The vials are thoroughly washed with water for injection – (WFI) the purest form of water – passed through a sterilisation tunnel where the temperature is set at 350 degree C before being filled with the vaccine in a high speed filling machine and getting loaded into the lyophiliser. It is exactly at this stage that scientists with Pune’s Gennova Biopharmaceuticals, after multiple trials, arrived at the key formulation that would ensure the country’s first homegrown mRNA Covid- 19 vaccine is heat stable.

“Yes, we have been the slowest in the process but the main aim was to ensure that the vaccine, unlike those in the West which have to be stored at sub-zero temperatures, can be stored between 2 to 8 degree celsius. We had to innovate to suit our local needs as to what is affordable and deployable. Our vaccine GEMCOVAC 19 can be stored at the temperature of a standard medical refrigerator,” said Dr Sanjay Singh, CEO of Gennova Biopharmaceuticals.

If the mRNA technology has been a gamechanger in how vaccines are made, what has been remarkable is the painstaking manner in which scientists, biotechnologists, pharmacists, analytical and production personnel at the firm have laboured for a year and a half to come out with the Indian version of mRNA Covid-19 vaccine. This process may have taken this long but for Dr Singh, a biochemist who had worked on malaria vaccines at the US-based National Institutes of Health, and the team, designing a vaccine using the same mRNA technology against the Omicron variant barely took 60 days.

“mRNA technology has an advantage where the raw material can be kept and a vaccine can be produced in a month or two or three if there is a new variant – That is precisely what we did with Omicron – we came out with the vaccine in 60 days,” Dr Singh adds.

The excitement is visible at the Research and Development building of Gennova Biopharmaceuticals at Hinjewadi. “Animal studies have been completed and now approval is awaited from the drug regulator to go ahead with human clinical trials,” said 45-year-old Dr Swarnendu Kaviraj, scientist and, in charge of analytical development and formulation development of the vaccine. “We knew that all mRNA vaccines have to be kept at sub-zero temperatures which is not possible in a country like India,” he said. “That was the foremost challenge. The lyophilisation technology is not new but the lyophilised mRNA vaccine is unique. We performed hundreds of trials before arriving at the right formulation and right condition to ensure a heat stable mRNA vaccine,” he said.

The conversion from liquid to powder form of the vaccine takes place via lyophilisation. (This is freeze drying – a prcess where the water is removed from the product after it is frozen and placed under vacuum, allowing the ice to change directly from solid to vapour without passing through a liquid phase). “However just removing water by lyophilising the mRNA vaccine will not work. Here, the surrounding pressure had to be tweaked and then kept stable to ensure the characteristics of the vaccine is the same as it was before lyophilisation. For that, the key part was to add an external agent which, at a certain critical concentration, keeps it stable under lyophilised conditions.”

Initially, the firm conducted the Phase 1 trial on 82 subjects with the liquid formulation of the mRNA vaccine. With the increasing need to make these mRNA vaccine shots thermo stable, scientists accepted the challenge. The initial Rs 25 crore seed money from DBT was followed by another Rs 100 crore for phase 2/3 human clinical trials. Dr Tathagata Mukherjee, scientist and general manager, business development, at Gennova admitted that the first question he is often asked by bankers mainly is regarding the vaccine’s thermostable feature. “From the beginning, our motto was to have the vaccine stable at 2-8 degree C.”

The process has been an unbelievable one, adds Dr Ajay Singh, scientist and in charge of the mRNA vaccine development department. “At the culture room, we have even made a dummy virus – which is not infective but can show that antibodies are working. It has the spiked protein from SARS-CoV-2 but does not have the replicating genome of the SARS-CoV2 virus. It will not infect and can be used in the lab and this pseudo virus neutralisation assay is used to test whether the antibodies generated against the vaccine can block the virus,” Dr Singh said. Assisting the team are dozens of young biochemists, biotechnologists and scientists like the youngest one, 24-year-old Renuka K, who had joined as an intern two years ago. “It just feels so amazing to be a part of this entire process,” she said.

At the manufacturing facility just 300 metres away from the main Research and Development building of Gennova, around 50,000 vials are loaded in the lyophiliser across 12 shelves. Abhijit Bhagwat, production in-charge, monitors whether vials are intact before being transferred to the manufacturing area. Senior manager Vinod Halnor who has to get into a series of changing rooms to wear the proper protective gear before handling an automatic machine just to press the command that starts the process of filling the vials, said it is great to be a part of this effort. It takes five days for the lyophiliser to run the cycle and then the vials are sent back via the conveyor belt for the final sealing and packing. “There are pre-defined parameters that are displayed on these machines with different temperatures and different time points to convert the liquid into powder. Once the government gives us the go ahead, we have the capacity to initially manufacture at least 80 lakh to a crore doses per month, with a plan in place to augment the production to 5 crore doses per month,” added Dr Mukherjee.

Dr Singh recalled the occasion when PM Narendra Modi after a virtual meeting with Bill Gates during the Grand Challenges annual meeting in October 2020 had asked the CEO about the possibility of an mRNA vaccine. “Yes we can,” Dr Singh had said. Phase 2 trial data across 400 participants has been submitted and while the phase 3 trial has been completed and data – which has a very good safety profile – is being presented. While it is anticipated that the product known by the trade name GEMCOVAC-19 will be in the market subject to regulatory clearance, the focus is also on booster trials using the vaccine designed against Omicron. “All documents have been submitted to the office of the DCGI for the Omicron clinical trial,” Dr Mukherjee added.

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Anuradha MascarenhasAnuradha Mascarenhas is a senior editor with The Indian Express, Pune.... read more