Covaxin safety has already been well-established from animal tests: Bharat Biotech MD

To work with this sort of virus, you need a Bio-Safety Level 3 (BSL-3) containment production facility.

India has been struggling with the coronavirus pandemic. There is, till date, no drug, and no vaccine. There are some vaccine candidates in the world. Now, in India, we have a very promising candidate from the stables of Bharat Biotech, a company well-known for making vaccines for India as well as the world. The Drugs Controller General of India (DCGI) has just given permission for human trials of this vaccine. Edited excerpts of veteran science journalist Pallava Bagla’s June 30 interview with Dr Krishna Ella, chairman & managing director, Bharat Biotech Ltd, Hyderabad:

Tell us what this vaccine is, and what are its origins.

We are working on three different vaccines against SARS-CoV-2. One is with Indian Council of Medical Research (ICMR), another with Thomas Jefferson University and the third with University of Wisconsin-Madison. The one that we have for which we have received DCGI permission for human trials is an inactivated (killed pathogen) vaccine that has been developed in partnership with public sector ICMR and National Institute of Virology, Pune.

Where did you get the virus for Covaxin from?
We got the virus from the National Institute of Virology, Pune. They have been most helpful. To work with this sort of virus, you need a Bio-Safety Level 3 (BSL-3) containment production facility. BSL-3 labs are there all over the world, including in India. But, as far as a BSL-3 production facility of human vaccines goes, I think we are the first in the world. Other countries, including the US and China, don’t have BSL-3 containment production facilities.

What was done after the virus was transferred from NIV-Pune? Who did it? What were the pre-clinical studies that were conducted, and what was the safety assessed?
We adapted the strain transferred from NIV for viro-cell culture. This is done to grow live viruses from a sample. Now, we had 200-300 litres of live virus in our facility. Then, you kill them with a chemical so that the RNA inside the virus is destroyed so that it is not able to multiply in the body. That’s the difference between a live, attenuated vaccine (in which the pathogen is alive but considerably weakened) and an inactivated vaccine (in which the pathogen is killed). Once it is inactivated, it is taken to a GMP (good manufacturing practices) facility, the product is produced and toxicology studies are carried out. We have carried out the toxicological studies over almost three months, in a three-animal model (rat, mice and rabbit), for compliance with Schedule Y (of the Drugs and Cosmetics Rules 1945). The animal toxicological studies are 98% complete, and we have submitted the findings to the regulator. About 2% of the studies are ongoing at the moment, that is not relevant to the safety aspect of the vaccine, and is yet to be submitted to the regulator. A 100% safety has already been well established in our animal toxicology studies.

Will you be going to monkeys before going to humans (for trials)?
So, we have done the toxicology and immunology studies in the animals (mentioned here). NIV-Pune was very co-operative. Whatever animal blood samples we would send to them, they would test in parallel, to verify whatever we were doing in our facility and what they were doing in their facility was the same, in what we call PRNT (plaque reduction neutralisation test) assay. That confirms whether the vaccine is working or not. Now, NIV Pune is studying the vaccine on hamsters in animal challenge studies (challenge studies involve deliberately infecting the test subject to study efficacy of a drug/vaccine), and the results will be coming in 15 days or so.

When do you plan to have the human trials, now that you have permission from DCGI?
We sent a batch of the vaccine to Central Research Institute, Kasauli, on June 1, and once we have their approval, the approval of the ethics committees of hospitals where the vaccine is to be tested will be required. Once we have the approvals, we will immediately start the trial.

In which hospitals will the trial be carried out?
We are looking at 10-12 different hospitals in the country, from Nizam’s Institute of Medical Sciences, Hyderabad, to AIIMS, Delhi.

How many people are to be recruited for the trial?
I am sorry, I am unable to recollect that bit at the moment. We have hired a statistics expert from the University of Maryland (the US) to analyse and project what the right number of recruits for the trial should be. [The clinical trial has been cleared by the DCGI to be done on 1,125 healthy individuals between 12-65 years of age across 12 Indian cities.]

Where did you get the funding for the project? Have you relied on the Government of India, because the PM CARES fund has some allocation for vaccine development?
We have not taken any money from the Government of India for the Covaxin project. But, ICMR is definitely aiding NIV Pune for some serological and animal challenge studies. When the larger society is suffering, we don’t want to exploit the government for money. We had the option to use our facility to produce injectable polio vaccines, but we shut down those operations to use it for the Covid vaccine project. We lost a market-growth opportunity of nearly Rs 200-300 crore in sales.

How many people have worked or are working on Covaxin?
Around 100 people are working on this project. These people are working with a live virus in a BSL-3 containment manufacturing facility. We left the decision to get involved in this project to them. We told them that your family can have no exposure to you. Some of those on the project haven’t seen their families for the last 2-3 months.

Is there anything that the government can do make sure that Covaxin can come into the market faster?
That is a decision for the government to take. If phase I & II data is good, it is up to the government and regulators. Our job is to execute the project and show the results.

How soon can we expect the vaccine, assuming that phase I, II and III of the trial all go well?
It is very difficult for us to say. The lockdown is also affecting us. This is where the government can possibly help, by allowing things like testing of people for recruitment—we will need Covid-19 seronegative people for the study—to be speeded up. There’s one observation I can make, though: based on global information, the inactivated alum (the alum is used as adjuvant) is working very well. Studies from China, that is if their data is right, show that inactivated vaccines are working very well in human trials.

Assuming you get it right, can you scale it up to give vaccine-access to 1.3 billion Indians?
The capacity is being created in parallel right now. Vaccines are a very tough field. We will get the answer on how much scaling up is possible in probably two months.

Any indication of what the cost is likely to be? How many doses will be required?
A two-dose schedule is planned for the trial, to be administered on the first and the fourteenth day, to ensure that, just in case the first dose doesn’t prime the participant properly, the second dose does this, and the person is protected by the 30th day. Chinese studies are also projecting that a day-zero and day-fourteen two-dose regimen is working very well. Whether a single dose will work or two doses will, only data can tell.

The PM is personally monitoring the vaccine development in India. Will the entire intellectual property for this vaccine be Indian, or is there anything that will be owned by any overseas company?
Covaxin, which we have just announced, is a 100% Indian vaccine. As for intellectual property, we can file patents for manufacturing and formulation. Even the Thomas Jefferson vaccine, we will be owning the rights globally.

So, it is an atmanirbhar product…

Yes. We don’t want to be controlled for IP by someone else in the future. That is very clear to us as a company.

Have you had a chance to speak to the PM about Covaxin?
No. I haven’t had the chance to speak to the PM on this matter. If I get a chance to interact with him, I would like to discuss how to get simple strategies to deliver a much bigger impact.

How much money would you require end-to-end to complete this project?
We closed down the injectable polio-vaccine operations for Covaxin and rabies vaccine operations for the Thomas Jefferson vaccine, losing nearly Rs 550 crore in the bargain.

How can India help you now?
I think volunteers are required. I believe even our army requires a Covid-19 vaccine. We can’t afford to lose policemen to the pandemic, or healthcare workers. I think we need some strategy on how to handle pandemics in the future. We also need to think on how vaccine science gets into global commerce, given vaccines will be a key traded product segment.

So can I have Covaxin vaccine shot sometime next year?
Yes, absolutely you can be confident. Definitely, you will have a vaccine from us, that’s for sure.

PS: The head of the Indian Council of Medical Research, Balram Bhargava, has written to 12 hospitals that have been selected for the trial, “to treat this project with the highest priority” and initiate subject enrolment no later than July 7, so that vaccine can be launched for public health use latest by August 15 (Independence Day). The letter also warns that “non-compliance will be viewed
very seriously”.