In 2009, when Pune-headquartered Serum Institute of India (SII) was called on to help in global efforts to develop a vaccine during the swine flu (H1N1) pandemic, it followed a decades-old technique using a commonly consumed household item — eggs.
Yet, today, the egg is out. Like the rest of the world, Indian vaccine makers — crucial in this pandemic also because of their large manufacturing capacities — have had to skill up.
Picture a laboratory where a fertilised hen’s egg is injected with a flu virus. The egg acts as a host, growing the virus, allowing it to replicate over time the way it would in a human. The fluid from this egg is then purified so that the vaccine maker is left with only the replicated virus which, depending on the type of vaccine, is then killed or passed through more eggs to weaken it.
The technology is around 70 years old, but such approaches have so far worked well for Indian vaccine makers in the last two decades, where the most long-standing pandemics were flu-related. During the H1N1 pandemic, one of SII’s biggest challenges had been sourcing pathogen-free chicken eggs, for which it dialed India’s largest poultry supplier, Venky’s (previously known as Venkateshwara Hatcheries).
Around 90 percent of influenza, mumps, measles, rubella and yellow fever vaccines can be made from egg technology, according to Chennai-based oncologist and vaccine specialist Dr Anita Ramesh.
Today, however, the stakes are higher and the challenges are unfortunately not as easy to overcome. The COVID-19 pandemic brought with it a realisation that traditional technology like the use of eggs may not cut it when finding solutions.
For one, this mainstay in flu vaccine production has no effective role in COVID-19 vaccine development. The SARS-CoV-2 virus, which causes COVID-19, does not replicate in such eggs, according to a June 25 study by Ian G Barr, Cleve Rynehart, Paul Whitney and Julian Druce published in the Euro Surveillance journal.
Secondly, the world simply does not have time to spare waiting for a vaccine that may take a long time to produce. With egg-based vaccines, for instance, the entire process — from the arrival of the egg to the publicly available vaccine — takes a few months, according to experts.
Apart from some traditional routes, the world is closely watching vaccine candidates made using platforms like DNA, mRNA and viral vectors. This is because, if successful, they can be scaled up much faster, say experts. DNA and mRNA vaccines, for instance, have the advantage of being chemically synthesised — they don’t need the virus to be cultivated and replicated, just the code for the most crucial part that the body’s immune system is to target. Another advantage is that they can be manufactured at a large scale in large vats called bioreactors.
“These are platforms that can work on demand. After getting the code (for the virus), it is possible to develop the vaccine within weeks for pre-clinical testing, compared with months taken for more traditional platforms,” said an Indian vaccine maker on condition of anonymity.
The latest pandemic, therefore, has called for Indian vaccine producers to push their own boundaries and gamble especially with newer technology that may speed up the process of development and production.
For instance, Ahmedabad-based Zydus Cadila is already testing a DNA plasmid vaccine on humans.
Standalone Indian efforts with newer technologies are evident during this pandemic, with firms ranging from Zydus to Biological E and Mynvax taking different avenues to fight the virus. Yet, not all efforts are individual.
“If you look at all the products that our companies have, the latest technology for those in the market is from the 1980s,” said a vaccine expert on condition of anonymity.
“Newer technologies are all imported. It’s Indian companies working with either small foreign biotech companies or academic organisations that are leading to us having any new technologies,” says the person cited above.
Some of the confidence in exploring uncharted territories comes from the willingness which Indian firms have shown in the last 5-10 years to try newer technologies, according to vaccine expert Dr Davinder Gill, also the former CEO of Hilleman Laboratories.
“We had seen Indian companies beginning to embrace newer platforms, including virus like particles (VLP) technology or non-replicating viral vectors…So far, these have only been at the R&D level. There are no commercial products derived from these technologies in India,” he told The Indian Express.
Where companies have not been able to perform the research and development on their own during this pandemic, there have been international tie-ups. At least five Indian firms have collaborated with international firms or universities to develop their COVID-19 vaccines.
Pune-headquartered Gennova Biopharmaceuticals, a subsidiary of Emcure, collaborated with Seattle-based HDT Bio to develop a messenger RNA vaccine. Bharat Biotech, which is testing an inactivated virus on humans, is also exploring non-replicating and replicating viral vectors in collaboration with two American institutes.
With tie-ups have come tech transfers and millions of dollars of investments into upgrading and ramping up manufacturing capacity here.
SII, which has a manufacturing agreement for the Oxford vaccine candidate that is currently ahead in the race, was investing over $100 million in a manufacturing facility for the vaccine, its CEO Adar Poonawalla had reportedly said in June. The CEO had also told The Indian Express earlier that the firm had dedicated two of its facilities to produce a million doses of this vaccine.
Gennova CEO Sanjay Singh had also told The Indian Express that the firm was planning to invest a “huge” amount to ramp up its manufacturing capacity.
Regardless of the vaccines that make it through the finish line, some experts and industry executives are hopeful these learnings could be used by India to efficiently produce older vaccines going forward, including those that have been made, for decades, using eggs.
“These technologies are modern, scalable and easy to use compared to eggs. But, they will be more expensive than egg technologies,” said Gill.
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