Corporate File

Bharat Biotech: More than just Covaxin

Raghuvir SrinivasanG Naga Sridhar | Updated on September 27, 2021

Krishna Ella, Chairman and MD, Bharat Biotech

The story behind the vaccine development and the dose of innovation the Ellas have brought to India’s biotech industry

Krishna Ella, Chairman and Managing Director, Bharat Biotech International, is not what you would imagine a successful businessman to be. He’s simple and warm, with no airs whatsoever for a person who founded and heads a company that has supplied about 10 billion doses of different vaccines to 123 countries in the world, and crucially, is at the forefront of India’s fight against the Covid-19 pandemic.

His wife, Suchitra Ella, Joint Managing Director, is equally self-effacing and charming. “Vaango”, they both chime in Tamil, with disarming smiles, as we step into the tastefully decorated conference room at their plant in Genome Valley, near Hyderabad. Turns out that Krishna Ella hails from a village near Tiruttani on the Tamil Nadu- Andhra Pradesh border and studied at the Pachaiyappa’s College in Chennai. Suchitra has her roots in Neyveli, where her father was one of the builders of the power plant. “I studied in Ethiraj College, Chennai, and my mother still lives there,” she says in chaste Tamil.

It’s been a long journey from there, to setting up a cutting-edge vaccine plant guarded by the CISF.

 

Suchitra Ella, Joint Managing Director, Bharat Biotech

 

Return to roots

As the story goes, the couple who were settled in the US, with successful careers, decided one fine morning in 1996 to return to India and help in its development. Krishna surrendered his American passport, the couple sold their house and put that money into starting Bharat Biotech with a seed capital of $3.5 million. They were joined in the project by two angel investors.

Genome Valley, which is now a bustling industrial area with more than a 100 biotech units, was nothing but dry land in 1997 with no roads or power. “We worked with a diesel genset and all that this land had then were snakes and custard apple trees,” says Ella. Since then, more than ₹800 crore has been invested in the venture, which boasts of the most technologically advanced vaccine manufacturing facility in India.

Scientists at heart

A scientist at heart, Krishna Ella rues the absence of innovation in India. “Innovation is lost due to our education system that prides rote learning, the coaching class ecosystem, and market and US-visa driven choice of studies,” he says, pointing out how India ranks a lowly 48 in the innovation index.

How does it feel for a scientist to be in business, we ask Ella. “We’re not a pure commercial company. Our competitors are infectious diseases, not companies,” he declares, pointing out that Bharat Biotech has not paid any dividend till now, with all the profits being reinvested in the business.

The company may be known best for Covaxin but much before Covid, Bharat Biotech cut its teeth with vaccines for a range of viral and bacterial diseases starting from Hepatitis B and Rotavirus to typhoid and Japanese encephalitis.

 

Several of its vaccine development programmes have been, and are funded by the likes of the Bill and Melinda Gates Foundation, Wellcome Trust and so on.

It has filed for 433 patents, of which 145 are now active. “We have 16 vaccines and four bio-therapeutics in our portfolio. We’ve participated in 90 clinical trials across 20 countries involving 7,00,000 volunteers, but our scientific prowess has been largely ignored in the vaccine debate,” rues Ella, adding, “as a scientist, I want India to stand out; it is not inferior to MNCs.”

That he’s hurt by the manufactured controversy over Covaxin approvals is evident.

Apart from Typbar, the conjugate typhoid vaccine developed in association with Oxford University in 2018, Bharat Biotech is also developing a non-typhoidal salmonella vaccine. Largely aimed at Africa, the vaccine, funded by Wellcome Trust, has completed Phase 1 trials in Baltimore and is now set for Phase 2 trials in Africa. There is also a cholera vaccine under Phase 3 trials now and a chikungunya vaccine undergoing clinical trials in Costa Rica and Colombia.

Making of Covaxin

The biggest challenge that the Ellas took on though, was developing Covaxin. “Once we made the public announcement on May 1, 2020, there was no going back. The entire team of scientists worked 18 hours a day during the development phase and it was most difficult for our colleagues, who had families with elders and yet had to expose themselves to the virus during the pandemic peak,” says Suchitra Ella.

The company chose to take the difficult route of producing an inactivated virus vaccine.

It is not just complicated technology but also more expensive to produce and time-consuming. Yet, Ella chose this because of his conviction that inactivated virus vaccines are superior to mRNA or adeno virus vaccines.

Safety shot: A Bharat Biotech lab

 

“We wanted to focus on both humoral and cell mediated responses, against not just spike proteins but also the nucleocapsid proteins which have also been determined to be immunogenic. Nucleocapsid proteins are known to be more stable and develop less variants, as seen with spike proteins. Our long experience in developing other inactivated virus vaccines helped us. The adjuvant in Covaxin triggers T-cell responses,” says Ella.

Unlike mRNA vaccines that induce the body to produce the antigen of interest, inactivated virus vaccines give a readymade antigen to stimulate the immune response. Not just this, Bharat Biotech selected 6 micrograms as the dosage even though 3 micrograms worked as well during Phase I/II trials, because the company wanted to be abundantly cautious.

The best answer to critics, says Ella, is that the Phase 3 trials of Covaxin happened in February, March and April when the country was in the grip of the second wave caused by the Delta variant, and the results prove the vaccine’s efficacy against Delta.

“Our Phase 3 results, soon to be published in a peer reviewed journal, proves Covaxin’s efficacy against the Delta variant,” he declares.

Innovative technology

The company’s Bio Safety Level (BSL)- 3 facility, one of the first in the world for human vaccines and the only one in India for non-animal vaccines, is critical in Covaxin production.

BSL-3 facilities have strict protocols and procedures, including negative pressured buildings and underground waste-water handling facilities.

A Bharat Biotech lab with Bio Safety Level (BSL)-3 facilities for Covaxin production

They are expensive to build and to maintain. Bharat Biotech has spent over ₹500 crore on its BSL-3 facilities, of which it has four in Genome Valley and one each in Bengaluru and Ankleshwar.

But why is Bharat Biotech producing barely 40 million doses a month when Serum Institute is rolling out 120 million a month?

“It is due to the complex technology with inactivated viruses. The entire manufacturing and testing process takes 90-120 days as viruses have to be cultivated in large quantities, inactivated and purified,” clarifies Ella.

Unlike in a live virus vaccine, which has about two to three touch-points during production, there are many more touch-points in inactivated virus vaccines. The virus, when dead, should maintain its size, shape etc. The nearest comparison is the embalming of a dead human, where the physical shape is kept intact even as the body is lifeless. The drug substance then has to be purified of other virus particles that may be present.

All this means that a lot of yield is lost during production. The final output is just about 10-15 per cent of what starts as raw material. “If we start with material for a 100 million doses, what eventually comes out at the end of the process is worth just 10 million doses,” says Ella.

The decision to go with a 6 microgram dose as opposed to 3 micrograms also cost the company volumes.

It could have doubled its output if it had gone ahead with 3 microgram doses, which were as effective.

As the long discussion winds down, we ask him about the long-awaited WHO approval for Covaxin. “They have their processes, which are comprehensive and time-consuming. We’ve worked with WHO for approvals for other vaccines and are familiar with the process. It will come in due course,” he replies as the two safari suit clad hulks guarding the Ellas glare at us for standing too close to them.

Covaxin, which was jointly developed with ICMR, is the best example of how a PPP can work to the country’s advantage, says Suchitra. “We need more public-private partnerships for science and for vaccines in this country,” Krishna Ella adds.

Incidentally, Krishna Ella is not just a scientist, but also an agriculturist at heart. He points out that Indian farmers need help in marketing and not production.

He has set up Ella Foods and a few other companies in the agribusiness space, whose products are available on Amazon under the Ella brand name. But that is another story for another time.

Published on September 26, 2021

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