The Subject Expert Committee, which evaluates applications for clinical trials of potential coronavirus vaccines, has said that Hyderabad-based pharmaceutical company Bharat Biotech should submit results of the Phase I clinical human trial of Covaxin to the Drugs Controller General of India before starting the Phase II trial, The Indian Express reported on Tuesday.
At a meeting on June 15, the expert committee of India’s drugs regulator also specified four conditions that companies have to meet for vaccine development. It did not set any deadline for the vaccine launch.
This happened a fortnight before the Indian Council for Medical Research wrote to 12 hospitals and medical institutions to speed up the trial process of Bharat Biotech’s vaccine and to launch Covaxin by August 15 for public use. Medical experts expressed concern that the speedy trials would compromise patient safety and ethics. However, the leading clinical research agency had last week claimed that its letter was simply meant to “cut unnecessary red tape” and “speed up recruitment of participants”. The letter, signed by ICMR Director General Balram Bhargava, became controversial after it was seen as exhorting scientists to speed up the processes.
An investigator who is part of the trial said “immunogenicity” – the ability to provoke an immune reaction – will be examined closely and will also decide if the trial of the vaccine can move from Phase I to II. “Even with Covid-19, those with a mild infection don’t have that many antibodies,” the investigator told the newspaper. “What immune response we will get, is the key question. This process may take a few months. You have to examine if the vaccine is able to produce enough neutralising antibodies to fight the virus.”
Covaxin was approved on June 29 for Phase I and Phase II clinical trials. To launch it by August 15 would involve either skipping or rushing through the Phase III trial, which tests the efficacy of the vaccine on a large number of participants and takes the longest to complete. Each phase can last months, if not years, and although regulators globally have been fast-tracking trials on medicines and vaccines to treat the infection, the timeline proposed in the ICMR letter is said to be unprecedented.
Another investigator said Phase I alone was likely to take at least three months. “Diverse populations have to be enrolled,” he told The Indian Express. “We have to check if the vaccine is equally effective in the young, elderly, and people with comorbidities. There is no way this can be done in a month. Besides the analysis of the data, the recruitment for the first phase will go on till October.”
The investigator further added that the process “cannot be fast-tracked”, adding that examining side effects will be the most important. “There is vaccine-related enhanced respiratory syndrome, where you have vaccine-led infections of lungs and airways that cause an immune reaction,” he said. “Then, you have a reaction because of the vaccine, which enhances the infection. This happened during the development of the vaccines for HIV and measles. The vaccine produces antibodies that are not sufficient – and they enhance the severity by allowing more of the virus to enter the cell.”
Meanwhile, the Subject Expert Committee said that clinical trial sites of the vaccine should have facilities to handle emergency situations such as anaphylaxis, which is a severe allergic reaction. It added that the investigators should have appropriate qualification and experiences necessary to undertake the study.
“RT-PCR [reverse transcription polymerase chain reaction] test should be used as confirmatory test for Covid-19 during screening,” the committee said. These conditions were laid out after the drug company presented data on “safety” and “immunogenicity” collected during pre-clinical trials conducted on rats, mice, and rabbits.
Experts said that the above conditions will take the coronavirus vaccine trial longer than the schedule set by the ICMR.
On July 5, the Ministry of Science and Technology had said that the development of a potential coronavirus vaccine “is unlikely to be ready for mass use before 2021”, but later edited the press release to remove that specific line.
World Health Organization Chief Scientist Soumya Swaminathan had also said that the development of a potential coronavirus vaccine must show efficacy and safety, adding that the completion of its trials could take six to nine months. So far, no vaccine has been approved for commercial use against the coronavirus.
The World Health Organization said last month that United Kingdom pharma firm AstraZeneca’s experimental vaccine was probably the leading candidate. The vaccine was developed by researchers at the University of Oxford. However, even this vaccine is not likely to be ready for human use until early next year.
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