A brick kiln worker receives a dose of COVISHIELD, a coronavirus disease (COVID-19) vaccine manufactured by Serum Institute of India, at Kavitha village on the outskirts of Ahmedabad, India, April 8, 2021.
Image: Amit Dave / REUTERS
Amid concerns of an uncontrollable surge in Covid-19 cases, and a severe shortage of vaccines, India has finally decided to fast-track approvals for vaccines already approved globally.
Until now, vaccines, even if approved globally, had to undergo rigorous trials in India before they were approved by the Indian government. The move made sense until early January when India began its vaccination drive and was well past its peak of Covid-19 cases.
Now, with cases spiralling out of control, and only expected to worsen in the next few days, the government’s move assumes significance as it can help meet a growing shortage of vaccines in the country. On April 13, a National Expert Group on Vaccine Administration for Covid-19 (NEGVAC), appointed by the Indian government, gave its nod to allow vaccine-makers such as Pfizer or Moderna to bring its vaccines to India without having to conduct the mandatory phase two and three clinical trials. Instead, they will need to do a bridging trial, which will mean the first 100 volunteers will be assessed and observed for seven days to monitor for more severe and immediate side effects. After that, the vaccines will be rolled out for the entire country.
“The NEGVAC, after comprehensive deliberation, recommended that vaccines for Covid-19, which have been developed and are being manufactured in foreign countries and which have been granted emergency approval for restricted use by USFDA, EMA, UK MHRA, PMDA Japan or which are listed in WHO (Emergency Use Listing) may be granted emergency use approval in India, mandating the requirement of post-approval parallel bridging clinical trial in place of conduct of local clinical trial as per the provisions prescribed under Second Schedule of the New Drugs & Clinical Trials Rules 2019,” the government said in a statement.
The decision came just a day after the government decided to allow for the sale of the Russia-made Sputnik V, being distributed by the Hyderabad-based Dr Reddy’s. The move comes at a time when state governments have been complaining of a shortage of vaccines amidst stringent localised curfews to contain the spread of the pandemic. On April 13, India recorded over 1.84 lakh cases, the single-highest spike in a day since the pandemic started last March.
“From now till April end, 20,122,960 doses are in the supply pipeline to states and union territories,” health secretary Rajesh Bhushan said on April 13, as concerns of a vaccine shortage keep rising. “This clearly shows that the problem is a lack of better planning, not of vaccine doses shortage. We have made available vaccine doses to states and UTs from time to time… to bigger states we give four days of supply at once and on the fourth and fifth day, we replenish it. For smaller states, at once we supply 7-8 days of vaccine doses and on the seventh or eighth day, their supply is replenished.”
Until now, the New Drugs & Clinical Trials Rules, 2019, required a foreign manufacturer to apply for emergency use authorisation of vaccines, and to mandatorily submit the result of local clinical trials even if they were approved globally. These trials, in which the manufacturers conducted phase 2 and 3 studies to collect safety and immunogenicity data, often included limited participants since the trials have already been conducted in another country. The move, the government also reckons, will help in importing of bulk drug material and optimal utilisation of domestic capacity, which will in turn provide a fillip to vaccine manufacturing capacity and total vaccine availability.
“We have noted the recent announcement with regard to the regulatory pathway for global vaccine,” a spokesperson for Pfizer told Forbes India
. “We remain committed to continuing our engagement with the government towards making the Pfizer and BioNTech vaccine available for use in the government’s immunisation programme in the country.”
Experts point out that bringing in more vaccines into the inoculation drive is crucial at this time, particularly Sputnik V, which appears to have manufacturing partnerships in India that can deliver about 800 million doses over the course of time.
Virologist Shahid Jameel, director of the Trivedi School of Biosciences at Ashoka University, points out how the rise in the number of cases during the second wave is faster than the first wave. With over 13 million cases at present, he says, “we have gone from 10 million to 11 million in 66 days, 11 million to 12 million in 34 days and now 12 million to 13 million in under 15 days. Active cases are now growing at an alarming rate of 6.8 percent daily,” he told Forbes India
on April 10.
Apart from measures like testing, isolation, and taking precautions to reduce person-to-person spread, the only feasible option to contain the coronavirus is to vaccinate at scale. Jameel explains that experience from other countries shows that the transmission slows down significantly at 40 percent vaccination coverage. “In India, by April 10, we have vaccinated only 0.8 percent of the population, with 6.3 percent receiving one dose,” he says. “We have far to go.”
According to Dilip Jose, MD and CEO of Manipal Health Enterprises, India’s vaccine demands could be met with no supply constraints if more vaccines are approved for use and production capabilities are scaled up for the two vaccines currently in use—Covishield, manufactured by Pune-based Serum Institute of India, and Covaxin by Hyderabad-based Bharat Biotech.
“The size of the population and the geographical spread is an enormous challenge in our context. While the pace [of vaccination] has picked up, the aim should be to achieve a much larger daily delivery rate so that we cover all adults as quickly as possible,” Jose says. “Logistics of vaccination, especially in small towns and villages, as well as production capabilities would be key.”
As of today, about 90 percent of India’s vaccination programme is fulfilled by Covishield, and the rest by Covaxin. The Serum Institute is producing close to 50 to 60 million vaccine doses a month, while the number for Bharat Biotech is reportedly close to 5 million doses. As per media reports, Bharat Biotech is likely to increase the Covaxin monthly production capacity to 12 million, with bulk production in its Bengaluru manufacturing facility. Bharat Biotech and Serum Institute have not responded to Forbes India’s
queries and the story will be updated when a response is received.
Jameel believes production of vaccines itself is not an issue. “Based on publicly available information, the production capacity of Covishield is 50-60 million doses per month, adding up to a production of 270 million doses. About 50 million doses of Covaxin have also been supplied. Publicly available data shows about 316 million doses were manufactured in India by the end of March,” he explains.
Jameel adds that as of April 8, only about 111.35 million doses have been delivered to states, of which 91.60 million have been consumed, leaving a balance of 19.75 million. “Another 24.5 million doses are reported to be in the pipeline.”
He explains how states have vaccinated at variable rates, with Maharashtra utilising over 390,000 doses daily since April 1 and Tamil Nadu using only 37,200 doses per day. Consequently, some states are running short while others have a stockpile. Maharashtra has doses remaining for less than four days, but Tamil Nadu has enough to last 45 days. “If we do some simple arithmetic, of the 316 million doses, 135.5 million have been delivered to states or are in the pipeline. About 64.5 million doses were exported. This totals to only about 200 million does. Where are the remaining 116 million doses?”
Experts also say that along with making these vaccines available, it is also equally crucial for authorities, particularly at the local level, to be informed about specific risks associated with vaccinations. There needs to be systematic and timely assessments of adverse events following immunisation (AEFIs), says public health activist Malini Aisola of the All India Drug Action Network.
As of March 29, according to a presentation made before the National AEFI Committee, at least 617 AEFIs have been reported across India, out of which at least 180 people died post-vaccination. Experts say AEFIs resulting in hospitalisation or deaths must be investigated to determine whether they are related to the vaccination. According to Aisola, so far, the assessments of AEFIs have not been able to keep up with the pace of vaccination.
“The purpose of reporting AEFIs informs the vaccination drive in important ways, be it ensuring there are adequate screenings, if there is a necessity to put out warnings, to ensure people have access to medical treatments and also to guide medical providers on how to treat certain events that may have found to be related to the vaccinations,” she says, adding there is a tendency among local or district-level authorities to immediately rule out any link between the adverse event and the vaccination.
“The National AEFI Committee must meet more frequently. There also has to be training and capacity-building of vaccine administrators at the local level, where the message should be that it is okay if they report AEFIs so that we can find and tackle all safety issues related to vaccination.”
How much of a difference will it make?
Currently, according to data tracking portal OurWorldinData, while India has inoculated about 6 percent of its 1.36 billion population with at least one dose, Israel and the UK have given one shot to 61 percent and 47 percent of the population respectively, while it is 36 percent of the population for the US.
India began what is touted as the world’s largest vaccination programme on January 16, when the government decided to vaccinate health care and frontline workers. On March 1, those above 60 and those above 45 but with co-morbidities were also allowed to vaccinate themselves. Since April 1, the vaccination has extended to all individuals above 45. Amidst all this, the government also embarked on Vaccine Maitri, a diplomatic initiative to send vaccines to other countries, and has so far sent some 65 million doses to 90 countries.
“It’s not that the recent approvals will help thwart the second wave,” Nandakumar Jairam, chairman and CEO, Columbia Asia Hospitals, told Forbes India
. “But having fast-tracked the process, it will help with controlling any future waves. Because, immunity develops two weeks after the second shot. It would have helped if the approvals had come earlier, but it is also a question of safety.”
Among others, so far, the government has ordered some 141 million doses from the Serum Institute of India since the vaccination began. With Bharat Biotech, the government had initially placed an order of about 5.5 million doses. As per a PTI
report earlier in March, the company has received an order for an additional 4.5 million doses.
The move, however, will help in fast-tracking vaccines that are currently in the pipeline. Currently, Covavax, a vaccine manufactured by the Serum Institute of India in partnership with the UK-based Novavax, is undergoing trials in India, even though it has been found to provide 89 percent efficacy in its Phase III trials. The company now expects the vaccine to be rolled out from September. Then, there are also the trials planned for Johnson & Johnson’s vaccine, which has been approved by the USFDA being manufactured by Hyderabad-based Biological E.
Another vaccine, manufactured by Ahmedabad-based Zydus Cadila, will be considered for approval once the company submits the data of its Phase III trials. The company had earlier expected to complete the process by March-end and laid out plans to manufacture some 200 million doses. For now, it is still waiting for all its dosings to be completed. Zydus’s candidate, ZyCov-D, will be the second indigenous vaccine after Covaxin.
“They (the approvals) are unlikely to help in the short term, since the approvals, except for Sputnik V, are dependent on following a hundred vaccinees for over a week before full emergency approvals for usage are given,” says Satyajit Rath, a scientist at the National Institute of Immunology. “That means, in practical terms, it is likely to take a month or so at best before any approvals actually come through and vaccinations begin.”
Even then, there could be some problems with supplies, logistics and vaccine hesitancy. “As the variety of vaccines available and approved grows, the logistical difficulties of keeping track of who has had which vaccine are going to multiply, especially since most of these (apart from the Janssen-J&J) are two-dose vaccines,” adds Rath. “As an aside, it would have been far better for the government to plan with more foresight (and less hubris) for this, by urging and facilitating in-country bridging trials for as many vaccines as possible; if that had been done in good time starting from late last year, yet another shortcut like the present one would not have been needed. Shortcuts tend to contribute to vaccine hesitancy.”
Rath adds that the possible deployment of foreign vaccines is unlikely to make any large difference, “since this so-called ‘second wave’ is likely to begin to ebb before these new vaccines come into deployment in large enough numbers to make a difference”, he explains. “It will, however, make a difference to the next series of outbreaks, and is therefore a welcome, though poorly managed and contrived, step.”