India's apex medical body ICMR said Friday that it aims to launch the world's first COVID-19 vaccine, the indigenously developed Covaxin, by August 15, and has told select medical institutions to fast-track its clinical trial approvals. But experts said such a timeline may not be realistic.
The Indian Council of Medical Research (ICMR) has identified 12 clinical trial sites, including medical institutions and hospitals, and has asked their principal investigators to ensure that the subject enrollment is initiated no later than July 7. The trial sites included AIIMS, New Delhi, AIIMS, Patna and SRM Medical College Hospital and Research Centre in Tamil Nadu.
COVID-19 vaccine candidate Covaxin, developed by the Hyderabad-based Bharat Biotech International Limited (BBIL) in collaboration with the ICMR and the National Institute of Virology (NIV), had recently got the nod for human clinical trials from the Drug Controller General of India (DCGI).
Separately, Zydus, which is part of Cadila Healthcare Ltd., said in a statement on Friday that it has received approval from authorities to start human trials for its COVID-19 vaccine contender.
The vaccine candidate, ZyCoV-D, showed a "strong immune response" in animal studies, and the antibodies produced were able to completely neutralise the wild type virus, Zydus said.
In its letter to principal investigators of the 12 sites, ICMR Director General Dr Balram Bhargava noted that the clinical trial of Covaxin is one of the "top priority projects which is being monitored at the top-most level of the government".
"It is envisaged to launch the vaccine for public health use latest by August 15 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," Bhargava said in the letter.
However, it is not clear how the clinical trials can be completed and the vaccine released on August 15 when the normal period for a vaccine to be approved is 12 to 18 months.
Anant Bhan, of the Department of Forensic Medicine at Kasturba Medical College, Manipal, questioned the timeline of the announcement.
"To my knowledge, such an accelerated development pathway has not been done EVER for any kind of vaccine, even for the ones being tried out in other countries. Even with accelerated timelines, this seems really rushed, and hence with potential risks, inadequate attention to process," Bhan wrote in a series of tweets.
"For a vaccine for which pre-clinical development is still ongoing, as per the letter itself, how can clinical trial recruitment be starting on 07th July? And that the vaccine will be launched on 15th August? A vaccine trial completed in little over a month, efficacy pre-decided?" Virologist Upasana Ray said in a pandemic situation like this we are all waiting for a therapeutic handle to manage COVID-19.
She noted while an accelerated launch or promise for launch for a vaccine against this novel coronavirus deserves applause, we also have to think if we are rushing too much.
"We must rush albeit carefully. Giving this project high priority is absolutely important. However, excess pressure might not necessarily lead to a positive product for public use," Ray, senior scientist at CSIR-IICB, Kolkata, told PTI.
In his letter to the 12 sites, ICMR chief Bhargava said: "You have been chosen as a clinical trial site of the BBV152 COVID vaccine. In view of the public health emergency due to COVID-19 pandemic and 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 enrolment is initiated no later than July 7."
Following a flurry of queries from the media about the authenticity of the letter dated July 2, ICMR spokesman Rajnikant Srivastava told PTI Friday that "the letter is genuine and a request has been made to fast track the vaccine trials."
Even though the letter makes it seem as if the apex health research body plans to launch the vaccine by August 15, a scientist from the ICMR clarified that the aim of the letter is to fast track the human clinical trials of the vaccine so that results can come out early.
"Only if the results are satisfactory only then can a vaccine be launched for public. It cannot be otherwise," the scientist, who did not want to be named, said.
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 pre-clinical as well as clinical development of this vaccine, the letter said.
The letter warned the 12 institutes that any non-compliance will be "viewed very seriously." "Therefore, you are advised to treat this project on highest priority and meet the given timelines without any lapse," the letter stated.
A copy of the letter has been sent to BBIL.
India's COVID-19 cases soared by over 20,000 in a day for the first time taking the country's total tally to 6,25,544 on Friday while the death toll climbed to 18,213 with 379 new fatalities, according to the Union Health Ministry data.
Over seven vaccines are being researched in India and only Covaxin and Zydus' ZyCoV-D have got the go-ahead to start human clinical trials, just this week. Globally, over 100 candidates are being tested on humans but no vaccine has yet been approved.
"Zydus has already manufactured clinical good manufacturing practice (GMP) batches of the vaccine candidate and plans to initiate the clinical trials in July 2020 across multiple sites in India in over 1,000 subjects," the company said.
It did not say when the vaccine will be ready for commercial use, unlike Covaxin, which is targeting for release on August 15.
ZyCoV-D, developed at the company's Vaccine Technology Centre in Ahmedabad, has now received permission from the DGCI-Central Drugs Standard Control Organisation (CDSCO) to initiate phase I/II human clinical trials in India, Cadila Healthcare said.
In animal studies, the vaccine was found to elicit a strong immune response in multiple animal species like mice, rats, guinea pigs and rabbits. The antibodies produced by the vaccine were able to completely neutralise the wild type virus in virus neutralisation assay indicating the protective potential of the vaccine candidate, it said.
It further said no safety concerns were observed for the vaccine candidate in repeat-dose toxicology studies by both intramuscular and intradermal routes of administration. In rabbits, up to three times the intended human dose was found to be safe, well-tolerated and immunogenic.
Zydus said, with its ZyCoV-D, it has successfully established the DNA vaccine platform in India using non-replicating and a non-integrating plasmid carrying the gene of interest making it very safe.
The company claimed that the vaccine candidate has no vector response and with the absence of any infectious agent, the platform provides ease of manufacturing the vaccine with minimal biosafety requirements.
It is also known to show much-improved vaccine stability and lower cold chain requirements making it easy for transportation to remotest parts of the country, it said.
"Furthermore, the platform can be rapidly used to modify the vaccine in a couple of weeks in case the virus mutates to ensure that the vaccine still elicits protection," it added.
The company now intends to rapidly ramp up the production capacities of ZyCoV-D at multiple sites and facilities to cater to Indian and global demand.