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Covid 2.0 Rampages India As Top Echelon Policy Makers Ignore Science

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‘India is in the endgame of COVID,’ announced the union health minister of India, just in the last month – March 08, 2021. Although, it was then clearly known to medical fraternity that today’s Covid vaccines won’t be magic bullets against rapidly mutating new Coronavirus. Interestingly, a scientific-data based MIT study, published last year – on July 01, 2020 predicted that India might record the highest ever in the world – 287,000 new Coronavirus cases per day, by February 2021. At that juncture also Covid vaccines were expected to be available in India before that predicted time frame. The MIT study warning received a wide coverage even in India - by almost all news dailies, on that very month of the last year. The national Covid management team did not seem to have taken it seriously, along with others. These include, besides the top echelon of governance – a vast majority of Indians – across the social, political, religious and economic strata.

The fallout of such callousness – both at the individual Covid-appropriate behavior level, as well as Covid governance level, have been more disastrous than what was forecasted even in the above MIT study. The ferocity and scale of the second Covid-19 wave in India did not just overwhelm the nation, but raised grave concern across the world too. On April 22, 2021, India recorded the world’s biggest ever single-day rise with 314,835 new cases of Covid-19, causing death to 2,104 people. The very next day, this number increased to 332,730 new cases with 2263 deaths.

But, the peak of the Covid second wave hasn’t come, just yet. According to a mathematical model developed by a team of scientists from the IIT Kanpur and reported by news media on April 22, 2021, the number of active covid-19 cases in India during the second wave is expected to peak in May. The daily infection count is expected to exceed 350,000 cases. In this article, I shall dwell on three specific areas – acknowledging that the current scenario is the outcome of national misjudgment, if not a humongous misgovernance to prepare India for Covid 2.0:

  • Current struggle of India’s fragile and long-ignored health care infrastructure.
  • Need to neutralize some general misgivings on Covid vaccines and associated dilemmas.
  • Who is equipped to save people, if no external remedial measures remain unavailable for some more time?

India’s fragile and long-ignored health infrastructure can’t take anymore:

Amid this calamity, India has run short of oxygen, hospital beds, important Covid medicines, including Remdesivir. Curiously, reports keep coming incessantly confirm and reconfirm: ‘Ever since the second wave of the pandemic started, the healthcare systems in India have been teetering on the brink, with many hospitals unable to handle the relentless inflow of patients whilst also running short of beds, oxygen cylinders and other essentials.’

Doctors and many health care workers are overwhelmed by the massive scale of the human tragedy and in tears, as they articulate: ‘Many lives could have been saved had there been enough beds, oxygen supplies, ventilators and other resources – if the healthcare system had been better prepared for the second wave.’

The Supreme Court intervened, noting the ‘grim situation’ in the country:

Meanwhile, the Supreme Court of India, reportedly, ‘Suo motu’ (on its own) took note of the grim situation in the country and the havoc caused due to shortage of Oxygen cylinders in hospitals. Consequently, on April 22, 2021, the top court said, ‘it expected the Centre to come out with a “national plan” on the supply of oxygen and essential drugs for treatment of infected patients and method and manner of vaccination against the disease.’  The Delhi High Court also observed, “We all know that this country is being run by God,” coming down heavily on the Centre over the Covid-19 management.

Some Covid vaccine related misgivings and dilemmas:

Many people are raising questions of the efficacy of two currently available Covid vaccines in India – Covishield and Covaxin, especially against our probably ‘desi’ double mutant variety of Covid-19. The trepidation increased manifold when India’s former Prime Minister – Dr. Manmohan Singh got Covid infected after taking two doses of Covaxin. Or, reports, such as: ‘Sri Lanka reports six cases of blood clots in AstraZeneca vaccine recipients, 3 dead.’ Incidentally, these vaccines were made in India. Some may not possibly know that both the issues have been deliberated by the Indian scientists, who haven’t expressed any concern, as yet. This has to be shared with all by all concerned, soon. Let me explore some of these related issues, as follows:

Re-infection after taking Covid vaccines:

Regarding re-infection rate after taking two doses of Covid vaccines, the scientists have now released data establishing that only a very small fraction of those vaccinated with either Covaxin or Covishield, have tested positive. In any case, instances of a few “breakthrough” infections do not undermine the efficacy of the vaccines, they added.

The ICMR has also clarified, “These vaccines definitely protect against disease. However, the immune response begins to develop usually two weeks after every dose and there are variations within individuals, too. Even after the first dose, if exposure to the virus happens, one can test positive.”

Efficacy of Covishield and Covaxin against double mutant strains:

Notably, both – the Indian Council of Medical Research (ICMR) and the Centre for Cellular and Molecular Biology (CCMB) have announced last week that Covishield and Covaxin protect patients even from the ‘double mutant’, B.1.617, variety of Covid-19. Scientists believe that the “double mutant” is responsible for the sudden spike in the number of cases in Maharashtra and other parts of the country. They had earlier feared that this “double mutant” or B.1.617, may escape the immune system and thus vaccines may not offer protection from this strain of the novel coronavirus.

Reported risk of blood clotting with Oxford-AstraZeneca’s Covid-19 vaccine:

No cases of blood clotting have come to light in India. However, a government panel of experts is,reportedly, investigating for any domestic cases of blood clotting, even mild ones, as a side effect of the two COVID-19 vaccines being administered in India. According to India’s leading virologist Gagandeep Kang, “blood clots reportedly caused as a result of Oxford-AstraZeneca’s Covid-19 vaccine amount to a very small risk.”

As reported on April 24, 2021, the United States has also decided to immediately resume the use of Johnson & Johnson’s Covid-19 vaccine, ending a 10-day pause to investigate its link to extremely rare but potentially deadly blood clots. These details, I reckon, need also to be shared with all people, soon, in order to neutralize any doubt on administering Covid vaccines.

Covid vaccine availability and pricing:

Recent media reports highlight, at least six states of India – Andhra Pradesh, Chhattisgarh, Haryana, Maharashtra, Odisha and Telangana – are facing Covid vaccine shortage, as Covid 2.0 overwhelms India. Most of these states have already apprised the Centre of the situation, as the Supreme Court of India also seeks the details from the center about its current status.

As on April 22, 2021, India has administered over 135 million vaccine doses, where each individual will require two doses. Whereas, as published in Bloomberg on April 23, 2021, ‘1 billion Covid-19 vaccines have been administered around the world.’ The good news is, effective May 01, 2021, everyone above the age of 18 years will be eligible to get vaccinated. The Central Government will also lift its singular control on supply and delivery of Covid-19 vaccines in a bid to tackle the massive rise of cases that have crippled the country’s health infrastructure.

That said, the key question that follows – would Covid vaccine manufacturers be able to meet this increasing demand in India, when there already exists more demand than its supply? According to Niti Aayog Covid-19: Vaccine availability will improve by July 2021. The two major vaccine manufacturers in India are also indicating broadly similar time frame.

Meanwhile, amid a deadly second wave of Covid infections, a third Coronavirus vaccine - Russia’s Sputnik V, has been approved for emergency use in India. Incidentally, Sputnik V’s approval came not before India overtook Brazil to become the country with the second-highest number of cases globally. According to its local distributor – Dr. Reddy’s Laboratories, India will start receiving Russia’s Sputnik V vaccine by end May.

Be that as it may, it is still unclear whether enough Covid vaccine doses will be available right from May 1, 2021, to start inoculating all Indians above 18 years of age, across the length and breadth of the country. Besides, SSI’s decision to fix the rate of Covishield vaccine for private hospitals and state governments, has attracted sharp criticism from the Opposition, who argued that there was no logic in charging the state governments a higher price, when the Centre is getting the same vaccine at Rs 150 per dose.

This question surfaces, especially when SII Chief himself acknowledged that they are making profit even with Rs.150/per dose price as the pandemic ravages the nation. A news item of April 24, 2021 also underscores ‘Serum Institute’s Rs.600/dose for Covishield in private hospitals is its highest rate in the world.’ Nonetheless, price sensitivity to Covid vaccines during the pandemic is not specific to India.

Shareholders of Pfizer, J&J, reportedly, are also pushing for detailed COVID-19 pricing strategies of the respective companies, at their annual meetings. Curiously, at the same, yet another report highlights: ‘With the competition struggling, Pfizer’s COVID vaccine sales could hit $24B this year.’ Amazing!

India utterly overwhelmed, angry outbursts of concern beyond its shores:

Witnessing the nature of rampage caused by Covid 2.0 in India, global press blames the Indian top policy makers for utter failure to anticipate and tackle the devastating second wave. For example, The Guardian of the UK flashed a headline on April 21, 2021 – ‘The system has collapsed’: India’s descent into Covid hell.’ It further elaborated: ‘Many falsely believed that the country had defeated Covid. Now hospitals are running out of oxygen and bodies are stacking up in morgues.’ The Times, UK was harsher. It reported, ‘Modi flounders in India’s gigantic second wave.’ It further added: ‘Record levels of infection have put huge strain on the health service and highlighted the perils of complacency in the nationalist government.’

The New York Times reported on April 23, 2021: ‘India’s Health System Cracks Under the Strain as Coronavirus Cases Surge.’ The report also cited examples of ‘recent political rallies held by Mr. Modi that have drawn thousands, as well as the government’s decision to allow an enormous Hindu festival to continue despite signs that it has become a super spreader event.’

Conclusion:

Keeping aside the responsibility, or rather lack of it, of the National Covid governance team, individual Indians – like you and me – can’t in any way shy away from our own responsibility of compliance to Covid appropriate behavior, religiously. We are equally responsible, at least, for our own lives and fate. Even today, many of those who are wearing a face mask, are wearing in the chin – keeping the nose exposed – forget about double masking! Moreover, how many of us were or are eligible for Covid vaccination till date, but did not or could not take?

Curiously, Covid 2.0 is no longer striking mostly the poor urban population, living in slums or hutments, or the migrant laborer. Nor it is attacking mainly the senior citizens or people with co-morbidities. More young people, including children are getting infected in Covid 2.0. In Covid 2.0 – over 90 per cent of Covid new cases concentrate in in high rise and other buildings in major cities, like Mumbai. While urban slums account for just 10 per cent. On April 24, 2021, Bloomberg also reported, ‘India’s Urban Affluent Hit By New Virus Wave After Dodging First.’

Terming Covid 2.0 as concerning and scaring‘, Tata Sons Chairman also said, ‘India needs to get as many different Covid-19 vaccine licenses as possible. And replicate multiple factories on a war footing to ramp up production in order to meet the requirements as the country reels under the devastating second wave of the pandemic.’ It’s incredible, how a small country in the Indian subcontinent – Bhutan with limited resources, got its vaccination plan right and carried out, reportedly, the world’s fastest immunization drive.

Coming back to the last year’s above MIT study forecast for 2021 Covid situation in India. It goes without saying that this one, among several others, was based on credible data. It also brought to the fore the scientific reasons of consequences for not following the norms of Covid appropriate behavior. Looking back and coming back to real life scenario of date, one thing becomes crystal clear. When science is ignored, both at the highest echelon of national governance where the buck stops – or at the individual, social, religious or political level – it is virtually inevitable that a disaster would strike. And in most cases, it will strike hard – very hard. Much beyond what a human can withstand to survive. We have choice for survival – even in today’s frightening scenario. Let’s individually and collectively behave, as the science demands. Life and livelihood are important – for all of us.

By: Tapan J. Ray    

Disclaimer: The views/opinions expressed in this article are entirely my own, written in my individual and personal capacity. I do not represent any other person or organization for this opinion.

 

 

3D Printing: An Emerging Game Changer in Pharma Business

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On August 3, 2015, Aprecia Pharmaceuticals in the United States took a game changing step towards a new paradigm of the global pharma business. The Company  announced that for the first time ever, the U.S. Food and Drug Administration (US FDA) approved a ‘Three-Dimensional (3D)’ – printed prescription drug for the oral use of epilepsy patients. Although, 3DP has already been used to manufacture medical devices and prosthetics, in the pharma world, this disruptive innovation was never practiced on the ground, till that magic moment came.

The drug is Spritam® (levetiracetam) used as a prescription adjunctive therapy in the treatment of partial onset seizures, myoclonic seizures and primary generalized tonic-clonic seizures in adults and children with epilepsy.

According to this announcement, Spritam® utilizes Aprecia’s proprietary ZipDose® Technology platform, that uses 3D Printing (3DP) to produce a porous formulation that rapidly disintegrates with a sip of liquid.

The 3DP technology:

3DP technology is broadly defined as a process for making a physical object from a three-dimensional digital model, typically by laying down many successive thin layers of a material.

The originator of this game changing development is the renowned academic institution – ‘The Massachusetts Institute of Technology (MIT)’in the United States. 

Later on, the MIT licensed out the patented 3DP technology for its use in many different other fields. Among pharma companies Aprecia Pharmaceuticals obtained the exclusive rights to 3D-printing technology for pharmaceutical purposes in 2007.

A high potential game changer:

In pharma, 3DP could possibly emerge as a game changing and disruptive innovation, sooner than later. It could radically change the traditional and well-established strategic and operational models of pharma business, especially the drug discovery process, manufacturing strategy and even the disease treatment process, paving a faster pathway for the much awaited ‘Personalized Medicines’, in a large scale. 

Lee Cronin, a Professor of Chemistry, Nanoscience and Chemical Complexity at the Glasgow University, says that the 3DP technology could potentially be used to print medicines of many types – cheaply and wherever it is needed. As Professor Cronin says: “What Apple did for music, I’d like to do for the discovery and distribution of prescription drugs.”

3D Printers would also throw open an opportunity of getting any drug tailor made for the individual patient’s needs, such as, exact dosage requirements, size, shape, color and flavor of the pill and also in the most appropriate delivery systems, just as what Aprecia Pharmaceuticals did with Spritam® by using this technology. 

In this article, I shall highlight the game changing impact of 3DP only in the following three areas of pharma business: 

  • The drug discovery process
  • Drug manufacturing strategy
  • Supply Chain effectiveness
A. Impact on drug discovery process:

A December 29, 2015 article titled, “Click chemistry, 3D-printing, and omics: the future of drug development”, published in ‘Oncotarget, Advance Publications 2015’ deliberates on the potential of 3DP in the drug discovery process.

The paper states, Genomics has unambiguously revealed that different types of cancers are just not highly complex, they also differ from patient to patient. Thus, conventional treatment approaches for such diseases fit poorly with genomic reality. It is also very likely that similar type of complexity will eventually be identified in many other life-threatening ailments.

Currently, a large number of patients are taking medications that may not help them, on the contrary could harm some of them. The top ten best-selling drugs in the United States are only effective in between 4 percent and 25 percent of the individuals for whom they are prescribed, the paper observes.

However, developing new drugs and tailoring such therapy to each patient’s complicated problem has still remained a major challenge.

One possible solution to this challenge could be to match patients to existing compounds with the help of an equally complicated modelling technique. Nonetheless, optimization of a complex therapy will eventually require designing compounds for patients using computer modeling and just-in-time production. 3DP shows a very high potential to effectively address this complex issue.

This is primarily because, 3DP is potentially transformative by virtue of its ability to rapidly generate almost limitless numbers of objects that previously required manufacturing facilities. 

It is also now becoming clearer that with 3DP, scientists will be able to print even the biologic materials, such as, tissues, and eventually organs. Thus, in the near future, it is plausible that high-throughput computing may be deployed to design customized drugs, which will reshape medicine, the article highlights.

In his short ‘Ted Talk Video Clip’ (please click on this link), Professor Lee Cronin explains his working on a 3D printer that, instead of objects, is able to print molecules for a new drug. It could throw open an exciting potential of a long-term application of 3DP for printing, our own customized new medicine by using chemical inks.

In a nutshell,  Professor Lee Cronin elucidates in his ‘Ted Talk’, how could the immense potential of 3D printers be leveraged to catalyze the chemical reactions in order to print real drugs, as and when required, according to the requirements of individual patients.

B. Impact on drug manufacturing strategy:

Not just in drug discovery, 3DP would equally be a game changer in pharma manufacturing, the way it is operated today, including the state of the art production facilities.

This could very much happen in tandem with the 3DP drug discovery research, moving towards personalized medicine, and simultaneously making the same 3DP an integral part of the new drug production line.

Moreover, besides the opportunity of getting any drug tailor made for individual patient needs, such as, exact dosage requirements, size, shape, color and flavor of the tablet and also the delivery system, 3DP technology can be most productively used to manufacture high priced low volume and patient-specific orphan drugs for the treatment of critical illnesses.

Even for Active Pharmaceutical Ingredients (API), the power and potential of 3DP technology can be well leveraged. On March 12, 2015 the ‘Howard Hughes Medical Institute (HHMI)’ of the United States announced that HHMI scientists have designed a revolutionary “3D printer” for small molecules that could open the power of customized chemistry to many. 

It further stated, small molecules hold tremendous potential in medicine and technology, but they are difficult to synthesize without proper expertise. The automated “3D printer” designed for small molecules is a way to get around this bottleneck. The new technology has the potential to unlock access to customized molecules in a way that will drive science forward, on many levels. Moreover, the potential for cost-savings with 3DP is huge, improving the drug profitability significantly.

C. Impact on 'supply chain' effectiveness: 

Currently, the traditional pharma ‘Supply Chain models’ are primarily based on the following:

  • Efficiency largely with high volume operation
  • Need to drive the cost as low as possible
  • Relatively higher-number of workers
  • The inventory cost
  • The real estate cost, owned directly or indirectly, for the entire ‘Supply Chain’ cycle

3DP technology would enable manufacturers shifting the ‘just in time production and distribution’ processes very close to consumers. Such well spread out and ‘just in time’ drug manufacturing activities catering to varying requirements, from very small to very high, would help reduce the cost of logistics, substantially.

This disruptive innovation will enable even the hospitals to print the required drugs at their own locations with, authorized 3DP file downloads, eliminating the need to keep huge inventory and also protecting patients from counterfeit medicines in the ‘Supply Chain’.

Thus, the bottom-line is, the drug companies will be able to print drugs with 3DP technology on real time demand at a large number of selected locations. This will significantly bring down the finished product inventory, starting from companies’ warehouses and distributors to retail and hospital shelves, to almost zero, making pharma supply chain significantly lean and highly effective.

Additionally, it will enable the pharma companies to manufacture drugs also in all developing countries, resulting in improved access to medicine, at a much lesser cost.

Conclusion:

I believe, this technology has already reached a critical juncture, where it is no longer a matter of conjecture that 3DP would ‘soon’ become a game changer, especially for the drug discovery process, manufacturing strategy and supply chain effectiveness of the pharma business, across the world, including India. Getting a prime mover advantage is vital. 

However, the question still remains: how soon will this ‘soon’ be? 

By: Tapan J. Ray

Disclaimer: The views/opinions expressed in this article are entirely my own, written in my individual and personal capacity. I do not represent any other person or organization for this opinion.