During pandemic, vaccine's restricted use considered based on safety, immunogenicity data: ICMR chief

In a pandemic situation, restricted emergency use of vaccines is considered based on safety and immunogenicity data while phase three clinical trial is underway, Indian Council of Medical Research (ICMR) chief Balram Bhargava said on Tuesday.

Explaining the process followed in granting nod to Oxford Covid-19 vaccine and indigenously developed Covaxin, he said, "The existing pandemic situation, high mortality, available science and lack of definitive treatments were considered by the subject expert committee (SEC) on Covid-19 of CDSCO for granting accelerated approval to these vaccines, and that is in our legal provision."

The Drugs Controller General of India (DCGI) had on Sunday approved Oxford Covid-19 vaccine Covishield, manufactured by the Serum Institute, and indigenously developed Covaxin of Bharat Biotech for restricted emergency use in the country, paving the way for a massive inoculation drive.

Industry experts and some opposition leaders have expressed concern over the absence of Phase 3 trial data on Covaxin. The critics have cautioned that "sidestepping" processes and giving "premature" clearance could risk lives and fuel vaccine hesitancy in India.

"In a pandemic situation, restricted use is considered based on safety and immunogenicity data while phase three clinical trail is still ongoing. The immunogenicity data generated through phase two clinical trial serves as a surrogate for efficacy. The Clinical Trial Rule, 2019, provides for considering phase two results to guide approval.

"Now the SEC guides the DCGI in the process of decision making for restricted use under emergency situation. Now we have two vaccines," Bhargava said.

Providing details of the UK studies of Covishield, the ICMR chief said animal studies showed that vaccine prevented SARS-CoV-2 pneumonia in monkeys and have elicited good immunogenicity in mice.

The phase one and two clinical trials in 1,077 participants showed an acceptable safety profile, and homologous boosting increased antibody responses. Phase two and three in prime-boost regimen in 560 participants showed it was better tolerated in older adults than in younger adults and has similar immunogenicity across all age groups after a boost dose. The result was published in the Lancet, the ICMR chief said.

Phase 3 trial in 11,636 participants from UK and Brazil, with two standard doses, showed vaccine efficacy was 62·1 per cent, in case of a low dose followed by a standard dose, the efficacy was 90 per cent. Overall, Covishield efficacy was 70·4 per cent. This has been published online last month, he said.

As for Covishield's phase two and three clinical trial in India, there were 1,600 participants aged than 18 years. Their immunogenicity data is being generated, more than half is available. Covishield is safe and immunogenic and the data showed that it is "non-inferior to the UK product," Bhargava said.

"It was an important point that led to the approval." he added.

As for Covaxin, Indian studies on animals such as rats, mice, rabbits, hamsters and monkeys showing excellent safety, immunogenicity. It showed robust viral clearance in both the upper and lower respiratory tract in large animals.

The phase one and two clinical trial on 375 and 380 participants respectively revealed very low adverse events, Bhargava said, adding, "It showed neutralising antibody responses equivalent to human convalescent serum, strong antibody responses to all structural proteins... three months after vaccination."

The phase three clinical trial will include 25,800 participants of which 24,000 have been enrolled so far. There are no safety concerns. They (participants) have been given their first dose and more than 5,000 give the second jab.

"Permission for restricted use in clinical trial mode has been allowed which means consent of participants has to be taken and there has to be a regular follow up of participants," Bhargava said.

Explaining further, he said the manufacturer of Covaxin has been requested by the drug controller to provide the protocol for the clinical trial mode.

Clinical mode means everyone will give consent for the vaccine, there will be no placebo and there will be a closer follow up.

"As for the publications of Covaxin (trail), the animal studies have been published in Nature Communications and High science which is a cell journal. The phase one trial was being published in Lancet Infectious Diseases... and the phase two paper is under review there. They also have the protocol of phase three which is also under review by the British Medical Journal."

"There is another important publication in the Indian Journal of medical research which has compared the large animal data in all vaccine products and has shown the efficacy of this as well," Bhargava said.

Referring to The New Drugs and Clinical Trial Rules issued on March 19, 2019, he said it clearly states that if remarkable efficacy is observed with a defined dose in the Phase 2 clinical trial of investigational new drug for the unmet medical needs of serious and life threatening diseases in the country, it may be considered for grant of marketing approval by the Central Licensing Authority based on Phase 2 clinical trial data.