Multifaceted Coronavirus Narrative Raises Multiple Questions

Posted on April 6, 2020 by Tapan Ray

Last night, amid the national lockdown, many people followed Prime Minister Modi’s video message, broadcasted on April 03 at 9 am for all, ‘to challenge the darkness of Coronavirus together – with a Diya, candle, torch or flashlight, at 9 pm for 9 minutes, from their respective balconies.’ That was the 12^th day of 21-day lockdown, when the deadly microbe – Covid19 infected, tested and detected cases climbed to 3,577 in the country, with the death toll rising to 83. This is against 564 - the total number of confirmed cases in India when the lockdown commenced on March 24, 2020.

With all this, a mind-boggling narrative is developing at an accelerating pace. It’s not just about the rogue microbe – rampaging the world hunting for its prey. But also pans over multiple dimensions of its fallout, impacting virtually everything, for all. People of all sections of the society are participating, deliberating or debating on this issue, as the invisible camera of destiny rolls on. Unprecedented!

That’s the real world where, despite fear of an unknown future, most people prefer freedom of expression while playing a constructive role in containing the menace, collectively. We are witnessing a similar scenario – the world over. But, more in the democratic nations. Relatively enlightened citizens will always want to participate in this emerging chronicle, shaping the overall narrative and help sharpening the nations Covid19 policy further – instead of being passive onlookers.

Meanwhile, the objective of maintaining physical distancing during 21-day national lockdown period and beyond must be achieved, regardless of any public discord on its mechanics. This has to happen, primarily because of the TINA factor. Likewise, it’s also a prerequisite that the lockdown is handled efficiently, with meticulous advance planning, deft and dignified handling of any situation, by all and for all. That said, the good news is, newer scientific, evidence-based data are revealing more actionable pathways, in this multifaceted narrative.

A multifaceted narrative raises multiple questions:

As I wrote above, Covid19 narrative is multifaceted and not just one dimensional. It’s true beyond doubt: ‘If there is life, there is the world.’ But, that has to be a life with dignity, a life that help protect families and facilitates contributing to the nation, in different ways – enabling a scope of fulfillment of all.

In this article, I shall, explore some important facets of the evolving narrative on the Covid19 outbreak to drive home this point. In that process some very valid questions, as raised by many, also deserve to be addressed. Some of these include:

Covid19 is a war like situation where no questions are asked about the strategic details of a warfare, why the same is not being followed today? In a war some collateral damages are inevitable, why so much of noises now?

Why has Covid19 created a general panic with stigma attached to it?

Panic is avoidable, but is the threat real. If so, why?

Why people violating national lockdown by migrating from the job location to respective hometowns – increasing the risk of the disease spread, must be brought to their senses mostly through the harsh measures?

In the absence of any vaccine or an effective curative drug, why all decisions of policymakers must be blindly accepted by all, during national lockdown and maybe beyond, as if there is ‘not to reason why, but to do or die?’

Let me now explore each of these questions.

A war like situation?

No doubt Covid19 is a war like situation, but with some striking dissimilarities between a conventional war and this war. A conventional war is fought by a well-trained and well-armed defense forces with already developed a gamut, against a known and visible enemy nation.

Whereas, the war against Covid19 is against an invisible and unknown microbe’s sudden attack, being fought in India by a limited army of health care professionals and workers. They fight this war, mostly without adequate or no battle gear, like Personal Protective Equipment (PPE), testing kits and ventilators, supported by a fragile health care infrastructure.

Moreover, in the conventional warfare, the type of advance information and intelligence that the Governments usually possess against the enemy nations, can’t be matched by any private domain experts.

Whereas, Covid 19 still being a lesser known entity to medical scientists, as on date, the remedial measures are still evolving. Only scientific-evidence-based data can create actionable pathways for combat, spearheaded by the W.H.O. Thus, most people expect the nation to comply with, at least, the current W.H.O guidelines for health-safety of the population.

Further, in the cyberspace, several latest and highly credible research data are available for all. These are being well-covered by the global media as a part of the narrative. Thus, unlike conventional warfare, external experts may know as much, if not even more than the Government on Covid19.

Some avoidable show-stoppers:

There are several such avoidable show-stoppers. For example, when one reads news like, ‘Delhi Government Hospital Shut As Doctor Tests Positive For Coronavirus,’ or something like, ‘Indian doctors fight Coronavirus with raincoats, helmets amid lack of equipment,’ alongside a jaw-dropping one, ‘India Sends COVID-19 Protective Gear To Serbia Amid Huge Shortage At Home,’ chaos in the narrative takes place.

In the tough fight against Covid19 menace, these much avoidable fallout may be construed as show-stoppers, if not counterproductive. Many may advocate to pass a gag order against revelation of such difficult to understand developments, and keep those beyond any public discussion. Instead, why not order a transparent enquiry by independent experts to find facts – holding concerned people accountable?

Why has the disease created so much of panic with stigma attached to it?

This is intriguing because, according to the W.H.O – China Joint Mission report on COVID-19, around 80 percent of the 55924 patients with laboratory-confirmed COVID-19 in China, had mild-to-moderate disease. This includes both non- pneumonia and pneumonia cases. While 13·8 percent developed severe disease, and 6·1 percent developed to a critical stage requiring intensive care.

Moreover, The Lancet paper of March 30, 2020 also highlighted, in all laboratory confirmed and clinically diagnosed cases from mainland China estimated case fatality ratio was of 3·67 percent. However, after demographic adjustment and under-ascertainment, the best estimate of the case fatality ratio in China was found to be of 1·38 percent, with substantially higher ratios in older age groups – 0·32 percent in those aged below 60 years versus 6·4 percent in those aged 60 years or more, up to 13·4 percent in those aged 80 years or older. Estimates of the case fatality ratio from international cases stratified by age were consistent with those from China, the paper underscored.

Even the Health Minister of India has emphasized, ‘around 80-85 percent of cases are likely to be mild.’ He also acknowledged: “My biggest challenge is to ensure that affected people are treated with compassion, and not stigmatized. This is also applicable for the health care workforce, which is working hard to counter this epidemic. It is through concerted, community-owned efforts, supported by the policies put in place by the government that we can contain this disease.” This subject, surely, needs to be debated by all, and effectively resolved.

Panic is avoidable, but does a real threat exist with Covid19?

As The Lancet paper of March 30, 2020 cautions by saying - although the case fatality ratio for COVID-19 is lower than some of the crude estimates made so far, with its rapid geographical spread observed to date, ‘COVID-19 represents a major global health threat in the coming weeks and months. Our estimate of the proportion of infected individuals requiring hospitalization, when combined with likely infection attack rates (around 50–80 percent), show that even the most advanced healthcare systems are likely to be overwhelmed. These estimates are therefore crucial to enable countries around the world to best prepare as the global pandemic continues to unfold.’ This facet of Covid19 also requires to be a part of the evolving narrative to mitigate the threat, collectively, with a robust and well thought out Plan A, Plan B, Plan C….

Violation of lockdown increases the risk manifold, but…

There isn’t a shade of doubt even on this count, in any responsible citizen. Besides individual violation, recently a huge exodus of migrant laborer’s ignoring the lockdown raised the level of risk for others. This exodus should have been stopped at the very start, by better planning and with empathy and dignity by the law enforcing authorities, as many believe. Curiously, even the current Chief Justice of India (CJI) commented, on March 30, 2020: “The fear and the panic over the Coronavirus pandemic is bigger that the virus itself,” during a hearing on the exodus of migrant laborers from workplace to their respective hometowns, due to Covid19 lockdown.

To mitigate the risk, the CJI advised the Government to ensure calming down ‘the fear of migrants about their future, after being abruptly left without jobs or homes because of the 21-day lockdown to prevent the spread of Coronavirus.’ The Court felt, ‘the panic will destroy more lives than the virus.’ Thus, the Government should “ensure trained counsellors and community leaders of all faiths visit relief camps and prevent panic.”

The CJI also directed the Government to take care of food, shelter, nourishment and medical aid of the migrants who have been stopped. This appears to be the desirable pathway of preventing the migrant exodus, causing greater risk to people, requiring better planning, deft situation management with empathy and dignity, by the law enforcing authorities. However, individual violations, if any, can be addressed by intimately involving the civil society, against any possibility of the disease spread.

Whatever decision the policy makers take, must be blindly accepted by all:

In this area, all must first follow what the Government expects us to do. Maintaining strict compliance with such requirements. But, some people do ask, is it in total conformance with the steps W.H.O recommends following? At the March 30, 2020 issue of the Financial Times reported, the W.H.O’s health emergency program has outlined four factors that might contribute to the differing mortality rates in Covid19 outbreak:

Who becomes infected?
What stage the epidemic has reached in a country?
How much testing a country is doing?
How well different health care systems are coping?

Many members of the civil society are also keen to know these facts, and may want to seek clarification, if a gap exists anywhere. After all, Covid19 outbreak has brought to the fore, an unprecedented future uncertainty of unknown duration, involving not just life, but a sustainable livelihood and a dignified living in the future, for a very large global population, including India.

Conclusion:

There seems to be a dose of chaos in an otherwise reasonably controlled scenario. One option of looking at it as a pure law and order issue, which needs to be brought to order only with a heavy hand. The second option is to accept it as a golden opportunity to take all on board, by clearly explaining what people want to know – with reasons, patience, persuasion, empathy and compassion, as is happening in many countries. Of course, without compromising on the urgency of the situation. This is a challenging task, but a sustainable one. Overcoming it successfully, will possibly be the acid test of true leadership, at all levels. However, the slowly unfolding narrative on the ground, doesn’t appear to be quite in sync with the second option.

In the largest democracy of the world, people want to get involved in a meaningful discussion on Covid19 crisis, collectively – based on evidence-based scientific data. Then, it’s up to the policy makers to decide what is right for the country and in which way to go. In tandem, fast evolving, multifaceted Coronavirus narrative, I reckon, will keep raising multiple questions.

As the disease spreads, the pathways of combating it decisively, is being charted by different experts, led by the World Health Organization (WHO). This is being widely covered by the mainstream global media, even in the din of a cacophony. Nonetheless, it is generally believed that a true relief will come, only after a vaccine is developed and made available and accessible to all sections of the world. Till such time a ‘hide and seek’ game, as it were, is expected to continue.

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.

Cacophony Over Coronavirus Lockdown

Posted on March 30, 2020 by Tapan Ray

Currently, the entire India is trying hard to comply with the 21-day lockdown of the country, as communicated by Prime Minister Narendra Modi to the nation at 8 pm on March 24, 2020. The very next day, while addressing his parliamentary constituency of Varanasi via video, he said, “the Mahabharata war was won in 18 days but this war against Coronavirus will take 21 days.”

After this announcement most people’s life, as I myself can feel it, has changed as never before in the past. Unlike the West, in India most of us are too much dependent on domestic help, for routine chores of the family. How difficult these are, at least, I never experienced in the past. Will life, in its entirety, ever be the same gain?

In addition, shortages of most of the essential items were felt everywhere, be these vegetables, grocery items or medicines. Leave aside, the non-essential necessities. But, the bottom-line is, the lockdown has to be followed. There isn’t any other effective alternative to protect ourselves, those working for us to make our lives easier and comfortable, our respective neighborhood and thereby our country. In its midst, a cacophony over this decision is palpable, whatever may be the reason. Many are from highly credible sources.

Exploring various facets of the cacophony, this article will dwell on the question that will arise at the moment of truth – on or after April 15, 2020: What happened after 21-day lockdown of the entire nation. I shall try to focus on this question with the most relevant facts.

The Government’s rationale behind 3 weeks lockdown:

As explained by the Prime Minister and later by several Indian experts, the rationale behind the 21-day lockdown will include primarily the following:

The incubation period of Covid19 is around 5 to 14 days. This is also the potential transmission period of the microbe. Effective social distancing of all, may contain or even stop its spread.

As all viruses can sustain or exist only by replicating, they are completely dependent on a host cell for survival and can’t reproduce outside a cell. Social distancing may help in this area, as well.

Since, the world doesn’t have any vaccine for Covid19, as yet, prevention alternatives are limited.

Cacophony includes: Is complete national lockdown the only answer?

Several highly credible voices are asking: Is the complete lockdown of the nation the only answer? For example, Professor Vikram Patel at Harvard Medical School, wondered about the relevance of national lockdown in his article of March 26, 2020. He wrote, without any widespread community transmission of the disease, the Government might have staved off the worst without a sledge-hammer approach of national lockdown, which no country at India’s stage of the epidemic has imposed.

Elaborating the alternative approach, he suggested to intensify case finding approach through testing and contact tracing, quarantining those who are infected, physical distancing by everyone, graded travel restrictions, preparing the health system to cater to those who may need intensive care and protect health care workers. Even locking-down limited populations with community transmission will be prudent. When properly implemented these steps ‘could have stopped the epidemic in its tracks.’ Citing examples, he wrote, many of our Asian neighbors have done it successfully. Even China, the original epicenter of the epidemic, did not lock down the entire country.

According to other reports, as well, the countries, such as, Singapore, Germany, Turkey, Taiwan and China, have so far handled Covid19 much better than other countries in containing the pandemic. They all ‘refrained from imposing a complete, nationwide curfew-like lockdown.’ China did bring only the Hubei province under complete lockdown, but not the whole country. Scientists expect that Covid19 will exist despite lockdown – till an effective vaccine is developed and made available for all.

Are our doctors adequately protected against Covid19?

Today, even the doctors and other health care workers remain extremely vulnerable to the disease. Even in AIIMS doctors, reportedly, are using masks and sanitizers made by themselves or buying them. There is already a shortage of Personal Protective Equipment (PPE), which doctors are worried about. PPE includes face masks, eye shield, shoe cover, gown and gloves. These can be used for only five or six hours before having to discard them. Even N-95 face masks cannot be used for more than a day or two. And there is an elaborate protocol in place, as well, on how to dispose them. As the report said, doctors fighting Covid19 asked: ‘Not just claps, give us personal protective gear.’

Further, the Huffpost article of March 20, 2020 had emphasized with details: “Staying home can be hard, but it’s not even an option for the health care workers and scientists on the front lines of our global effort to thwart the COVID-19 pandemic. They have to arm themselves to face potentially infected patients and deadly viruses every day.” This gets vindicated by a March 26, 2020 report. It brought to our notice that 900 people have been quarantined after a Delhi Doctor unprotected by PPE tests COVID19 positive.

Another news article reported: “A day after the entire nation flocked to their balconies to clap for the heroes in the medical field, who are working relentlessly to arrest the Coronavirus pandemic, doctors in Telangana and Andhra Pradesh were greeted with humiliation and assault.”

Cacophony expands to religious solutions and explanations:

With the panic on Coronavirus spreading, the cacophony also includes religious solutions to the disease. For example, as reported by Reuters on March 14, 2020, ‘Hindu group offers cow urine in a bid to ward off Coronavirus.’ Another YouTube video also shows: ‘Hindu activists in India drink cow urine to ‘protect’ themselves from Coronavirus.’ According to many there are many takers of such concepts, whether one likes it or not.

Intriguingly, a top film star with 40.7 million twitter followers twitted on March 22, justifying public clapping at 5 pm during ‘Janata curfew’ and attributing a bizarre reason to it: ‘clapping vibrations destroy virus potency,’ which he later deleted against strong adverse comment from the scientific community. However, a number of, apparently responsible people, a few of whom are also known to me, often comment – such things can happen and do happen in a vast country like India. It isn’t a big deal. The cacophony goes on.

Be that as it may, regardless of enthusiastic public clapping and availability of cow-urine based solutions – fighting deadly Covid19 of potentially infected patients – without PPE, I reckon, is quite akin to asking a professional army to fight a tough battle without having adequate battle-gear.

Level of India’s preparedness just before national lockdown:

To ascertain this, leaving aside other critical areas, such as, quarantine and isolation facilities, let me cite a few examples related to PPE and testing kits. A news that came just a day before the national lockdown, reported a Government official commenting on a textile material used for masks and other PPEs: “Currently, demand is for 8 lakh bodysuits and N95 masks of the material. Orders for these have been placed.”

However, the Directorate General of Foreign Trade (DGFT), reportedly, banned the export of textile material for masks and coveralls, under the Foreign Trade (Development) and Regulation Act, just recently. Interestingly, as Reuters reported on March 28, 2020, ‘India needs at least 38 million masks and 6.2 million pieces of personal protective equipment as it confronts the spread of Coronavirus.”

Further, when testing is the only acid test to diagnose Covide19 infection – as on March 19, 2020, India, reportedly, had tested 14,175 people in 72 state-run labs, which is regarded as one of the lowest testing rates in the world. This is because: India has limited testing facilities. Thus, only those people who have been in touch with an infected person or those who have travelled to high-risk countries, or health workers managing patients with severe respiratory disease and developing Covid-19 symptoms are eligible for testing. Whereas, according to W.H.O, “All countries should be able to test all suspected cases, they cannot fight this pandemic blindfolded”.

However, after declaration of the national lockdown, the Indian Council of Medical Research (ICMR) on March 25, 2020, reportedly, invited quotations from manufacturers for supply of 1 million kits to test patients suspected of suffering from COVID-19. After getting a glimpse of the cacophony over the national lockdown for Coronavirus supported by a few examples, let us see what steps the W.H.O advises for all countries to follow in this pandemic.

The steps W.H.O recommends following:

On March 16, 2020, the Director General (DG) of the World Health Organization (W.H.O) said: “We have a simple message to all countries – test, test, test.” On that day, observing that more cases and deaths have been reported in the rest of the world than in China, as compared to the past week, the DG elaborated the following:

Although, there has been a rapid escalation in social distancing measures, like closing schools and cancelling sporting events and other gatherings, but, not an urgent enough escalation in testing, isolation and contact tracing – which is the backbone of the response.
Social distancing measures can help reduce transmission and enable health systems to cope with. Handwashing and coughing into your elbow can also reduce the risk for yourself and others. But on their own, they are not enough to extinguish this pandemic. It’s the combination that makes the difference. Thus, all countries must take a comprehensive approach.
The most effective way to prevent infections and save lives is breaking the chains of transmission. And to do that, you must test and isolate. You cannot fight a fire blindfolded. And we cannot stop this pandemic if we don’t know who is infected. We have a simple message for all countries: test, test, test. Test every suspected case.
If they test positive, isolate them and find out who they have been in close contact with up to 2 days before they developed symptoms, and test those people too. Every day, more tests are being produced to meet the global demand.

Curiously, even three months after the massive outbreak of the Coronavirus epidemic in China, India doesn’t seem to have procured enough PPEs for the doctors and testing kits to diagnose the disease. Besides, lack of advance preparation to create adequate quarantine and isolation facilities in the country make the situation even more complex to effectively deal with.

Other challenges and frugal options:

With eight doctors per 10,000 people in India, compared to 41 in Italy and 71 in Korea and one state-run hospital for more than 55,000 people, the general population has developed a much avoidable habit, over a period of time. It is quite likely, even in the event of getting flu-like symptoms, the majority may not go to doctors. Instead, may try home remedies or go to a retail chemist for drugs. Some may even resort to self-medication, until a full-blown disease surfaces, complicating the situation further.

Hence, only two options are left. One – for each individual to take care of personal hygiene and physical distancing, and second – for the Government to announce a national lockdown, through its second sudden and late evening order, effective midnight of the same day. This took almost everybody by surprise and possibly creating a widespread panic – not so much about the disease – at least initially, but more for regular availability of essential daily necessities – food and for many people – medicines, besides means for daily living of scores of families. This was further fueled by the gross lack of empathy by the law enforcers.

Conclusion:

As reported, if Covid19 continues to spread at its current pace, India could face between around 100,000 and 1.3 million confirmed cases of the disease caused by the new Coronavirus by mid-May, according to a team of scientists based mainly in the United States. It’s important to note that with just 6.8 tests per million, one of the lowest rates in the world, India has been criticized for not testing enough.

Moreover, besides panic and economic fallout of the disease, the long-term impact that Covid19 may have on the mental health of different people, for various reasons, will also need to be ascertained. As Professor Vikram Patel of Harvard Medical School said in his above article, ‘the deliverable is not how many people clanged pots and pans’ or how many obediently followed the Prime Minister’s advice of staying indoors. “The deliverable is how many people got tested, how many doctors have protective gear, how many ventilators the government managed to manufacture or buy overnight.” Another deliverable is isolation centers, temporary hospitals in indoor stadia and quarantine facilities that are fit for human beings, he added.

On November 24, 2020 – when 21-day national lockdown commenced, the total number of confirmed cases in the country were reported as 564. Just at the beginning of the 5^th day of the lockdown on March 29, 2020, as I write this piece, as many as 1032 people have been tested positive for Covid19 with 28 deaths. Against the above backdrop, some critical points that surfaced while exploring the cacophony over the national lockdown, can possibly be wished away only at one’s own peril.

Nevertheless, under the prevailing circumstances, there was no other alternative for the Government, but to announce immediate national lockdown, which all should abide by, religiously. However, whether Coronavirus will be won in India with 21-day of national lockdown – just three days more of what the Mahabharata war took, as the Prime Minister expects, will start revealing from April 15, 20120 – as the moment of truth arrives.

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.

Generic Drug Quality: Cacophony Masks An Important Note, Creates A Pariah

Posted on May 8, 2017 by Tapan Ray

In the ongoing debate between branded-generics and generic drugs without brand names, the concern about drug quality is occupying the center stage, with the former generally being painted in white, and the later in black – with no shades of gray in-between. Interestingly, many large domestic companies manufacture and sell both these genres of generic medicines, and the marketing approval process of both is no different, in a relative yardstick. The degree of difficulty in testing their quality standards, across the country, is no different, either.

On February 25, 2017, even the USFDA, reportedly, raised concerns, for the first time, on the quality and efficacy of medicines, in general, being sold within India. The news report further highlighted: ‘Over the past two years, many domestic majors, including Sun Pharma, Dr. Reddy’s, Cipla and Zydus Cadila have faced regulatory ire over quality of medicines exported from here and sold in the US and other overseas markets’.

It is undeniable, if prescriptions in generic names are made mandatory, there could be direct job losses within the industry, just as loss of significant business clientele of many professional service providers for branded generic business, directly or indirectly. Its net impact needs to be factored-in too, while taking a final decision on this subject.

Lack of enough credible scientific data establishing superiority of branded-generics over their non-branded equivalents are also striking, so are few instances of doctors filing Pharmacovigilance reports with the DCGI on the inferior quality of non-branded generic drugs. Neither is the most competent body in this area – the Central Drugs Standard Control Organization (CDSCO), has concurred with any such claims, so far. Without these, the whole debate based on seemingly over the top claims of superiority of branded generics as a class, is based no more than a matter of conjecture.

I discussed most of these points in one of my earlier articles published in this blog on April 24, 2017. Thus, in this article, I shall focus mostly on an important generic-drug-quality related amendment, very recently made in the Drugs and Cosmetics Act of India, which hasn’t received as much attention as it deserves. This finer note in the drug regulatory playbook, in fact, got nearly masked in the high-decibel cacophony of arguments and counterarguments on Prime Minister Modi’s recent hint on making prescriptions in generic drug names mandatory.

The core issue remains the same, both for non-branded and branded generics:

In the marketing approval process of any branded generic or a non-branded generic drug, Bioequivalence (BE) studies hold immense scientific importance. It ascertains whether the generic equivalent possesses similar efficacy and safety profile as the original molecule for interchangeability. Which is why, in most countries, including Europe and the United States, BE testing is mandatory for approval of any generic drug. Even the large buyers of these drugs, such as the World Health Organization, buy only those generics with proven BE.

Nonetheless, like many other nations, in India, as well, the marketing approval standards for all generic drugs, with or without a brand name, are exactly the same. However, this approval process gets alarmingly relaxed, for both these generic types, with the passage of time, which is the core issue.

New drug definition in India:

According to section 122-E of Drugs and Cosmetics Rules, 1945 (D&C Rules) new drugs will include unapproved drugs, modified or new claims, such as, indications, dosage forms (including sustained release dosage form) and route of administration of already approved drugs and combination of two or more drugs. A new drug shall continue to be considered as new for a period of four years from the date of its first approval or its inclusion in the Indian Pharmacopoeia, whichever is earlier.

BE studies necessary only for ‘New Drugs’:

For all such new drugs and their Fixed Dose Combinations (FDC), including those which are not covered by a patent, if introduced for the first time in India, would necessarily require its applicant to submit the marketing approval documents well-supported by phase III clinical trial data, which includes BE studies against the original molecules. BE of a drug product is achieved if its extent and rate of absorption do not show statistically significant differences from those of the reference product when administered at the same molar dose.

After the 4-year period BE tests not necessary:

Interestingly, after the 4-year period, D&C rules allow subsequent manufacturers of similar drugs to generally rely on the data generated by other pharma companies to obtain marketing approvals for their drugs. In other words, after this 4-year period, manufacturers of branded or non-branded generic drugs are not required to establish comparable safety and efficacy of their formulations with the original molecule through BE and other studies. It is worth noting here, unlike India, BE tests are mandatory for approval of all generic drugs at any time, in most countries across the world.

How would a doctor select only those branded-generics with BE studies?

As there isn’t any easy way to know and identify, both by the doctors and also the patients, which branded or non-branded generics were introduced without BE studies, both these categories pose equal risks to patients – not just the cheaper generic drugs sans brand names.

Changes recommended:

This laxity in the regulatory framework in India did create a lot of uneasiness about the quality of branded and non-branded generic medicines approved by the drug regulators and sold in the country. Responding to this issue, Professor Ranjit Roy Chowdhury Committee Report recommended in July 2013 to make BE and bioavailability studies mandatory for all types of generic drugs, even after the 4-year period.

Cacophony masks an important note:

The good news is, on April 3, 2017, by a Gazette Notification, Indian Government enacted amendments to the Drug and Cosmetics Act (1940) requiring mandatory BE studies for marketing approval of all generic drugs even beyond the 4-year period of the ‘new drug’ definition. It says, “The applicant shall submit the result of bioequivalence study referred to in Schedule Y, along with the application for the grant of a license of the oral dosage form of drugs specified under category II and category IV of the biopharmaceutical classification system.”

Biopharmaceutics Classification System:

The Biopharmaceutics Classification System (BCS) is a scientific framework to differentiate the drug formulations based on their aqueous solubility and intestinal permeability, and mainly depends on two factors:

How well the drug dissolves in the stomach and intestinal fluids (drug solubility)
How readily the drug passes through the intestinal wall into the blood flow (drug permeability)

The BCS was introduced by Gordon L. Amidon in 1995 to classify drugs into the four categories based on these parameters, as follows:

Class I: High Solubility – High Permeability
Class II: Low Solubility – High Permeability
Class III: High Solubility – Low Permeability
Class IV: Low Solubility – Low Permeability

CDSCO still needs to find the right answer to a key question:

Interestingly, this so important note in the regulatory playbook of India got masked in the high-voltage cacophony on branded and non-branded-generics. However, CDSCO would still require finding out the right answer to a key question: how would a doctor or a patient possibly know on which branded and non-branded generic drugs BE tests were not carried out, before the above amendment came into force.

Reported data on substandard drugs in India:

Quoting CDSCO data, the September-October 2015 issue of the ‘Indian Journal of Endocrinology and Metabolism’ summarized that ‘during the years 2011-2014, the regional laboratories tested samples at 91 percent of the installed capacity, but their overall detection rate of sub-standard drugs were only 3.6 percent’. Many have expressed doubts about these numbers though, nevertheless, these are Government data, and don’t fall in the realm of any conjecture.

In any case, the Union Ministry of Health doesn’t seem to concur that the issue of substandard drugs in India, that includes both the branded and non-branded generics, has assumed a public health menace in India or even alarming.

No qualms on value added branding of generic drugs, but fix the loophole for all:

It is understandable, when generic drugs are branded for tangible value-added product differentiation even within the identical or the same drug molecules. There are no qualms on such branding per se, though it comes at a high cost.

Marketing approval requirements being the same for all branded and non-branded generic drugs with the same pitfalls of no mandatory BE-testing requirement after the 4-year period, branding should add commensurate tangible value. Otherwise, why should most patients pay a significantly extra amount for heavily promoted branded-generics? Is it to help the pharma companies fighting with each other to increase their respective pies of revenue and profit on an essential commodity? Instead, stakeholders should now focus on easy detection of all those branded and non-branded generic drug formulations that avoided mandatory BE studies, prior to April 3, 2017.

In conclusion:

Despite CDSCO’s statistical data on substandard drugs, the general concern regarding the efficacy and safety of medicines manufactured in India is often raised both inside the country, as well as by some well-respected overseas drug regulators. Curiously, when raising the same concern CDSCO banned hundreds of branded FDCs, as these drugs came to the market without carrying out required scientific tests due to some major lacunae in the regulatory system, there was a huge protest in the country raised by almost the same people, as business interests prevailed over patients’ health interest.

Interestingly, displaying a sharp contradiction in today’s cacophony, patients’ health interest has been put in the forefront to protect business interests, especially when the CDSCO has raised no such concern, whatsoever.

The reverberating claims on superior drug quality for branded-generics as a class, over their cheaper non-branded equivalents, with the former generally being painted in white, and the later in black – with no shades of gray in-between, as I said before, is based mostly on conjecture rather than enough hard facts. Thus, the question comes up, who is responsible for ensuring drug efficacy and safety for the patients in India – CDSCO or non-fact based claims being raised mostly by those who have a direct or indirect financial interest in branded-generic business?

Keeping this in perspective, it is indeed intriguing, why such an important regulatory step of April 3, 2017 requiring mandatory BE studies for marketing approval of all generic drugs, even after the 4-year period, is getting masked in the cacophony, mostly favoring the branded-generics as a category. However, it’s no-brainer to understand that this din would continue, projecting all generic drugs sans brand names – a pariah!

By: Tapan J. Ray

Access to Medicine: Losing Track in Cacophony

Posted on December 30, 2013 by Tapan Ray

Indian Healthcare space is by and large an arena, where perceptions prevail over the changing reality in many important areas. Consequently, fierce discourse in those areas mostly gives rise to a cacophony of ‘Your Perceptions Against Mine’.

It is intriguing, why even in some well-hyped research studies of recent times, multiple interpretations are made not based on specific analytics-based numbers, but around critical data gaps and then the vital ‘conclusion’ is craftily packaged in a particular way to reinforce a set of perceptions and view points.

Serious discourse on ‘Access to Medicine’ in India often falls in these data crevasses, resulting nothing more than abject cynicism and expert sermons sans accountability from all quarters. Suggestions for precise quantification of magnitude of the problem, so far as ‘Access to Medicine’ is concerned, and then measuring the same periodically for sustainable corrective measures, obviously fade away in the din of multiple shrill voices, heavily loaded with self-perceptions attempting to score favorable brownie points.

A quantifiable number on overall ‘access to medicines’ remains illusive:

A quantifiable recent number on overall ‘Access to Modern Medicines’ in India, which could well form the base to measure progress of the country in this critical area subsequently, still remains illusive.

It is an irony, no one seems to know today what is the current ‘Access to Modern Medicines’ in India, in real term.

A recent study too goes around it, but NOT into it:

A 2012 industry sponsored study carried out by IMS Consulting, instead of giving just one number for overall ‘Access to Modern Medicines’ in India, went around it by reiterating the obvious that ‘access’ has 4 dimensions such as, Physical Reach, Availability/Capacity, Quality/Functionality and Affordability.

That is fine. No issue. However, the much sought after number of overall ‘Access to Modern Medicines’ still remained illusory in this study too. Interestingly, there are no numbers available to public for each of the above 4 important dimensions either. Thus the cacophony got shriller.

Clutching on to ‘Dinosaurian data’ in modern times:

Against the above backdrop, like many others, both local and global, even the honorable President of India on January 16, 2013, while addressing the ASSOCHAM 10th Knowledge Millennium Summit, quoted the ‘World Medicines Situation of 2004 report’, the base year of which is reportedly 1999. This study indicated, ‘only 35% of the population of India, against 53% in Africa and 85% in China has access to modern medicines’.

Thus in the absence of any recently updated number, the ‘Dinosaurian data’ of 1999 (published in 2004) is being considered relevant by many even in 2013, including the esteemed industry body that probably provided those irrelevant data to the president of India’s office for his speech, at the beginning of this year.

Importance of capturing today’s ‘Access’ data to provide ‘Healthcare to all’:

There should not be even an iota of doubt that the above reported scenario has changed quite significantly, at least, during the last decade in India, making the 1999 (published in 2004) ‘Access to Medicines’ numbers irrelevant, having no sense whatsoever in 2013.

To drive home this point, I shall now focus on just three sets of parameters, besides many others, to vindicate my comment on ‘dinosaurian data’. These parameters are as follows:

Compounded Annual Growth Rate (CAGR) in per-capita expenditure on healthcare from 2006-11
Compounded Annual Growth Rate (CAGR) of the domestic pharmaceutical industry in this period
Quantum of increase in use of public healthcare facilities

1. Per capita Healthcare expenditure from 2006-11:

Year	US $
1999	18.2
2004	28.7
2006	33.0
2007	39.9
2008	42.7
2009	43.6
2010	51.4
2011	59.1

(Source WHO Data)

The above table vey clearly highlights that in 1999, the base year of the above study, per capita healthcare expenditure in India was just US$ 18.2. The figure rose to US$ 28.7 in year 2004, when that study was published. The number reached to US $ 59.1 in 2011. This reflects a double digit Compounded Annual Growth Rate (CAGR) in per capita healthcare expenditure of the country from the 2004 study to 2011.

No doubt, this number is still much less than many other countries. Nevertheless, in 2013, per capita healthcare expenditure in India will be even more, indicating significant increase in ‘Access’ as compared to 2004.

2. Growth of domestic pharmaceutical market:

According to the PwC – CII report titled “India Pharma Inc.: Gearing up for the next level of growth”, the domestic drug market has been clocking a CAGR of more than 15 percent over the last five years. Thus, high growth of the Indian Pharmaceutical Market (IPM) since the last decade, both from the urban and the rural areas, would certainly signal towards significant increase in the domestic consumption of medicines. Moreover, fast growing rural and semi-urban markets would also clearly support the argument in favor of increasing ‘Access to Modern Medicines’ in India.

A back of the envelope calculation:

Improvement in access as compared to what ‘World Medicines Situation of 2004 report’ had highlighted, may not have a linear relationship to the volume growth of the industry during this period. However, a large part of this growth could indeed be attributed to increase in overall consumption of drugs, leading to improvement in access to medicines in India.

For example, out of the reported 15 percent CAGR of the IPM, if one attributes just 8 percent volume growth/year to increased access to drugs, a back of the envelope calculation would indicate that during last nine years over the base year of 2004, the access to medicines has improved at least to 70 percent of the population, if not more, and has NOT remained just at 35 percent, as many tend to establish a point or two by quoting the above dated report.

Unfortunately, even the Government of India does not seem to be aware of this gradually improving trend, as evidenced in the honorable President of India’s speech in 2013, as quoted above. Official communications of the government also keep quoting the outdated statistics stating that 65 percent of the population of India does not have ‘Access to Modern Medicines’ even today.

Be that as it may, around 30 percent of Indian population would still perhaps not have ‘Access to Medicines’ in India. This issue needs immediate attention of the policy makers and can possibly be achieved through effective implementation of a holistic public health policy model like, ‘Universal Health Care (UHC)’.

3. Increase in use of public healthcare facilities:

According to a study done by the IMS Consulting Group in 2012, in rural India, which constitutes around 70 percent of the total 1.2 billion populations of India, usage of Government facilities for Out Patient (OP) care has increased from 22 percent in 2004 to 29 percent in 2012, mainly due to the impact of National Rural Health Mission (NRHM). This increase will have significant impact in reducing ‘Out of pocket (OoP)’ healthcare expenses of the rural poor.

Overall impact on some key health indicators:

The same 2012 study of IMS Consulting highlights that an objective and comprehensive assessment of healthcare access in India was last undertaken in 2004, through a survey performed by the National Survey Sample Organization (NSSO).  The survey reported on multiple parameters related to healthcare, including morbidity in broad age groups, immunization status, episodes of outpatient/ inpatient treatment across geography/ income segments together with expenditure on treatment. These measures, the study indicates, were taken collectively to indicate the status of healthcare access.

According to this report, the Government of India had undertaken multiple programs to improve healthcare access. These programs have addressed numerous issues, in varying proportion, that are linked to healthcare access, including lack of infrastructure, high cost of treatment, and the quality and availability of treatment. Some of these programs have been enormously successful: for example, India is a polio-free country today, the study reinforces.

The study also highlights significant progress in some basic healthcare indicators. The examples cited are as follows:

Maternal mortality rate has decreased by ~50 percent, and was reported at 200 deaths per 100,000 live births in the year 2010 as compared to 390 a decade ago. A few states such as Tamil Nadu, Maharashtra, and Kerala have already achieved the Millennium Development Goal (MDG) of a maternal mortality ratio less than 109 maternal death per 100,000 live births, with multiple other states close to achieving this target.

Infant mortality rate has decreased by greater than 25 percent over the period 2000–2009, and was reported at 50 deaths per 1,000 live births. Correspondingly, the under-5 child mortality rate (U5MR) has decreased by similar percentage levels, and was reported at 64 deaths per 1,000 live births. While U5MR for urban India has achieved the MDG target of 42 the same for rural of 71 is significantly lagging the target level.

Immunization coverage has increased significantly, for example diphtheria-tetanus-pertussis immunization among 1 year olds has increased from 60% to 70%, and the Hepatitis B coverage has increased from 68% in 2005 to 91% in 2010.

National programs have successfully improved detection and cure rates for tuberculosis and leprosy.

No direct relationship established between healthcare spend and outcomes:

Though India’s per-capita healthcare spend has been lowest among the usually compared BRIC countries, the following quick example would clearly establish that the healthcare outcomes do not have a linear relationship with the per-capita healthcare spend either:

Per capita Healthcare expenditure in 2011: Country Comparison

Country	US $	World Rank	Physician/1000 people	Hospital/1000 people	Life expectancy at birth (years)
Brazil	1120.56	41	1.76	2.3	73.4
Russia	806.7	55	4.31	9.6	69.0
India	59.1	152	0.65	0.9	67.08
China	278.02	99	1.82	3.8	73.5

(Source: WHO data)

Thus, taking a cue from these numbers, India should decide at what percapita spend the country would possibly be able to ensure quality ‘access’ to healthcare for 100 percent of its population. Mere, comparison of percapita spend of each country, I reckon, may thus not mean much.

Conclusion:

The moot point, I reckon, is that, to measure progress in any sphere of activity, one will need to have a robust well-derived base point. Thereafter, progress needs to be monitored and quantified periodically from one point to the next.

So far as the access to healthcare in general and medicines in particular are concerned, it becomes difficult to fathom why is this basic approach still not being considered to measure progress in ‘Access’ and its rate in India.

As a result, discussions among the stakeholders do not take place around those updated numbers, either. Instead, what we hear is a high decibel cacophony of perceptions, at times groping around various dimensions of ‘Access’ and that too without quantification of each, as stated above. This makes the task all the more complicated in pursuit of providing ‘Healthcare to All’ in India.

That said, the question to ponder now:

Does any one know what is the current ‘Access to Modern Medicines’ number in India and at what rate the progress is being made in that direction to achieve ‘Health for All’ objective of the country?

By: Tapan J. Ray

In the cacophony of FDI in the pharmaceutical sector of India

Posted on June 6, 2011 by Tapan Ray

It is a widely accepted fact that Foreign Direct Investment (FDI) in the Pharmaceutical industry, just like in any other industry, is important for an emerging economy like India, mainly because of various important benefits that the country would derive out of such investments, like for example:

Job creation
World class infrastructure development
Transfer of modern technology
Help creating a talent pool through international training and development
Meeting unmet needs of patients through innovative medicines
Help imbibing the best practices of the world

Types of FDIs in the Pharmaceutical sector of India:

There are mainly three types of FDIs that we have witnessed so far in India:

Green field investment: Like, setting up new manufacturing facility at Vizag by Eisai of Japan
Brown field investment: Like, acquisition of Ranbaxy by Daiichi Sankyo of Japan, Piramal Healthcare by Abbott USA or Shantha Biotech by Sanofi Aventis of France.
Joint venture: Like, Bayer Healthcare and Cadila Healthcare or Sun Pharma and MSD etc.

Besides these, as mentioned below, there have been some collaborative arrangements, as well, between global and Indian Pharmaceutical companies in the last five years like, GSK with Dr. Reddy’s Laboratories (DRL), Pfizer with Biocon etc.

Key drivers for FDI:

Following are the key factors, which attract FDI in the pharmaceutical sector, especially in an emerging market like India:

Domestic market size, prospects for future market growth,
Cheaper operating cost
Cheaper input and English-speaking skilled manpower cost
Regulatory environment
Pricing environment
Robust IT infrastructure
Legal, IPR and financial framework

Relationship between FDI and Intellectual Property (IP) Environment:

Some recent media reports in various parts of the world including India had highlighted that China attracts more investment from foreign drug makers due to more robust Intellectual Property (IP) laws in that country.

US Trade Representatives (USTR) is one such agency which evaluates the adequacy and effectiveness of protection of Intellectual Property Rights (IPR) with US trading partners in various countries of the world through annual release of their ‘Special 301 Report’.

The report of US Trade Representatives (USTR 2011 Special 301) rates IPR regime of both China and India as unsatisfactory, so far as law enforcement, piracy prevention and transparency are concerned. The two main categories in the report are the ‘Priority Watch List’ and the ‘Watch List’. Both India and China fall under ‘Priority Watch List’ of this report.

An apparent contradiction:
The key question, in this context, that is being raised for quite some time now is, whether the decisions of foreign drug makers to invest in the emerging markets, like India and China are predominantly dependent on the IPR scenario in the respective countries.

If it is so, some would obviously like to know whether or not the ‘USTR 2011 Special 301 Report’ contradicts the above hypotheses.

Notwithstanding ‘USTR Special 301 Reports’ and being featured in their ‘Priority Watch List’ year after year, China continues to attract more and more FDI in pharmaceuticals over a long period of time. In any case, the FDI from USA in China was just around 12% of the total FDI that the country attracted in 2008. The same trend continues even today.

However, without going into the details of any report, relative robustness of IPR regime could at best be just one of the several key factors for a research based global pharmaceutical company to decide on FDI in any emerging market of the world.

Relatively speaking:

China is certainly attracting more FDI in the Pharma space than India. According to “The Survey of Foreign Investments in China’s Medicine Industry” of the Government of China, the FDI in the pharmaceutical industry of the country for a three year period commencing from 2006 to 2008 was around US $ 1772 million. The percentage of total investments made by the major countries is as follows:

Country wise pharmaceutical FDI % in China in 2008

Rank	Country	%
1.	Hong Kong	39.69
2.	United States	11.95
3.	British Virgin Island	11.64
4.	Bermuda	6.45
5.	Singapore	4.91

(Source: Invest in China 2009, Ministry of Commerce of the People’s Republic of China)

Whereas, as per Mr. Jyotiraditya Scindia, Minister of State, Ministry of Commerce and Industry, from the year 2006-07 up to September 2009, India attracted FDI of US $ 817.39 million, as follows:

FDI ( US$ million)

Sector	2006-07	2007-08	2008-09	2009-10 (upto Sept.09)	Cumulative
DRUGS & PHARMACEUTICALS	214.84	334.09	181.61	86.85	817.39

These figures would change significantly if FDI through M&A is taken into consideration.

In any case, this trend should not necessarily be exclusively correlated to the relative robustness of the IPR regime in India and China, notwithstanding the fact that 5.5% of all global pharmaceutical patent applications named one inventor or more located in India as against 8.4% located in China (Based on WIPO PCT applications)

Impact of FDI on the Indian Pharmaceutical Sector:

Some important FDI in India from 2006 to 2011

Year	Indian Companies	Multinational Companies	Value ($Mn)	Type
2006
	Matrix Labs	Mylan	736	Acquisition
	Dabur Pharma	Fresenius Kabi	219	Acquisition
	Ranbaxy Labs	Daiichi Sankyo	4,600	Acquisition
	Shantha Biotech	Sanofi-aventis	783	Acquisition
2009
	Orchid Chemicals	Hospira	400	Business Buyout
	Aurobindo Pharma	Pfizer	Not disclosed	Generic Development and Supply
	Dr Reddy’s Labs	GlaxoSmithKline	Not disclosed	Generic Development and Supply
2010
	Piramal Healthcare	Abbott	3,720	Business Buyout
	Paras Pharma	Reckitt Benkiser	726	Acquisition
	Claris Lifesciences	Pfizer	Not disclosed	Generic Development and Supply
	Biocon	Pfizer	350	Insulin Marketing Deal
2011
	Cadila Healthcare	Bayer	Not disclosed	Marketing Joint Venture
	Sun Pharma	Merck & Co.	Not disclosed	Marketing, Manufacturing Joint Venture

There is no published data, as yet, to justify that the inflow of FDI in the pharmaceutical sector of India, including acquisition of large domestic pharmaceutical players like, Ranbaxy, Piramal Healthcare etc., had any adverse impact whatsoever on the country.

However, the reality is that such apprehension, especially the acquisition of some ‘Pharma Crown Jewels’ of India by the Multinational Companies (MNCs), though not fact-based, are apparently getting reverberated as a ‘sinister and sordid design’ even in the corridors of power ranging from the Ministry of Commerce, Cabinet Committee of Economic Affairs (CCEA), Planning Commission of India to Joint Parliamentary committee for Commerce.

It appears that the government is adopting a ‘wait and watch’ policy in this area for now, presumably because of the fact that the newly formed ‘Competition Commission of India (CCI)’ from now onwards will keep a careful vigil on such mega acquisitions.

Poor healthcare coverage could be a key barrier:

As indicated above, relative size and growth of the domestic pharmaceutical market together with healthcare coverage and delivery mechanism of a country could well be the most critical factor to influence foreign investment decision of the global pharmaceutical companies.

In global ranking, China is currently the seventh (India: 14) largest pharmaceutical market and is expected to be the fifth (India: 10) largest market by 2015 and the third largest by 2020. Chinese pharmaceutical market is expected to grow by over 15% per annum in the next five years, which is higher than India, even without considering the current base of both the countries.
Even in Health Insurance space, “India ranks 136th on penetration levels and lags behind China (106), Thailand (87), Russia (86), Brazil (85), Japan (61) and the US (9),” reported ‘Indo-Asian News Service (IANS)’ on July 21, 2009, in a paper titled, “India’s insurance penetration lower than world average”, jointly prepared by Crisil and Assocham.

Moreover, ‘out of pocket’ healthcare expenditure in India is one of the highest in the world at around 80% against 61% in China.

Country Attractiveness Index (CAI):

‘A.T. Kearney’ developed a CAI for clinical trials, for the use of, especially, the pharmaceutical industry executives to make more informed decision on offshore clinical trials. As per this study, the CAI of China is 6.10 against 5.58 of India. This could mainly be due to prevailing lackadaisical regulatory environment in India.
Other reasons to influence FDI:
I would reckon, all foreign direct investments (FDI) by the global pharmaceutical companies are driven by a combination of key business factors, as mentioned above, IPR ecosystem in the country is just one of them. This is vindicated by a recent report, which is as follows:

“Novartis has signed an agreement to build a pharmaceutical manufacturing facility in St. Petersburg, Russia. The plant is part of a $500 million Novartis investment in infrastructure, health care initiatives, and R&D in Russia over the next five years”.

The reason behind this investment was reported as follows:
“The announcement follows a pledge late last year by Russian Prime Minister Vladimir Putin of some $4 billion in federal funding for pharmaceutical industry development over the next 10 years. The government has set a goal for local industry to produce 90% of Russia’s “essential medicines”—about half of the country’s total pharmaceutical sales—by 2020.”
Other recent examples of FDI made by the global majors in other countries, which will support my above statement, are as follows:

1. Novo Nordisk: US $100 million in Russia 2. Sanofi-Aventis: a plant in Saudi Arabia. 3. Eisai: relocated global Aricept manufacturing facility to India for worldwide export.

Conclusion:

‘The Journal of International Business Studies’ (1999) 30, 1–24 based on the results from an econometric analysis of 136 laboratory investments reconfirms that relative market size, growth and the strength of science base of a country would ultimately influence FDI in pharmaceutical research and development in an emerging market. The study also reiterated that these factors hold good for even Japanese, European and U.S. pharmaceutical companies.

Thus, to attract more FDI in the pharmaceutical sector and effectively compete with China, India should primarily focus in creating a vibrant and large domestic pharmaceutical product and services market reflecting sustainable high inclusive growth. A comprehensive ecosystem to provide healthcare to all, efficient regulatory mechanism, effective well balanced IP environment and a robust legal and financial framework will further hasten the process.

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.

PILMAN

A Tapan Ray Website

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