Explained: What is emergency use approval, why is it done, how is it done, grey areas, and more

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Pfizer and Serum Institute of India have applied for emergency use authorisation of their respective COVID-19 vaccines from the Drug Controller General of India (DCGI).  Bharat Biotech hasn’t officially confirmed, but media reports quoting sources within DCGI, have said that Bharat Biotech, too, has filed for emergency approval.

Pfizer has done a global trial, but India wasn't part of that. To be sure, this may not pose a problem, as, in the past, the DCGI has waived the requirement of local bridge trials on a select basis.

Serum Institute, on November 12, has completed the enrollment of volunteers as part of the bridge trial, and would be relying on its partner AstraZeneca-University of Oxford data for approval. Bharat Biotech has just begun enrolling participants for its phase-3 trials. It hasn't yet published any interim review.

Now, what is an emergency use authorisation, why are companies seeking it even without full data and what are the risks and benefits in allowing the emergency use of vaccines that will be tested on healthy people.

What is emergency use authorisation and when is it triggered?

In an emergency situation, like a pandemic that is causing great human loss and damage to the economy, it may not be possible to have all the data related to safety and efficacy that regulators expect in normal times.

The regulator will have to rely on preliminary data to assess whether the particular vaccine or drug will actually save lives and whether its benefits outweigh risks. The regulators may also take a cue from what the other regulators have done. Based on all this, the regulator will take a call on allowing emergency use.

What is the legal position in India on emergency use approval?

Unlike in the US, in India, the Drugs & Cosmetics Act doesn’t have any specific provision that allows the special use of drugs and other medical products during emergencies like pandemics.

The DCGI approved restricted emergency use of drugs such as broad spectrum antiviral drug Remdesivir, influenza drug Favipiravir and Itolizumab for treating COVID-19 patients.

Gopakumar Nair, a Mumbai-based consultant for Intellectual Property (IP) and other legal matters for drug companies, says if there is an emergency and unmet medical need, and the drug in question has evidence of safety and efficacy, the Indian regulator has the flexibility to approve the drug.

“But once it is approved, they will ask for pharmacovigilance data,” says Nair. Pharmcovigilance refers to post-marketing surveillance.

What is the process of emergency use approval?

To speed up the vaccine approval process, the regulator said it is following an accelerated rolling review, which means it conducts interim analysis of clinical trial data at pre-defined stages like pre-clinical stage, phase-1, phase-2 and phase-3.

The DCGI has established Subject Experts Committees (SEC), which have 10-12 members, to review the data and protocols, and make recommendations on approvals to the DCGI.

Follow Moneycontrol's COVID-19 Vaccine Tracker here.

The minutes of the meetings of SECs are published periodically by the regulator to ensure transparency. Once the emergency use is granted, the DCGI insists companies, hospitals and doctors to monitor patients for side effects. Public health experts have been urging DCGI to disclose details of the members of the Subject Experts Committees to ensure that there is no conflict of interest.

Grey side of emergency approvals?

The DCGI has drawn flak from public health experts for approving drugs such as Favipiravir, Remdesivir and Itolizumab for treating COVID-19 patients, based on limited evidence.

The Indian drug regulator isn't alone, even the USFDA decision to grant emergency use authorisation to antimalarial drug hydroxychloroquine, convalescent plasma therapy and Remdesivir, has generated a lot of criticism.

Many experts alleged that more than scientific evidence, it was political pressure that led to approvals. The USFDA later revoked emergency approval to hydroxychloroquine, after many studies have found that there isn't much evidence that the drug is effective against COVID-19, and also has serious side-effects.

That bitter experience has made USFDA much more cautious while it is reviewing the emergency use applications of Pfizer’s and Moderna’s COVID vaccines. While the USFDA is still reviewing the data, UK’s MHRA went ahead and approved Pfizer’s vaccine for emergency use. The decision baffled even the US government's top infectious disease expert like Anthony Fauci.

Why vaccine may be different from drugs

The approvals of HCQ, Remdesivir and Convalescent Plasma were given, based on limited clinical data, but not randomised clinical trials. Experts say things are different for vaccines as vaccine developers have to conduct double blind randomised control trials - where the volunteers who get the vaccine (vaccine arm) are compared to those who get placebo (control arm).

To ensure there isn’t any bias, both the persons taking the vaccine, and the one who is administering it are blinded, which means they don't know whether it is a vaccine or a placebo.

"So if you look at Pfizer’s vaccine, they did conduct a global randomised clinical trial and they did show that their vaccine is 95 percent effective or the same thing with that of AstraZeneca-University of Oxford. In the case of vaccines, there is data from randomised clinical trials, which is kind of the gold standard and that's the reason why I feel the risk is much less,” Davinder Gill, entrepreneur and former CEO of Hilleman Laboratories, which is into developing novel vaccines.

Gill says that it was only after randomised clinical trials done in blinded fashion that people found out the drugs like HCQ don't have any effect.

"But the risk is still there. Even Pfizer doesn’t have the long-term safety data. That's the reason they are not giving the full licensure to its vaccine. For emergency approval, the USFDA said it needs a follow-up of at least two months for safety data,” he said.

In normal circumstances, companies have to submit follow-up data of vaccinated groups for six months to a year to generate long-term safety data. The Indian drug regulator has stated that if a vaccine demonstrates at least a 50 percent reduction in Coronavirus infection, it will be considered for approval.