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Covid-19 Drugs: Accessibility, Affordability And Availability

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Covid-19 continues refusing to unravel the key to neutralize its destructive power – for bringing human life and the socioeconomic fabric of a country back to the old normal again. Just as India, all other countries are, apparently, awaiting a ‘magic bullet’ to come, breaking the shackles of this labyrinth, so to speak.

General expectation is, all concerned will understand that coming out of the new Coronavirus maze, sooner, at any cost – is the only way to bring back life, livelihoods, social fabric and the national economy on to the rail, again. Consequently, every entity in the world would require making moderate sacrifices in this unprecedented endeavor.

Right at this time, accessibility, affordability and availability of emergency use Covid-19 drugs, for various reasons, are going beyond the reach of a large number of the population who need those the most. This is happening not just beyond the shores of India, but in the country, as well, perhaps much more than expected. Interestingly, the issue pertains more to Covid-10 repurposed older drugs, and not so much for vaccines – just yet, as I shall deliberate below.

In this article, I shall focus on this issue, hoping for a reversal of the current trend through active involvement of the both the drug company leadership, and also the national decision makers to safeguard public health interest. Interestingly, the drug pricing issue, mostly with repurposed older drugs, is both global and local. Thus, let me first dwell on the subject of drug price increases during this global public health emergency.

Drug price increases during a global public health emergency: 

According to the July 08, 2020 report of IHS Markit, prices of critical drugs are increasing at a time when they are needed the most, as the governments and individual patients potentially struggle to pay for them.

The findings brought to the fore, prices for the 10 most critical drugs to treat COVID-19 have risen a highly unusual 4 percent globally, during the crisis. The cost for over half of these essential COVID-19 medicines rose across 80 countries between February and June 2020. Let me illustrate this point with one example each of Covid-19 emergency treatment options, starting with the global outcry for the same.

Global skepticism on remdesivir pricing:

As the world anxiously awaits a Covid-19 vaccine to hit the market, an experimental repurposed older drug – remdesivir of Gilead Sciences Inc. was introduced as an emergency treatment option for this infection. Pending detail clinical trial results, currently the drug has received only emergency regulatory approvals with an expectation that it may shorten the recovery period in some severely ill Covid-19 patients.

Gilead Sciences, on June 29, 2020, announced its price of $2,340 for a typical treatment course for people covered by government health programs in the United States and other developed countries.However, it will cost $3,120 for patients with private insurance. This price was swiftly and widely criticized, because the drug has received at least $70 million in public funding toward its development - the report highlighted.

Elaborating what would be affordable pricing for this drug in the developed world, another reportquoted the watchdog group – Public Citizen. This group maintains $1 per day is fair. It points to a cost-recovery model developed by the University of Liverpool, which calculated that the cost of manufacturing remdesivir at scale would be 93 cents per dose, leaving the remainder as, in its view, “a reasonable profit to Gilead,” as the report underscored.

Interestingly, analysts expect Gilead to make $525 million on remdesivir sales this year and $2.1 billion next year. This isn’t the first time Gilead is facing public criticism on life saving drug pricing. Just to recap, in 2013, the company also received ‘brickbats’ for its $84,000 price tag for groundbreaking hepatitis C treatment Sovaldi—followed up by its combo pill Harvoni, priced at $94,500. But those were first in class new and innovative drugs. Nevertheless, the remdesivir pricing issue is viewed differently, because it is not just a repurposed older drug, but indicated to combat a global public health crisis.

Let me now give an Indian example on a similar issue, but with a different anti-Covid-19 drug.

Criticism in India with Covid- 19 drug pricing: 

The Drug Controller General of India (DCGI) had on June19, 2020 approved anti-viral drug favipiravir, manufactured in India by Glenmark Pharmaceuticals Ltd. This approval was for “restricted emergency use” of the drug in mild to moderate cases of COVID-19 in the country, in view of the urgent medical need during the pandemic. Favipiravir is made under the brand name Avigan by Japan’s Fujifilm Holdings Corp and was approved for use as an anti-flu drug there in 2014.

According to media reports, Glenmark launched the drug on June 20, 2020 with the brand name FabiFlu at a price of Rs 103 per tablet. On this pricing issue, a member of the Indian Parliament, reportedly, made a representation to the DCGI stating, as a patient has to take 122 tablets of the drug in 14 days, the total cost of the treatment will come to around Rs 12,500. The M.P argued, “price quoted for this drug is definitely not affordable to the common people,” and ‘is definitely not in the interest of the poor, lower middle class and middle-class people of India.’ Additionally, the submission mentioned that ‘Glenmark has also claimed that this drug is effective in co-morbid conditions like hypertension, diabetes, whereas in reality, as per protocol summary, this trial was not designed to assess the FabiFlu in comorbid condition,’ as the letter read.

However, on July 13, 2020, Glenmark reportedly said that it had reduced Favipiravir price from Rs103 to Rs75 per tablet. The Company said, “The price reduction has been made possible through benefits gained from higher yields and better scale, as both the API (Active Pharmaceutical Ingredient) and formulations are made at Glenmark’s facilities in India, the benefits of which are being passed on to patients in the country.”

Thereafter, as reported on July 19, 2020, after receiving a complaint from a member of Parliament, the DCGI sought a clarification from Glenmark over its alleged “false claims” about the use of FabiFlu on Covid-19 patients with comorbidities, including the “pricing” of the drug.

In response Glenmark stated, “Compared to other therapies approved for emergency use in Covid-19, FabiFlu is much more economical and an effective treatment option.” The comparing argued, the estimated total cost for the full course of Favipiravir is Rs 9,150. Whereas, the same for Remdesivir, Tocilizumab and Itolizumab will come to Rs 24,000-30,000, Rs 44,000 and Rs 32,000, respectively.

Importantly, seriously ill Covid-19 patients will often be given many of these drugs, such as, tocilizumab, remdesivir and favipiravir, either one after the other, or simultaneously, making the overall price of treatment hefty for many. From this perspective, the bottom line is, Covid-19 drug treatment in India – where the out of pocket drug expenses is one of the highest in the world, won’t be affordable to many. Besides, there are other critical issues related to Covid-19 drug access and availability to Indian patients. The question that surfaces in this situation, are Covid-19 drug prices are high where there is no or less competition. If, so this is an avoidable situation.

Could this be due to less or no competition?

Continuing with the example of Favipiravir against the above backdrop, Cipla also, reportedly, received the DCGI approval for the launch of experimental Covid-19 drug Favipiravir in India on July 24, 2020. The brand will be marketed under the brand name Ciplenza in the first week of August and is priced much less than Glenmark’s Favipiravir – at Rs 68 per tablet. Could this be due to market competition?

Possibly so, because another report of July 25, 2020 indicated, nearly 10 other Favipiravir formulations will be launched shortly, despite inconclusive scientific clinical evidence as on date. Favipiravir price is expected to fall further due to competition. In that case, what could be the takeaway message, when this price trend is viewed against the response of Glenmark to the DCGI letter, justifying FabiFlu pricing?

Other issues of Covid-19 drug availability and access to Indian patients:

Other critical issues related to Covid-19 drug availability and access to Indian patients include, prices of Covid-19 drugs shooting up in short supply. There have been reports of difficulty in accessing remdesivir in India, too, although, Gilead Sciences has licensed this drug out to a few Indian generic pharmaceutical companies such as Hetero Healthcare, which has announced that it would manufacture and sell it at Rs 5,400 per vial. According to the latest protocol of the health ministry, the dosage of remdesivir should be 200 mg IV on day 1 followed by 100 mg IV daily for 4 days (5 days in total). From this one can easily work out the treatment cost with remdesivir for each patient.

Moreover, a BBC investigation has found that two life-saving drugs used to treat Covid-19 patients in India – remdesivir and tocilizumab – are in short supply and being sold for excessive rates on a thriving black market. Yet another recent investigation has unraveled a growing black-market for plasma therapy, ‘born out of the desperation of families willing to do anything to save their loved ones infected with Covid-19.’

I am citing these examples to give a sense of the plight of common Covid-19 patients from the drug availability, affordability and accessibility perspective – to save lives. However, the good news is, in this otherwise gloomy scenario, as perceived by many, a more empathetic scenario has been reported from many Covid-19 vaccine manufacturers.

More empathetic scenario with Covid-19 vaccine manufacturers: 

According to the World Health Organization (W.H.O), over 160 groups are working on COVID-19 vaccines, and 24 candidates have already reached human testing, Some are, reportedly gearing up for phase 3. It is widely expected, vaccines might be ready later this year or early next year. Vaccine developers are racing ahead at record speed, supported by Governments and facilitated by the drug regulators, to translate billion dreams coming true amid a public health catastrophe.

For the world population to acquire immunity against the Covid-19 onslaught, the key question remains: ‘At what price’, when vaccines are available? According to reports, the encouraging news is, some major vaccine makers, such as:

  • AstraZeneca (with Oxford University) plans to price at “no profit” during the pandemic “to support broad and equitable access around the world.” The company has entered several agreements with governments and other groups to provide about 2 billion doses around the world, at no profit.
  • Similarly, J&J has also “committed to bringing a safe and effective vaccine to the public on a not-for-profit basis for emergency pandemic use.”
  • Pfizer CEO has also said the company “will make a very, very marginal profit at this stage.” He pointed out that the company hasn’t taken any governmental funding, unlike other players. The company and its partner BioNTech have entered a deal with the U.K. government for 30 million doses. Moreover, Pfizer and BioNTech will get $1.95 billion from the US government to produce and deliver 100 million doses of their Covid-19 vaccine candidate.
  • Moderna CEO said, there’s “no world, I think, where we would contemplate to price this higher than other respiratory virus vaccines.”
  • Sanofi, which has separate COVID-19 vaccine partnerships with GlaxoSmithKline and Translate Bio, has “been committed to working with governments, partners and payers to ensure that when new vaccines are approved, we will make them available and affordable,”
  • Merck CEO also said the company has committed to “broad, equitable, affordable access.”
  • Nearer home, Serum Institute of India, has pledged to make 1 billion doses of the Oxford-AstraZeneca jointly formed COVID-19 vaccine at under Rs1000 per shot. The production could start as early as first quarter next year. Company CEO said this is not the time to make money from a vaccine against the novel Coronavirus, which has caused a global pandemic.

These pledges do give a comfort to many. Because, unlike Covid-19 repurposed older drug manufacturers, Covid-19 vaccine makers seem to be more empathetic to make these accessible and available to the world population at an affordable price.

Conclusion:

Well past a million mark, as on July 26, 2020 morning, the recorded Coronavirus cases in the country reached 1,339,176 with 31,425 deaths. With the number of daily cases being more than Brazil, India is poised to bridge its gap with the South American country. The steep unenviable climb continues.

The July 21, 2020 article – ‘Drug Pricing Back in the Spotlight,’ published in the PharmaExec.com, quoted the ICER Executive Vice-President saying,’ the drug pricing conversation is different in a pandemic.’ The system needs to ensure public access to drugs and vaccines in this global health crisis. If it does not happen, I reckon, appropriate authorities must step in with specific remedial measures.

Otherwise, the kudos showered on the drug industry for promptly offering a number of repurposed older drugs for emergency use against Covid-19 may not last long, if these treatments are not affordable and accessible to a vast majority. From this perspective, the questions being raised on accessibility, affordability and availability of many Covid-19 drugs, need to be addressed and resolved – soon.

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.

Deadly Climate Change Impact On Human Health: How Prepared Is India?

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It’s not uncommon to find many people, including heads of countries, expressing their serious apprehensions in public, about the scary impact of climate change. Just the last year, on November 26, 2018, BBC News captured one of such incidences with the astonishing headline: “Trump on climate change report: I don’t believe it.” The findings of this report have underscored, ‘unchecked global warming would wreak havoc on the US economy.’

Similarly, a few years ago, on September 05, 2014,CNN News 18 quoted Prime Minister Narendra Modi as saying: “Climate has not changed. We have changed. Our habits have changed,’ while answering to a question on climate change. Regardless of the outcome of any split-hair analysis of the rationale behind such statements from the world leaders, such public discourse could trivialize the possible catastrophic impact of climate change on the planet earth.

Be that as it may, that climate change is taking place, carrying all its ill-effects, is real now, without any ambiguity. There is also widespread consensus among the members of the United Nations that ‘the Earth is warming at a rate unprecedented during post hunter-gatherer human existence.’

It is worth noting that way back in 2001, the ‘Third Assessment Report of the Intergovernmental Panel on Climate Change’, further recorded: “There is new and stronger evidence that most of the warming observed over the last 50 years is likely to be attributable to human activities”, most importantly the release of greenhouse gases from fossil fuels.

Several ‘International Agreements’, including the Paris Agreement on Climate Change - all supported by hard scientific data, have called for immediate, quantifiable measures in each country to address the ‘wide-ranging environmental threats, such as ozone depletion and long-range transboundary air pollution.’ Against this backdrop, in this article, I shall focus on the dreadful effect of climate change in the proliferation of a wide-variety of ailments, especially infectious diseases, within a few decades. While doing so, let me first have a quick recap on what is ‘Climate Change’, in a simple language.

Climate Change – a quick recap:

According to the United Nations, ‘Climate Change is the defining issue of our time and we are at a defining moment. From shifting weather patterns that threaten food production, to rising sea levels that increase the risk of catastrophic flooding, the impacts of climate change are global in scope and unprecedented in scale. Without drastic action today, adapting to these impacts in the future will be more difficult and costly.’

It’s important to note, although, the planet Earth’s climate is constantly changing over geological time, the current period of warming is occurring more rapidly than many past events. Scientists are concerned that the natural fluctuation or variance, is being overtaken by a rapid human-induced warming, as they emit more greenhouse gases. As these gases get trapped in the atmosphere, more heat is retained that has serious implications for the stability of the planet’s climate, even impacting human health with grave consequences. The World Health Organization (W.H.O) has also warned that the health of millions could be threatened by increases in malaria, waterborne disease and malnutrition.

Its impact human health:

The direct and indirect impact of climate change on human health is profound. Before I go into the specifics, let me indicate some of the direct ones, as captured by the Center for Health and the Global Environment (CHanGE), University of Washington. This is sans any charts and maps, unlike the usual practice:

  • Increasing temperatures are causing poor air quality that can affect the heart and worsen cardiovascular disease.
  • Increasing exposure to pollen, molds, and air pollution, all of which can worsen allergies and other lung diseases, such as asthma.
  • Changes in the geographic range of disease-carrying insects, such as mosquitoes, ticks, fleas and other similar ones, which can fast spread many tropical ailments, such as dengue fever and malaria to humans.
  • Increasing frequency and severity of extreme weather and climate events can cause, besides many physical illnesses, several kinds of mental illnesses – increasing both morbidity and mortality.
  • Frequent flooding events and sea level rise can contaminate water with harmful pathogens and chemicals, potentially causing food-borne and waterborne illnesses.
  • Changing weather patterns affect the quality and quantity of nutritious foods with increasing incidence of under-nutrition and micronutrient deficiencies.
  • Additional stress placed on hospital and public health systems, could limit people’s ability to obtain adequate health care during extreme weather events and disease outbreaks.

Most specific and the deadly one:

The World Health Organization (W.H.O) publication - ‘Climate change and human health – Risks and Responses,’ clearly flagged that ‘Changes in infectious disease transmission patterns are a likely major consequence of climate change.’

Citing a pertinent analogy to explain the reason, it said: “Humans have known that climatic conditions affect epidemic diseases from long before the role of infectious agents was discovered, late in the nineteenth century. Roman aristocrats retreated to hill resorts each summer to avoid malaria. South Asians learnt early that, in high summer, strongly curried foods were less likely to cause diarrhea.”

Would pharma players convert these problems into opportunities?

Curiously, some pharmaceutical investors are researching to fathom potential business opportunities lying underneath the above problem, especially for vaccines and newer antimicrobials. It’s probably a blessing in disguise not just for the drug companies, but also for the general public, considering the following two issues, prevailing in the current scenario:

  • According to W.H.O, Antimicrobial Resistance (AMR) is an increasingly serious threat to global public health. It threatens the effective prevention and treatment of an ever-increasing range of infections caused by bacteria, parasites, viruses and fungi, causing the success of even major surgery and cancer chemotherapy seriously compromised.
  • ‘Pharmaceutical companies are backing away from a growing threat that could kill 10 million people a year by 2050’, reported a July 19, 2018 article. This is because, ‘Antibiotics Aren’t Profitable Enough for Big Pharma to Make More,’ wrote another article, published in Bloomberg Businessweek, on May 3, 2019.

Interestingly, a recent report analyzed and evaluated how this can be done, and which companies will be benefitted most in that process. 

“Climate change to fetch a big business opportunity for pharma”:

As reported on July 25, 2019, Morgan Stanley told investors that climate change will cause an increased prevalence and rapid spread of infectious diseases that may be a boon for some drug companies with big vaccine portfolios. It also highlighted, between 383 million and 725 million more people may be exposed to Zika, dengue and other diseases by 2050, depending on the pace and severity of global warming.

The analysts estimated, especially 7 pharma companies will be critical to fighting infectious diseases brought on by climate change. According to the research note of thebank, ‘the USD 500 billion infectious disease market could see demand for an added USD 125 billion in new vaccines, or as much as USD 200 billion assuming premium pricing for more complex new treatments.’

The top possible gainers:

Identifying the top possible gainers, Morgan Stanley apprised, vaccine development being more difficult and expensive, companies that are already in that business will have an upper hand.

Hence, Sanofi and GlaxoSmithKline are expected at the top, given their existing pipelines and manufacturing capacity. Takeda and Merck both have vaccines in the works for dengue fever, one of the diseases that climate change is likely to exacerbate. Janssen and Pfizer are both active in the vaccines market, but would need to establish new research programs to take on tropical diseases. ‘Moderna’ is also in a good position because it has demonstrated a potential pipeline for drugs combating the Zika virus., as Morgan Stanley further elaborated.

Nevertheless, Morgan Stanley isn’t the only bank looking at investment opportunities from climate change, on July 24, 2019, Goldman Sachs also, reportedly, said it was hiring a sustainable-finance group that is looking into issues related to sustainability. Thus, on the positive side, climate change could fetch a big business opportunity for many pharma players, across the world.

600 million people at risk for climate change in India:

On June 24, 2019, a reputed national business news daily of India reported, “600 million people at risk: Climate change may soon turn critical in India.” Against this threat, the current public health care infrastructure in the country, continues to remain fragile, as stated in India’s National Health Profile, 13th Issue.

It also states, the cost of treatment has been on the rise in India and it has led to inequity in access to health care services. Intriguingly, the country spends around 1.02 percent of its GDP towards public health, which has remained static to declining over a long period of time. Although, health insurance is a growing segment, it hasn’t taken off fully. Several measures are needed to improve and expand insurance coverage.

Further, according to the report by the Center for Disease Dynamics, Economics & Policy (CDDEP) in the US, India is facing shortage of 600,000 doctors and 2 million nurses. This report was widely quoted by the Indian media, on April 14, 2019.

These facts give a perspective on what is India’s level of preparedness to address the critical health issues related to climate change, especially the havoc that the dreaded infectious diseases can cause to so many.

Conclusion:

Astute health policy makers, including a large section of the top political echelon of the country are, apparently, aware of various ill effects of climate change. They also seem to be cognizant that these are likely to accelerate the worsening health problems of the population, including infectious diseases, asthma and other respiratory diseases.

Assuming, new and modern drugs will keep coming to help treat these ailments, do we have a functioning and efficient public health infrastructure to grapple with such issues. What about high out of pocket expenditure towards healthcare for a large section of the population, regardless of Ayushman Bharat?

As the (W.H.O) publication - ‘Climate change and human health – Risks and Responses’ recommended, ‘early planning for health is essential to reduce, hopefully avoid, near future and long-term health impacts of global climate change. The optimal solution, however, is in the hands of governments, society and every individual—a commitment to a change in values, to enable a full transition to sustainable development.’

That said, as India is also a signatory to the latest Paris Agreement on Climate Change, can we assume, India will walk the talk to significantly contain its deadly impact on human health? How is India preparing itself to meet this great challenge of Probably it is anybody’s guess, at least, as on date?

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.

Immunization Still Remains A Low-Budget Neglected Area In India

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Although India is a leading producer and exporter of vaccines, the country has the greatest number of deaths among children under 5, and the majority are from vaccine-preventable diseases. Less than 44 percent of India’s young children receive the full schedule of immunizations, commented a research study of Michigan University of the United States.

This is noteworthy, as vaccines are one of the most successful and cost-effective public health interventions. The World Health Organization (WHO) defines vaccines as:

“A vaccine is any preparation intended to produce immunity to a disease by stimulating the production of antibodies. Vaccines include, for example, suspensions of killed or attenuated microorganisms, or products or derivatives of microorganisms. The most common method of administering vaccines is by injection, but some are given by mouth or nasal spray.”

Vaccines help prevent over two to three million children each year. However, another 1.5 million children still die from diseases that could be prevented by routine vaccines, as estimated by the WHO.

“The developing world should no longer experience 450,000 preventable deaths each year from rotavirus, nor 145,000 from measles. By the same token, there should no longer be 2000 preventable deaths each year from influenza in Australia. It is time to use our global health efforts to address the most pressing risks, both at home and abroad,” expects another article published in the Volume 45, No.1, January-February 2016 edition of the journal of ‘Australian Family Physician (afp)’

Nevertheless, the bottom line is, an estimated 19.4 million infants worldwide is still missing out on basic vaccines, which otherwise come rather easily to the children of the developed nations of the world, as per the ‘Fact Sheet’ of the World Health Organization (W.H.O) of September 2016.

A commendable global initiative:

To resolve this inequity, in January 2000, the Global Alliance for Vaccines and Immunization (GAVI) was formed. This initiative was mainly aimed at generating sufficient fund to ensure availability of vaccines for children living in the 70 poorest countries of the world.

The GAVI Alliance has been instrumental in improving access to six common infant vaccines, including those for hepatitis B and yellow fever. GAVI is also working to introduce pneumococcal, rotavirus, human papilloma virus, meningococcal, rubella and typhoid vaccines in not too distant future.

Current ground situation in India:

In this area, the prevailing situation in India is much worse.

The Global consulting major – McKinsey in its report titled, “India Pharma 2020: Propelling access and acceptance, realizing true potential” stated that at 2 percent penetration, the vaccines market of India is significantly under-penetrated with an estimated turnover of around US$ 250 million, where the private segment accounts for two-thirds of the total. McKinsey expects the market to grow to US$ 1.7 billion by 2020.

Some of the important reasons for poor penetration of the vaccine market in India can be found in a March 02, 2016 research article published in the ‘Michigan News’ of the University of Michigan. The paper articulated some important facts, as follows:

  • Out of 26 million children born in India every year, two-thirds of them do not receive their vaccinations on time, prolonging their susceptibility to diseases and contributing to untimely deaths.
  • Only 18 percent of children are vaccinated with the recommended three doses of DPT vaccine.
  • Only 12 percent of children are vaccinated with the measles vaccine by the required age of 9 months, although 75 percent are vaccinated by age 5. This delay in vaccination can contribute to frequent outbreaks of measles in India.
  • India is adding vast numbers of new children who need vaccination, while the older ones remain under or unvaccinated because of immunization delays, is like “walking too slowly on a moving treadmill – you continually fall further back.”
  • India hopes to add rotavirus to its Universal Immunization Program, a free government-approved vaccination program that was looked at in this study.
  • The government has the infrastructure to deliver vaccines, but the motivations for delivering all vaccination doses decreases over time.
  • India hopes to add rotavirus to its Universal Immunization Program, a free government-approved vaccination program that was looked at in this study.

Needs both policy and budgetary support:

As stated above, the overall immunization scenario in India, as on date, is rather grim. Besides, in view of the humongous disease burden of India, immunization program with various types of vaccines should receive active encouragement from the government as disease prevention initiatives, at least, keeping the future generation in mind. In the next Union Budget of India, this issue should attract fresh policy measures, spearheaded by the Central Government, with requisite fund allocation both by the Central and State Governments.

Low immunization budget and other key barriers:

‘Health Affairs’ – a leading peer-reviewed journal on health policy thought and research, highlighted that India spends woefully little on routine immunization. Quoting data published by the Union Ministry of Health the report stated, only 2.1 percent of the national government’s health budget is allocated to routine immunization – a small amount given the country’s large population and the number of births. Although vaccines used in India are primarily provided free and through the government channels, over 30 percent of the population still purchase vaccines from the private market as a part of their out of pocket expenses.

Besides, there is a long list of other challenges to India’s immunization program. These include a shortage of trained personnel to manage the program at both the national and state levels; the need to undertake innovations in vaccines, disease surveillance, vaccine procurement, and effective vaccine management; the absence of good data on disease burden to inform vaccination priorities; the lack of baseline surveillance data for monitoring the effects of vaccination; and the absence of a system of routine reporting and surveillance, the report stated.

Everyone in the country is expected to fulfill the individual responsibility to get their own children properly vaccinated by properly following, and completing the vaccination schedule. Better all-round and ongoing communication of the long-term benefits of vaccination for many serious disease prevention against negligible side effects, could create greater awareness for compliance.

Indian vaccine market and the key local players:

A report titled ‘Vaccines Market in India 2013’, published by Netherlands Office of Science & Technology, New Delhi, estimated that vaccines contributed largest share in the total Biopharma sales with estimated sales of US$ 602 million in FY 2011-12 over US$ 417.5 million of the previous year. Over half of the top 10 firms in the industry are active in the private sector vaccines market has recorded a growth of about 25 percent.

India is not just a leading producer and exporter of vaccines, it develops and markets complex vaccines, such as, pentavalent rotavirus vaccine. There are around 13 major vaccine manufacturers in India. Companies like, Serum Institute, Shantha Biotecnics, Bharat Biotech and Panacea Biotech are taking commendable strides in this direction. Bharat Biotech is incidentally the largest Hepatitis B vaccine producer in the world.

Around 43 percent of the global Universal Immunization Program vaccine supply (more than 70 percent in the case of single vaccine) reportedly comes from India. Indian vaccine major Serum Institute is reportedly one of the largest suppliers of vaccines to over a 130 countries of the world and claim that ’1 out of every 2 children immunized worldwide gets at least one vaccine produced by Serum Institute.’

Expand Government immunization product spectrum:

It is high time for the Union Ministry of Health to expand the product spectrum for vaccines, as an integral part of its disease prevention program. It is recommended that the routine immunization program of India should now include other important vaccines, such as, Haemophilus influenzae type b, hepatitis B, and rotavirus, as recommended by the National Technical Advisory Board (DTAB) on Immunization.

Conclusion:

Against this backdrop, a holistic immunization program can no longer remain a low-budget and virtually neglected area in India.

Effective resolution of this important issue by the Government would require both the Union and the State Governments to increase their respective budget significantly. It would help launching a well-integrated multi-pronged approach to include most of the remaining one third of the population in the state-run immunization program.

In tandem a strategic pathway needs to be crafted to expand the immunization product spectrum, increase awareness to encourage more household to take part in the holistic immunization initiatives for disease prevention, and counter the anti-vaccine advocates effectively. There is also an urgent need to make more investments in disease surveillance. An integrated approach towards all these initiatives would significantly help reduce the overall burden of disease in 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.

NDDS as New Drug: Good for Patients, Great for Pharma

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The Ministry of Health of India has reportedly decided to amend Rule 122 (E) of the Drugs and Cosmetics Rules, 1945 to categorize the New Drug Delivery Systems (NDDS), including ‘Controlled Release (CR)’ or ‘Modified Release (MR)’ formulations, whether a copy of studied and approved drugs or a new one, as ‘New Drugs’.

After the amendment, all vaccines and recombinant DNA (r-DNA) derived drugs would also fall under this nomenclature. Accordingly, to obtain ‘Marketing Approval’, such formulations would be subjected to requisite studies, including ‘Clinical Trials (CT), as specified for ‘New Drugs’ under the Drugs and Cosmetics Act of India.

It has however been clarified though, that these applications will not be treated as Investigational New Drugs (IND) and the Central Drugs Standard Control Organization (CDSCO) shall prepare appropriate regulatory guidelines for all NDDS formulations.

The main reason for the amendment is possibly much late realization of CDSCO that such formulations are vastly different from each other with respect to both efficacy and toxicity.

Besides, it has been widely alleged that some pharma companies in India, mainly to hoodwink the Drug Price Control Orders (DPCO) in the past, used to switch over from ‘Immediate Release (IR)’ formulations to products with CR/MR technology of the same molecule. However, that loophole has since been plugged in DPCO 2013, creating almost a furore in the industry.

A long overdue decision for patients’ health safety:

As stated earlier, this is indeed a long overdue decision of the Indian drug regulatory policy makers, solely considering patients’ health interest.

The primary reason being, any NDDS formulation with CR/MR technology is designed to release the drug substance in a controlled manner with high precision to achieve desired efficacy and safety, quite unlike its IR equivalent, if available in the market. It is important to note that inappropriate release of the drug in any CR/MR formulation would result in lesser efficacy or increased toxicity, jeopardizing patients’ health.

Process followed by US-FDA for CR/MR formulations:

In the United States, for marketing approval of such products, FDA usually requires submission of New Drug Applications (NDAs) providing details based on the evidence of adequate drug exposure expressed by blood levels or dose, and the response framework validated by clinical or surrogate endpoint(s).

US-FDA has three types of NDAs for MR drug products:

  • IR to CR/MR switch
  • MR/CR to MR/CR switch with unequal dosing intervals
  • MR/CR to MR/CR switch with equal dosing intervals

For switching from an IR to a CR/MR product, which is more common in India, the key requirement is to establish that the new CR/MR product has similar exposure course of the drug as compared to the previously approved IR product, backed by well-documented efficacy and safety profile. If not, one efficacy and/or safety trial would be necessary, in addition to three clinical pharmacology studies.

Good for patients:

The good news for patients is that, being categorized as ‘New Drugs’, all NDDS formulations, without any exceptions whatsoever, would henceforth obtain marketing approval only from the Drug Controller General of India (DCGI), after having passed through intense data scrutiny, instead of State Drug Authorities where getting a manufacturing license of such formulations is alleged to be a ‘child’s play’. Thus, with the proposed amendment, efficacy and safety concerns of CR/MR formulations are expected to be addressed adequately.

Great for Pharma:

Currently, while fixing the ‘Ceiling Prices (CP)’ under DPCO 2013, National Pharmaceutical Pricing Authority (NPPA) treats CR/MR formulations at par with IR varieties of the same molecules having the same dosage strength.

Thus, categorization of all NDDS formulations as ‘New Drugs’, irrespective of the fact whether these are copies of studied and approved drugs or new ones, would be lapped up by the manufacturers from product pricing point of view. All these formulations, after the proposed amendment, would go outside the purview of drug price control under Para 32 (iii) of DPCO 2013, which categorically states that the provisions of this order shall not apply to:

“A manufacturer producing a ‘new drug’ involving a new delivery system developed through indigenous Research and Development for a period of five years from the date of its market approval in India.”

A similar past issue still haunts:

Similar callousness was exhibited in the past, while granting marketing approval for a large number of highly questionable Fixed Dose Combination (FDC) drugs by the same drug regulators. Unfortunately, that saga is still not over, not just yet. 

All these irrational FDC formulations, even after being identified so by the Drug Technical Advisory Board (DTAB), have been caught in the quagmire of protracted litigations. Consequently, such dubious products are still being promoted by the respective pharma players intensively, prescribed by the doctors uninhibitedly, sold by the chemists freely and consumed by patients ignorantly. With ‘pharmacovigilance’ being almost non-functional in India, the harmful impact of these drugs on patients’ health cannot just be fathomed.

Conclusion: 

With the above examples, it is quite clear that technological precision of high order is absolutely imperative to manufacture any effective CR/MR formulation. In addition, stark regulatory laxity in the marketing approval process for these drugs is a matter of great concern.

In such a scenario, one could well imagine how patients’ health interests are being compromised by not formalizing and adhering to appropriate regulatory pathways for marketing approval of such drugs in the country, since decades.

That said, as the saying goes “Better Late, Than Never”. The ‘New Drug’ nomenclature of all CR/MR formulations or for that matter entire NDDS as a category, including vaccines and recombinant DNA (r-DNA) derived drugs, would now hopefully be implemented in India, though rather too late, a much welcoming decision nevertheless.

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.

Vaccines Development: Is it Just a Business Based on Fear?

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‘Vaccination – A Business based on fear’, is the title of a book written by Dr. Gerhard Buchwald M.D, a German medical doctor and a vaccination critic. This book talks about:

“The damage and the deaths caused by vaccination are written off as ‘pure coincidence’, as something which would have occurred anyway, even without vaccination. Often damage is trivialized by claiming that vaccine damage occurs only very, very rarely, or the damage is covered up by naming as the cause, the most unlikely syndromes which can only be found in special literature.”

However, his critics and pro-vaccination experts do opine that this book “is a pathetic presentation of vaccination, from a self-proclaimed anti-vaccination lobbyist. It is full of half-truths, blatant lies and misrepresented statistics”.

Vaccination – one of the most important development in medicines: 

Quite in contrary to what Dr. Gerhard Buchwald wrote, vaccination was voted as one of the four most important developments in medicine of the past 150 years, alongside sanitation, antibiotics and anesthesia by readers of the ‘British Medical Journal’ in 2007. No wonder, Vaccines are one of the most successful and cost-effective public health interventions, which help preventing over 3 million deaths every year throughout the world topping the list in terms of lives saved.

Vaccines that are being developed and marketed today, though provide high level of protection against increasing number of diseases with reduction of associated morbidity and mortality, there is still a crying need for greater encouragement, more resource deployment and sharper focus towards newer vaccines development for many more dreaded and difficult diseases.

In tandem, concerted efforts need to be made by both the industry and the government to improve affordable access to all these vaccines for a larger section of the population, especially in the developing world.

Rejuvenating trend:

However, from the business perspective, the vaccine market, though initially considered to be a low-profit initiative, now has started being under rejuvenated focus keeping pace with improved understanding of the human immune system. The future scope of vaccines is immense, as the management of several potentially preventable diseases remains still unaddressed.

Consequently, the focus of the global vaccine industry is getting expanded from prophylactic vaccination for communicable disease (e.g. DTP vaccine) to therapeutic vaccines (e.g. Anti-cancer vaccines) and then possibly non-communicable disease vaccines (e.g. vaccines for coronary artery disease).

Shifting focus on vaccines types:

As per the ‘National Institute of Health (NIH)’ of USA, following are some types of vaccines that researchers usually work on:

  • Live, attenuated vaccines
  • Inactivated vaccines
  • Subunit vaccines
  • Toxoid vaccines
  • Conjugate vaccines
  • DNA vaccines
  • Recombinant vector vaccines

Among all these segments, sub-unit vaccine is the largest revenue generator, though synthetic vaccines, recombinant vector vaccines, and DNA vaccines are emerging as the fastest-growing segments.

The first vaccine of the world:

In 1796, Edward Anthony Jenner not only discovered the process of vaccination, alongside developed the first vaccine of the world for mankind – smallpox vaccine. To develop this vaccine Jenner acted upon the observation that milkmaids who caught the cowpox virus did not catch smallpox.

As per published data prior to his discovery the mortality rate for smallpox was as high as up to 35%. Thus, Jenner is very often referred to as the “Father of Immunology”, whose pioneering work has “saved more lives than the work of any other person.”

Later on in 1901 Emil Von Behring received the first Nobel Prize (ever) for discovering Diphtheria serum therapy.

R&D costs for vaccines:

According to a paper published by the US National Library of Medicine and National Institute of Health (NIH):

“A vaccine candidate entering pre-clinical development in 2011 would be expected to achieve licensure in 2022; all costs are reported in 2022 Canadian dollars (CAD). After applying a 9% cost of capital, the capitalized total R&D expenditure amounts to $ 474.88 million CAD.”

Issues and challenges:

To produce a safe and effective marketable vaccine, besides R&D costs, it takes reportedly around 12 to 15 years of painstaking research and development process.

Moreover, one will need to realize that the actual cost of vaccines will always go much beyond their R&D expenses. This is mainly because of dedicated and highly specialized manufacturing facilities required for mass-scale production of vaccines and then for the distribution of the same mostly using cold-chains.

Around 60% of the production costs for vaccines are fixed in nature (National Health Policy Forum. 25. January 2006:14). Thus such products will need to have a decent market size to be profitable.

Unlike many other medications for chronic ailments, which need to be taken for a long duration, vaccines are administered for a limited number of times, restricting their business potential.

Thus, the long lead time required for the ‘mind to market’ process for vaccine development together with high cost involved in their clinical trials/marketing approval process, special bulk/institutional purchase price and limited demand through retail outlets, restrict the research and development initiatives for vaccines, unlike many other pharmaceutical products.

Besides, even the newer vaccines will mostly be required for the diseases of the poor, like Malaria, Tuberculosis, HIV and ‘Non Communicable Diseases (NCDs)’ in the developing countries, which may not necessarily guarantee a decent return on investments for vaccines, unlike many other newer drugs. As a result, the key issue for developing a right type of newer vaccine will continue to be a matter of pure economics.

A great initiative called GAVI: 

Around 23 million children of the developing countries are still denied of important and life-saving vaccines, which otherwise come rather easily to the children of the developed nations of the world.

To resolve this inequity, in January 2000, the Global Alliance for Vaccines and Immunization (GAVI) was formed. This initiative was mainly aimed at generating sufficient fund to ensure availability of vaccines for children living in the 70 poorest countries of the world.

The GAVI Alliance has been instrumental in improving access to six common infant vaccines, including those for hepatitis B and yellow fever. GAVI is also working to introduce pneumococcal, rotavirus, human papilloma virus, meningococcal, rubella and typhoid vaccines in not too distant future.

In August 2013, GAVI has reportedly launched a campaign in Kenya to fight the world’s leading killer of children under five with a new Pneumococcal Vaccine for prevention from pneumonia, meningitis and sepsis, which kill more than half a million people a year.

GAVI hopes to avert 700,000 deaths by 2015 through the immunization of 90 million children with pneumococcal vaccines.

Global pharma majors Pfizer and GlaxoSmithKline (GSK) are producing the vaccines as a part of a deal part-funded by Britain, Italy, Canada, Russia, Norway and the Bill Melinda Gates Foundation.

Current trend in newer vaccine development:

Malaria Vaccine:

According to the National Institute of Health (NIH) of the United States, the results of an early-stage clinical trial published in August 8, 2013 in the ‘Journal Science’ for an investigational malaria vaccine has been found to be safe to generate an immune system response and to offer protection against malaria infection in healthy adults.

The scientists at Sanaria Inc., of Rockville, Md. Research Center developed this vaccine known as PfSPZ. The researchers reportedly found that injecting patients with live-but-weakened malaria causing parasites appeared to create a protective effect.

Earlier, Reuters on December 20, 2011 reported that the British scientists have developed an experimental malaria vaccine, which has the potential to neutralize all strains of the most deadly species of malaria parasite.

In October 2011, the data published for a large clinical trial conducted in Africa by GlaxoSmithKline on their experimental malaria vaccine revealed that the risk of children getting malaria had halved with this vaccine. Reuters also reported that other teams of researchers around the world are now working on different approaches to develop a malaria vaccine.

Tuberculosis vaccines:

The Lancet reported in March 2013, as BCG vaccination provides incomplete protection against tuberculosis in infants, a new vaccine, modified Vaccinia Ankara virus expressing antigen 85A (MVA85A), has been designed to enhance the protective efficacy of BCG. MVA85A was found well-tolerated and induced modest cell-mediated immune responses. However, the reasons for the absence of MVA85A efficacy against tuberculosis or M tuberculosis infection in infants would need exploration.

Universal Cancer vaccines:

In a breakthrough development, the Israeli company Vaxil BioTherapeutics has reportedly formulated a therapeutic cancer vaccine, now in clinical trials at Hadassah University Medical Center in Jerusalem.

If everything falls in place, the vaccine could be available about six years down the road, to administer on a regular basis not only to help treating cancer but also to keep the disease from recurring.

Though the vaccine is being tested against a type of blood cancer called multiple myeloma, if it works as the initial results indicate, its platform technology VaxHit could be applied to 90 percent of all known cancers, including prostate and breast cancer, solid and non-solid tumors.

HIV Vaccine:

A recent effort to find a vaccine for HIV is reportedly beginning in 2013 at laboratories in a London hospital and two centers in Africa. The work will be split equally between London, the Rwandan capital Kigali and Nairobi in Kenya.

It has been reported that scientists are recruiting 64 healthy adult volunteers for the trial, which is expected to take up to two years.

Vaccines requirements of the developing world: 

Developing countries of the world are now demanding more of those vaccines, which no longer feature in the immunization schedules of the developed nations. Thus to supply these vaccines at low cost will be a challenge, especially for the global vaccine manufacturers, unless the low margins get well compensated by high institutional demand.

India needs a vibrant vaccine business sector:

For greater focus on all important disease prevention initiatives, there is a need to build a vibrant vaccine business sector in India. To achieve this objective the government should create an enabling ecosystem for the vaccine manufacturers and the academics to work in unison. At the same time, the state funded vaccine R&D centers should be encouraged to concentrate more on the relevant vaccine development projects ensuring a decent return on their investments, for longer-term economic sustainability.

More often than not, these stakeholders find it difficult to deploy sufficient fund to take their vaccines projects successfully through various stages of clinical development in order to obtain marketing approval from the drug regulator, while registering a decent return on investments. This critical issue needs to be appropriately and urgently addressed by the Government to make the disease prevention initiatives in the country sustainable.

Changing market dynamics: 

Even in a couple of decades back, ‘Vaccines Market’ in India did not use to be considered as a focus area by many pharmaceutical companies. Commoditization of this market with low profit margin and unpredictable interest of the government/the doctors towards immunization were the main reasons. Large global players like Glaxo exited the vaccine market at that time by withdrawing products like, Tetanus Toxoid, Triple Antigen and other vaccines from the market.

Currently, the above scenario is fast changing. The vaccine market, as stated above, is getting rejuvenated not only with the National Immunization Program (NIP) of the country, but also with the emergence of newer domestic vaccines players and introduction of novel vaccines by the global players, which we shall discuss below.

In addition, the ‘Indian Academy of Pediatrics (IAP) Committee on Immunization’ now recommends the ‘best individual practices schedule’ for the children in consultation with their respective parents. Such schedule may not conform to NIP and include newer vaccines, broadening the scope of use of vaccines in general.

Global Market:

According to GBI Research Report, overall global vaccines market was valued at US$ 28 billion in 2010 and is expected to reach US$ 56.7 billion by 2017 with a CAGR of 11.5%. The key growth driver of this segment will be introduction of newer vaccines, which are currently either in the regulatory filing stage or in the late stages of clinical development.

The important international players in the vaccines market are GlaxoSmithKline, Sanofi, Pfizer, Novartis AG, Merck and SP-MSD. Together they represent around 88% of the total vaccine segment globally, the report highlights.

Indian Market:

McKinsey in its report titled, “India Pharma 2020: Propelling access and acceptance, realizing true potential“ stated that at 2% penetration, the vaccines market of India is significantly under-penetrated with an estimated turnover of around US$ 250 million, where the private segment accounts for two-thirds of the total. McKinsey expects the market to grow to US$ 1.7 billion by 2020.

India is one of largest markets for all types of vaccines in the world. The new generation and combination vaccines, like DPT with Hepatitis B, Hepatitis A and Injectable polio vaccine, are driving the growth. The demand for veterinary vaccines is also showing ascending trend. Pediatric vaccines contribute to around 60% of the total vaccines market in India.

Domestic Indian players like, Serum Institute, Shantha Biotecnics, Bharat Biotech and Panacea Biotech are poised to take greater strides in this direction. Bharat Biotech is incidentally the largest Hepatitis B vaccine producer in the world. Likewise, Serum Institute is reportedly one of the largest suppliers of vaccines to over 130 countries and claim that ’1 out of every 2 children immunized worldwide gets at least one vaccine produced by Serum Institute.’

The first new vaccine developed in India:

Indian scientists from Bharat Biotech Ltd in Hyderabad have reportedly developed a new oral vaccine against the Rotavirus induced diarrhea, where both vomiting and loose motion can severely dehydrate children very quickly. This is the first new vaccine developed in India, establishing itself as the first developing country to achieve this unique distinction.

Two recent vaccine JV and Partnership agreements in India:

British drug major GlaxoSmithKline (GSK) has reportedly agreed to form a 50-50 venture with the domestic Indian vaccine manufacturer Biological E Limited in January 2013 to develop a product that would combine GSK’s injectable polio shot with a vaccine produced by Biological E to protect against five diseases including diphtheria and tetanus.

In addition, MSD pharma of the United States and Indian drug major Lupin have announced a partnership agreement to market, promote and distribute, MSD’s 23-valent Pneumococcal Polysaccharide Vaccines under a different brand name in India for prevention of Pneumococcal disease, pneumonia being its most common form affecting adults.

A possible threat: 

As per reports most Indian vaccines manufacturers get a major chunk of their sales revenue from exports to UN agencies, charitable organizations like, the Bill & Melinda Gates Foundation and GAVI, and other country-specific immunization programs.

The report predicts, the virtual monopoly that Indian vaccines manufacturers have enjoyed in these areas, will now be challenged by China, as for the first time, in 2012, the Chinese national regulatory authority received World Health Organization’s (WHO) ‘pre-qualification’ certification that allows it to approve locally manufactured vaccines to compete for UN tenders. 

Action areas to drive growth:

McKinsey in its above report ‘India Pharma 2020’ indicated that the action in the following 4 areas by the vaccine players would drive the vaccine market growth in India:

  • Companies need to go for local production of vaccines or leverage supply partnerships. MSD and GlaxoSmithKline’s local partnership in India and for the HiB vaccine with Bio-manguinhos in Brazil may be cited as examples.
  • Companies will need to conduct studies on the economic impact of vaccination and establish vaccine safety and performance standards.
  • Extension of vaccine coverage beyond pediatricians and inclusion of general practitioners, consulting physicians and gynecologists will be essential.
  • Companies will need to enhance supply chain reliability and reduce costs.

Conclusion: 

On January 7, 2012, while requesting the ‘Overseas Indian Medical Professionals’ to partner with the institutions in India, the Health Minister, in his address, announced that the Ministry of Health has already introduced the second dose of measles vaccine and Hepatitis-B vaccination across the country. Moreover, from December 2011 a ‘Pentavalent Vaccine’ has been introduced, initially in 2 States, covering 1.5 million children of India.

All these augur quite well for the country. However, keeping in view of the humongous disease burden of India, immunization program with various types of vaccines should receive active encouragement from the government as disease prevention initiatives, keeping the future generation in mind.

If vaccine related pragmatic policy measures, with equal focus on their effective implementation, are initiated in the country, without delay, the domestic vaccine market, in turn, will receive much awaited further growth momentum. Such initiatives together with newer foreign players and modern imported vaccines coming in, would help the country addressing effectively a prime healthcare concern of the country in a holistic way.

It is about time to aggressively garner adequate resources to develop more modern vaccines in the country, promote and implement vaccine awareness campaigns in the nation’s endeavor for disease prevention before they strike hard and at times fatally.

That said, taking available real world facts into account, doesn’t Dr. Gerhard Buchwald’s and today’s anti-vaccination lobbyists’ postulation, ‘Vaccination – A Business based on fear’, appear to be emanating from a self created world of doom and gloom, defying public health interest for effective disease prevention?

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.