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COVID-19 Vaccine Production in India: Challenges, Opportunities and Solutions

Editor, TRANSFIN.
Jul 16, 2021 4:41 PM 13 min read
Editorial

COVID-19 continues to ravage the world over a year after it was declared a pandemic.

But the dynamics of 2021 are clearly different for two main reasons. One: unlike last year, we have a clear-cut path to defeat the virus i.e. mass vaccination. And two: unlike 2020, when the threat was relatively universal, this year while coronavirus continues to infect and kill en masse in some countries, there are select nations which have more or less tamed their COVID curves. So much so that some parts of the world are now dropping mask mandates and reopening fully.

But in a highly globalised world of 7 billion people, the dictum “Nobody is safe until everybody is” rings ever so loud and true. As new variants prop up and vaccine inequalities worsen, whatever modest gains the world has made against the virus are under risk of being lost. Unless, that is, the shortfalls are fixed.

Above all this means manufacturing enough doses for people in every country at the earliest. This undertaking, historic, titanic, and already underway...risks being derailed due to supply crunches. The current global vaccine manufacturing capacity is just not sufficient to inoculate humanity against the virus anytime soon. At the current pace, international herd immunity may take as late as 2024 to be achieved. Assuming of course a lethal, vaccine-resistant variant doesn’t suddenly emerge.

To understand what various countries, especially India - the so-called “pharmacy of the world” - are doing to boost manufacturing and what more can be done, it is important to first understand how vaccines are produced and what underlying issues emerge on the way.

What Goes into Vaccine Production?

Vaccine development is a long and complicated process. It usually takes years, if not decades. Before 2020, the fastest a vaccine was developed was for mumps, and that took nearly five years.

Development of the COVID-19 vaccine took much less time mainly due to the emergency induced by the pandemic. The various stages that go into developing a vaccine were overlapped, manufacturing was pre-empted, and billions of dollars were poured in from governments, humanitarian agencies and private players around the world.

Naturally, vaccine production begins in the lab. This research process is determined by what type of vaccine is being developed. It could contain an inactivated virus (like Covaxin does) or use technology that infuses the virus’s genetic material such as mRNA (Pfizer, Moderna) or DNA (AstraZeneca) to evoke an immune response. The latter tech is relatively new and has a leg-up over conventional vaccines in that it expedites the research phase.

Within a lab, vaccine development involves numerous sub-stages. This includes cultivating the pathogen, purifying samples, deactivating it, isolating and replicating its genetic material or protein etc. Finally, the “vaccine” part of the vaccine is usually in powder form. For administration purposes, it is mixed with a "diluent", the mixture of which is what you see in vials.

That’s the research phase. Then come the trials. Scientists begin with tests on animals, then proceed to larger and larger groups of human subjects. Every phase is scrutinised by experts and peer-reviewed. It’s not unusual for trials to be temporarily suspended if unforeseen side-effects emerge.

Finally, if all goes well, the trial’s results are published for the world to see and review. The metric most often looked for here is the “efficacy rate”, a measure of how effective the vaccine candidate is in preventing infection in an inoculated person. For what it’s worth, this is a flawed and misunderstood metric. You may be led to believe that Pfizer and Moderna vaccines are “better” than, say, J&J’s or AstraZeneca’s simply because the first two have efficacies above 90%. But this number is determined by a variety of trial-period factors and is thus misleading (watch this video to learn more).

The bottom line is that all vaccines work to the same degree in preventing extreme reactions or death from COVID infections. The “best” vaccine is simply the available one.

So, now we have a vaccine candidate which goes for regulatory review. The currently available coronavirus vaccines were granted “emergency use authorisation” (EUA) by the WHO or different countries’ health bodies once they were judged to be safe and effective.

Now comes the distribution phase.

 

What Goes into Vaccine Distribution?

This is where the doses leave the manufacturing facilities and get transported to hospitals and vaccination sites so that they reach you and me. Obviously, this is a wildly complicated operation involving innumerable moving parts spread across vast geographies. To say that it is a logistical challenge would be a gross understatement.

FYI: India's COVID-19 vaccination drive is tapping into its existing Universal Immunisation Programme (UIP) network - a famously sophisticated maze of over 700 refrigerator vans, 70,000 vaccinators and 28,000 functional cold chain points, 95% of which are located below the district level. The UIP is also the backbone of India’s crusade against BCG, polio and hepatitis.

Now, the distribution phase is where cold storage becomes a headache. Most vaccines need to be stored in low temperatures to remain usable. India’s cold chain network was in dire need of modernisation when the pandemic struck, and things haven’t changed enough since. This is why even if Pfizer and Moderna come to India, distributing them will be an uphill and costly affair.

 

Supply-Side Conundrums

Now, you have not one but several viable vaccines against the virus. You have a flawed but intricate network in place for distribution. And you have no dearth of demand. The vaccination drive now becomes a matter of manufacturing enough doses for the world’s second-populous nation (probably most-populous by now, seeing what’s happening in China).

Last year, it was lost on nobody that once a vaccine hit the market, India would have to churn out doses at a pace never seen before. Not only because it had a mammoth domestic population, but also because, as the home of the largest vaccine industry, many countries relied on Indian pharma to inoculate their own populations.

But by April, the "world's largest vaccine drive" had disastrously derailed even as the deadly Second Wave shut down the country again. A series of policy missteps led to a dangerous situation where vaccination targets were off-track, supplies were dwindling, some inoculation centres shut down altogether, and manufacturers struggled to make enough doses for the country, let alone the rest of the world. (Read this to understand how India devolved to such an unenviable position.)

Today, about six months since the rollout commenced, only about 4% of the population has been fully vaccinated. Despite the Centre’s recent U-turn on vaccine procurement and the call for foreign pharma companies to apply for EUA, there are doubts whether there will be enough doses to inoculate the entire adult population before December 31st (which is the Government's new sanguine target).

In other countries, the picture is not all bleak. Boosted by strong vaccine rollouts, the US has fully reopened much of its economy. The UK has all but lifted its wide-ranging lockdown; on June 1st it happily reported zero deaths for the first time since March 2020. Germany and France, despite dragging their feet in administering doses, are relaxing restrictions too. As many as seven countries have reported no new cases for four weeks in a row.

But in most other countries, the COVID curve is either still rising or slowly plateauing; distinctive dips are still rare or short-lived. As such, ensuring the availability of enough doses for everybody is of paramount importance.

In a 2019 study, the WHO projected a "best-case scenario" of 4.15-8.31 billion doses' global manufacturing capacity in the event of a pandemic. Estimates now say anywhere between 9.5 billion to 12 billion doses could be produced by the end of 2021. However, supply chain disruptions remain a threat. Another embargo on raw materials could stifle production targets. A predicted Third Wave in India could further delay doses for COVAX countries. And a resurgence of infections globally could invite a return of vaccine nationalism.

It therefore becomes extremely critical to boost manufacturing capacities urgently. But how?

 

Government Investment

Looking back, a key reason why the US and UK were able to race ahead in vaccinations is because their governments had the foresight (and capital) to shower researchers with money and place pre-orders months before the first public dose was administered.

Washington, for example, placed an order for 100 million of Pfizer doses with an option to purchase 500 million more. It signed similar deals with Moderna, J&J, Novavax and AstraZeneca. The impressive success of America’s Operation Warp Speed is a testament to both efficient government intervention and private sector competency.

Meanwhile, the Indian Government took a different approach - that of dragging its feet. By its own admission, “no governmental aid, assistance or grant” was given for the R&D of Covishield or Covaxin.

Vaccine makers like Serum Institute (SII) had to largely rely on their own capital or approached investors. In August, for instance, SII raised $150m from the Bill and Melinda Gates Foundation and invested $100m of its own money to expand its facilities. In April, citing “very stressed” timelines, it appealed to New Delhi for a ₹3,000cr ($400m) lifeline. The latter relented, giving SII its desired sum and Bharat Biotech ₹1,500cr ($201.6m). (Point to note: these sums were advance payments for doses, not capital to invest in capex.)

More monetary aid announcements followed, but had such steps been taken earlier, tens of thousands of deaths could have been avoided and millions more doses administered. The bulk of the Government’s direct investment since last year had to do with distribution (for instance, the ₹35,000cr ($4.67bn) Budgetary allocation) rather than manufacturing, which was largely left to the private sector.

What can the Government do now? A University of Chicago study suggests that countries should directly pay the costs associated with increasing capacity rather than just promising vaccine manufacturers higher prices or giving advances, which isn’t as attractive an incentive. The Centre for Global Development adds the benefits of production subsidies (tax credits or payments for each unit of output), capacity subsidies (grants proportional to capacity), low-interest loans, and volume guarantees.

Government investments in modernising other aspects of the supply chain (like cold storage) and mass-producing and stockpiling materials like vials and syringes are also vital. Not just to tide over the current pandemic, but also to prepare for inevitable future crises.

Granted, one could argue that the cash-strapped Government probably had its hands tied and couldn’t afford to support vaccine manufacturers - and probably might not be able to in the near-term either. But we’re in the middle of a health emergency, and vaccines are the only way out. The pandemic is eating into crores in lost economic growth; it only makes sense to invest crores in vaccines on priority to prevent more damage.

The Government can afford to spend taxpayer money logically for a change by literally paying for a panacea!

 

Patent Waivers

India has been a vocal proponent of gaining an exception to the WTO's Trade-Related Aspects of Intellectual Property (TRIPS) rules to waive patent rights on COVID-19 vaccines. This would enable manufacturers in developing countries to access the intellectual property (IP) of big pharma companies to produce cheaper versions of their vaccines.

Basically, the idea is to decentralise manufacturing and scale up production of generic drug-equivalents of the vaccines. By enlisting the help of firms in developing countries, more doses can be manufactured sooner and at cheaper prices. This also had the added benefit of addressing vaccine inequality.

This proposition - which has been in the works for months - received a major boost recently when the Joe Biden White House announced an abrupt turnaround and backed the policy, However, it is far from a done deal, given the opposition from the UK and the EU, among others. (The WTO works on a consensus-based system, so all 164 members need to agree for a decision to pass.)

However, India should think twice before putting all its eggs in the patent waiver basket. Besides the improbability of its passage, the fact remains that vaccine manufacturing is not everybody's cup of tea. Unlike typical medicines, which can be reproduced by typical generic drug manufacturers, vaccines are more complicated. Hastily lifting IP bottlenecks could result in millions of ineffective and unsafe doses, which could potentially harm recipients, encourage mutations and fuel vaccine scepticism. Moreover, mRNA vaccines are a new technology and the expertise required for them is in short-supply and difficult to replicate.

An alternative exists, though. Big Pharma could license their IP rights to third parties in a "technology transfer" arrangement - akin to AstraZeneca’s deal with SII or the Uncle Sam-brokered partnership between Merck and J&J. This would safeguard the pharma cos’ interests and ensure the safety of the doses.

A note here: The only “Indian” vaccine approved for public use right now is Covaxin (Covishield is licensed from UK’s AstraZeneca). Currently, only Bharat Biotech has the licence to manufacture Covaxin, which was developed in collaboration with scientists from ICMR’s Pune-based National Institute of Virology (NIV).

As recently as May, the Supreme Court asked the Centre why it wasn’t resorting to compulsory licensing under the Patents Act - which would override IP obligations. Basically, the domestic equivalent of a patent waiver. The Centre refused to do any such thing for a long time. Until last month, that is, when ICMR appeared to suggest that it was ready to share the technical know-how about Covaxin production with interested firms.

 

More is Merrier

In early 2021, the US vaccination drive was slackening even as infections mushroomed. But beginning March, it picked up pace - to such an extent that nearly half the country is now fully vaccinated.

A large part of what enabled this transition was inter-company alliances. Sanofi and Pfizer, Novartis and Pfizer, Baxter and Novavax, Merck and J&J… Rivals came together to shed differences and work as one to defeat the virus. A pandemic makes for strange bedfellows.

There are also more conventional partnerships i.e. Technology transfers or “strategic” tie-ups. These include Biological E-J&J, Novovax-SII, AstraZeneca-SII etc.

Thankfully, the Indian Government is at least not dragging its feet on this front. PSUs are being tapped for this purpose. Haffkine Biopharmaceutical Corp. will receive ₹65cr in financial support to make 20 million doses per month. Bharat Immunologicals and Biologicals Limited (BIBCOL) is preparing its facility to provide 10-15 million doses per month using a ₹30cr ($4m) Government grant. Indian Immunologicals Limited (IIL), a Hyderabad facility under the National Dairy Development Board, is being provided a ₹60cr ($8m) grant.

Other entities could also be enlisted soon. These include Gujarat Biotechnology Research Centre, Hester Biosciences and OmniBRx (each for Covaxin). Pfizer, J&J and Moderna have also been contacted to source and locally manufacture their vaccines. But such a step would require a patent waiver. As of June 29th, J&J's single-dose vaccine is expected to hit Indian shores soon - but directly sourced from the company.

But India can do more. At the risk of sounding trivial, the onset of the pandemic was accompanied by ballooning demand for PPE like face masks, hand sanitisers, gloves, nose-swabs etc. The initial hiccups were overcome in part because affiliated and unaffiliated industries from auto to fashion chipped in and diverted their prowess to manufacture these items. Now, you can’t expect Haldiram’s to manufacture Covishield doses. But relevant firms - at the very least, other pharma companies - could be mobilised for the cause.

Also, the mammoth Integrated Vaccine Complex at Tamil Nadu has a capacity for 585 million doses per year - and it is still inexplicably sitting idly. There are also other PSUs that could roll out doses, like the Central Research Institute, BCG Vaccine Laboratory and the Pasteur Institute of India.

 

Caution is Key

This is a long-term pursuit in the event of another wave or future pandemics, and thus no less crucial.

The brutal truth is that this pandemic has exposed not only the fragile state of India’s healthcare (which was anyway hardly a secret) but also the shortcomings of its pharmaceutical sector. It has also proved to be a woeful reminder of the dangers of myopic planning by an overconfident polity. Had there been sufficient foresight, the required oversight, and the necessary planning in place, tens of thousands of lives could have been saved, countless livelihoods and jobs could have been salvaged, and the economy could have been spared further damage.

Instead, a delayed vaccine-rollout without a clear-cut plan was allowed to proceed knowing that manufacturing capacity was severely limited and manufacturers - of which initially there were only two - were cash-starved. Recklessly optimistic signalling from the Government about India having somehow defeated the virus bred complacency, which bred carelessness. Timely warnings from experts - and an inter-ministerial Government-appointed panel - were callously ignored. Politicians’ paeans to shore up infrastructure before the peak of the First Wave were never followed through, leading to a calamitous situation where citizens, begging desperately for oxygen, had to rely on total strangers to survive.

With the highly contagious Delta Plus variant being viewed with increasing concern and a Third Wave predicted to hit sometime soon, one can only hope that the Government and the country have learnt the hard way to not underestimate the virus again.

 

In It for the Long Haul

Now, to use Churchill’s words - and at the risk of sounding insensitive - India must not waste a crisis.

As per a report by the IQVIA Institute for Human Data Science, global sales of COVID-19 vaccines through 2025 could add up to $157bn. For the (former?) vaccine powerhouse of the world, this is a lucrative opportunity. One that shows how boosting domestic manufacturing capacity would help the country fight the virus and give the economy a much-needed pick-me-up.

Given that the average vaccine price per year is likely to gradually climb down - from $22 in 2021 to $5 by 2025 - this provides a golden opportunity for Indian pharma companies to fill the void that their big foreign peers will leave once vaccine manufacturing becomes less profitable for them.

India’s vaccine makers need this. The ban on exports has hurt their credibility on the world stage, even evoked unsavoury situations such as when AstraZeneca threatened to sue SII for breach of contract. Retaking their position as a reliable partner is essential for them to retain their premier place in the global industry.

 

The Hard Truth: Vaccines May Not End COVID-19

Can we ever eradicate the SARS-CoV-​2 virus from the face of the Earth?

Factors like vaccine efficacy, vaccine hesitancy and virus mutations suggest that we may have to learn to live with the virus, to contain it rather than eliminate it.

Such a scenario would become all the more likely if global manufacturing doesn’t pick up pace. Variants could emerge, each more vaccine-proof than the other. Vaccine-induced immunity could fade over time, requiring booster or periodic shots. Over time, the coronavirus may become something akin to the seasonal flu - something we understand and know how to beat, but something that can never completely go away.

But before that blessed future of blissful nonchalance can arrive, the pandemic has to end. Right now, everything hinges on how widely and how swiftly humanity can be vaccinated.

FIN.
 

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