The Covaxin Conundrum: Has India’s Drug Regulator Wrongly Invoked The Emergency Use Law?

The approval granted to one of the two Covid-19 vaccines, Covaxin, is under severe criticism from medical experts. Covaxin is an indigenously developed vaccine, produced by Bharat Biotech in collaboration with the Indian Council of Medical Research (ICMR).

The Indian drug regulator, Drug Controller General of India (DCGI), approved it for emergency use along with another vaccine Covishield on January 3. Covaxin’s Phase III trial started from November 11 and it was granted emergency use approval in less than two months.

Dr. Balram Bhargava, DG, ICMR, referred to the legal provision in the New Drugs and Clinical Trials Rules, 2019 in a media briefing and said that according to the rules, a new drug can be granted approval after a Phase II trial in an emergency situation.

Section 1 (2) (ii) (A) (d) of the second schedule of the New Drugs and Clinical Trials Rules, 2019 says, “If the remarkable efficacy is observed with a defined dose in the Phase II 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 Licencing Authority based on Phase II clinical trial data.”

It further states, “In such cases, additional post licensure studies may be required to be conducted after approval to generate the data on larger population to further verify and describe the clinical benefits, as per the protocol approved by the Central Licencing Authority.”

However, many legal and medical experts have opposed the drug regulator’s move and said that the government has invoked this provision in a highly inappropriate and objectionable manner. “In a highly emergency situation, you can do that. But is there an emergency in India?” noted epidemiologist Dr. Jayaprakash Muliyil questioned.

Dr. Muliyil also said that things are already returning to normal in India while other countries are still suffering. “I think some people don’t want to recognise the fact that it is happening through a natural process in India. They want to come and claim that they beat coronavirus. No one can beat Coronavirus. It is the people of India who have defeated the virus,” he added.

India is the only country that is using a vaccine for universal immunisation without having any data of phase III trial.

According to the New Drugs and Clinical Trial Rules, 2019, the first phase tests the safety and tolerability on a very small group of volunteers; the second phase assesses effectiveness on a comparatively large group, and then the third phase confirms the finding of phase II on more number of participants. The fourth phase involves post-marketing trial after the drug is approved.

Supreme Court lawyer DK Garg says that according to the law if the Phase II trial shows remarkable efficacy then the regulator can permit a drug for emergency use. "Where is the Phase II data? How do we know how many volunteers participated and what is the result? I think this is an abuse of the law by the regulator."

Garg also questions the regulator's decision to use Covaxin under 'clinical trial mode'. "There is no mention of clinical trial mode in the law," he said.

The drug regulators in the US and the UK have given approval for emergency use only after examining the phase III Clinical trial data.

In a recent Facebook interaction, Dr. Anthony Stephen Fauci, the top US physician and immunologist, said that to grant emergency use authorisation to Pfizer and Moderna vaccine, the US Drug regulator, Food and Drugs Administration (FDA) asked them to wait 60 days from the time 50 percent of the people in the Phase III trial got their last dose.

37,000 and 30,000 volunteers had completed phase III trial of Pfizer and Moderna respectively. The purpose of 60 days wait was to identify the toxic side effects of the vaccine.

“The overwhelming majority of 90 plus percent of them (adverse side effects) occur between 30 and 45 days after the vaccine trial ends,” Dr. Fauci said adding, “If you wait for 60 days, you are already beyond when essentially all of the long-term effects occur.”

Doctors say that the most crucial aspect before giving approval to any drug for an emergency situation is to see if the benefits outweigh its risk.

“Where was the occasion for the government to assess if the benefits outweigh the risk where there was no data for phase III trial?” Dr. Rahul Bhargava, Director, Department of Clinical Hematology & Bone Marrow Transplant, Fortis Hospital in Gurugram, said.

He added, “If the phase III trial was started on November 11, very few volunteers would have got their second shot by January 3. We didn’t even wait for 30 days to see the adverse effects.”

Dr. Srinivas Rajkumar, General Secretary, Residents Doctors Associations, AIIMS Delhi has also flagged a similar concern.

“Eminent microbiologists like Dr. Gagandeep Kang have expressed their reservations over the deployment of Covaxin for universal immunization in the absence of any data on its efficacy. I think the government is invoking the available legal provision in a wrong and inappropriate manner,” Dr. Srinivas said.

Many doctors say that irrespective of what is there in the New Drugs and Clinical Trials Rules, 2019, the DCGI had said in its guidelines that vaccine manufacturers need to have 50 percent efficacy data for emergency use authorisation. Now, the DCGI has departed from its own guidelines.

Resident Doctors' Association of Ram Manohar Lohia Hospital in Delhi has already written to hospital administration that doctors are apprehensive about the lack of complete trial in case of Covaxin and might not participate in huge numbers thus defeating the purpose of vaccination.

It has asked the hospital administration to vaccinate them with Covishield which has completed all stages of the trial before its rollout.

Amulya Nidhi, a petitioner in Supreme Court on Clinical Trial issues, said, “I have been fighting a case in Supreme Court on various shortcomings in the Clinical Trial rules in India. The Emergency Use Authorization issue has come to my knowledge and I will challenge its validity too.”