As COVID-19 cases continue rising to record levels during India's second wave, one medium- to longer-term solution could have been an effective roll-out of COVID-19 vaccines. India has administered 95 million vaccine doses to 84 million people--6% of the total population--by April 10, 2021. India has also exported about 64 million vaccine doses, per commitments made by private sector manufacturers like the Serum Institute of India before the current crisis.
While health and frontline workers, the 45-plus and those with comorbidities are being prioritised, younger age groups--such as the 55% who are under 30 years of age--will need to be vaccinated at some point. But already, India seems to need more vaccines than it has, with vaccination centres and state governments announcing shortfalls, and is unlikely to reach the desired scale anytime soon. Although vaccines are manufactured by private companies, all flow within the country and for export is controlled by the central government. To get the market perspective on where India stands in terms of vaccine manufacturing capacity and distribution logistics, both domestically and globally, we spoke with Nithya Balasubramanian, pharmaceutical and healthcare sector analyst at research and brokerage firm Sanford Bernstein.
What could a likely vaccine shortfall mean, from a public health perspective, when India is seeing over 120,000 cases a day? Could the situation get worse? Should India start thinking of more aggressive solutions to arrest the spread of COVID-19? We asked Giridhar R. Babu, professor and head, life-course epidemiology at the Public Health Foundation of India in Bengaluru. Babu has a Master's in Public Health and a PhD from the University of California at Los Angeles, and began as a resident at the All India Institute of Medical Sciences, New Delhi.
Dr Babu, give us a sense of the public health challenge facing India right now.
GRB: If we were to look at just the vulnerable people [with comorbidities] in India, one in three adults has high blood pressure/hypertension and one in 10 has diabetes mellitus type-II. If they are not vaccinated in the next few months, the risk of seriousness and mortality from COVID-19 they face is high. So it is imperative to cover at least the vulnerable groups as soon as possible, and then think of expanding to other age groups. We also need to vaccinate at the same time as containing [the spread of COVID-19] because different COVID-19 variants are developing because of high circulation. Once there is high circulation, there are chances of higher degree of mutation [viruses constantly change through mutation], and some of these mutants might result in newer COVID-19 variants. So updating the vaccines for these newer variants is also a challenge. Therefore, vaccine manufacturers will have to be kept in the loop about the changing scenario. From a public health point of view, it is important to not only expand the vaccination coverage as soon as possible, but also to update the vaccines based on the emerging scenario.
Govind Ethiraj: Could you put a number to the vulnerable population?
GRB: The government's initial data said the vulnerable population within the country is 300 million. The good thing is we do not have to diagnose [these comorbidities]. Anybody over 45 years has to be reached now; then, probably a younger age group in the next expansion.
Ms Balasubramaniam, give us a sense of COVID-19 vaccine production capacity, both globally and in India.
NB: Globally, adding up all the capacities that have been announced by all the vaccine manufacturers--Pfizer, AstraZeneca, Novavax, Johnson & Johnson, etc.--totals 14 billion doses. The number is heartening if you assume that the global population is 7 billion and 60% need to be covered with two doses each to get to COVID-19 herd immunity, as [14 billion doses] is enough to cover the global population. Unfortunately, though announcements have been made, some of the actual capacities still remain unidentified. There is also a huge disparity between the capacities announced for the developed nations versus those announced for the developing countries. There is a fairly wide supply-demand gap, from a market perspective. The United States and Europe, for instance, have double- or triple-booked the number of vaccines actually required for their populations, while that is not the case in markets like Chile, Argentina or Ukraine, which are all seeing a very high COVID-19 burden.
Now, dialling into India. Before COVID-19, between the Serum Institute, Bharat Biotech and Biological E, India had about 2.3 billion doses' capacity [to manufacture vaccines of any kind]. Serum Institute has so far struck two manufacturing relationships [to produce COVID-19 vaccines], one with AstraZeneca promising a billion doses, and one with Novavax, again promising a billion doses. I understand that their plan is to repurpose as much of their existing capacities as possible, but they had also announced that they are setting up additional manufacturing capacities for up to another billion doses. That will not materialise overnight; 2022 is possibly when the new capacity can actually see the light of day.
Serum Institute's existing capacity is around 1.3-1.5 billion doses, total. So, based on all the reports that we have seen, their current manufacturing capacity of the AstraZeneca vaccine [called Covishield in India] is about 70-odd million doses per month [Editor's note: the capacity is between 70 and 100 million per month, as per a Rajya Sabha committee report]. Bharat Biotech, unfortunately, is much lower than that, at around 5-10 million doses [Editor's note: 12.5 million per month, per the Rajya Sabha report].
If you add all of that up, it's at the run rate [the current rate of COVID-19 immunisations per day]--that is, however much they are producing, we are actually consuming. [Editor's note: On April 9, India administered 3.6 million doses; the past week's average has been 3.1 million daily doses]. We really need them to step up so that we can actually get ahead of the game.
When you say Serum Institute has 1.3-1.5 billion COVID-19 vaccine doses capacity, you mean annually?
NB: Yes, we are talking about annual capacities and we are also talking about capacities for different types of vaccines. Every capacity can't be repurposed to suddenly start making COVID-19 vaccines. Different vaccines are based on very different technologies, so repurposing doesn't happen overnight. So they have been able to repurpose up to 70-80 million doses per month right now, and even that is not likely enough, because remember they have also committed up to 200 million doses to GAVI, to the COVAX facility, and some of that they have supplied but those commitments still remain.
Is the current run rate close, in terms of how many vaccines are being produced and how many are being consumed every day?
NB: Yes, we are very close in terms of how much we are producing and how much we are consuming. And if India wants to expand the eligible population, which I'm assuming we would want to sometime soon, it's imperative that manufacturers like Serum Institute and Bharat Biotech step up their capacities.
Dr Babu, have many people and most frontline health workers got their first, maybe even second doses?
GRB: Initially there were some problems in terms of communication, regarding what kind of regulatory status Covaxin's clinical trial mode meant, and when it would be available. So there was some time required for health workers to catch up with vaccinations. But the moment vaccination was opened up for those above 60 and those above 45 years with comorbidities, at least those who are well aware of the vaccination process, who have the wherewithal of registering on their own, are all able to get vaccinated.
While the supply constraint is one issue, special efforts are also required to administer the vaccination in field settings and to mobilise people, especially those who are less aware, or who cannot register on their own. Even the prime minister was hinting on April 8 that people have to mobilise others for vaccination. But since there are supply constraints, I am not sure improving communication and going into a campaign mode will be beneficial. Once the supply constraints are removed, you can facilitate higher demand and then there will not be major problems in the field.
Here in Mumbai, even into the first week of April, not all centres were utilising vaccine stocks to the fullest, and that was reportedly the case in many other parts of the country as well. But now, in the second week of April, many centres have run out of vaccine supplies and are asking people to come back later.
GRB: There are two things happening. First, there is micro-planning for other vaccination programmes. The beneficiaries, vaccination sites and how many can be covered by one vaccination site are known, in most vaccination programmes. With COVID-19 vaccination, there is centralised registration, and people can choose any vaccination centre they want. Some centres also have walk-in registration. Therefore, it is difficult to predict and plan how much supply any centre needs. Second, initially people wanted to enable others--health workers, family, friends--to get vaccinated, before getting vaccinated themselves. Now that the second wave has begun, there seems to be magical thinking, that maybe now since cases are rising, we will benefit from vaccination. The benefit, however, will kick in only two weeks after second doses, and that too only in preventing severe illness or death. Even states are demanding that eligibility expand to every person above 18 years, with this notion that vaccination will reduce cases. This is not going to help them, if that is the objective. So the second wave created this panic. Communication from the local governments and central government in terms of improving the vaccination numbers [has also led to a rush for vaccination]. Once you strengthen interpersonal communication campaigns around vaccination among the general.population, the coverage will automatically increase.
It's an interesting conundrum, that we have to address both vaccine hesitancy and vaccine supply and high demand at the same time. It is like advertising a product and not being ready with the launch. Ms Subramaniam, you mentioned a global figure of a likely commitment of almost 14 billion vaccine doses, which on paper at least covers the entire planet. Assuming much of this supply were to start rolling out, what is the likely timeline, where could it go, who is likely to grab it first?
NB: That unfortunately is the billion dollar question. About three billion doses' capacity has been announced by two Chinese manufacturers, Sinovac and Sinopharm. Pfizer has announced a billion doses or more just from the BioNTech manufacturing facility. Now, after Johnson & Johnson (J&J) got a manufacturing partnership with another large Indian manufacturer, Biological E, those capacities should kick in once they start manufacturing the J&J vaccines. I am actually not able to give you a straight answer because often announced capacities don't pan out the way it is anticipated. We have seen several hiccups along the way. For example, Emergent is a contract manufacturer who both J&J and AstraZeneca partnered with in the US, but they have had a lot of manufacturing challenges. [Millions of] doses went to waste because of various issues that they had at their plant, which J&J has now taken over. So, I don't have a straight answer for you. 15 billion doses is what has been announced. I am hoping that a lot of it will materialise. But it's anybody's guess as to exactly how much we'll see in 2021.
Assuming India were to free up COVID-19 vaccine imports and pricing outside of government dispensaries and hospitals, which could potentially send the right price signals out into the market, could that change things in terms of supply, purely looking at it as a business analyst?
NB: Dr Reddy's Laboratories (DRL) and the Sputnik V vaccine is one where possibly an emergency use authorisation is imminent. Through DRL, Sputnik V has announced that the Russian Direct Investment Fund has promised about 250 million treatments, or 500 million doses. So if they do get an emergency use authorisation soon, those are additional capacities that are likely to show up for India. The other one to watch out for is Zydus, which is hopefully wrapping up their phase 3 clinical trial. That is another 140 million doses of additional capacity that would show up in the market. Beyond that, if import restrictions are removed, the Pfizer and the Moderna vaccines are again options that can be made available. But I think the Drugs Controller General of India has been particular that they want to see bridging studies in India before giving companies an approval to sell vaccines here.
So even if the import restrictions are lifted and the pricing challenge is no longer relevant, these companies will need enough of an incentive to do the bridging study and then register the product in India. I am far more hopeful of Sputnik V or Zydus' capacities showing up soon, than Pfizer or Moderna's.The last one to watch out for would be the Biological E vaccine, which they have been working on in partnership with Baylor College, London. Again, as I mentioned, they have fairly large capacities. It would be good to see their capacities coming in.
Dr Babu, what is the desired run rate of vaccination per day, and where are we in terms of pure domestic availability?
GRB: We have reached nearly 4 million doses per day, but what we really require is at least 7-10 million doses per day, just to cover the vulnerable population in the next 2-3 months. That is, if we want to make a dent in terms of reducing mortality, which is the ultimate goal. I don't see that happening with the current availability of only two vaccines.
As Nithya rightly pointed out, Sputnik and Zydus have bright potential and even the government has announced that they might be approved in a month or two. I am also hopeful about J&J. I just heard the news today that they are interested in submitting an application. I am of the opinion that if the Government of India could approve Covishield based on data from the UK, even before the bridging study results were made available, the same logic should be applied to all the other vaccines. Phase 3 is done, has proved safety, efficacy and immunogenicity. Now bridging data is required, so why can't they be given emergency use authorisation? I am only talking in terms of the modus operandi. If we have done this once, why can't we use the same rationale for the other vaccines?
Ms Balasubramaniam, again, just a numbers question. India is administering 3- to 3.5 million vaccines a day, but as Dr Babu says, we ideally need about 7-10 million a day to cover the vulnerable population. Where do we stand in terms of meeting that target?
NB: At 10 million shots per day, India needs 300 million doses a month. Hopefully Serum Institute can scale up. I think I saw an announcement that they have requested some monies from the government to scale up the capacities. [Editor's note: As noted above, SI is producing between 70 and 100 million doses of Covishield per month, as per a Rajya Sabha committee report]. Bharat Biotech has been working on trying to scale up their capacities to 50-60 million doses. So that takes us to 150-160 a day.
We will, for sure, need Zydus and Sputnik V's capacities to kick in if we want to hit that 300 million run-rate.
So, from a pure numbers point of view, India is nowhere near what is desired even in the next three months?
NB: It doesn't seem like that.
Dr Babu, assuming we are not going to hit the target anytime soon, and assuming the government is not going to open up imports of some of these other vaccines, what should be India's Plan B?
GRB: Our Plan B, which is sort of pushed to Plan A right now, is to contain the ongoing surge of cases. Let's imagine the government approves all the other vaccines. Even then, we will not be able to tackle the ongoing surge in cases by vaccination [alone]. It will take at least three months just for the effect to be visible in terms of reducing mortality. So what we right now need are very strong and aggressive containment measures, not necessarily a lockdown. Lockdown is a lazy option at this stage, if we don't do better containment efforts. Two reasons why we should be able to reduce the transmission are: one, mortality has to be brought down, and two, the more the circulation of the virus, the more are the chances of mutations leading to variants of concern. So let the vaccination pace pick up on its own independently. At the same time, we have to pursue an aggressive containment strategy.
Could you define further what an aggressive containment strategy would be at this point of time?
GRB: More than two is a crowd. Can we at least try to define crowd as more than 10, and then try to limit the crowds? Let's remind ourselves that we were in lockdown for many months. We don't want to be in a lockdown-like situation, especially for the poor, because it's going to be doubly fatal. If the cases increase, they are the ones who will suffer and if there is a lockdown, they will suffer. So for their sake, the more privileged sections of society should exercise responsibility. So, crowd control is one and another is testing.
This has been emphasised by the prime minister in his address on April 8. Even now, many states are doing rapid antigen tests. Everybody is speaking of Maharashtra and Karnataka which have reported high cases both in the first and second waves. There are states that are not reporting cases at all to the level you expect. I am more concerned about those states. Because the variants which will develop there, because of high circulation, will be a threat everywhere. New Zealand has already stopped the entry of people from India. Should we then be on the list of [other countries]? Should each state be in trouble because of variants developing in different parts of the country?
When I say aggressive containment strategy, there cannot be a differential strategy. We all have to be very careful. We have to follow a very strict review in terms of the 'silent' areas, and ensure that we are not missing high circulation anywhere.
That's an important point: the virus is mutating all the time, and each subsequent mutation will behave differently--some will be more dangerous, some less. Am I right?
GRB: That's right. See, when the virus replicates more, the more the mutations. Not all mutations are fatal. Only maybe one in a million may be problematic. But we have millions of mutations going on. So we have to be careful to prevent it.
Ms Balasubramaniam, vaccines are the only sure fix right now. What's the best way to incentivise more vaccine production, supply flows and roll out to as many people as possible, when you look at the pharma industry as a whole and the way it solves problems?
NB: When I look at what other governments have done, for instance the United States or European Union, they have extended significant support to both vaccine developers as well as manufacturers to scale up production. That has been something sorely lacking in India since the COVID-19 crisis began. For example, the Biomedical Advanced Research and Development Authority in the US has spent several billions of dollars supporting R&D. They've also given proper procurement contracts, which is what is lacking in India today. If you can support your manufacturers monetarily, the scale-up is not a big challenge. We have the technology, we have the knowhow. For a manufacturer like Serum Institute which is globally the largest vaccine manufacturer, to be able to produce more vaccines should not really be a challenge. I think the government can step up in terms of monetary support going into manufacturing vaccines.
This article was republished from IndiaSpend.com