ICMR chief Balram Bhargava: "The pandemic created an urgent need for expedited approaches worldwide"

Phase 3 trials of Covaxin showed the vaccine has 77.8% efficacy against Covid. The findings of the study, funded by the ICMR and Bharat Biotech, were published online by 'The Lancet' on November 11, 2021.

Efficacy against new variants

All RNA viruses, including SARS-CoV-2, mutate or change over time. Most changes have little to no impact on the virus’ properties. However, some mutations may affect the way the virus behaves, such as how easily it spreads, the associated disease severity, or the performance of vaccines, therapeutic medicines, diagnostic tools. WHO has labelled virus strains carrying such mutations, as variants of concern (VoCs) in order to prioritize global monitoring, research and inform the ongoing response to the COVID-19 pandemic.

The bulk of the cases recently recorded in different parts of India as part of the second wave of COVID-1912 are believed to be due to highly transmissible B.1.617.2 variant, called ‘delta’ in the WHO’s new naming system. The WHO has described delta variant as a VoC. Besides the delta variant, other VoCs include the alpha variant, first detected in the UK; beta variant, detected initially in South Africa and gamma variant detected first in Brazil.

In order to assess the protective efficacy of Covaxin against the VoCs, the ICMR-NIV undertook a study to evaluate the neutralization potential of antibodies in blood samples of Covaxin vaccinated individuals against the live variant virus culture samples.

The researchers measured the levels of neutralizing antibodies in the vaccines against the original SARS-CoV-2 strain and compared the neutralizing potential of these antibodies against the four VoCs. Findings of the study demonstrated that the neutralization potential of Covaxin against the alpha VoC was at par with the original SARS-CoV-2 strain. The results further suggested that as compared to the original strain, the neutralizing potential of Covaxin was reduced against beta, gamma and delta VoCs, but still the antibody titres were good enough to neutralize these VoCs.

‘The COVID-19 vaccines have set the record for fastest development of any vaccine in history,’ Dr Krishna Ella said, with a justifiable amount of pride. He pointed out that in normal times it would take close to 10 years to develop a vaccine, sequentially carry out all the different trials required for safety and efficacy and then get the necessary regulatory clearances.

However, the pandemic created an urgent need for expedited approaches worldwide. Innovative designs were instituted by researchers and industry wherein established and previously tested platforms of vaccine development such as prequalified cell lines, vector backbones, recombinant gene approaches, virus like particles, nanoparticles, lipid envelopes and tested adjuvants were used. Additionally, preclinical and clinical development pathways were run concurrently and not sequentially, cutting down the timeline to about 10 months.

The Indian regulator, DCGI, adopted the innovative mechanism of a ‘rolling review’ of data emerging from ongoing vaccine trials, to speed up the process of authorizing new vaccines for public use. It also devised strategies for granting EUA on humanitarian grounds in a public health emergency, while prioritizing science and ethics.

For example, the DCGI accorded EUA to two vaccines, Covishield and Covaxin, on the first two days of 2021, following which India became one of the global leads in COVID-19 vaccine introduction. The rules safeguarding the integrity and ethics of medical research are the toughest among regulatory mechanisms anywhere. This is simply because anything to do with medicine is usually a matter of life and death and only the highest standards are acceptable.

However, in the kind of dire health crisis created by the COVID-19 pandemic, such rules worldwide have had to be tweaked to speed up research or clinical trials that may be of great public benefit if proven successful. This calls for innovations to regulatory processes that may never have been tried out earlier under normal circumstances, with uncompromised scientific quality, participant safety and ethical practices.

For example, in the course of the COVID-19 pandemic, several therapies that showed promising results were approved by Indian drug regulators under the EUA powers vested with them. This was done on the grounds that the known and potential benefits of the therapy outweighed its known and potential risks. However, some of these were also withdrawn subsequently with availability of new research that showed their benefits were not significant enough.

An innovation to the rules was similarly required, when the developers of Covaxin presented their implementation plan, after completion of animal studies to check for safety and efficacy, to test out the vaccine on human subjects. The clearance was given in early 2021 under the novel  concept of ‘clinical trial mode’, used for the first time in India. This was done while the Phase III trials of the vaccine were ongoing and clinical efficacy was yet to be established.

While giving it the green light, the Central Drugs Standard Control Organization (CDSCO), which approves all new drugs and clinical trials in the country, imposed various restrictions and conditions to be followed. It stipulated, for example, that the vaccine be used after informed consent of the individual and all recipients be followed for safety and tracking of adverse events. 

Since the term ‘Clinical Trial Mode’, was used for the first time by the CDSCO, there were still many grey areas regarding its meaning, components and implementation. To help obtain greater clarity the ICMR-Central Ethics Committee on Human Research (CECHR) decided to put together a panel of experts to discuss its implications, especially concerns regarding medical ethics and also the implementation modalities.

Recommendations from the experts focused on measures to minimize risk and improve transparency and accountability. These included a simple yet fully informative consent form—translated into all Indian regional languages—and distribution of good quality advocacy and information material for better public understanding of the trial process.

Excerpted with permission from Rupa Publications.

Also read: Ideal time for booster dose for COVID vaccine is 6 months after 2nd dose: Bharat Biotech MD Krishna Ella