Transparency Critical In COVID-19 Vaccine Trials: Kiran Mazumdar-Shaw

Mumbai: Administering a vaccine to all Indians for COVID-19 when it becomes available is a “complex ask”, and needs infrastructure such as cold-chain technologies and logistics, and specialised human resources including nurses, doctors and medical students, says Kiran Mazumdar-Shaw, executive chairperson of Biocon

After healthcare workers, the military, the police and anyone who is on the frontlines, teachers and the young working class--not the elderly and the vulnerable--should be given the vaccines, so they can get back to work & get the economy to be resurgent, Shaw adds.

If it is possible to shrink regulatory processes and timelines during COVID, why can’t it be done beyond COVID?, Shaw asks, explaining why emergency-use authorisations for life-threatening diseases are “a sensible regulatory pathway going forward”.

Edited excerpts:

When you look at past investments in India’s healthcare, particularly in public health, how do you think that stacks up in the context of our response to COVID-19?

I think we have focused a lot on rural healthcare, on immunisation, and as a result, we have understood how to deploy vaccines at a large scale in populations. We have, of course, used our ASHA workers [accredited social health activists], and our ANM workers [auxiliary nurse midwives] to see how we can utilise them to deliver many of these healthcare needs in terms of public health.

We have come a long way. I think many of these interventions have helped a lot. We have some of these indicators improving in many parts of the world. But at the same time, there is much to do. COVID has actually exposed the weaknesses and has also highlighted some of the strengths in our system.

Today, we have a daunting challenge of immunising such a large population in India with the on-coming COVID vaccine. Whilst we have had excellent success with the polio vaccine, remember that it was an orally delivered vaccine, it was also a vaccine delivered to children, and it was done over an extended period of time. Now, we have to address both speed and scale when it comes to the COVID vaccine.

It is made even more complex because you will have multiple vaccines and they will be staggered: They have two doses for some vaccines, an adjuvant for some vaccines, a single dose for some vaccines. And you need to do all of this at speed, and in terms of prioritisation because the vaccine is not going to be available at one shot. It is going to come in stages.

How are you going to deal with all this? For someone like me, I feel that our past learnings are going to be very important, but equally, we need to dovetail it with some smart technology and understand what infrastructure we need to put in place to deal with the cold-chain logistics and storage of these vaccines, because you have to do it one month apart and things like that. So I think it is a very complex ask.

Also, you must remember that giving an injection is very different to giving polio drops, and that requires specialised human resource: You must have an army of nurses, doctors, MBBS students to do all of that. So, it is a big challenge but a very interesting one, because if you can actually deliver on this promise of vaccinating India with the COVID vaccines, I think it will actually create a very strong public health ecosystem, and it will strengthen our whole healthcare structure.

It is interesting that you say all of this--the framing of the solution in the context of the vaccine. Why not drugs or treatments or eventually a cure?

Well, all of these are necessary--I am not saying one or the other. But because the whole focus is on immunisation and vaccination, I think it basically allows you to look at the weaknesses in your system, and what we need to do to get people back to work etc.

Yes, there are many many treatments. And the fact that you have seen the numbers of fatalities coming down shows that we are actually treating our patients better. In the early days, we did not even understand what was happening. We now have basically understood what this disease is all about. It has two phases: The first phase is the viral phase and 90% of the people just go through dealing with the virus and getting rid of the virus. But there are 10% of people, where the virus elicits a hyper-immune response, and it is those 10% who really are the vulnerable ones, who are actually at risk, because it does create a cytokine response and many of those do then succumb to it. That is how we have learnt to treat the disease--not just with antivirals, but we have used steroids, cytokine interrupters etc. So over time, I think we have treated much better.

You spoke of a pandemic preparedness platform, and what you said now was in the context of this preparedness linked to vaccines. Are you saying that if we get our vaccine infrastructure right or better and link everything else to it--the public health and the community health infrastructure--then, in a way, we have evolved or improved our overall public health infrastructure?

What I am saying is, today, we are going to get a whole bunch of vaccines which are going to be approved by regulators around the world. They are only going to give it emergency-use authorisations. We really do not have convincing data to show that this vaccine indeed is going to protect you for a long time. We are already seeing in our populations that the antibody titers that people who have had COVID generate start deteriorating after a few months. Why won't it be the same case when it comes to the vaccine? After all, you are trying to do the same thing--mimicking what your body does with the vaccine. So if you are going to start seeing a falling off of antibodies after several months, then it is not the ideal vaccine. We have started somewhere, we have got something at least to give to people, but it is not enough.

What we need to really see is how do we create a pandemic preparedness technology platform. You will have to first have an approach for surveillance, to look for the next epidemic at the early stages, to keep tracking viruses. The second aspect is that if you do have an outbreak of a viral disease, how quickly can you respond to that with a vaccine? Today, we have actually done it very fast. Within nine months, we are going to get a vaccine approved. But we don't know whether that is going to be the right vaccine.

So from this particular pandemic, we must look at various platform technologies, and over time--maybe in the next year or two--we will be able to find out which is the most effective vaccine. Is the mRNA really the best vaccine? Or is the adenovirus vaccine the best? Or is some other vaccine better? We need to get all that data generated over the next few years, and then create platforms of vaccine development technologies, so that when you have the next outbreak, you can indeed develop a vaccine within four months with confidence that it will work.

You also see this helping, as a country, our response to diseases like tuberculosis and everything that we also suffer from at a large scale?

The problem right now is that the focus is so much on COVID, that in fact there is a pretty serious concern that a lot of the immunisation programmes have not happened because of COVID. And there is actually a drop in the number of children immunised. Secondly, even [with] TB--a disease where we have been very good at making sure with the DOTS programme that people take their TB medication--we know that during the COVID times, even this has not been optimally done and so a lot of people are at risk in terms of TB itself.

So I think we need to understand that at a time of an epidemic, you need to catch the outbreak and contain it very fast. China seems to have done it quite well because the way they go about these things, they could actually pounce on the outbreak in Wuhan and restrict it to a small area. We also need to keep looking for outbreaks and when there is an outbreak, you have to pounce on it and contain it. Because only then can you prevent it from spreading.

When you look back at the scientific investment in India, what do we need to do more to build our upstream pipeline of people, skills and infrastructure in order to better prepare and to contribute to a more sounder, efficient pandemic response platform that you are talking about?

If you think about it, we have all the bits and pieces of capabilities and scientific understanding in our country. The scientists in our country, the vaccine development, are very good. What we need to now invest in is true innovation. We need to focus on genomics, CRISPR technologies, this whole area of immunology. We have to do a lot more.

Also, the investments that we have made thus far have served us very well. These scientific investments allowed us to quickly develop diagnostic tests. If you remember, at the start of the pandemic, we were very short of diagnostic tests. Today, we do not have that shortage. We are able to do over a million tests a day--it is not enough, but I still think it is a big change from where we started. We are also developing novel tests based on CRISPR technologies like the Feluda tests which, of course, other parts of the world have also done, but we are right up there. So I think our scientific investments have served us very well. Whether it is our CSIR [Centre for Scientific and Industrial Research] labs or our National Institutes of Virology, we have done a lot in this very short time, and we have unleashed a lot of the potential of these national laboratories.

On the other hand, the private sector has also demonstrated its capabilities--whether it is the vaccine manufacturers or whether the research in vaccines, all that has happened in a big way. Startups have also blossomed because these small startups, who are always starved for capital, have suddenly seen that these are times when they can access more capital. So that has been a very big positive from this COVID pandemic.

So I, for one, believe that we should keep investing in science and innovation, and we must start encouraging these startup companies and the more mature companies to get better and better and be an integral part of the global innovation ecosystem.

If I were to put the same question in a different way, you said that the pieces are there, and have come together in many ways because it is a crisis, and sometimes crisis brings out the best in everyone. So if you were to look ahead now, how do you see this coming together, or what do we need to do to bring this together in a more cohesive way--from the start up ecosystem to policy and everything in between?

First and foremost, the way I look at it is, we need to have diverse vaccine platforms. You cannot just focus on one type of platform. Then, as I said, you need to have surveillance and you need to invest a lot in the genomic databases that we are creating. You will need to use AI, big data analytics etc. to keep a vigil on any kind of infectious disease. And thirdly, we need to invest in some of these new emerging cutting-edge areas.

For instance, we do not have enough capabilities in mRNA technology for vaccines. mRNA has a big challenge: It requires -80°C transportation, which makes it very difficult in a country like India. Can we work on thermostable vaccines?

So when you look at innovation, you need to focus on cutting-edge areas like CRISPR, some of these antibody technologies, some mRNA technology, many other DNA-based technologies, and other viral vector technologies that will make you complete in terms of having a diverse platform of vaccine technologies.

Then, you need to focus on some other key issues: How do you basically bring down the cost of vaccine production? How do you make them thermostable? How do you measure the efficacy? Can you use technology to predict the safety and efficacy of the vaccines? These are very important times, but if we start focusing on that, then I think we will make a lot of progress.

As you look ahead, one of the challenges is the conundrum that exists between the speed that we want and need, and the ability of policy and regulation to keep pace. This also happens in the broader technology world but in this case, we are talking of technology in medicine, which makes things more sensitive. A lot of manufacturers, for instance, are being pushed at one level by policymakers and politicians to roll out medicines faster, including vaccines or treatments. On the other hand, you will have criticism that you are doing it too fast, cutting corners, not doing the right number of trials etc. How do we manage this going forward?

This pandemic has actually opened our eyes to what is possible. For instance, I think we all agree that the rate-limiting steps in any kind of drug or vaccine programme are the sequential regulatory approvals that we all need. In this case, where they called it Operation Warp Speed, where we had emergency-use authorisation based on small amounts of data, it showed that it is possible to shrink regulatory processes and timelines. For instance, in the vaccine development itself, they did parallel clinical trials--phase 1, phase 2 and phase 3 in many cases. And it was actually done in a well-thought out way. If that is possible during COVID, why can’t it be done beyond COVID, is what we are asking. That kind of shaves off almost a year if you want to--in the case of vaccines and in drugs.

Secondly, when you start looking at the emergency authorisations of vaccines or drugs, you are basically saying that as long as you have safety data and building the efficacy data, we will give you the emergency-use authorisation. I think that is a very good way of making sure that anything promising can reach the patient faster. Now, you think about COVID or cancer or any of these life-threatening diseases. If it is going to take five or seven years before that drug can reach the patient, you are going to lose so many patients. But if you can actually give an emergency-use authorisation for many of these life-saving medicines and then ask them to collect real-world evidence of safety and efficacy and then give your final approval when you get all that data, I think that is a sensible regulatory pathway going forward.

Are there better ways to keep the public at large--including those who are going to buy the drug--informed or aware of how this is happening, because there is fear and there is anticipation and expectation on both ends?

No, I think there is a lot of merit because first and foremost, I think all of us are being asked to conduct phase-4 studies. And whenever you conduct studies, you have to share it in the public domain. You cannot just keep it to yourself. So the transparency is there. But I think to keep having real time tracking of every trial becomes very difficult.

For instance, there was a report that a Brazilian participant of the AstraZeneca vaccine trial died. But we do not have enough data on that--we do not even know whether that person was on a placebo or the vaccine to begin with. And what was the death due to? I think also in this time and age, people want more data and more transparency for one reason: This is public money being used to fund a huge public health challenge through vaccine development, in a rapid way. I think when you are taking all these shortcuts, when you are compressing timelines, the public needs to know what is happening.

That I agree with. I think the public must be made aware of any adverse event. If there is an adverse event, the public should know, especially in this vaccine trial. Why do we have to second guess? Why did Johnson & Johnson stop its trial? We do not know the reason, they just said there was a patient [with unexplained illness]. What happened to that patient? People need to know. I do not think pharma companies have the luxury of selecting what they want to share in the public domain and keeping things to themselves when it suits them--because this is not their money. This is public money and they have to share it.

When you say that, I am assuming that you are also applying it to yourself?

Of course. And that is why we shared a lot of our data.

As we emerge from crisis to maybe more normalisation, what are the lessons? What are the good parts of the crisis that you are using personally or as Biocon to normalise or set a new normal?

I think all companies have learnt to work remotely. And remote working is actually very good, because in many ways only the critical jobs, which you cannot do remotely, have to be done by the people who need to be there. But anything that is a support role that can be done remotely is being done remotely. And that is helping us to be more efficient. A lot of the women are benefitting from this because you almost naturally give them a work-life balance. At the same time, I do not want women to be overworked at home--that is another negative side of this. But by and large, I think remote working is very important because you can actually then think of a four-day working regimen.

Another aspect that I am really concerned about is how to prioritise vaccination when it finally arrives. Right now, there is no debate that the healthcare workers, the military, the police, and anyone who is in the frontline ought to be given the first round of vaccines. Who is going to be the second and third?

I have a slightly contrarian view to most people who say that elderly and the vulnerable should be given next. I think teachers and the young working class should be given the vaccines, so that they can get back to work and get the economy to be resurgent--because the elderly in our population are a smaller part. In fact, India is fortunate that 90% of our population is below the age of 60. So if you think about it, the elderly actually get affected because the young are infecting them. They generally stay at home. And we do not have elderly-care centres and things where we have a problem. Most of them stay in joint families at home and it is the young who are infecting them. So if the young are protected by vaccines, they will not infect the elders. And secondly, we do not know enough about the vaccines, so why would you want to then vaccinate the elderly and the vulnerable until you know more? So there are lots of discussions to be had in terms of how we prioritise vaccination.

You have fought and recovered from COVID-19 as well. What is your advice, because people tend to take things lightly and may forget what this can really do?

To begin with, in my case of course, I was one of those fortunate ones who had a moderate case of COVID. So I recovered quite fast. I did not have to use any of the medication that President Trump used, but I anyway came out of it fine. In a week’s time, I was over it and in two weeks’ time, I was rid of the virus. And of course, I got back to work thereafter and I feel fine. I think 90% of the people will have my kind of experience. I want to give most people that comfort that there are very few people who actually get into that severe phase. And young people are actually able to cope with this disease very easily.

For instance, on our campuses, I think we are one of the safest campuses. We have a testing facility and we are testing very rigorously. An employee gets tested every two weeks. We have seen that we have reduced the test-positivity rates and they are half of the state and the national average--which is a good thing. We are doing a lot of correlation between CT values [cycle threshold, the number of cycles it takes to detect the virus in an RT-PCR test] and the severity of the disease. Most people who are testing positive are asymptomatic when they come to work, and these people get very mild versions of the disease. They are showing high CT values, which means low viral load, which is why they are not showing symptoms also, and they all come out of this quite well.

We must make sure that we are also tracking antibody levels. What we are also seeing is that these mild cases do not actually develop a lot of antibodies, which means they can be reinfected. So there is a lot of more learning to do in terms of the disease itself.

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