Unprecedented and herculean efforts by the scientific community across the world over the past few months have yielded at least two promising Covid-19 vaccines — by Pfizer and Moderna — that have been developed following all the mandatory clinical trial stages. While the average time to develop and make a vaccine publicly available until now has been 15 years, according to the World Health Organisation, it remains an extraordinary feat to have built a vaccine, and shown it to be safe and effective, for a novel disease that is just one-year old but has upended economies and claimed the lives of 1.65 million people.
The developments mark a remarkable turnaround since there was no antidote to the virus and the most optimistic prediction was a vaccine by the middle of 2021. In fact, the vaccine that comes remotely close in matching the Covid-19 pace is the mumps vaccine, which took close to 4 years to get all necessary permissions and licensing. So far, only smallpox has been declared officially eradicated by vaccination.
Vaccine nationalism and COVAX facility
Besides the breakneck pace of development, the vaccine race also saw enormous amount of funding unparalleled in history, with the US, China, the UK and European nations pumping in billions of dollars in investment and entering into pre-purchase agreements with manufacturers, a development that has come to be known as “vaccine nationalism”. More than 10 billion doses have already been pre-ordered, including most of the 2021 manufacturing capacity for the leading candidates, according to analytics firm Airfinity.
Thus, most of the low- and middle-income countries are relying on contributions from COVAX, a joint fund for equitable distribution of vaccines, being co-led by Gavi, the Vaccine Alliance, the Coalition for Epidemic Preparedness Innovations and WHO. So far, more than 190 countries have signed up to COVAX, which aims to provide vaccines to at least 20 per cent of the population of participating countries.
Moderna, Pfizer, Oxford kick off vaccine trials
Two months after the genetic sequences for SARS-CoV-2 were identified, American biotechnology firm Moderna reportedly was the first to kick off human trials on March 16 followed by University of Oxford-AstraZeneca on April 23 and Pfizer-BioNTech on May 5.
However, what aided scientists in developing a Covid-19 vaccine in record time is the fact that it was not required to be made from scratch. Scientists had begun making vaccines for SARS and MERS, which belong to the coronavirus family, during their outbreaks in 2003 and 2012, respectively, only to abandon the efforts when the outbreaks petered out.
Moreover, Pfizer and Moderna used the novel mRNA technology for their vaccines that are faster to develop as they do not require companies to produce protein or weakened pathogens for the vaccine. The genetic material mRNA is easy to make in a laboratory and manufacturing an mRNA vaccine rather than a protein one can save months in time.
How clinical trials were completed in months
Normally, a vaccine goes through multiple stages before being approved for public use. Following the initial research and development stage, a vaccine is first tested on animals and then it goes through three stages of human clinical trials. In normal circumstances, each step can take two years or more to complete. However, for Covid-19 vaccines some of those phases were combined to hasten the process. For example:
Phase I: In this step, the experimental vaccine is given to humans, usually between 20-80 subjects, to test its safety and dosage besides gauging whether it stimulates the immune system. While this process typically takes one to two years, for Covid-19 trials, it was done in about three months.
Phase II: In this stage, about several hundred individuals, split into groups age-wise such as children and elderly, are dosed in a randomized, double blind, placebo-controlled study. This process usually takes about three years but for Covid-19 vaccines, it was completed in 2-3 months.
Phase III: This is the most crucial stage, where the vaccine candidate is given to thousands of people, and can typically take two to four years. However, most of the drugmakers combined this with Phase II to expedite the process.
Regulatory review: After Phase III trials, the vaccine developer submits a license application to the regulatory authority in their respective country, and final approval may take months or years. However, in emergency situations, like the Covid-19 pandemic, authorities grant emergency-use authorisation (EUA) in weeks.
Interestingly, countries like China and Russia had granted regulatory approval to Covid-19 vaccines even before their efficacy had been proven in Phase 3 trials — the most critical step in the process.
While China had approved an experimental vaccine for use by its military as early as late June, Russia announced the registration of a vaccine named Sputnik V, the first in the world to be approved for public use, on August 11, leading to scepticism among Western scientists regarding its safety and effectiveness. When the Sputnik V vaccine was approved, only the results of Phase-I of the clinical trials were in public domain, which claimed the shot was successful and produced the desired immune response.
Vaccines show high efficacy rates
However, despite the race among drugmakers to roll out their vaccines, experts have warned that the first batch of Covid-19 shots might not necessarily be the best. “The first generation of vaccines is likely to be imperfect, and we should be prepared that they might not prevent infection but rather reduce symptoms, and, even then, might not work for everyone or for long,” Kate Bingham, Chair of the UK’s Vaccine Taskforce, wrote in an article for the medical journal ‘The Lancet’.
This comes even as the vaccine frontrunners have shown high efficacy as per interim late-stage findings. While Pfizer, Moderna and Russia’s Sputnik V vaccine have shown to be around 94 per cent effective against Covid-19, the one developed by Oxford has been found to be ranging from 62-90 per cent as per dosing regimen. The success rates are way above WHO and FDA recommendations, which mandates that successful vaccines should show disease risk reduction of at least 50 per cent.
Ramping up logistics and cold chain
The quest to vaccinate such a humongous population worldwide has also exposed gaps in the pharmaceutical supply chain and investments in infrastructure and storage facilities, especially ultracold freezing capabilities, have not been at the same pace as for a vaccine.
Distributing vaccines like that of Pfizer’s mRNA candidate, which needs to be stored at -70 degrees Celsius, will be challenging for countries lacking ultracold storage facilities. This is so because traditional vaccines like BCG usually require them to be stored at temperatures between 2-8 degrees Celsius.
Besides, a number of other components like vials, stoppers, gauze, alcohol swabs, syringes are also required in huge quantities to inoculate the masses. India, which has the capacity to manufacture more than 2 billion units of these vials, is being tapped by international players for supplies.
For India, what bodes well is that it has much of the infrastructure in place for vaccine distribution, thanks to its Universal Immunisation Programme (UIP), one of the largest public health schemes in the world. The government had identified as many as 28,947 cold chain points, which are adequate for vaccines needed to be given in the first phase to healthcare workers.
“Since 1984, when the UIP was started, India has created a network of more than 26,000 cold chain points with temperature trackers for vaccines. Now we only need to augment this,” a senior Health Ministry official told The Indian Express.
Another crucial aspect of the supply chain is tracking the vaccine all through its transit until it is dosed. Here too, India is well equipped in the form of a software called eVIN or Electronic Vaccine Intelligence Network, which works through a smartphone application, has digital information on vaccine stocks and the temperatures in the cold chain.
The software, now called Co-VIN, can also track the beneficiary and allocate a vaccination session. A QR-based digital certification is generated once a person is vaccinated and there is no adverse event. “Tracking each of the vaccines as it moves across the supply chain is important as patient safety is the key driver for adopting these standards,” S Swaminathan, COO GS1 India, a standards organisation set up by the Ministry of Commerce, told indianexpress.com.
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