India approved its own Covid-19 vaccine before it completed its human trials

New kid on the block.
New kid on the block.
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This post was updated following a Bharat Biotech press conference today (Jan. 4).

India’s drugs regulator has finally granted approvals to two Covid-19 vaccines, nearly a month after the drug makers filed an application.

At a press conference yesterday (Jan. 3), VG Somani, head of the Central Drugs Standard Control Organisation (CDSCO), announced that India had granted emergency-use authorisation to Covishield, the Oxford-AstraZeneca vaccine being manufactured by the Serum Institute of India, as well as to the locally developed Covaxin, from Bharat Biotech. Earlier reports said that Pfizer had made a similar application in India, but neither the Indian government nor the vaccine maker has an official update on the progress of that filing.

The nod for Covishield was expected after it was approved in the UK, where it is being administered from today. AstraZeneca began its phase 3 global trials in August, and released interim results from those trials in December, with some question marks along the way. But the green light for Bharat Biotech’s Covaxin has drawn even more questions from experts.

Covaxin is India’s first indigenous vaccine against the novel coronavirus, developed through a collaboration between Hyderabad-based pharmaceutical company Bharat Biotech and the Indian Council of Medical Research, the Indian government’s top body for medical research. The fact that it was granted an approval for emergency use just seven weeks into its phase 3 human trials has raised eyebrows in the medical community.

“The decision to approve an incompletely studied vaccine, even under accelerated process, raises more questions than answers and likely will not reinforce faith in our scientific decision-making bodies,” Malini Aisola, of the All India Drug Action Network (AIDAN), an independent collective of healthcare non-profits, said in a statement.

While AIDAN has raised concerns over the lack of complete data for Covishield—both from Indian and international trials—it has opposed the approval for Covaxin entirely.

What we know about Covaxin’s human trials

The Indian government, in its press release, said that the approval for Covaxin has been granted on the basis of “safety and immunogenicity data,” which is generally derived from phases 1 and 2 of clinical trials. The statement announcing the approval lacks any efficacy data for this vaccine, which is arrived at once phase 3 trials are concluded. After a dosing regimen that involves two shots, the volunteers need to be tracked and tested until enough of them have contracted Covid-19 to allow the jab’s efficacy to be analyzed.

In Bharat Biotech’s case, the phase 3 trials for Covaxin began on Nov. 16, 2020. In a Dec. 22 statement, Covaxin said it had recruited 13,000, or half of its target for these trials. The government’s statement states that roughly 22,500 volunteers have been vaccinated, and the vaccine has been found to be “safe,” but didn’t provide further details.

The Indian drugs authority also said that it had read Bharat Biotech’s data from animal trials in“species such as mice, rats, rabbits, Syrian hamster.” The drug maker’s phase 1 and 2 trials, concluded with 800 participants, “have demonstrated that the vaccine is safe and provides a robust immune response,” according to the drug authority.

Bharat Biotech released its phase 2 trial study (pdf) 10 days ago, in which is stated that its SARS-CoV-2 vaccine “led to tolerable safety outcomes and enhanced humoral and cell-mediated immune responses.” This study has not been peer-reviewed yet.

At a press conference today (Jan. 4), Krishna Ella, chairman and managing director of Bharat Biotech, said that the fast approval from India’s drugs regulator came because Covaxin has been developed on top of a proven vaccine platform. He referred to a notification from the CDSCO in 2019: “If yours is a proven platform technology, safe platform technology, and good pre-clinical trial data is available, then you can get emergency license for the product.”

Covaxin uses the Vero cell line manufacturing platform—using cells from the kidneys of African green monkeys—to deliver the inactivated novel coronavirus strain. Unlike the new mRNA technology that Pfizer uses, the Vero cell vaccines have been in use for a long time against diseases such as rabies and polio virus.

Still, the phrasing of the government statement announcing Covaxin’s approval has also contributed to confusion.

Approval, but “in clinical trial mode”

While approving Serum Institute of India’s Covishield, the India drug regulator used fairly standard language.

“After detailed deliberations, the Subject Expert Committee has recommended for the grant of permission for restricted use in emergency situations subject to certain regulatory conditions. The clinical trial ongoing within the country by the firm will continue,” the statement read.

It said it had examined data from close to 24,000 trial participants overseas that showed the jab had a 70% efficacy rate, and that the data was comparable to interim results from a small phase 3 trial in India.

For Covaxin, however, the regulator granted an approval “in clinical trial mode.”

Experts appeared surprised by this qualifier. When asked what the phrase means, Gagandeep Kang, a microbiology professor at Christian Medical College in the southern city of Vellore, told The Times of India, “I have no clue. I have never seen anything like this before.”

Health minister Vardhan has explained that the “clinical trial mode” would mean that all vaccine recipients will be tracked as if they’re in a trial, and that the approval would add another tool to India’s arsenal against the coronavirus. But given that all vaccine recipients must register with the government, it’s unclear how tracking for Covaxin will differ or be more robust than that for the Covishield vaccine.

Randeep Guleria, director at the All India Institute of Medical Sciences, has said that Bharat Biotech’s vaccine can be used as a “backup” in an extreme emergency, for example if the variant strain of the virus—first noticed in the UK and believed to be more infectious—causes an exponential rise in the number of Covid-19 cases in India.

What definitely isn’t known about the vaccine

Though Covaxin’s efficacy trials and data aren’t complete yet, top health officials in India have still made major claims about how it might perform for mutations of the virus.

For example, Balram Bhargava, the ICMR chief, claimed yesterday that Covaxin can potentially act against such strains more effectively. His statement appeared to be based on the fact that Covaxin uses the inactivated coronavirus, unlike Pfizer’s mRNA carrier, or Oxford’s adenovirus.

“We know that the virus has undergone mutations including in the spike protein. Pfizer has said that they will need six weeks to modify the vaccine. But because Covaxin is basically the whole virus killed, it is more likely to act against the mutant strain too,” he told ThePrint in an interview. This was a view echoed by India’s health minister Harsh Vardhan, too.

Neither the government nor the ICMR have released any data to back this claim, and health experts say that therefore isn’t any way to substantiate such a claim.

“I’m completely unaware of any data that suggests that Covaxin has any efficacy against any strain of [Covid-19], let alone special efficacy against the variant (UK) strain,” Kang, the microbiology professor, told CNBC-TV18 in an interview.