Regulatory approval of COVID-19 vaccine for restricted use in clinical trial mode

Covaxin is India's first indigenous vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), developed through a collaboration between Bharat Biotech and the National Institute of Virology, which is a branch of the Indian Council of Medical Research, the Indian official authority for medical research. The development team isolated a strain of SARS-CoV-2 from patients with asymptomatic infection and developed a vaccine on a Vero cell-line manufacturing platform to deliver the inactivated coronavirus strain. On Jan 3, 2021, the vaccine was granted approval “for restricted use in emergency situation in public interest as an abundant precaution, in clinical trial mode”,¹ which raised several concerns across the scientific society.²

There is an urgency and a feeling of moral obligation to get the vaccine to the public as early as possible, based on large-scale evidence on its safety and efficacy. However, the approval of a partly studied vaccine through an accelerated process on the basis of results from phase 1 and 2 clinical trials³ and incomplete data on the vaccine's efficacy for peer review has raised more questions than answers. Emergency-use authorisation can be given only after confirmation of safety and efficacy in a phase 3 clinical study that is usually designed and conducted to meet requirements of subject-expert committees and regulatory authorities. In exceptional circumstances, approval might be considered when the ongoing trial is based on strong evidence of safety and efficacy.

It is difficult to understand the term restricted use when applied to vaccines, as it is ordinarily applicable to drugs. Even greater confusion arises with use of the phrase clinical trial mode since its meaning is ambiguous. It is understood that clinical trials are yet to be completed and need consent and follow-up. It is unclear which factors will guide the selection of individuals for vaccination. In clinical trials, volunteers are usually not aware of whether they have been given the vaccine or a placebo.²

India's innovation in vaccine development might be considered a giant leap and source of pride for its scientists, but there is a need to clear the air and gather public trust through transparency. When public trust in an indigenous vaccine is low, manufacturers, their academic partners, and regulators must disclose protocols and results data. Lack of desirable diligence and conscientiousness in conducting confirmatory clinical trials is a matter of concern for citizens. Once public trust in Covaxin is compromised through the public media, it is difficult to revive. This distrust in the vaccine can fuel apprehension and lead to a vaccine-hesitancy chain reaction, which could contribute to resurgences in the virus and lack of control of the pandemic.