indigenous vaccine development process from slow file from slow file movement.” The ICMR said that it wanted to finish these phases at the earliest, so it could begin the population-based trials soon. While welcoming the issues raised by public commentators, the ICMR stated that the “best of India's medical professionals and research scientists should not be second guessed for their professionalism or adherence to the highest scientific rigour”.
An official with the ICMR told THE WEEK that most scientists within the agency's network were uneasy, and “not aligned” with the contents of the letter, as well as the August 15 deadline for the vaccine. “Science has been overtaken by agenda-driven politics,” the official added. This, however, is not the first time during the pandemic that those within the system had been disappointed and disillusioned, the official stated. They had felt similarly at an earlier occasion, too, when the ICMR did not publish the results of the sero-surveillance study and instead, the highlights were merely announced at a press conference. “Individual members in the system are working hard, but with these events, it is being felt that the agency's image and credentials could get affected,” the source added.
It may be noted that a few days prior to the letter, on June 30, the prime minister had chaired a high level meeting to review the planning and preparations for vaccinating the large population of India. A four-pronged strategy had been discussed for a large scale vaccination programme, and issues such as management of medical supply chains, prioritisation of at-risk populations, coordination between different agencies involved in the process, as well as the role of private sector and civil society were discussed. It was decided that vulnerable groups such as doctors, nurses, healthcare workers, non-medical frontline coronavirus warriors, and vulnerable people among the general population would form the first lot of those who would recieve the vaccination.
Post that, the it was decided that the vaccination of “anyone, anywhere” would take place in the second phase, and that the vaccine must be affordable and universal.
However, Rajiv Nath, managing director, Hindustan syringes and medical devices, points out that the government and vaccine manufacturers had still not worked out the delivery mechanism. “Mass vaccination would need adequate supplies of auto-disabled syringes, which few companies in the world can provide. These are specialised syringes for vaccination, and are one-time use only. Few companies in the world have the WHO certification to make these. We have communicated to the PMO and the health ministry that they would need to stockpile these if they are planning to launch the vaccine in the coming months,” said Nath, who is also forum co-ordinator, association of Indian medical device industry. As of now, Nath said that it was unclear what the delivery mechanism would be—vaccines can be different kinds such as nasal spray, intra-dermal—for companies to prepare themselves to supply the required device for vaccine delivery. “If they don't prepare well in advance, there would be shortages. At the last minute, we won't be able to provide the syringes since we already have committed stocks for the immunization programme,” Nath said.
The ICMR may have shot off the letter to fast-track the process, but it seems that there's enough ground to cover than it had accounted for. A vaccine is given to healthy persons, and so, experts say, due processes and scientific rigour are even more important. Else, India will encounter a major loss of face on the international stage, where it is eager to make a mark.
