COVID-19 vaccine approval: Expert committee meeting minutes do little to inspire confidence in process

It has come to light from a perusal of the minutes of the Subject Expert Committee (SEC) meetings, which were released by the Central Drugs Standard Control Organisation (CDSCO) on Tuesday, that the SEC changed its mind about Bharat Biotech’s Covaxin within a span of two days.

Further, the approval for Serum Institute of India’s vaccine candidate Covishield has been given on the condition that the firm would submit safety, efficacy and immunogenicity data from the ongoing national clinical trials. Covishield is the Indian version of the vaccine developed by the University of Oxford and pharma company AstraZeneca.

India’s drug regulator approved the two COVID-19 vaccines on January 3 and the Drugs Controller General of India VG Somani said that though Covaxin was still recruiting participants, it was needed to control the spread of the new variant of SARS COV2, which was first found in the United Kingdom.

Minutes of the SEC’s meetings show that on December 30, the members had asked Bharat Biotech to present the immunogenicity, safety and efficacy data for consideration. On January 1, 2021, the committee noted that efficacy was yet to be demonstrated through the clinical trials and requested the company to expedite recruitment for Phase 3 trial. The committee members noted that the company could perform interim efficacy analysis, which could then be submitted for consideration of restricted use.

But on January 2, the firm presented ‘updated data’, though it was not specified what the ‘updated data’ was. The company only presented efficacy data from the non-human primate challenge study. At the meeting, Bharat Biotech provided justification for the data provided and additionally requested consideration of their proposal in the wake of incidence of new mutated corona virus infection.

Eventually, the SEC “recommended for grant of permission for restricted use in emergency situation in public interest as an abundant precaution, in clinical trial mode, to have more options for vaccinations, especially in case of infection by mutant strains”.

It is not known if there was political pressure to approve the locally developed vaccine during these three days. There were several tweets and posts questioning the approval for the so-called ‘English vaccine’ and not the Indian vaccine.

“If you look at the minutes of the meeting from December 30 and Jan 1, 2, there is an intellectual leap. On the first two days, they are asking for data on immunogenicity and efficacy and then on Jan 2, they are saying they have considered Bharat Bio’s request and will be giving them ‘emergency approval’. There is no mention of data. The minutes do not reveal what made the SEC change its mind about the data submitted by Bharat Biotech over the course of two days,” said Chinu Srinivasan of All India Drug Action Network (AIDAN).

Public health expert Dr Anant Phadke agreed. “ On December 30, the committee members had one view and two days later, they had another view when in reality the material reality has not changed. These are experts, so why did they not realise the same thing on December 30 itself,” asked Phadke. He added that this significant shift of stand and the CDSCO’s decision hardly inspires confidence.

He said that the minutes still did not clarify what ‘in clinical trial mode’ meant. “Does it mean the vaccine-recipients will get compensation if there is a vaccine injury? In a clinical trial, all participants are eligible to get compensation in case of adverse events. There is silence on this. This has to be clarified,” pointed out Phadke..

In America, Pfizer was given emergency-use approval only after the efficacy data was submitted. “Why didn’t they wait for the interim efficacy data before the permission was given?” questioned Srinivasan.

The Serum Institute of India (SII) on December 30 submitted safety immunogenicity and efficacy data of phase 2 and 3 clinical trials of AstraZeneca vaccine carried out in UK, Brazil and South Africa. Along with it, safety and immunogenicity data from the ongoing Phase 2/3 clinical trial of Covishield vaccine being manufactured by SII was also submitted. The SII informed the committee that AstraZeneca had received emergency use authorisation for the vaccine in UK subject to various conditions and restrictions.

Then on January 1, SEC observed that the safety and immunogenicity data presented by the firm from the Indian study is comparable with that of the overseas clinical trial data.

Here too, the committee decided to consider the serious nature of the COVID-19 pandemic to grant of permission for restricted emergency use of the vaccine subject to certain conditions. SEC noted that it could only be administered to those above 18 years of age and SII must submit safety, efficacy and immunogenicity data from the ongoing clinical trials nationally and internationally for review. The company has also been asked to submit the India specific risk management plan.

“We heard from the reliable sources that SII only submitted data for 100 persons and not that of all the 1,600 participants. The government should clarify this and release the data they relied on. Did they consider only UK's Medicines and Healthcare Products Regulatory Agency (MHRA) data? It is not clear as to why SII has not submitted independent efficacy studies comparing efficacy of the SII produced vaccine and the Oxford-produced vaccine,” said Srinivasan.

Dr Phadke asked whether the situation in India is desparate like in UK? On the contrary, Covid-19 cases are on a downward trend. He contended that when such quick approvals are given there is always some compromise.

“The new virus is only faster, not deadlier. At the most, what will happen is that the spread will be faster. The possibility of a faster spread has been exhausted in Indian cities. All of this does not inspire confidence in the decision-making process,” underscored Phadke.

Earlier, AIDAN had said that CDSCO guidelines state that SII is required to carry out a bridging study to prove that its vaccine Covishield can elicit an immune response comparable with the original AstraZeneca vaccine amongst Indians.

Dr Gagandeep Kang, microbiologist at the Christian Medical College in Vellore and a board member of the Coalition for Epidemic Preparedness Innovations, had underscored, in a news report, that vaccine makers must show a minimum efficacy of 50% in phase 3 trials for their vaccines to be approved. “CDSCO has gone against its own guidelines,” pointed out Dr Kang.