Two years into the pandemic – Challenges, successes and what next
Panelists:
Dr. Soumya Swaminathan, Chief Scientist, WHO
Mr. Amitabh Kant, CEO, NITI Aayog
Dr. Rajesh S Gokhale, Secretary, Dept. of Biotechnology, Government of India
Dr. Peter Piot, EU Chief Scientific Advisor
Dr. Krishna Ella, Managing Director, Bharat Biotech International Ltd.
Ms. Mahima Datla, Managing Director, Biological E Ltd.
Dr. Gagandeep Kang welcomed the Panelists.
Q. To Amitabh Kant: Give us the Indian and the global perspective on how we responded to the urgency of the challenge and to delve a little bit on what worked well and what did not and what changed with time.
Amitabh Kant: The pandemic was an extraordinary experience for the 21st century. It impacted the economy and burdened the health systems. And therefore, to deal with this we followed an agile approach, used feedback to assess outcomes, safety nets were very critical, they were put in place through provision of relief measures to support various sections of the society, we came up with the largest free food programme, direct cash transfers and relief measures for businesses. the Reserve Bank of India simultaneously provided monetary support to the economy, the Pradhan Mantri Garib Kalyan Ann Yojana provided additional free of cost food subsidies to 80 crore national foods beneficiaries which was a huge thing. We invoked the disaster management act to empower groups to identify problems, provide immediate effective solutions and various empowered groups acted on this. We had an expert group which was NEGVAC. There were several other challenges. Regular guidelines were provided by Health and Family Welfare to State Government on Covid appropriate norms. There were challenges on the health system and that led to a very major approach of masks being ‘Made in India’, Oxygen plants being provided. 1563 oxygen generation plants were sanctioned, mobile ICU bedded facilities were provided. But more than that there was a whole focus of vaccine. Huge efforts were provided by companies like Bharat Biotech, Biological E., Zydus Cadilla, Serum Institute to come out with Indian-made vaccines. And that was a sterling work. Normally a vaccine development process takes 6-8 years for research and trials, but path-breaking work has been done in India. In addition to that the telemedicine guidelines came out. The ‘Swasth App’ which driven by the Indian tech garage had a huge impact, the Sanjeevani app for telemedicine were some of the initiatives. But states across the country increasingly adopted the digital tool technology across the healthcare systems. There were several major challenges because a crisis like this was never confronted by anyone before. Therefore we must be constantly proactive, constantly take responsible measures, we also worked as a Government approach. But the second wave was very lethal, it was never anticipated and therefore all our resources were pooled to the maximum, we tried to do our best in the given circumstances.
We’ve worked very closely in partnership with WHO all through the crisis. In a crisis of this nature, extension, mass communication, guidelines are very critical – whether guidelines are released for senior citizens, adults, mothers, children, infants – we took WHO’s support. Also took their support of better management of Covid patients, took their support on a whole range of aspects like scientific method ranging from genomic sequencing. We took their guidance on vaccine development because Indian Government departments worked in partnership with WHO all through including aspects related to not only the country but the states and we have got some sterling support from Dr. Soumya Swaminathan all through this crisis.
Q to Soumya: Can you give a global perspective on how the WHO engaged with the rest of the world, particularly with the R&D agenda which has been absolutely critical on the development of interventions.
A. From the perspective of WHO, it was on the New Year’s Eve that the reports were coming out of Wuhan and our emergency teams were picking that up and on 4th of January we put out a disease outbreak notice. And remarkably by around the 10th of January, the sequences of the novel coronavirus had been uploaded and within 48 hours we had activated our networks of collaborating centres. WHO has a long history of influenza laboratory network which has worked on influenza virus for many decades. It was that network that sprang into action and immediately started working on this new pathogen. In 48 hours we had RT-PCR standard operating procedure and protocol release so that labs around the world could start designing and using the primers that would detect this virus. It was the first pandemic in the era of this type of genomic sequencing technology that was available. Around the same time we started activating networks around Research and Development. Thanks to the outbreak and the lessons that were learnt. WHO has set up something called the R&D blueprint for the epidemics which essentially had listed priority pathogens likely to cause epidemics and pandemics. One of those pathogens is called Pathogen X for disease X which is an unknown virus – most likely Zoonotic, most likely respiratory, but it is something you have to be prepared for. And because of the work in the last few years, we actually had the system and a global network of scientists in place that were immediately contacted and virtual meetings which were new started happening in January and in February about 400 people from all over the world came to Geneva and developed a research roadmap – not just for diagnostics and therapeutics but also to look at public health and implementation research to look at ethics, the origins of the virus, epidemiology. So, a number of different working groups were developed. This was very critical. The fact that WHO acted very early on in this kind of global coordination of research, developing target product profiles, developing standard clinical protocols that could be adapted and used by any country, developing the regulatory benchmarks for what a vaccine should hope or what a diagnostic should achieve. This actually sets the stage for developers and funders of research because then you have a target or a roadmap. We also then setup a solidarity trial platform because we realized that there were too many small clinical trials going on in countries that were not actually answering the important questions of how do we reduce mortality of hospitalisd patients which at that was quite high. We didn’t have any known treatments for this disease. The solidarity trial which today operates in over 50 countries and India was one of the countries to join that trial platform provided as an opportunity to test new therapies as they came along and a similar approach is now being used for vaccines. That was an innovation we should learn lesson from, for the future. Since then we have been able to advance a lot in different areas. Reflecting on the challenges and lesson learnt – I think while the scientific achievements have been absolutely outstanding such as vaccines in less than a year and a lot of progress on diagnostics, self-test kits and antivirals, technology and the genomic surveillance which has allowed us to track the evolution of the virus – but where we fell short was a global coordination the harmonized way of approaching the pandemic. Even thought WHO put out a framework for equitable healthcare access and share them equitably, countries did not play by that and each country was trying to look after itself which has resulted in over 70% of people in high income countries vaccinate against less than 10% of people in African countries. Countries are now discussing a Treaty for a pandemic agreement for binding principles or agreements on how countries must act. The worst affected were poor, the marginalized or those who had poor safety net. The science was amazing but the solidarity was lacking.
Q. Peter, can I ask you to reflect on equity?
A. Peter: In terms of speed, on the science side or the development of vaccines, has been on record high. I was optimistic with the thoughts that first there would be therapies for treatments and then vaccines. Today the treatment of Covid disease is a very complex issue. It’s not just giving an antiviral and once you kill the virus it’s over. It is the speed with which sharing of information or data has happened can always be better, but it was unprecedent in comparison to the previous outbreaks. The speed on the societal levels of what to do is equally important. And certainly, the first year was without a vaccine and that’s where all the other measures are important. This is not an advertisement but the title of my memoire is ‘No Time to Lose’ and this is really about when it comes to outbreaks to epidemics. The earlier you are effective intervening, the more lives you will save, the more cases you prevent. You can limit the contagion in the beginning, you will prevent not only the first generation but also everybody who will be infected. When something new occurs that nobody has been confronted with, where the level of uncertainty is enormous, those in power who are not technical experts and the technical experts can’t agree in the beginning. Hence, leadership is the key. My mantra there is: hoping for the best, preparing for the worst. You can’t take a risk. The leadership is to be informed. There is a complex interaction between science advice and political decision-making with different driver that we have to recognize. At EU level, we are lucky that the President of the European Commission has a medical background a Masters in Economics and Public Health and she got on it early on and put it on the agenda of the European Council where every month, the heads of states or heads of Governments come together but rarely discuss health. Health is not a legal competency in the EU. The initial reaction was closing the borders, banning of exports, protective gears. That was not a health issue, but it was important to protect the people. Leadership is very important and to have a sound science advice. Secondly, the better prepared you are and the better systems you have, the more you can act rapidly. You need to have fire brigade before even deploying it. Certain countries who have taken measures out of experience, for example, dealing with Sars, could act much faster. Thirdly, a combination of resilience in society but trusting government. There are countries that have heavily politicised and polarized Covid wherein it becomes difficult to recommend something as simple as vaccination or mask wearing becomes an issue, whereas in some countries such as the Nordic countries, there is a very high level of trust in Government, so the Governments do not have to issues rules that are very strict. Trust is a very important element when it comes to vaccine deployment, supply and for people to take it. The track record has been very mixed. Also, because the strategy in the beginning was not so clear. Saars was eliminated almost completely and formed the strategy for South East Asia while in Europe we had the Influenza model in limiting the damage and protecting the vulnerable situations and have issues access with healthcare. Scarcity is the enemy of equity. The speed with which the new vaccines were developed is one thing, but the speed with which you can set up to manufacture for billions is another matter.
There is also the issue of domestic accountability. We have seen procurements that have exceeded far the needs of certain countries. We should make sure that there are no excesses and we have the mechanisms for distributing the mechanisms so that we are protected from politically or epidemically driven bans.
The whole world is counting on India for Covaxin. We should ensure that manufacturing is spread over regions and not restricted to a specific country. We should protect ourselves against another epidemic by having a better distribution, better invention and innovation and also manufacturing.
Q. To Mahima Datla: Vaccine Manufacturing technologies that you’ve chosen are high volume vaccines which presumably contribute to equity in the future. What have been the challenges in the approach and how would you have done differently?
A. Mahima Datla: Before Sars-Covid, people would ask whether we had a pandemic portfolio, we would say no because it is too unpredictable, too risky, and if jump into something unpredictable or risky, it jeopardizes our ability to supply to the predictable pediatric population. It was an unprecedented situation. We were called to action, but at the outset we had three things on mind – 1)that it works and is effective 2) safety was a huge concern because the deployment was going to be literally for an entire population of the world so wanted to make sure that safety was taken care of 3) it was going to be affordable because we understand that when the pandemic first broke out, resources were made available, but health budgets were severely constrained in many countries. Ultimately we came to know that if it was to be a full-blown pandemic something like a multi-year, we knew that there wouldn’t be unlimited resources. It needed to be affordable enough for each countries health systems with somewhat to take accountability for the cost systems associated with it. 4) The fourth thing was a match to our infrastructure. Our ability to scale or be fast predicated upon what large-scale infrastructure we already had. If we had to set up green-field manufacturing facilities, we would still be talking about a vaccine launch two years from now. So these four factors helped us choose the vaccine platform that we did which is the recombinant subunit – of course because a lot of our experience with Hepatitis B vaccine with several hundred million of doses supplied, both individually and in the form of a pentavalent and the large scale infrastructure that supports it. But I also felt that by and large we could down select the clones and engineered clones whether it was for this or another variant fairly quickly once the manufacturing system was set. Did it give the speed of mRNA technology? No, but it gave us the scale and the give us the opportunity to deploy this in a manner that makes it extremely affordable.
The IP landscape also helped, not that I suggest it would have been a hindrance, because globally people have been extremely generous in sharing technology and knowledge this time. But if we had to all over again, we would do exactly as we did.
Q. To Dr. Ella: You were very quick in getting going with clinical trials, bringing the product to approval, and you are furthest along with a nasal vaccine which a lot of people are waiting to see. What did you choose what you chose and would you change anything now?
A. Krishna Ella: I looked at only one thing – safety in adult vaccination. I looked at our expertise in viral vaccination. And we are extremely good in the inactivated vaccine. And we have seven vaccines on inactivated vaccines strategy. So we are meticulously planned from – from Chikungunya, Zika, Rabies, Japanese encephalitis. We are one of the very few people in the world who have expertise in inactivated vaccine strategy domain. And the vero cell culture – we are Number 1 with 13 vaccines platform on vero cell culture. We wanted to pool in what we are good at.
What we are not good at is – had we diverted the immunogenicity to more T cell response with an adjuvant which is where we partnered with ViroVax in US and we licensed … quinolone which are TLR adjuvants, we scaled up with IICT in Hyderabad. We also need public private partnership because as private companies we cannot do studies on monkeys in India. National Institute of Virology in Pune has got that expertise. We used the facility to prove that it works on animals.
What is important is an efficacy trial. Also, the regulatory was a bit delayed in the beginning in India. If that was a little activated, the mRNA vaccine could shift before the animal trial also and we could shift straight to human trial. Had we had that luxury in India, we would have got it in the efficacy trial when the delta was there. But we vaccinated in Phase 3 trial and there was no disease for four months. Then suddenly the delta variant came. And we were the only ones doing an efficacy trial during a delta epidemic and we captured that time very quickly with the entire efficacy trial over in 15 days.
The learning curve here -if the regulatory can understand when to do the efficacy and if they understand the relation between clinical trial and the disease burden, but that knowledge is not there in this country. That knowledge helped us with the efficacy trials in India.
Whether I would do it differently? I would certainly do the same thing. But I will look at how to bring in broad protection where all the variants are taken care of from the perspective of classical virologist.
Q. To Dr. Gokhale: If we were to think about the future pandemics, what should we be thinking about in terms of platform technologies? And what support can we give the existing and new vaccine manufacturers?
A. Dr. Gokhale: From a scientist’s perspective, one of the most important things is an embedded scientific thinking in the society that we have seen. If there were demonstrations in India, it would have got challenging. People showed their belief in diagnostics. We had focused only the pathogen, but it is the post-Covid issue that needs to be critically addressed.
The role of Department of Biotechnology in creating a vaccine development ecosystem that came in the market – from setting up immune assay laboratories, setting up animal challenge facilities, clinical trial sites, or regulatory approvals. Our regulatory committees are not like venture capital mindset right now. The incomplete scientific data or fluid scientific analysis cannot be accepted as one is bound by duty and law which is where things can be slow. But with a venture capitalist mindset, it might be possible to do wonders.
There is a new confidence that has been built in the effectiveness of Government in the life science sector. The life science industry requires a supporting system unlike the IT industry for it to wholesomely evolve and grow. The important role that the DBT played in terms of self-sufficiency of diagnostic sector wherein DBT very early on started funding startups which came in very handy by enabling manufacture of a large number of kits and now most importantly do genome sequencing and tracking every variant. All this has been possible due to the DBT years’ of investment in Human Resource Development and setting up a variety of infrastructure and institutions that allows you to utilize them when you really need them. It has been a learning experience for all of us in diagnostics and vaccine trials.
Q. To Amitabh Kant and Dr. Gokhale: How much risk is Govt. willing to take, is the Govt. recognizing unknown challenges such as pathogen X which might not be as easy a target as Sars-Cov2 was.
Dr. Gokhale: Biosecurity is as relevant and important as other security aspects. Government is excited about co-development and co-creative activities with companies and industries. There is a confidence building measure that we can develop and deploy quickly. How far we can go ahead is something that can be worked out as we move along.
Amitabh Kant: Government handholds a critical place in boosting R&D which is critical to the future. It is also important to boost the pharma and medtech sector. We have been a major importer of APIs, but we need to push the indigenous drug development. We have pushed production development incentive schemes, we have supported medical devices through PLI. We have done a lot of structural reforms in clinical trials and regulatory processes. But we might have to be far more radical in a crisis by streamlining processes through digitization and transparency in the application approval process. Government also needs to incentivize research in Biopharma to help India transition from a low-volume, high value player to a high volume, high value player. We are also examining the ways to strengthen the R&D system and push for greater industry-academic collaborations. There is a need to promote innovation, global partnerships, knowledge sharing amongst our scientific community. We need to look at research in emerging areas such as complex generics, biosimilars, orphan drugs etc. We need to integrate in a bigger way with the global supply chain to achieve unprecedented synergies of scale and make us a global player. Focus on personalized care and speedy delivery through real time data and analytics. Speedy response is the future.
Q. Right now we are in a situation where particularly for Sars-Cov2 they’ve managed to make last year 11 billion doses of the vaccine while the year before that it was about 4 billion globally for all vaccines put together. Are we at risk with over supply of this one product and should we think about diversification?
Mahima: We are in a situation where supply security of vaccines is the biggest topic of conversation and we feel reassured that there are enough vaccines to share. Over supply may be true for only some countries. We were able to give countries choices in vaccine technology that gives them reassurance of vaccine hesitancy. The problem in business area would be that if companies were supplying only Covid vaccines and don’t have repurposing or redeploying them for a different pipeline. Investments in certain technology platforms that can be deployed either for routine vaccines or for future pandemics so you keep the infrastructure warm to allow a rapid deployment. But right now over supply is not true for majority of the countries. But to be able to cover at least 60% of the world’s population we might feel comfortable about the vaccine situation as it helps in the context of equity. Very few countries have been able to go down to immunizing children. India must consider how to bring equity supplies for rest of the world.
Q. Covax had issues with supplies initially. What would you see Covax doing in the coming year and how would it shape future pandemics?
A. Soumya Swaminathn: We are over the phase of supply shortage we saw in 2021. We have enough visibility to supply for the demand. The challenge is going to be that there are many countries that are not able to mount the vaccination programmes which India has successfully been able to do. There is a lot of support needed on the ground in terms of technical support, workforce, funding, logistic support etc. Covax will have to with boots on the ground and help these countries scale up the high targets. We have to plan for variants – WHO is working on scenarios where we might need variant proof and broadly acting vaccines and inhaled vaccines that the likes of Bharat Biotech are working on. For the future we need distributing manufacturing network for which we have the mRNA technology transfer hub in South Africa. We are now initiating various spokes. Many companies are working on second generation mRNA technology. No region must be dependent on other countries for imports of vaccines or other health products. I would like to see India also take TB as a challenge and develop new generation vaccines for TB and eliminate it.
Q. To Dr. Ella: What are you future targets are going to be in TB vaccines?
A. Dr. Ella: Today’s neglected diseases are tomorrow’s pandemic. We have done analysis on why nasal vaccines by a certain company would have failed. It gives as a moral boost to learn from what has not worked. India has created a huge database unlike anywhere in the world. In the next one week, we are releasing a public statement on tuberculosis such as a partnership on a phase 3 trial. India has 4 cities with BSL-4 facilities other than the UK. Three of them are in Hyderabad which can be utilized as hub by international community in an event of any problem. Tuberculosis elimination is on the Prime Minister’s agenda for 2025.
Q. To Peter: Would you like to comment on what’s happening in the EU and whether you have any advice for Indian academia, industry and policy makers?
A. Peter: One is to strengthen the basic institutions in public health. At the European level there is legislation that allows to strengthen European Centre for Disease Control and also the European Medicines Agency. Regulatory Affairs has been an obstacle in the deployment of vaccines in some countries. Secondly, HERA – Health Emergency Response Agency – has been set up in one year in the EU which is a record. It includes more of public health approach. What’s relevant here is that there is an international pillar there with an explicit commitment to work with others. Reaching out to India on joint activities could be beneficial to all sides. Thirdly, going back to the equity and the issue of obstacles of sharing or exports. The EU has allocated over 1bn Euros for the development vaccines in sub-Saharan Africa. We have to look beyond just vaccines and fortify global partnerships to overcome the obstacles. Never miss a good crisis and build institutions that will survive.
