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India Not To Vaccinate All For Covid Control: Upsides And Unknowns

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With 9.46 million cases and 137,621 deaths, India has currently the world’s second-highest number of coronavirus infections, behind only the United States, reported Reuters on December 01, 2020.

Fathoming seriousness of rapidly unfolding Covid induced all round disruptions across the nation, on October 17, 2020, the Indian Prime Minister issued a clarion call. He called for full preparedness of the country to ensure speedy access to Covid vaccines for every citizen.

However, the above view was subsequently changed. On December 02, 2020, quoting Union Health Ministry of India, it was reported, ‘the Government has never spoken about vaccinating the entire country.’ The Director General of the Indian Council of Medical Research (ICMR) said, “the Indian government is of the opinion that vaccination against the deadly pandemic may be needed only to the extent of ‘breaking the chain.’ If we’re able to vaccinate a critical mass of people and break virus transmission, then we may not have to vaccinate the entire population.”

Why the PM said ‘Covid vaccines for every citizen’ at that time?

In my view, what the PM said made perfect sense at that time. This is also vindicated by a fact-based interesting discussion in The Wire on July 16, 2020, carrying a title – ‘How Effective Does a Vaccine Need to Be to Stop the Pandemic? It quoted an in-depth study concluding, “a vaccine with an efficacy as low as 60% could still stop the pandemic and allow society to return to normal. However, most, if not all of the population would have to be vaccinated.”

This research article, titled ‘Vaccine Efficacy Needed for a COVID-19 Coronavirus Vaccine to Prevent or Stop an Epidemic as the Sole Intervention,’ was published in The American Journal of Preventive Medicine (AJPM) on July 15, 2020. The study found that the vaccine has to have an efficacy of at least 70% to prevent an epidemic and of at least 80% to largely extinguish an epidemic without any other measures (e.g., social distancing).

The PM’s observation will make even better sense, while taking into account the draft ‘Regulatory Guidelines for Development of Vaccines with Special Consideration for Covid-19 vaccine in India. This guidance document for vaccine developers was issued by the Central Drugs Standard Control Organization (CDSCO), and was reported by the media on September 23, 2020. It also says, among other specifics, a COVID-19 vaccine candidate should show at least 50 per cent efficacy during phase III of clinical trials for it to be widely deployed.”

Why health ministry’s current plan of not vaccinating all, also makes sense:

Indian Health Ministry’s latest assessment that vaccination against the deadly pandemic may be needed only to the extent of ‘breaking the chain,’ also makes sense in the rapidly emerging contemporary scenario.

It makes sense, considering, even the World Health Organization (WHO) experts have, reportedlypointed to a 65%-70% vaccine coverage rate as sufficient to reach population immunity, based on scientific reasons. This raises the subsequent question of who in India will get priority for vaccination.

The priority group for Covid vaccination in India:

As reported on November 26, 2020, according to the Principal Scientific Advisor of India, about 300 million people will be part of the first ‘wave’ to receive Covid vaccines in India. This number includes, health care workers, totaling 30 million, police personnel and those above 50 and those younger with underlying illnesses that make them vulnerable. However, everything in this area doesn’t seem to be as clear or straight forward as is widely expected. India’s Covid vaccination plan still seems to be a work in progress.

India’s Covid vaccine plan is still a work in progress:

This is evident from many reports, such as one of December 01, 2020. This report says, experts still believe that the government should spell out whether the vaccination should be confined to only uninfected individuals or encompass everyone. These reports may vindicate the murmur in the corridors of power that many details of Covid vaccination in India are yet to crystallize.

Let me quote the Indian Prime Minister in this regard, as he is not only the head of the current Government, but is also the national voice on all contemporary issues in the external world.

Interestingly, on November 24, the Prime Minister himself acknowledged: ‘Will go by scientific advice on Covid vaccine, don’t have many answers yet.’ He made it clear that he did not yet have answers to:

  • Vaccine dosage
  • Pricing or sourcing

Although, his Government has been in touch with local and global vaccine developers, nations and multilateral institutions to ensure vaccine procurement, the PM added.

Curiously, unlike what the Principal Scientific Advisor of India, reportedly articulated on November 26, 2020, just a couple of days before that, on November 24, 2020, the PM has put it quite differently.He then said, priority groups for vaccine administration would be fixed based on state inputs and added that additional cold storage must be created by states. These confirm, India’s final plan on Covid vaccination is still a work in progress.

The Covid vaccination plan is still evolving in India:

Interestingly, on December 04, 2020, in an all-party meeting chaired by the Prime Minister, it was further announced - the first set to receive the Covid -19 vaccine will be about one Crore frontline health workers and the next will be two Crore armed forces, police, and municipal personnel. Besides, around 27 Crore senior citizens, too, would be receiving the vaccine. Thus, the Government’s vaccination plan seems to be still evolving. Meanwhile, something sensational happened in the global race for having a Covid vaccine for a country’s population.

Curiously, much before the commencement of Covid vaccine prioritization discussion in India, on September 14, 2020, it was reported that China is also not going for its entire population. They are prioritizing frontline workers and high-risk populations in its fight against the new Coronavirus.

The first emergency-use authorization for a Covid-19 vaccine happened:

On December 02, 2020, both the local and global media, such as The Wall Street Journal (WSJ) reported: ‘The U.K. became the first Western nation to grant emergency-use authorization for a Covid-19 vaccine, clearing a shot developed by Pfizer Inc. of the U.S. and BioNTech SE of Germany to be distributed in limited numbers within days.’

In the war against Covid pandemic, it also marks a key milestone in efforts to translate a promising new vaccine technology into a widely available shot, the report highlighted. It was developed, tested and authorized and is now poised to be distributed amid a pandemic that has sickened tens of millions of people and killed more than 1.4 million around the world, the news article added.

Interestingly, the U.K could make it happen, even before the United States, where this vaccine is now being reviewed by the USFDA, where a similar authorization could come later this month and a rollout before the end of the year. It’s noteworthy that the USFDA Commissioner has defended the pace of review of Pfizer’s COVID-19 vaccine on the grounds that a thorough assessment is needed to reassure a skeptical public.

NIAID director of the US also believes so, and has claimed, “We have the gold standard of a regulatory approach with the FDA.” This brings us to the question – will Pfizer’s Covid vaccine be available in India soon?

Will Pfizer’s Covid vaccine be available in India soon?

Just a day after U.K’s emergency approval of Pfizer’s Covid vaccine to be rolled out to the public early next week, Pfizer, reportedly, said, the Company is in discussions with many governments around the world, and “… will supply this vaccine only through government contracts based on agreements with respective government authorities and following regulatory authorization or approval.”

However, as reported on December 06, 2020, Pfizer has now sought approval from the DCGI for emergency use authorization of its Coronavirus vaccine. In its application dated December 4, Pfizer India has sought approval to “import the vaccine for sale and distribution in the country, besides waiver of clinical trials on Indian population in accordance with the special provisions under the New Drugs and Clinical Trials Rules, 2019.”

It’s worth noting, conducting Phase III clinical trials on Indian volunteers has, so far, been a pre-requisite for the DCGI to give authorization to a particular investigational Covid vaccine. For example, AstraZeneca-Oxford vaccine is, reportedly being tested in a phase-3 trial on over 1,600 subjects in India by Serum Institute. So is the Sputnik V, developed by Russia, and touted as the world’s “first registered Covid-19 vaccine” after it received Russian regulatory approval in early August 2020.

Further, the head of the Indian National Task Force on COVID-19, had also said the arrival of the Pfizer vaccine in India might take some months. This is, reportedly for two reasons. One, the vaccine has stringent temperature requirements (-75 degree Celsius), which make it unviable for the current cold-chain logistics in India. And the second, could possibly be, its Indian clinical trial requirements, as has been the practice of even Russia approved Sputnik V vaccine.

Thus, it appears, India is now looking at the vaccines being developed by Oxford-AstraZeneca or Bharat Biotech against the pandemic, as these are expected to complete clinical trials and seek a regulatory approval at an early date.

Upsides and unknowns of the current status of Covid vaccines in India:

Along the obvious upsides, such as – not all in the country needs to be vaccinated and, at least, one Covid vaccine is widely expected to come shortly that is being manufactured in India, there are several critical unknown factors, too. For example, apace with several similar articles, the research paper titled, ‘Will covid-19 vaccines save lives? Current trials aren’t designed to tell us,’ published in The BMJ on October 21, 2020, also raised this issue.

It pointed out: “Ideally, you want an antiviral vaccine to do two things . . . first, reduce the likelihood you will get severely ill and go to the hospital, and two, prevent infection and therefore interrupt disease transmission.” Yet the current phase III trials are not actually set up to prove either, it emphasized. None of the trials currently underway are designed to detect a reduction in any serious outcome, such as hospital admissions, use of intensive care, or deaths. Nor are the vaccines being studied to determine whether they can interrupt transmission of the virus.

Conclusion: 

As of December 06, 2020 morning, India recorded a staggering figure of 9,644,529 of new Coronavirus cases with 140,216 deaths. The threat of subsequent waves for further spread of Covid infection now looms large in many states. The Prime Minister of India is also intimately involved in search of a meaningful solution to end the pandemic.

In this scenario, that a Covid vaccine is coming so soon, is a very good news, undoubtedly. There are several obvious upsides of this development, alongside many critical unknown areas, including how long the immunity will last after administration of a Covid vaccine. Incidentally, ‘Moderna vaccine-induced antibodies last for 3 months’ says NIAID study. Even in India a ‘Minister tested positive after the first dose of vaccine.

I am sure, the right answers will surface as the research will progress. Meanwhile, there doesn’t seem to be any other alternative sans vaccines, to kick start the globalized world – for a holistic and inclusive long-term progress, economic prosperity and, if not survival with dignity, for all.

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.

Combating Covid Pandemic: When ‘Something Is Better Than Nothing’

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As the new Coronavirus overwhelms the world, since its global outbreak, up until November 29, 2020, over 1,458,305 people have died from this pandemic. Understandably, the Governments in all countries are frantically searching for some robust remedial measures to prevent these unfortunate deaths, besides protecting livelihoods of a vast majority of people.

For this purpose, experts considered effective preventive measures, such as vaccines could help taming this menace, alongside existing personal prevention measures. Accordingly, scientists around the world, have are hard to accelerate development and manufacturing of safe and effective Covod-19 vaccines, within the prescribed guidelines. Equally important is the fact these vaccines must be safe with predictable effectiveness- for all age groups.

The good news is, vaccines are now a distinct possibility in the near future, with the positive interim Phase III clinical trial reports pouring in. It gets reflected in the remark of the Director General of the World Health Organization (WHO), on November 23, 2020, at the media briefing on Covid-19. He said: There is now real hope that vaccines – in combination with other tried and tested public health measures – will help to end the pandemic.

Interestingly, amid these reports, a lurking fear of many experts also surfaces – on the impact of possible side effects, that Covid vaccine may cause, besides their medium to long term efficacy in human subjects. But, with the mounting number of deaths, near collapse of the global economy, including India, there isn’t any more time to watch and wait.

Apparently, all governments now want some scientifically relevant vaccines, instead of nothing. This article will deliberate on the one hand – an unprecedented achievement, alongside some critical concerns – voiced even by the Indian Prime Minister. Let me begin with the apprehensions, as expressed by some domain experts on some rough edges, as it were, in the process of its development.

Queries on vaccine dosing, efficacy, safety and testing:

On November 23, 2020, AstraZeneca and Oxford reported interim results of their vaccine with the average efficacy of 70% prevention. This sounded good to many, as it falls within the expectations of above a 50% standard that the FDA had set for Covid vaccines. However, the puzzling part in this result was – bigger (standard) doses of the vaccines were less efficacious. The vaccine was only 62% effective in a group that got two full doses spaced about a month apart. But among about 2,700 people who got a half-dose followed by a full, the number rose to 90%, the report highlighted. This incident prompted several questions about the most effective dose of AstraZeneca and Oxford vaccine, including its safety record and the approach to testing. Consequently, apprehensions surfaced whether the Drug regulators will clear it, based on the currently available data.

It now appears, AstraZeneca ‘s Covid-19 vaccine is ‘headed for an additional global trial as the drug maker tries to clear up the uncertainty and confusion surrounding favorable results in its current study.’ Incidentally, in India - AstraZeneca and Oxford vaccine will be manufactured by Pune-based Serum Institute of India (SII) under a collaborative arrangement. Let me now dwell on a broader as aspect in this space.

Could current Covid vaccines become useless in the future?

There isn’t an iota of doubt that developing Covid vaccine in ten months, which otherwise takes around ten years – is an unprecedented achievement. However, there are several other important areas in this space, where pundits have expressed uneasiness through various articles.

One such paper is titled, ‘Don’t rush to deploy COVID-19 vaccines and drugs without sufficient safety guarantees,’ published in the Nature on March 16, 2020. According to the author, a critical point in this regard is to consider ‘the potential for emerging and re-emerging Coronaviruses to cause future outbreaks.’

This is because, ‘the virus behind COVID-19 might mutate in ways that would make previously effective vaccines and antivirals useless.’ Testing vaccines and medicines without taking the time to fully understand safety risks, could bring unwarranted setbacks during the current pandemic, and into the future. ‘Despite the genuine need for urgency, the old saying holds – ‘measure twice, cut once’, the author commented.

The article concluded by suggesting, ‘any regulatory agency considering ways to accelerate treatments into testing should also weigh up how likely these drugs are to work beyond this particular Coronavirus.’ Moreover, according to the WHO, it’s too early to know if COVID-19 vaccines will provide long-term protection.

Possible side-effects of COVID-19 vaccines:

As people’s hopes swell, expecting Covid vaccines to ultimately end the deadly global pandemic, experts caution about their reported – annoying and unpleasant side effects. The November 12, 2020 paper – ‘Time to Discuss Potentially Unpleasant Side Effects of COVID Shots? Scientists Say Yes,’ published by the Kaiser Health News (KHN), also articulated similar apprehension.

It said, most Covid vaccines, including much publicized ones from Pfizer and Moderna, will require two doses to work, injections that must be given weeks apart, as company protocols show. Scientists anticipate the shots will cause enervating flu-like side effects — including sore arms, muscle aches and fever — that could last days and temporarily sideline some people from work or school.

Even with the Pfizer vaccine, which is touted to be over 90% effective, 1 in 10 recipients would still be vulnerable. There could also be a possibility that a vaccine may not suit everyone due to side-effects, especially the most vulnerable elderly population. That means, at least in the short term, as population-level immunity grows, people can’t stop social distancing and throw away their masks, the report emphasized. Even Prime Minister Modi has informed the nation about possible side effects of Covid vaccines.

PM Modi also warns of possible vaccine side-effects:

Being adequately briefed on the above perspectives related to Covid vaccines, the PM has also warned the nation about the possible side-effects. This is probably to ensure that the unpleasant experience of side-effects, after being administered the first dose, do not catch the population off-guard. Mostly because, no one should miss the second dose of vaccine for the same.

He said, during a recent video conference with the state chief ministers, ‘like many other popular medicines, any COVID-19 vaccine could lead to side-effects in some people.’ Emphasizing that both speed and safety are equally important in launching a vaccine, he assured that ‘the government would only go by science in finalizing a vaccine for the country.’

Is something better than nothing?

In the current situation, it appears so, as there is no other alternatives, except maintenance of social distancing, frequent hand sanitizing and wearing masks while outdoors. The Prime Minister also articulated sans any ambiguity: ‘Whatever vaccine makes it through the world’s certified processes, we will have to accept them and move ahead.’

In the meantime, he urged the states to keep distribution infrastructure, such as cold storages ready, the report said. Interestingly, according to Serum Institute CEO Adar Poonawalla, India could approve the emergency use of the Oxford-AstraZeneca COVID-19 vaccine by December 2020.

That said, for mass vaccination of the population across India, another factor that is extremely important to decide which vaccine to go for – is the required storage temperature of various Covid Vaccines under development.

Required cold chain storage temperature of various Covid vaccines:

Required cold chain storage temperatures of various Covid vaccines are as follows:

Company

Type

Doses

Effectiveness*

Storage
Oxford-AstraZeneca Viral Vector (genetically modified virus) Two 62-90%** Regular fridge temp.
Moderna RNA (part of virus genetic code) Two 95% -20C up to six months
Pfizer-BioNTech RNA Two 95% -70C
Gamaleya (Sputnik V) Viral Vector Two 92% Regular fridge temp.

Source: Respective Companies, WHO – BBC News. *Preliminary Phase III results. **Two full doses: 62%, A half dose followed by a full dose: 90%, Average: 70%

From the above table, it appears, from the perspective of continuous cold chain storage facility of vaccines – till these are administered to each person, Oxford-AstraZeneca and Russian Sputnik vaccines will be more practical, despite issues with them. Viewing from this perspective, as well, it appears ‘something is better than nothing’ term can be applied in this area, as well.

Conclusion:

The Covid pandemic continues to worry India, immensely. As on November 29, 2020 morning, India recorded a staggering figure of 9,393,039 of Coronavirus cases with 136,733 deaths. The threat of subsequent waves for further spread of Covid infection now looms large in many states.

Unprecedented speed in developing vaccines to effectively combat Covid Pandemic has created some initial issues. Some of these Covid vaccine challenges include, vaccine side effects, its future usefulness, or challenges towards maintaining required stringent cold chain storage requirements, especially in a country like India. Powder version of Covid vaccines, in the future, would possibly resolve this issue for all countries, across the world.

Currently, in tandem with keeping the cold-chain distribution infrastructure ready, at least, for vaccines that require regular fridge temperature, there is a need to make people aware of Covid vaccine side-effects. Otherwise, after getting first shot of a Coronavirus vaccine, many people may get so scared of its side effects that they may not come back for the second dose. If this happens, the very purpose of mass vaccination will get defeated.

However, from the Indian perspective, Covid vaccines that the country, hopefully, will shortly get, may not be the best, out of the available ones, in terms of safety and efficacy. But, for combating Covid Pandemic across India at this juncture, I reckon, the good old dictum still holds good – ‘something is better than nothing.’

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

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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

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.

The Curious Imbroglio: Innovation, IPR, India and ‘Uncle Sam’

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Last week, the Office of the United States Trade Representative (USTR) released the “2015 Special 301 Report”, which is its annual review of the global state of Intellectual Property Rights (IPR) protection and enforcement.

While looking through the Kaleidoscope of business interests of the United States, variegated changing patterns of a wide variety of country-specific observations can be noted in this report.

It is widely believed that the report ‘pontificates’ about the adequacy and effectiveness of IPR protection and enforcement of its trading partners against USTR’s own yardstick, hinting unhesitantly at the possible consequences, if found lacking.

USTR reviewed seventy-two (72) trading partners for this year’s Special 301 Report, and placed thirty-seven (37) of them on the ‘Priority Watch List’ or ‘Watch List’. Thirteen (13) countries – Algeria, Argentina, Chile, China, Ecuador, India, Indonesia, Kuwait, Pakistan, Russia, Thailand, Ukraine, and Venezuela, are on the ‘Priority Watch List’.  These countries will be the subjects of particularly intense bilateral engagement during the coming year.

India specific significant elements of the 2015 Special 301 Report include the following:

  • Increased bilateral engagement in 2015 between the United States and India on IPR concerns, following the 2014 Out-of-Cycle Review (OCR) of India on this issue.
  • India will remain on the ‘Priority Watch List’ in 2015, but with the full expectation of US about substantive and measurable improvements in India’s IPR regime for the benefit of a broad range of innovative and creative industries.
  • The US offered to work with India to achieve these goals.
  • No OCR at this time for India, but US will monitor progress in India over the coming months, and is prepared to take further action, if necessary.

The 2015 report also highlights:

“While it is impossible to determine an exact figure, studies have suggested that up to 20% of drugs sold in the Indian market are counterfeit and could represent a serious threat to patient health and safety.”

According to media report, a senior Commerce & Industry Ministry official has commented, “India is disappointed at being featured yet again in the US ‘Priority Watch List’ of weak IPR countries. But it is not worried.”

Recent Action by India:

In October 2014, almost immediately after Prime Minister Modi’s return to India from the US, the Government formed a six-member ‘Think Tank’ to draft ‘National IPR Policy’ and suggest ways and legal means to handle undue pressure exerted by other countries in IPR related areas.

The notification mandated the ‘Think Tank’ to examine the current issues raised in such reports and give suggestions to the ministry of Commerce & Industry as appropriate.

However, the domestic pharma industry, many international and national experts together with the local stakeholders, continue to strongly argue against any fundamental changes in the prevailing robust patent regime of India.

In the same month, the Department of Industrial Policy and Promotion (DIPP) constituted a six-member ‘Think Tank’ chaired by Justice (Retd.) Prabha Sridevan to draft the ‘National IPR Policy’ of India. Taking quick strides, on December 19, 2014, the Think Tank’ released its first draft of 29 pages seeking stakeholders’ comments and suggestions on or before January 30, 2015. A meeting with the stakeholders was also scheduled on February 5, 2015 to take it forward.

Possible reasons of US concern on the draft ‘National IPR Policy’:

As I discussed in my blog post of January 19, 2015 titled, “New “National IPR Policy” of India – A Pharma Perspective”, I reckon, there are three possible key areas of concern of American pharma industry against Indian patent regime. However, in the draft National IPR Policy India seems to have stood its ground in all those areas.

The draft IPR policy responded to those concerns as follows:

Concern 1: “India’s patentability requirements are in violations of ‘Trade Related Aspects of Intellectual Property Rights (TRIPS)’ Agreement.” (Though it has not yet been challenged at the WTO forum)

Draft IPR Policy states: “India recognizes that effective protection of IP rights is essential for making optimal use of the innovative and creative capabilities of its people. India has a long history of IP laws, which have evolved taking into consideration national needs and international commitments. The existing laws were either enacted or revised after the TRIPS Agreement and are fully compliant with it. These laws along with various judicial pronouncements provide a stable and effective legal framework for protection and promotion of IP.”

A recent vindication: On January 15, 2015, Indian Patent Office’s (IPO’s) rejection of a key patent claim on Hepatitis C drug Sovaldi (sofosbuvir) of Gilead Sciences further reinforces that India’s patent regime is robust and on course.

Gilead’s patent application was opposed by Hyderabad based Natco Pharma. According to the ruling of the IPO, a new “molecule with minor changes, in addition to the novelty, must show significantly enhanced therapeutic efficacy” when compared with a prior compound. This is essential to be in conformity with the Indian Patents Act 2005. Gilead’s patent application failed to comply with this legal requirement.

Although Sovaldi ((sofosbuvir) carries an international price tag of US$84,000 for just one treatment course, Gilead, probably evaluating the robustness of Sovaldi patent against Indian Patents Act, had already planned to sell this drug in India at a rice of US$ 900 for the same 12 weeks of therapy.

It is envisaged that this new development at the IPO would prompt entry of a good number of generic equivalents of Sovaldi. As a result, the price of sofosbuvir (Sovaldi) formulations would further come down.

However, reacting to this development Gilead has said, “The main patent applications covering sofosbuvir are still pending before the Indian Patent Office…This rejection relates to the patent application covering the metabolites of sofosbuvir. We (Gilead) are pleased that the Patent Office found in favor of the novelty and inventiveness of our claims, but believe their Section 3(d) decision to be improper. Gilead strongly defends its intellectual property. The company will be appealing the decision as well as exploring additional procedural options.”

For more on this subject, please read my blog post of September 22, 2014 titled, “Gilead: Caught Between A Rock And A Hard Place In India”

Concern 2: “Future negotiations in international forums and with other countries.”

Draft IPR Policy states: “In future negotiations in international forums and with other countries, India shall continue to give precedence to its national development priorities whilst adhering to its international commitments and avoiding TRIPS plus provisions.”

Concern 3: “Data Exclusivity or Regulatory Data Protection.”

Draft IPR Policy states: “Protection of undisclosed information not extending to data exclusivity.”

I discussed a similar subject in my blog post of October 20, 2014 titled, “Unilateral American Action on Agreed Bilateral Issues: Would India Remain Unfazed?”

Confusion with the Prime Minister’s recent statement:

It is worth noting that in end April 2015, Prime Minister Narendra Modi reportedly remarked to align India’s patent laws with “international standards”.

What the Prime Minister really meant by patent laws with “international standards” could be of anybody’s guess. This is because, even the World Trade Organization (WTO) considers Indian Patents Act compliant to TRIPS Agreement, which has been globally accepted as the ‘Gold Standard’ in the realm of IPR…unless, of course, Prime Minister Modi intends to accept ‘TRIPS Plus’ provisions for India, under US pressure and at the cost of health interest of majority of Indian patients.

It is noteworthy though, his own Ministry of Commerce & Industry has categorically emphasized and re-emphasized several times in the past that India’s patent regime is fully TRIPS compliant.

To add greater credence to this argument, the noted free market economist and Professor of Economics at Columbia University – Arvind Panagariya, who has recently been appointed to run Prime Minister Narendra Modi’s new NITI Aayog, has also endorsed it in his published articles, unambiguously.

As usual, leaving nothing to chance, immediately after the above remark of the Indian PM to align India’s patent laws with “international standards”, the USTR urged India to ‘expeditiously undertake’ initiatives stated by PM Modi, flashing across a long list of changes that the US wants to get incorporated in the Indian IP Acts and policies.

Pressure for amendment of Indian Patent Law:

From the intensity of pressure that the US Pharma industry is generating on the US Government, it is clear that American pharma industry will not be satisfied till Modi Government brings in changes in the Indian Patents Act 2005, as dictated by its constituents.

At the top of much publicized US wish list on IPR, features abolition of Section 3(d) of the Indian patent law. This provision of the Act denies patents to frivolous and incremental innovations without offering any significant value to the patients in terms of improved clinical efficacy of the drug. Many would term such innovation as attempts towards evergreening of patents through minor molecular manipulation or similar other means. This kind of innovation gives already a very high priced blockbuster drug another full term of patent monopoly, often with even higher price, at the cost of patients.

Pressure for a relook at the National IPR Policy:

In fact, the USTR 2015 report, also asks India to have yet another round of consultations with stakeholders before finalizing its IPR policy. This is widely construed as an attempt on the part of the US Government and industry to conclude their unfinished IPR agenda for India.

Whether Modi Government would be bullied by the American Pharma industry to succumb to its pressure at the cost of the Indian patients and going against the national and international experts’ opinion, only time would tell.

Benefits of Innovation and India:

India has amply demonstrated time and again that it does understand the value and benefits of innovation in different facets of life and business. The country endeavors to protect it too, according to the law of the land. However, there are still some procedural loose knots existing in the IPR environment of the country.

As stated above, for effective remedial measures in those areas, a ‘Think Tank’ has already been constituted by Modi Government to formulate a robust and comprehensive National IPR Policy.

In this context, a media report quoted a senior official from the Union Ministry of Commerce & Industry saying, “We hope this year we can convince the US that our laws are drafted in a way so as to protect both our consumer and industry’s interest. The new IPR policy that we are coming out with will take care of any anomalies or vagueness in our existing regime and make it tight and also fast-track clearances of patent applications.”

Would there be a ‘Ghost Writer’ for Indian IPR Policy?

The first draft of the policy has already been circulated in January 2015 and discussed in the following month with the stakeholders. However, American Pharma industry does not seem to be satisfied with its overall content, leave aside the nitty-gritty.

Going by this development some apprehends that a powerful lobby group probably wants to be the ‘Ghost Writer’ for the IPR Policy of India. Coincidentally enough, we also see the USTR blowing hot and cold on this critical issue…blowing hot through its ‘Special 301 Report’ and cold by praising Prime Minister Modi’s remark to align India’s patent laws with “international standards”.

India should play a catalytic role in changing the drug innovation model:

A paradigm shift in the drug innovation model can materialize only when there will be a desire to step into the uncharted frontier…coming out of the comfort zone of much familiar independent money spinning silos of all kinds of drug innovations…from break-through drugs to me-too varieties. Dove tailing scientific and business excellence with patients’ health interest, dispassionately, would then be the name of the game.

Though arduous, playing a catalytic role to bring out this transformation sooner, is extremely important for India. This is because, drug innovation with significant value addition would continue to remain as critical as access to important medicines for all, in perpetuity. India understands that just as clearly as USTR …for its ‘make in India’ campaign or otherwise. No well-orchestrated and spoon-fed pontification required in this area…uncalled for.

Conclusion:  

The bottom line is, the US Pharma industry continues to flex its muscle relentlessly under the very often used, misused and even abused façade that India does not understand the value of innovation.

On the other hand, the general sentiment in this area, both national and international, favors India.

As the new Vice Chairman of NITI Aayog of India, Dr. Arvind Panagariya wrote, “India must call the US’ bluff on patents,” it’s indeed time to demonstrate the same, once and for all.

However, in the context of upholding patients’ health interest in India, a lurking fear does creep in, after PM Modi’s well publicized recent remark to align India’s patent laws with “international standards”, especially when Indian Patents Act 2005 is already TRIPS compliant, according to WTO requirements.

That said, in the midst of a raging debate involving innovation, IPR, India and ‘Uncle Sam’, the moot question that floats at the top of mind is:

Has seemingly tough-minded Prime Minister Modi already yielded to ‘Uncle Sam’s’ bullying tactics to effect changes in an otherwise robust Indian patent regime, and that too at the cost of health interest of needy patients of the country?

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.