Health workers at a Boston hospital broke into a celebratory dance on receiving their first doses of COVID-19 vaccine recently. In India, even before the vials are ready, competition is emerging over who will have the first access. With the vaccine in the final trial phase, India faces the looming challenge of producing the quantities necessary to provide immunity to all its citizens.
Globally, pharma companies are racing ahead to roll out vaccines to fight COVID-19, including the new highly infectious strain that has been found in Britain. Daily life cannot find a new normal until populations have built up antibodies to fend off the virus. Never in history has the entire world come together to produce and distribute globally the much-awaited vaccines.
England took the lead on December 8th to administer the vaccine, developed jointly by Pfizer and BioNTech. It was followed by the US, which has approved two vaccines, with other countries set to follow suit soon.
India will start vaccinating its 1.39 billion population once the drugs are formally approved. But is the country prepared to cover the massive numbers?
“The current plans do not show signs of being based on any realistic numbers or estimates,” says Dr Satyajit Rath, Visiting Professor, IISER Pune.
India’s mega vaccination campaign, expected to begin in the first quarter of 2021, will cover 300 million citizens in the first round by August. The first shots will be given to 30 million people,10 million health care providers, and 20 million frontline workers, including police, defence and municipal workers. Next will be 270 million people above 50, and anyone with associated co-morbidities. Later, depending on the disease epidemiology and vaccine availability, the remaining population will be immunised.
States have been asked to prepare vaccination strategies and some have formed task forces at state, district and block levels. Over 20,000 health workers in about 260 districts have been trained so far to administer the vaccine.
So far, three vaccine groups have sought emergency approval in India –Pfizer, Serum Institute of India (SII) and Bharat Biotech. SII is conducting phase-3 trials of the Covishield vaccine, developed by AstraZeneca and Oxford University. Trials are on for COVAXIN, developed indigenously by Bharat Biotech (BB) and the Indian Council of Medical Research (ICMR). Dr Reddy’s Laboratories is on the phase 2/3 trials of the Russian Sputnik V. Another pharma company Biological E. Ltd has recently started early phase 1 and 2 human trials of its COVID-19 vaccine candidate.
The vaccines can be approved only after complete data on Phase 3 trials is submitted to the country’s drug controller which has so far refused to fast track approvals sought. Pfizer, for instance, does not have enough data on trial participants of Indian ethnicity, and hence may be asked by the drug regulator to conduct a local trial.
Dr Rakesh Mishra, Director, CSIR-Centre for Cellular and Molecular Biology (CCMB), points out that credibility is a major issue. “We shouldn’t take shortcuts which may backfire,” says Dr. Mishra. “I am not sure how good these vaccines are. That we will only know after one or two years. But, at least, the process will begin, though it is not known for how long the vaccines will offer protection. Most probably they are triggering immune response. But whether that immune response is protected from infection for six months to a year we don’t know. That is why vaccines take four years to develop. We have now done it in one year.”
Pfizer and BioNTech SE claim that their vaccine candidate is 95% effective, while Moderna’s vaccine candidate has an efficacy of 94.5%, it claims. Their vaccine needs to be kept at -70C (94F) and lasts only five days in a regular fridge. Experts believe that India-made vaccines would be better suited for use in the home climate and more easily available.
Lack of clarity
Dr Nirmal Kumar Ganguly, former director-general of ICMR, however offers a different view. “Since the Pfizer vaccine is the only available vaccine which has undergone reviews from UK FDA, US FDA, Canada health, Israel FDA and Saudi Arabian FDA, it can be first given in India to frontline health care workers,” says Dr Ganguly. “These can be assembled at the point of vaccination within hospitals or designated points in the districts”.
Some vaccine groups may get a licence in the next few weeks, the health ministry has said, even though their efficacy is yet not clear. But the ministry has not specified a date. There is also the issue of liability to be sorted out, in case the vaccines cause serious side effects among recipients.
After receiving the Covishield (SII) vaccine on October 1st, a 40-year-old volunteer from Chennai had experienced severe headaches and was unable to respond to questions. Apart from SII, BB also saw an adverse event during clinical trials in August of its Covaxin. But these incidents did not lead to suspension of trials unlike the UK’s AstraZeneca and the US’ Johnson and Johnson, which had paused its clinical trials. In the US, roughly five serious adverse reactions to Pfizer and BioNTech SE’s vaccine were reported since the drive started on December 14th.
India’s decision makers say adverse events “will not affect the timelines in any manner whatsoever.” Ahead of the mass immunisation programme, the government expects to share guidelines on vaccine safety with states to make people aware of the benefits of a vaccine.
Once approved, vaccine distribution is bound to face a mammoth task in logistics, storage, supply and distribution. However, the government appears confident. The health ministry says that 29,000 cold chain points, 240 walk-in coolers, 70 walk-in freezers, 45,000 ice-lined refrigerators, 41,000 deep freezers and 300 solar refrigerators have already reached state governments.
The government plans to use its existing universal immunisation programme (UIP) infrastructure. UIP, one of the largest and most cost-effective public health interventions in the world, covers nearly 27 million newborns and 29 million pregnant women annually.
However, public health experts believe that the government will have to increase the infrastructure manifold for COVID vaccination, especially in large and dense population areas. This would mean colossal funding. The Serum Institute has said that a whopping Rs 80,000 crore would be required for vaccine distribution for the next one year.
There is still no clarity from government on the distribution plan. “The first step is dependable clarity on the kinds, numbers and delivery time schedules for the supply of vaccines from manufacturers,” says Prof Rath. Major concerns are vaccine transportation and storage in far-flung and hard-to-reach regions.
“For remote destinations, vaccine boxes with dry ice are shipped,” says Dr Ganguly. “The vaccine, once unpacked, can stay at 2 to 8 degrees C for one week in the case of Pfizer. The vaccines are taken out of their storage three hours before vaccination. India already handles -20 degree C for Rota vaccine”.
Prof Rath disagrees, arguing that ultra-low-temperature-storage vaccines cannot be effectively deployed for large-scale vaccination for public healthcare in India as reliable decentralised storage facilities “do not exist, nor can be created quickly enough on the appropriate scale. Such vaccines will have a relatively limited role, perhaps through the private health care market in metropolitan centres”.
But Dr Shahid Jameel, Director, Trivedi School of Biosciences, Ashoka University, feels that all these challenges have already been handled in India’s UIP. “There is experience and knowledge for managing all this,” says Dr Jameel. “The real challenge would be to achieve significant coverage.
“Very large numbers of adults would have to be immunised in a relatively short period, and the behaviour of adults is a factor. This has never been done earlier. One is already seeing all kinds of misinformation and recent studies show only 50% people are willing to take COVID vaccines. Good communication will be the key, adds Dr Jameel, who believes herd immunity is the goal. “That is how you end the pandemic. Herd immunity is a concept better applied to vaccines than infection. When a lot of people in a community are vaccinated, the virus has a hard time spreading as most people will develop immunity”.
Prof Rath, however, adds that ‘herd immunity’ is a post-facto explanatory concept for how a disease disappears even when absolutely everyone has not yet been vaccinated. “I do not think there is any credible way of ‘planning’ for ‘herd immunity’, especially for a disease that we do not understand too well”.
An unexpected hurdle may be rising vaccine hesitancy, and apprehension among people about immunisation. According to a study by the Local Circles, a community social media platform at least 69% (increase from 61% in October) are in no hurry, as they are unsure of the vaccine’s efficacy, safety and side effects. The study was based on a survey of 18,000 participants. Many also believe that the population is naturally moving towards herd immunity, hence would prefer to wait and observe the vaccine’s efficacy before getting the jab.
So far, most vaccine makers have not submitted data on the phase 1 and phase 2 trials, except Bharat Biotech whose study of its “COVAXIN in nearly 1,000 subjects in Phase 1 and Phase 2 clinical trials showed “promising safety and immunogenicity results.”
Most vaccines may require at least two doses, possibly the second one after 21 days, which increases difficulties in logistics, supply and delivery. Oxford-AstraZeneca has signed a strategic deal with COVAX4, which will allow it to market it in developing countries at affordable rates. For India, a shot could be Rs. 250-300. Russia’s Sputnik V, which will be conducting phase 3 trials in India, has said a shot may cost Rs. 500-750.
The government has not clarified whether private health care networks will also be involved. The real picture will unfold once millions the world over, including India, start getting the shots.
Related link: https://www.medrxiv.org/content/10.1101/2020.12.11.20210419v1.full.pdf