Making of Covaxin: How ICMR decided to collaborate with Bharat Biotech for indigenous COVID-19 vaccine

Legend has it that Edward Jenner, the eighteenth century British scientist, discovered the vaccine for smallpox becuse of an incident that took place when he was in his early teens. Apparently, as a 13-year-old boy, he overheard a beautiful milkmaid boast that her flawless complexion was because she had cowpox, a disease caused by virus found in cattle.

The cowpox, according to her, protected her from smallpox and prevented her from getting an ugly pockmarked face. This was the hypothesis that Jenner would later test and confirm, leading to the vaccine for smallpox, a disease that had been the scourge of humanity for millennia. Not surprisingly, the term 'vaccine' that Jenner used, comes from the Latin word vacca, which means cow.

Vaccination is inarguably one of humanity's greatest innovations. It is the most significant pharmaceutical intervention for the prevention of any infectious disease. It is no exaggeration to say that vaccination can, and has, changed the course of generations and civilisations.

Vaccines have helped not just control but even completely wipe out diseases that have held humanity hostage for millennia. Apart from smallpox — the dragon  85 An Indian Vaccine: From Dream to Roll-Out that was finally slain worldwide in 1980 — vaccines also helped halt the spread and impact of diseases such as measles, mumps, diphtheria, tetanus and polio in most countries around the world.

While everyone knew that a vaccine was essential to stop COVID-19, nobody believed it would take less than (at least) two years to develop one. Before this, the shortest time for producing a vaccine was four years — for mumps.

However, as COVID-19 wreaked havoc by disrupting health systems and disrupting economies across the globe, the world put in an unprecedented effort to develop both treatments and vaccines. These are desperate times. We are living through a moment that future generations will read about in their history books and certainly in their medical textbooks.

Scientists in research labs across the globe raced against time to work on innovative solutions using new technologies or products, some of them repurposed from other uses. Vaccine development was speeded up by combining what we already knew about coronaviruses, such as previous research done on the SARS and MERS viruses. We also tapped our accumulated know-how on RNA vaccines.

With the SARS-CoV-2 virus finally isolated, cultured and better understood, we at the ICMR started thinking seriously about developing a vaccine of our own. The global and national situations were dire; it was clearly time for bold action.

It is important to remember that while COVID-19 is new, we were not completely starting from scratch. We had seen coronaviruses before and had worked on vaccines before. This prior experience was an excellent foundation.

Apart from hard science, vaccine development also requires manufacturing power and a whole lot of logistical maneuvering. The average time from discovery to production for any vaccine in the past was 10 years. We were on the lookout for industrial partners with whom we could collaborate for a vaccine. The first company to approach us was Bharat Biotech. The Bharat Biotech proposal was an exciting one as it fitted well with the Indian government's publicly stated prioritisation of indigenous technology, production and capabilities in all sectors.

I personally knew Krishna Ella, founder and chairman of Bharat Biotech, as a competent scientist, a good researcher who had returned from the US in 1996 and set up this model biotech firm in India. We had a common friend from Stanford University, where he worked on the Rotavirus vaccine project. I had been engaged with the bio-design programme with Stanford University with certain mentors there, to develop low-cost medical devices and we were successful in developing several such devices through a fruitful collaboration of engineers and doctors. Thus, we were familiar with each  other’s work culture.

This medium-sized private vaccine maker based in Hyderabad proposed to join hands with the ICMR to produce a COVID-19 vaccine. Bharat Biotech already had a track record of producing a range of vaccines for neglected diseases such as rotavirus and typhoid.
Thus, Bharat Biotech had the experience and it was the only manufacturing facility in the country which had a BSL-3 laboratory and BSL-3 is the basic prerequisite for building a killed virus vaccine for COVID-19.

"There was an environment that was charged with possibilities, for this collaboration. The time was demanding and the environment was ready," Dr Samiran Panda recalls.

The ideal partner

Bharat Biotech International Ltd (BBIL) is the brainchild of its chairman, Dr Krishna Ella. Dr Ella is a molecular biologist who returned to India in 1996 after working as a researcher in the US, where he had conceptualised a new hepatitis B vaccine.

Bharat Biotech's first major success was to produce the hepatitis B vaccine3 at prices affordable to low-income countries in Asia and Africa.

The company, based in Hyderabad, was launched with just Rs 12.5 crore as its seed capital. Within three years, its first hepatitis vaccine was out in the market. Sold at Rs 10 per dose to India's national immunisation programme, the vaccine was one of many the company would develop and launch in the following years. Today, Bharat Biotech has over 700 employees, comprising research scientists and manufacturing professionals. It owns 160 global patents, exports to over 65 countries and has delivered more than three billion vaccine doses all over the world.

"Our company's mission is to deliver affordable, safe and high-quality vaccines and bio-therapeutics that help people prevail over diseases," Dr Krishna Ella proudly said.

The company's next major vaccine was Rotavac, to protect against the highly contagious rotavirus, which causes infant diarrhoea in many low-income countries. The vaccine was the product of a unique joint venture between Indian and international researchers as well as public and private sectors and sold at just $1 per dose.

"I believe that partnering between public research institutions and private companies is essential to produce good science as they can help validate each other," says Dr Krishna Ella. According to him, Rotavac demonstrated that an Indian company could conduct high-quality research in advanced sciences.

Subsequently, Bharat Biotech also went on to produce a low-cost vaccine for typhoid, a neglected tropical disease. The company was among the first to initiate developing vaccines for viral diseases like chikungunya and Zika. Today, besides Covaxin, the company is involved with three other COVID-19 vaccine development initiatives.

Professor Balram Bhargava is presently the director-general of the ICMR and continues to be professor of cardiology at AIIMS, New Delhi. The article is an edited excerpt from his latest book, 'Going Viral: Making of Covaxin.'