The emergency use approval in India to the Serum Institute of India (SII) vaccine against Covid-19 developed by AstraZeneca and Oxford University, and the “restricted use in emergency situation” consent to Bharat Biotech International Limited’s locally developed vaccine has triggered a debate among experts — particularly over the decision to clear the Bharat Biotech vaccine despite the shorter duration of human trials and relatively less data.
India’s nationwide vaccination drive is scheduled to begin in January with the AstraZeneca-Oxford shot. Bharat Biotech’s vaccine, according to experts aware of the matter, is a back-up in clinical trial conditions if a spike in cases triggers the need of doses.
AstraZeneca-Oxford got the Drug Control General of India nod based on the safety, immunogenicity and efficacy data generated on 23,745 participants from overseas studies, as well as interim data from Phase 2/3 trials on 1,600 people in India. What boosted its case was that it was granted approval last week by the Medicine and Healthcare products Regulatory Authority in the UK.
Bharat Biotech’s vaccine was approved for “restricted use in emergency situation in public interest as an abundant precaution, in clinical mode, especially in the context of infection by mutant strains” based on safety and immunogenicity data from tests done mice, rats, rabbits, Syrian hamsters; and so-called challenge studies on Rhesus macaques and hamsters, and Phase I and Phase II clinical trials on around 800 participants, according to the drug regulator.
Early-stage trials found the vaccine to be safe and able to invoke a robust immune response, but Phase 2 data is under peer review and has not been published. Phase 3 trials were announced on November 16, and around 22,500 of 25,800 volunteers have enrolled of which around half have received two doses.
“The terminology is very different for the two vaccines, so it does acknowledge that the stages of research for the two vaccines is different. The government will begin vaccinating with the Serum vaccine in the first few weeks, and keep the Bharat Biotech vaccine as a backup till the data becomes robust by the end of this month or the beginning of next month,” said Dr Randeep Guleria, director of the All India Institute of Medical Sciences (AIIMS), New Delhi.
“Emergency use authorisation is standard, which Serum has got. The emergency situation nod for Bharat Biotech means that if there is a surge in the number of cases or if there are issues with vaccine efficacy as far as the first one is concerned, then the vaccine may be used in a clinical trial situation, which will be closely monitored because the data is not sufficient. It is a backup plan for a possible surge in cases, like in the UK, where they have changed the vaccinations schedule from four weeks to 12 weeks because they want to vaccinate as many as people possible. If we are in a similar situation, we will not be able to do it with one vaccine. This (the approval) is just to tell them, okay, go ahead, your current data is good,” he added.
Some other experts, however, argued that even in emergency situations, approval must be granted only after safety and efficacy is irrefutably established.
“It’s absolutely shocking that the regulator has approved the Bharat Biotech vaccine, which has limited data for safety and immunogenicity and no data for efficacy. The Phase 3 trials are still completing enrolment and it is too early for data to meet the criterion for an interim analysis. The only human data available on safety and immunogenicity is on 755 participants in Phase 1 and 2 trials. This amounts to rolling out an untested and unproven vaccine,” said Malini Aisola, co-convenor of All India Drug Action Network (AIDAN), which is a network of non-profit organisation working to increase access to and rational use of medicines.
The vaccines use two different and established delivery platforms. While SII has a recombinant chimpanzee adenovirus vector vaccine (Covishield), Bharat Biotech has developed a whole virion inactivated coronavirus vaccine (Covaxin).
“Covaxin is a whole-viron inactivated vaccine with more potential to target all parts of the virus rather than specific parts. This makes it a more effective tool against the new virus strain found in the UK… even Pfizer recently said that it needs about four to six weeks to make tweaks to their vaccine to adjust to the new mutations in the virus,” said Dr Balram Bhargava, director general, Indian Council of Medical Research, in an interview to HT. ICMR has also partnered in developing the vaccine.
But other experts were not so sure.
“I’m not aware of any data that demonstrates that Covaxin has any efficacy against any strain of the new coronavirus, let alone special efficacy against the (UK) variant strain,” said Dr Gagandeep Kang, clinician scientist, and professor of gastrointestinal sciences at the Christian Medical College, Vellore.
Both vaccines will be administered under government supervision and will not be available to the general public till the data is complete and all trial results are out.
“Restricted emergency use authorisation means only the government will procure the vaccines and decide who will get it under supervision. Under restricted emergency use, these vaccines will not be available commercially, they will not be available to the public on demand. As far as we know as of yesterday, there are no safety issues. The government will give free vaccination to people where protection delayed can be protection denied,” said Dr T Jacob John, senior virologist anda former professor at Christian Medical College, Vellore, Tamil Nadu.