Tag Archives: Medicines

Improving Patient Access To Biosimilar Drugs: Two Key Barriers

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Novel biologic medicines have unlocked a new frontier offering more effective treatment for a host of chronic and life-threatening diseases, such as varieties of cancer, rheumatoid arthritis and diabetes, to name just a few. However, these drugs being hugely expensive, many patients do not have any access, or adequate access, to them. According to the Biosimilar Council of GPhA, only 50 percent of severe Rheumatoid Arthritis patients receive biologic medicines, even in the United States, Europe and Japan, leave aside India.

Realizing the gravity of this situation, a need to develop high quality, reasonably affordable and similar to original biologic brands, was felt about ten years ago. These were intended to be launched immediately after patent expiry of the original biologic. Such medicines are termed as biosimilar drugs. It is worth noting, even biosimilar drug development involves complex manufacturing processes and handling, while dealing with derivatives of highly sensitive living organisms.

The regulatory approval process of these drugs is also very stringent, which demands robust clinical data, demonstrating high similarity, both in effectiveness and safety profile, to original biologic brands, known as the reference product. The clinical data requirements for all new biosimilars include data on patients switching from the originator’s brand, and also between other biosimilars. Clinical evidences such as these, are expected to provide enough confidence to physicians for use of these products.

An article published in the PharmaTimes magazine in January 2016, reiterated that over the last couple of years, a wealth of supporting data has been published in medical journals and presented at global congresses, including real-world data of patients who have been switched to the new drug from the originator. This has led to a positive change in physician and patient attitudes towards biosimilars.

The good news is, besides many other regulated markets, as of May 2017, five biosimilar drugs have been approved even by the US-FDA, and several others are in the pipeline of its approval process.

That said, in this article I shall mainly focus on the two key barriers for improving patient access to biosimilar drugs, as I see it.

Two major barriers and their impact:

As I see it, there appear to be the following two key barriers for more affordable biosimilar drugs coming into the market, improving patients’ access to these important biologic medicines:

  • The first barrier involves fierce legal resistance from the original biologic manufacturers of the world, on various grounds, resisting entry of biosimilar varieties of their respective brands. This compels the biosimilar drug manufacturers incurring heavy expenditure on litigation, adding avoidable cost. A glimpse of this saga, we are ‘privy’ to witness even in India, while following Roche versus Biocon and Mylan case related to ‘Trastuzumab’. This barrier is one of the most basic types, that delays biosimilar drug entry depriving many new patients to have access to lower priced effective biologic for the treatment of serious diseases.
  • The other major barrier that exists today, involves ‘interchangeability’ of original biologic with biosimilar drugs. It simple means that in addition to being highly similar, a biosimilar drug manufacturer would require producing indisputable clinical evidence that it gives the same result for any given patient just as the original biologic. We shall discuss the reason behind this regulatory requirement later in this article. However, this is an expensive process, and the absence of it creates a barrier, making the physicians hesitant to switch all those existing patients who are on expensive original biologic drugs with less expensive available biosimilar alternatives.

The first or the initial barrier:

The first or the initial barrier predominantly involves patent related legal disputes, that can only be settled in a court of law and after incurring heavy expenditure towards litigation. Provided, of course, the dispute is not mutually resolved, or the law makers do not amend the law.

An interesting case in India:

Interestingly, in India, a similar dispute has knocked the doors of both the high court and the Competition Commission of India (CCI). From a common man’s perspective, it appears to me that the laws under which these two institutions will approach this specific issue are seemingly conflicting in nature. This is because, while the patent law encourages no market competition or a monopoly situation for a patented product, competition law encourages more market competition among all related products. Nonetheless, in this specific case CCI is reportedly investigating on the alleged ‘abuse of the regulatory process’, as it has opined ‘abuse of regulatory process can constitute an abuse of dominance under the (CCI) Act.’                                                                                            

The second barrier:

I am not going to discuss in this article the relevance of this barrier, in detail. Nevertheless, this one is also apparently equally tough to comply with. The very fact that none out of five biosimilar drugs approved in the United States, so far, has been considered ‘interchangeable’ by the US-FDA, vindicates the point.

That this specific regulatory demand is tough to comply with, is quite understandable from the requirements of the US-FDA in this regard, which goes as follows:

“To support a demonstration of interchangeability, the data and information submitted to FDA must show that a proposed interchangeable product is biosimilar to the reference product and that it can be expected to produce the same clinical results as the reference product in any given patient. Also, for products that will be administered more than once, the data and information must show that switching a patient back and forth between the reference product and the proposed interchangeable product presents no greater risk to the patient in terms of safety or diminished efficacy when compared to treating them with the reference product continuously.”

The reasoning of innovative biologic drug makers:

On this subject, the stand taken by different innovative drug makers is the same. To illustrate the point, let me quote just one of them. It basically sates, while biosimilar drugs are highly similar to the original medicine, the patient’s immune system may react differently due to slight differences between the two medicines when they are alternated or switched multiple times. This phenomenon, known as immunogenicity, is not a common occurrence, though. But there have been rare instances when very small differences between biologic medicines have caused immune system reactions that changed the way a medicine was metabolized, or reduced its effectiveness.

It further reiterates, the US-FDA requirements to establish ‘interchangeability’ between a biosimilar drug and the original one, or between biosimilars may seem like nuances, but are important because ‘interchangeability’ allows pharmacists to substitute biosimilars without consulting the doctor or patient first.

It may, therefore, indicate to many that innovative biologic drug manufacturers won’t want substitution of their expensive biologic with more affordable biosimilar drugs, on the ground of patient safety issues related to immunogenicity, though its instances are rather uncommon.

Some key players in biosimilar drug development:

Having deliberated on the core subject of this article, let me now very briefly name the major players in biosimilar drug development, both in the developed world, and also in India.

The first biosimilar drug was approved by the US-FDA in 2006, and the product was Omnitrope (somatropin) of Novartis (Sandoz). It was the same in the European Union (EU), as well. Subsequently, many other companies reportedly expressed interest in this field, across the globe, including Pfizer, Merck, Johnson and Johnson, Amgen, AbbVie, Hospira, AstraZeneca and Teva, among many others.

Similarly, in India, the major players in this field include, Biocon, Sun Pharma, Shantha Biotech, Dr. Reddy’s Lab, Zydus Cadila, Panacea Biotech and Reliance Life Sciences.

As featured on the Amgen website, given the complexity and cost of development and manufacturing, biosimilars are expected to be more affordable therapeutic options, but are not expected to generate the same level of cost savings as generics. This is because, a biosimilar will cost US$100 to US$200 million and take eight to ten years to develop. Whereas, a small molecule generic will cost US$1 to US$5 million and take three to five years to develop.

The market:

According to the 2017 report titled “Biosimilar Market: Global Industry Analysis, Trends, Market Size & Forecasts to 2023” of Research and Markets, the market size of the global biosimilar market was valued over US$ 2.5 billion during 2014, and it surpassed US$ 3.30 billion during 2016. The global biosimilar market is projected to surpass US$ 10.50 billion by 2023, growing with a CAGR between 25.0 percent and 26.0 percent from 2017 to 2023.

According to this report, gradually increasing awareness, doctors’ confidence and the lower drug cost are expected to boost the demand and drive the growth of the global biosimilar market during the forecast period. Segments related to diabetes medicine and oncology are expected to attain faster growth during the forecast period. Patent expiry of several blockbuster drugs is a major basic factor for growth of the global biosimilar market, as it may encourage the smaller manufacturers to consider producing such biologic drugs in those segments.

Conclusion:

Biosimilar drugs are expected to benefit especially many of those patients who can’t afford high cost biologic medicines offering better treatment outcomes than conventional drugs, in the longer term. These drugs are now being used to effectively manage and treat many chronic and life-threatening illnesses, such cardiac conditions, diabetes, rheumatoid arthritis, psoriasis, multiple sclerosis, Crohn’s disease, HIV/AIDS and cancer.

However, improving patient access to high quality biosimilar drugs, at an affordable price, with increasing competition, could be a challenge, as two key barriers are envisaged to attain this goal. Overcoming these meaningfully, I reckon, will involve choosing thoughtfully a middle path, creating a win-win situation, both for the patients, as well as the industry.

Adequate competition in the biologic drug market is essential – not only among high-priced original biologic brands and biosimilars, but also between biosimilar drugs. This is so important to increase patient access to biologic drugs, in general, across the world, including India.

The current situation demands a sense of urgency in searching for a middle path, which may be created either through a legal framework, or any other effective means as would deem fair and appropriate, without compromising with patient safety, at least, from where it is today.

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.

Prescriptions in Generic Names Be Made A Must in India?

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Would prescriptions in generic names be made a must in India?

Yes, that’s what Prime Minister Modi distinctly hinted at on April 17, 2017, during the inauguration function of a charitable hospital in Surat. To facilitate this process, his government may bring in a legal framework under which doctors will have to prescribe generic medicines, the PM assured without any ambiguity whatsoever.

“In our country doctors are less, hospitals are less and medicines are expensive. If one person falls ill in a middle-class family, then the financial health of the family gets wrecked. He cannot buy a house, cannot conduct the marriage of a daughter,” he reiterated.

“It is the government’s responsibility that everybody should get health services at a minimal price,” the Prime Minister further reinforced, as he referred to the National Health Policy 2017. His clear assurance on this much-debated issue is indeed music to many ears.

Some eyebrows have already been raised on this decision of the Prime Minister, which primarily include the pharma industry, and its traditional torch bearers. Understandably, a distinct echo of the same one can also be sensed in some English business dailies. Keeping aside these expected naysayers, in this article, after giving a brief backdrop on the subject, I shall argue for the relevance of this critical issue, in today’s perspective.

Anything wrong with generic drugs sans brand names?

At the very outset, let me submit, there aren’t enough credible data to claim so. On the contrary, there are enough reports vindicating that generic drugs without brand names are generally as good as their branded equivalents. For example, a 2017 study on this subject and also in the Indian context reported, ‘93 percent of generic and 87 percent branded drug users believed that their drugs were effective in controlling their ailments.’

Thus, in my view, all generic medicines without any brand names, approved by the drug regulatory authorities can’t be inferred as inferior to equivalent branded generics – formulated with the same molecules, in the same strength and in the same dosage form; and vice versa. Both these varieties have undergone similar efficacy, safety and quality checks, if either of these are not spurious. There isn’t enough evidence either that more of generic drugs sans brand names are spurious.

However, turning the point that generic drugs without brand name cost much less to patients than their branded generic equivalents on its head, an ongoing concerted effort of vested interests is systematically trying to malign the minds of many, projecting that those cheaper drugs are inferior in quality. Many medical practitioners are also not excluded from nurturing this possible spoon-fed and make-believe perception, including a section of the media. This reminds me of the famous quote of Joseph Goebbels – the German politician and Minister of Propaganda of Nazi Germany till 1945: “If you tell a lie big enough and keep repeating it, people will eventually come to believe it.”

The lower prices of generic drugs without brand names are primarily because their manufacturers don’t need to incur huge expenditure towards marketing and sales promotion, including contentious activities, such as, so called ‘Continuing Medical Education (CME)’ for the doctors in exotic locales, and several others of its ilk.

Thus, Prime Minister Modi’s concern, I reckon, is genuine to the core. If any doctor prescribes an expensive branded generic medicine, the concerned patient should have the legal option available to ask the retailer for its substitution with a less expensive generic or even any other branded generic equivalent, which is supposed to work just as well as the prescribed branded generic. For this drug prescriptions in INN is critical.

Provide Unique Identification Code to all drug manufacturers:

When in India, we can have a digitally coded unique identification number, issued by the Government for every individual resident, in the form of ‘Aadhaar’, why can’t each drug manufacturer be also provided with a similar digitally coded number for their easy traceability and also to decipher the trail of manufacturing and sales transactions. If it’s not possible, any other effective digital ‘track and trace’ mechanism for all drugs would help bringing the wrongdoers, including those manufacturing and selling spurious and substandard drugs to justice, sooner. In case a GST system can help ferret out these details, then nothing else in this regard may probably be necessary.

Past initiatives:

In India, ‘Out of Pocket (OoP) expenditure’ as a percentage of total health care expenses being around 70 percent, is one of the highest in the world. A study by the World Bank conducted in May 2001 titled, “India – Raising the Sights: Better Health Systems for India’s Poor” indicates that out-of-pocket medical costs alone may push 2.2 percent of the population below the poverty line in one year. This situation hasn’t improved much even today, as the Prime Minister said.

Although, ‘prescribe drugs by generic names’ initiative was reported in July 2015, in the current context, I shall focus only on the recent past. Just in the last year, several initiatives were taken by the current Government to help patients reduce the OoP expenses on medicines, which constitute over 60 percent of around 70 percent of the total treatment cost. Regrettably, none of these steps have been working effectively. I shall cite hereunder, just three examples:

  • On February 29, 2016, during the Union Budget presentation for the financial year 2016-17 before the Parliament, the Finance Minister announced the launch of ‘Pradhan Mantri Jan-Aushadhi Yojana (PMJAY)’ to open 3,000 Stores under PMJAY during 2016-17.
  • On August 04, 2016, it was widely reported that a new digital initiative of the National Pharmaceutical Pricing Authority (NPPA), named, “Search Medicine Price”, would be launched on August 29, 2016. According to NPPA, “Consumers can use the app before paying for a medicine to ensure that they get the right price.”
  • In October 2016, a circular of the Medical Council of India (MCI), clearly directed the medical practitioners that: “Every physician should prescribe drugs with generic names legibly and preferably in capital letters and he/she shall ensure that there is a rational prescription and use of drugs”

A critical hurdle to overcome:

Besides, stark inefficiency of the MCI to implement its own directive for generic prescriptions, there is a key legal hurdle too, as I see it.

For example, in the current situation, the only way the JAS can sell more of essential generic drugs for greater patient access, is by allowing the store pharmacists substituting high price branded generics with their exact generic equivalents available in the JAS. However, such substitution would be grossly illegal in India, because the section 65 (11) (c) in the Drugs and Cosmetics Rules, 1945 states as follows:

“At the time of dispensing there must be noted on the prescription above the signature of the prescriber the name and address of the seller and the date on which the prescription is dispensed. 20 [(11A) No person dispensing a prescription containing substances specified in 21 [Schedule H or X] may supply any other preparation, whether containing the same substances or not in lieu thereof.]”

A move that faltered:

To address this legal issue, the Ministry of Health reportedly had submitted a proposal to the Drug Technical Advisory Board (DTAB) to the Drug Controller General of India (DCGI), for consideration. In the proposal, the Health Ministry reportedly suggested an amendment of Rule 65 of the Drugs and Cosmetics Rules, 1945 to enable the retail chemists substituting a branded drug formulation with its cheaper equivalent, containing the same generic ingredient, in the same strength and the dosage form, with or without a brand name.

However, in the 71st meeting of the DTAB held on May 13, 2016, its members reportedly turned down that proposal of the ministry. DTAB apparently felt that given the structure of the Indian retail pharmaceutical market, the practical impact of this recommendation may be limited.

The focus should now move beyond affordability:

In my view, the Government focus now should move beyond just drug affordability, because affordability is a highly relative yardstick. What is affordable to an average middle class population may not be affordable to the rest of the population above the poverty line. Similarly, below the poverty line population may not be able to afford perhaps any cost towards medicines or health care, in general.

Moreover, affordability will have no meaning, if one does not have even easy access to medicines. Thus, in my view, there are five key factors, which could ensure smooth access to medicines to the common man, across the country; affordable price being one of these factors:

1. A robust healthcare infrastructure
2. Affordable health care costs, including, doctors’ fees, drugs and diagnostics
3. Rational selection and usage of drugs by all concerned
4. Availability of health care financing system like, health insurance
5. Efficient logistics and supply chain support throughout the country

In this scenario, just putting in place a legal framework for drug prescription in generic names, as the Prime Minister has articulated, may bring some temporary relief, but won’t be a long-term solution for public health care needs. There arises a crying need to put in place an appropriate Universal Health Care (UHC) model in India, soon, as detailed in the National Health Policy 2017.

Brand names aren’t going to disappear:

Prime Minister Modi’s assertion to bring in a legal framework under which doctors will have to prescribe generic medicines, probably will also legally empower the retailers for substitution of high priced branded generics with low priced generic or branded generic equivalents.

This promise of the Prime Minister, when fulfilled, will facilitate making a larger quantum of lower price and high quality generic drugs available to patients, improving overall access to essential medicines. Hopefully, similar substitution will be authorized not just for the JAS outlets, but by all retail drug stores, as well.

Brand names for generic drugs will continue to exist, but with much lesser relevance. the Drugs & Cosmetic Rules of India has already made it mandatory to mention the ‘generic names or INN’ of Drugs on all packing labels in a more conspicuous manner than the trade (brand) name, if any. Hence, if a doctor prescribes in generic names, it will be easier for all retail pharmacists and even the patients, to choose cheaper alternatives from different available price-bands.

Possible changes in the sales and marketing strategies:

If it really happens, the strategic marketing focus should shift – from primarily product-brand marketing and stakeholders’ engagement for the same, to intensive corporate-brand marketing with more intense stakeholder engagement strategies, for better top of mind recall as a patient friendly and caring corporation.

Similarly, the sales promotion strategy for branded generics would possibly shift from – primarily the doctors to also the top retailers. It won’t be unlikely to know that the major retailers are participating in pharma company sponsored ‘Continuing Pharmacy Education (CPE)’ in similar or even more exotic places than the doctor!

There are many more.

International examples:

There are enough international examples on what Prime Minister Modi has since proposed in his speech on this issue. All these are working quite well. To illustrate the point with a few examples, I shall underscore that prescribing in generic name or in other words “International Nonproprietary Name (INN)’ is permitted in two-thirds of OECD countries like the United States, and is mandatory in several other nations, such as, France, Spain, Portugal and Estonia. Similarly, pharmacists can legally substitute brand-name drugs with generic equivalents in most OECD countries, while such substitution has been mandatory in countries, such as, Denmark, Finland, Spain, Sweden, Italy. Further, in several different countries, pharmacists have also the obligation to inform patients about the availability of a cheaper alternative.

However, the naysayers would continue saying: ‘But India is different.’

Impact on the pharma industry:

The March 2017 report of ‘India Brand Equity Foundation (IBEF)’ states that Indian pharmaceutical sector accounts for about 2.4 per cent of the global pharmaceutical industry in value terms, 10 per cent in volume terms and is expected to expand at a Compound Annual Growth Rate (CAGR) of 15.92 per cent to US$ 55 billion by 2020 from US$ 20 billion in 2015. With 70 per cent market share (in terms of value), generic drugs constitute its largest segment. Over the Counter (OTC) medicines and patented drugs constitute the balance 21 percent and 9 percent, respectively. Branded generics constitute around 90 percent of the generic market. In my view, if the above decision of the Prime Minister is implemented the way I deliberated here in this article, we are likely to witness perceptible changes in the market dynamics and individual company’s performance outlook. A few of my top of mind examples are as follows:

  • No long-term overall adverse market impact is envisaged, as ‘the prices of 700 essential medicines have already been capped by the National Pharmaceutical Pricing Authority (NPPA). However, some short-term market adjustments are possible, because of several other factors.
  • There could be a significant impact on the (brand) market shares of various companies. Some will have greater exposure and some lesser, depending on their current sales and marketing models and business outlook.
  • Valuation of those companies, which had acquired mega branded generics, such as Piramal brands by Abbott Healthcare, or Ranbaxy brands by Sun pharma, may undergo considerable changes, unless timely, innovative and proactive measures are taken forthwith, as I had deliberated before in this blog.
  • Together with much awaited implementation of the mandatory Uniform Code of Pharmaceutical Marketing Practices (UCPMP) sooner than later, the sales and marketing expenditure of the branded generic players could come down significantly, improving the bottom-line.
  • Pharma marketing ballgame in this segment would undergo a metamorphosis, with brighter creative minds scoring higher, aided by the cutting-edge strategies, and digital marketing playing a much greater role than what it does today.
  • A significant reduction in the number of field forces is also possible, as the sales promotion focus gets sharper on the retailers and digitally enabled patient engagement initiatives.

The above examples are just illustrative. I hasten to add that at this stage it should not be considered as any more than an educates guess. We all need to wait, and watch how these promises get translated into reality, of course, without underestimating the quiet lobbying power of the powerful pharma industry. That said, the long-term macro picture of the Indian pharma industry continues to remain as bright, if appropriate and timely strategic interventions are put well in place, as I see it.

In conclusion:

It is an irony that despite being the 4th largest producer of pharmaceuticals, and catering to the needs of 20 percent of the global requirements for generic medicines, India is still unable to ensure access to many modern medicines to a large section of its population.

Despite this situation in India, Prime Minister Modi’s encouraging words on this issue have reportedly attracted the wrath of some section of the pharma industry, which, incidentally, he is aware of it, as evident from his speech.

Some have expressed serious concern that it would shift the decision of choosing a specific generic formulation of the same molecule for the patients from doctors to chemists. My counter question is, so what? The drug regulator of the country ensures, and has also repeatedly affirmed that there is no difference in efficacy, safety and quality profile between any approved branded generic and its generic equivalents. Moreover, by implementing an effective track and trace system for all drugs, such misgiving on spurious generic medicines, both with or without brand names, can be more effectively addressed, if not eliminated. Incidentally, reported incidences of USFDA import bans on drug quality parameters and breach of data integrity, include many large Indian branded generic manufacturers. Thus, can anyone really vouch for high drug quality even from the branded generics in India?

Further, the expensive branding exercise of essential medicines, just for commercial gain, and adversely impacting patients’ access to these drugs, has now been questioned without any ambiguity, none else than the Prime Minster of India. The generic drug manufacturers will need to quickly adapt to ‘low margin – high volume’ business models, leveraging economies of scale, and accepting the stark reality, as was expressed in an article published in Forbes – ‘the age of commodity medicines approaches’. Even otherwise, what’s wrong in the term commodity, either, especially when generic medicines have been officially and legally classified as essential commodities in India?

Overall, the clear signal from Prime Minister Modi that ‘prescriptions in generic names be made a must in India ‘, well supported by appropriate legal and regulatory mechanisms – is indeed a good beginning, while paving the way for a new era of Universal Health Care in India. God willing!

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.

Dry New Antibiotic Pipeline: Increasing Incidence Of Deadly Antibiotic Resistance

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On January 13, 2017, ‘The Telegraph’ quoting the ‘Centers for Disease Control and Prevention (CDC)’ reported that a woman in Nevada was killed by a superbug that proved resistant to every antibiotic available in the United States (US). She was in her 70s, and had recently returned to the US after an extended visit to India. The CDC found her blood containing ‘New Delhi metallo-beta-lactamase (NDM)’ – an enzyme that was first detected in India, makes bacteria resistant to many antibiotics. Nevertheless, this is just not a solitary example. It’s fast giving rise to a snowballing effect.

The magnitude of this problem has now assumed a global dimension. A May 2016 review of ‘Antimicrobial Resistance (AMR)’ estimates: ‘By 2050, 10 million lives a year and a cumulative 100 trillion USD of economic output is at risk due to the rise of drug – resistant infections, if we do not find proactive solutions now to slow down the rise of drug resistance. Even today, 700,000 people die of resistant infections every year.

According to the World Health Organization (W.H.O), AMR is the ability of a microorganism (like bacteria, viruses, and some parasites) to stop an antimicrobial (such as antibiotics, antivirals and antimalarials) from working against it. Consequently, standard treatments become ineffective, infections persist and may spread to others.

As antibiotics are a special category of antimicrobial drugs that underpin modern medicine as we know it: if they lose their effectiveness, key medical procedures (such as gut surgery, caesarean sections, joint replacements, and treatments that depress the immune system, such as chemotherapy for cancer) could become too dangerous to perform. Most of the direct and much of the indirect impact of AMR will fall on low and middle-income countries – the above review reiterates.

The first global report on AMR:

Not so long ago, In 2014, the first global report on AMR, published by the W.H.O reiterated that this scary scenario is no longer a prediction for the future. It is happening right now, and is not a country specific issue, but a global concern that is jeopardizing global health security.

“Hundreds of thousands of antibiotic-resistant infections and tens of thousands of related deaths go uncounted each year. But even if they were closely tracked, the lack of new drugs to meet the rising tide of resistance means the toll will only mount,” Reported Reuters in another article titled “Stronger superbugs and no new drugs to fight them”, on December 15, 2016.

Thus, there isn’t even an iota of doubt now that in the battle against bacterial infections, drug-resistant superbugs are fast emerging as one of the deadliest issues in the health care space, across the world, including India.

Interestingly, no one knows who will fall victim of this scary scenario and when. Neither can one eliminate this risk completely, even in the developed world. Only painstaking medical research, sans sole focus on creamy bottom-line, and with the application of cutting edge technology, can help overcome this fast-growing health menace to mankind.

“It’s all about the bottom line”:

Quoting a biochemistry professor at Indiana University, Bloomington, the above article reported, in 1980, 36 large American and European pharmaceutical companies were involved in research into new antibiotics. This number currently reduces to just four: Novartis AG, Merck & Co, GlaxoSmithKline Plc and Sanofi SA.

The May 2016 Data Table of ‘The Pew Charitable Trust’ indicates, as of March 2016, an estimated 37 new antibiotics with the potential to treat serious bacterial infections are in clinical development for the U.S. market. It is worth noting, the success rate of clinical drug development is low. Historical data show that, generally, only 1 in 5 infectious disease products that enter human testing (phase 1 clinical trial) will be approved for patients.

Moreover, most of these new antibiotics are based on existing drugs. Although, this approach is cheaper and easier to develop a new antibiotic, as compared to new classes of drugs, bacteria may rather quickly succeed in developing resistance to them.

It keeps happening, primarily because the return on investment for antibiotics, which are typically prescribed for a short period of 7 to 14 days, is much lower than the new drugs used for virtually a life treatment of chronic conditions, such as hypertension, hyperlipidemia, or diabetes.

Consequently, most of the constituents of Big Pharma have virtually fled the antibiotic business, as the new drug development ball game today “is all about the bottom line”, the article quoted.

Antibiotic resistance in India:

As W.H.O articulates in its above report, AMR poses a greater challenge in the developing nations, such as India, where the burden of infectious disease is high and health care spending is too low. The problem assumes a more critical dimension in India, that records among the highest bacterial disease burden in the world, with antibiotics playing a critical role in limiting morbidity and mortality.

The 2015 multi-country survey of the W.H.O unveiled a widespread public misunderstanding about antibiotic usage and resistance in India. Some of the major highlights are as follows:

  • Three quarters (75 percent) of respondents think, incorrectly, that colds and flu can be treated with antibiotics, and only 58 percent know that they should stop taking antibiotics only when they finish the course as directed.
  • More than three quarters (76 percent) of respondents report having taken antibiotics within the past 6 months; 90 percent say they were prescribed or provided by a doctor or nurse.
  • While 75 percent agree that antibiotic resistance is one of the biggest problems in the world, 72 percent of respondents believe experts will solve the problem before it becomes too serious.

Nowhere AMR is as stark as in India:

Another article published in the ‘PLOS Medicine’ on March 2, 2016, is quite in tune with the above W.H.O report. It also reiterates that antibiotic resistance is a global public health threat, but nowhere is it as stark as in India. The crude infectious disease mortality rate in India today is 416.75 per 100,000 persons and is twice the rate prevailing in the United States when antibiotics were introduced (roughly 200 per 100,000 persons).

It also captures the following burning issues in this area:

  • Antibiotic use is a major driver of resistance. In 2010, India was the world’s largest consumer for human health.
  • Access to antibiotics is rising, which portends well for the large proportion of India’s population that thus far had poor access to these life-saving drugs.
  • The convergence of factors such as poor public health infrastructure, rising incomes, a high burden of disease, and cheap, unregulated sales of antibiotics have created ideal conditions for a rapid rise in resistant infections in India.
  • Over-the-counter, nonprescription sales of carbapenems in India are among the highest in the world, and contribute to growing carbapenem resistance among gram-negative organisms.
  • Improving regulations of drug production and sales, better managing physician compensation, and encouraging behavior change among doctors and patients, are of immediate priority.

More serious than local perception:

The new report released by the Center for Disease Dynamics, Economics & Policy (CDDEP) in September 2015, has flagged an alarming trend of bacterial resistance to last-resort antibiotics that can lead to life-threatening infections across the world.

While the developed countries still use far more antibiotics per capita, high AMR rates in the developing nations, such as India, Kenya and Vietnam send a strong warning signal to the world.

For example, in India, 57 per cent of the infections caused by Klebsiella pneumoniae, a deadly superbug found in hospitals, were found to be resistant to one type of last-resort drug in 2014 – an increase from 29 per cent in 2008. It is worth noting that these drugs, known as carbapenems, are still effective against Klebsiellainfections in 90 per cent of cases in the U.S, and over 95 per cent in Europe.

A new class of antibiotics discovered with iChip technology:

The good news is, as reported in the June 18, 2015 issue of the Journal of Antimicrobial Chemotherapy, scientists could produce a new class of antibiotic, named Teixobactin, from a hitherto undescribed soil microorganism (provisionally named Eleftheria terrae). It was isolated with a new tool – the iChip, that allowed the environmental bacterium to grow and for the antibiotic it produced to be isolated and subsequently identified.

Working together with collaborators at the University of Central Florida and the Hong Kong Polytechnic University, a research team of Hong Kong University (HKU) has successfully synthesized this ‘game-changing’ antibiotic that can kill a wide range of bacteria seemingly without developing resistance.

Teixobactin has activity against Gram-positive (but not Gram-negative) organisms and mycobacteria and a novel mode of action inhibiting peptidoglycan biosynthesis. Teixobactin, a still-experimental drug that may herald a new era of antibiotic discovery. However, there are no guarantees that it will be able to reach the market post regulatory acid tests, though the use of the iChip will hopefully result in the discovery of further potential new antibiotics.

Country specific frugal innovation is also necessary:

Alongside, various academic initiatives in search of new, path breaking antibiotics, frugal innovation in various countries to address the local issues in this area, could also play a very significant role to contain this menace.

In this context, I shall quote from the example of a small country, such as Singapore, which is contributing significantly to medical research and development in this area.

An article published in a new daily of Singapore – ‘Today’, on December 29, 2016, highlighted that drug-resistant superbugs have become one of the most pressing problems in the healthcare space of even one of the cleanest cities of the world.

Driven by the need to find a more suitable alternative, researchers at the Institute of Bioengineering and Nanotechnology (IBN) of Singapore, have developed a new material that can kill E coli bacteria within seconds. E coli is a type of bacteria found in the intestines of humans and animals, and some strains can cause severe diarrhea, abdominal pain and fever.

The article, reported that the novel synthetic material, known as imidazolium oligomers, can kill 99.7 percent of the bacteria within 30 seconds, more rapidly than any existing antimicrobial product on the market, such as hand wash or surface sprays. Existing products take minutes to hours to kill the bacteria. It was also tested and found to be effective against other common strains of antibiotic-resistant bacteria and fungi, such as Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans. It has been licensed by a multinational firm for commercial development in October.

If Singapore can take its own initiatives in this crucial health care space, why can’t India?

Conclusion:

Strict enforcement of the existing regulations of the medical sector, particularly in the prescription of medicines, is of crucial importance. Lack of knowledge among medical practitioners, as well as public on rational use of antibiotics, aggravates the issue.

Notwithstanding fast drying-up of global research pipeline for new antibiotics due to several reasons, India needs to address this fast escalating life-threatening problem through various other practical means. One such could be, putting in place a comprehensive National Action Plan for AMR, quite in line with the Global one, which the W.H.O has already recommended.

This critical issue gets further compounded, as a very significant part of an out-of-pocket expenditure on health care is on medicines, and longer treatment with ineffective drugs and/or second line expensive antibiotics, are pushing the treatment costs higher. On the other side, higher priced drug regimens are less likely to be adhered to, which again contributes to the AMR.

“This situation needs to be interrupted and reversed, not only for safeguarding people’s health, but also for providing protection against health care costs and people going into poverty,” advises the premier World Health body.

Finally, it is important for all to bear in mind, no one knows who will fall victim of this scary scenario and when. So, a decisive action from all concerned can’t wait any longer.

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.

Awaiting The Two To Tango: Pharma Innovation And Public Health Interest

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“The rewards for the breakthrough drug discovery must be substantial, but if prices are the only mechanism through which returns on research flow, affordability will be compromised,” articulated an article titled, ‘Pharmaceutical Policy Reform – Balancing Affordability with Incentives for Innovation’, published in The New England Journal of Medicine (NEJM) on February 25, 2016.

The article arrived at this conclusion, on the backdrop of the high prices of prescription drugs becoming an issue of paramount concern, not just in the United States, but across the world. This concern is so acute that it found its way into policy proposals from both the prime candidates, in the American Presidential election held on November 8, 2016.

Through last several decades, healthcare sector in general and particularly the pharmaceutical industry, witnessed many innovations that cure and effectively manage ailments to improve the general quality of life. It enormously impacted the lives of many in the developed countries, and a few others which offer high quality Universal Health Care in a comprehensive format, for all.

A trickle-down impact:

Nevertheless, even no more than its just a trickle-down impact, helped increase overall life expectancy of the population in many developing and poor countries, mostly driven by the expanding number of cheaper generic drugs, fueled by more treatment and disease management options.

The paper titled, ‘World Population Prospects – The 2015 Revision’ of the Department of Economic and Social Affairs, Population Division of the United Nations’ reported that the life expectancy at birth rose by 3 years between 2000-2005 and 2010-2015, that is from 67 to 70 years. All major areas shared in the life expectancy gains over this period, but the greatest increases were in Africa, where life expectancy rose by 6 years in the 2000s, after rising by only 2 years in the previous decade.

Similarly, the global life expectancy at birth is projected to rise from 70 years in 2010-2015 to 77 years in 2045- 2050 and to 83 years in 2095-2100. Africa is projected to gain about 19 years of life expectancy by the end of the century, reaching 70 years in 2045-2050 and 78 years in 2095-2100. Such increases are contingent on further reductions in the spread of HIV, and combating successfully other infectious as well as non-communicable diseases.

The availability of cheaper generics gave some respite:

Out of a total population of 7.3 billion, as the above report says, the World Bank estimated that in 2013, 767 million people still lived on less than US$ 1.90 a day. Unfortunately, despite the greater availability of a large variety of cheaper generic drugs, the basic health care remains elusive to hundreds of millions of people in the world.

What causes more concern is the fact that 6 percent of people in low and middle-income countries are tipped into or pushed further into extreme poverty because of health spending, as the June 12, 2015 report of the World Health Organization (W.H.O) and the World Bank highlights. W.H.O has estimated that over a billion population of the world still suffer from neglected tropical diseases.

How many people benefitted from pricey patented drugs?

Nevertheless, despite so much innovation in the pharma industry, access to these new drugs remains elusive to a large section of even some the most developed nations, such as the United States, as they can’t afford these high-priced drugs. The overall situation, in this regard, is going from bad to worse. For example, the March 16, 2015 study published in the Mayo Clinic Proceedings reveals that the average annual cost of cancer drugs increased from roughly US$ 10,000 prior to 2000 to an astounding over US$  100,000 by 2012.

Further, an August 31, 2015 article published in the ‘Health Affairs’ also gave examples of Biogen Idec’s multiple sclerosis drug, Tecfidera, which costs US$ 54,900 per patient per year; hepatitis C cures from Gilead Sciences, with a sticker price of $84,000 per patient; and Orkambi, a cystic fibrosis drug from Vertex Pharmaceuticals approved this month, priced at a whopping US$ 259,000 per year. A Kaiser Health Tracking Poll last July 2015 found that 73 percent of Americans find the cost of drugs to be unreasonable, and most blamed drug manufacturers for setting prices too high, the article stated.

The health care scenario in India is no better:

A study conducted by the ‘National Sample Survey Organization (NSSO)’ from January to June 2014, which was the 71st round of the ‘National Sample Survey’, and published in the ‘Health in India’ report, narrates a very gloomy picture for India, especially for a clear majority of those who incur ‘out of pocket’ expenses on medicines. The report states, out of all health expenditure, 72 percent in rural and 68 percent in urban areas was for buying medicines for non-hospitalized treatment.

Thus, many patients cannot afford health services, even when these are needed the most. As many as 68 percent of patients in urban India and 57 percent in rural areas attributed “financial constraints” as the main reason to take treatment without any medical advice, the report adds.

In this situation, the challenges that the Governments and the civil society are facing in many developing, and to some extent even in some developed countries, though for different reasons, are multi-factorial. It has been well established that the humongous global health care challenges are mostly of economic origin.

Pharma innovation benefitted the developed countries more:

A study  titled, ‘Pharmaceutical innovation and the burden of disease in developing and developed countries’ of Columbia University and National Bureau of Economic Research, to ascertain the relationship across diseases between pharmaceutical innovation and the burden of disease both in the developed and developing countries, reported that pharmaceutical innovation is positively related to the burden of disease in the developed countries but not so in the developing countries.

Making the two to tango:

These facts prompt the need to make the pharma innovation and public health interest to tango. Several suggestions have been made and initiatives taken in this direction. Some of which are as follows:

  • Responding to this need, in 2006 W.H.O created the ‘Intergovernmental Working Group on Public Health, Innovation and Intellectual Property (IGWG)’. The primary focus of IGWG is on promoting sustainable, needs-driven pharmaceutical R&D for the diseases that disproportionately affect developing countries. One positive effect of this global debate is that some global pharmaceutical companies have initiated their R&D activities for neglected tropical diseases, such as, Malaria and Tuberculosis. Many charitable organizations like, Bill & Melinda Gates Foundation and Clinton Foundation, are allocating significant funds for this purpose.
  • A paper  titled, “Optional reward for new drugs for developing countries” published by the Department of Economics, University of Calgary, Institute of Health Economics, proposed an optional reward fund for pharmaceutical innovation aimed at the developing world to the pharmaceutical companies, which would develop new drugs while ensuring their adequate access to the poor. The paper suggests that innovations with very high market value will use the existing patent system, as usual. However, the medicines with high therapeutic value but low market potential would be encouraged to opt for the optional reward system. It was proposed that the optional reward fund should be created by the governments of the developed countries and charitable institutions to ensure a novel way for access to innovative medicines by the poor.
  • ‘Open Innovation’ or the ‘Open Source Drug Discovery (OSDD)’ is another model of discovering a New Chemical Entity (NCE) or a New Molecular Entity (NME). Imbibing ‘Open Innovation’ for commercial results in pharmaceuticals, just has what has happened to android smartphones, would encourage drug discovery initiatives, especially for the dreaded disease like cancer, to make these drugs affordable for a very large section of people across the globe. In this model, all data generated related to the discovery research will be available in the open for collaborative inputs. In ‘Open Innovation’, the key component is the supportive pathway of its information network, which is driven by three key parameters of open development, open access and open source. This concept was successfully used in the ‘Human Genome Project’ where many scientists, and microbiologists participated from across the world to sequence and understand the human genes. Currently, pharmaceutical R&D is a well-protected in-house initiative of innovator global companies to maximize commercial benefits. For this reason, only a limited number of scientists working for the respective innovator companies will have access to these projects. In India, the Council of Scientific and Industrial Research (CSIR) is the champion of the OSDD movement, locally. CSIR believes that for a developing country like India, OSDD will help the common man to meet his or her unmet medical needs in the areas of mainly neglected tropical diseases.

Conclusion:

Thus, the ongoing heated debate on Innovation, Intellectual Property Rights (IPR) and Public Health Interest is gathering steam all over the globe.

Argumentative Indians are also participating in this raging debate. I reckon rightly so, as India is not only the largest democracy of the world contributing 16.7 percent of the global population, it is also afflicted with 21 percent of the global burden of disease. Considering this, the reason for similar heated debate in our country is indeed no-brainer to anyone.

Many would possibly not disagree, both encouraging innovation and safeguarding the public health interest are equally important to any society, be it in the developed nations or developing countries. Nevertheless, some constituents of ‘Big Pharma’ and their trade association still highlight that ensuring access to high price innovative drugs is the responsibility of the respective Governments. Any other regulatory mechanism to bring down such prices will be construed as a barrier to encouraging, protecting and rewarding innovation.

Be that as it may, most other stakeholders, across the world, especially the patients, are awaiting these two goals to tango. From that point, I reckon, giving a quick shape to commercially well-tested initiatives, such as, ‘Open Innovation’ model could well be an important step to ensure access to innovative new medicines for a larger number of patients of the world, meeting their unmet medical needs with greater care.

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.

Drug Price Control in India: When A Local Media Goes Against, A Global CEO Doesn’t

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‘Variety is the spice of life’, as the good old saying goes. The week, just gone by, was indeed packed with a wide variety of surprises, well encompassing various important areas, some of which are as follows:

  • Effective November 08, 2016 midnight, Indian currency notes of ₹500 and ₹1000 denominations ceased to remain legal tenders. This demonetization followed extensive media coverage, both national and international, on unprecedented administrative and public chaos around this otherwise bold and good intent.
  • The same day witnessed much unexpected triumph of Trump as the 45th President-Elect and the Commander-in-Chief of the United States of America. It is entirely a different matter though, that post-election, millions of Americans reportedly took to streets across the United states to vent their fury over the billionaire’s election victory.
  • On November 07, 2016, a well-known Indian business daily, ‘The Economic Times’, in its editorial, apparently expressed its solidarity with the pharma industry, in general, to do away with drug price control in India. The key reason for this advocacy, as I could sense, is to encourage the drug players to grow by making more profits. I respect this view of the editor will all humility. However, the point that I am unable to ferret out though, what happens to especially the poor patients in such an eventuality. With hands-on experience in the pharma industry over several decades, it appears to me that the editorial suggestions, as well, grossly lack in requisite depth of understanding of the core issue.
  • On November 09, 2016, quite opposite to what the above editorial of ‘The Economic Times’, the current global CEO of GlaxoSmithKline – Sir Andrew Witty, in an interview, strongly argued in favor of the necessity of drug price control in India, that improves access to medicines for a vast majority of the country’s population. To substantiate this point Sir Andrew said in another interview on the same day, “We’ve seen demand of products jump 45 percent after the price is cut by 20 percent. The problem arises when we don’t have supply to cater to the demand, leaving patients frustrated. A bit more predictability (on the part of government) will help.”
  • As if this diametrically opposite views are not enough, on November 10, 2016, the well-known civil society organization – ‘All India Drug Action Network (AIDAN)’, reportedly sent legal notices to the CEO of Niti Aayog CEO and secretaries to the Health Ministry, Department of Pharmaceuticals and Department of Industrial Policy and Promotion over their talks to cut the powers of the National Pharmaceutical Pricing Authority (NPPA). AIDAN has termed this Government move “anti-national” and “anti-people”, further adding that it affects an ongoing case at the Supreme Court over various aspects of the drug price control.

In this article, I shall restrict myself to the pharma related issue of the past week, especially on the interesting advocacy through editorial, against the drug price control in India. Simultaneously, I shall also underscore its relevance in the country, primarily to improve access to medicines for millions of Indians, as articulated by one of the leading voices from the global pharma industry.

Is the yardstick of judging pharma industry different?

This particular question floats in my mind because of several reasons. One such is, almost regularly sponsoring fully paid trips for doctors, especially in an exotic foreign land, by many pharma companies. Such practices of the drug companies are generally inferred, more often than not spearheaded by a large section of the media, as dubious means of the organization to entice, or influence prescribing decisions of physicians in favor of their respective high priced brands, ignoring the health and economic interest of patients.

In similar context, just after having a quick glance over a not so important article, written on various operations at the headquarter of a global drug company situated in a beautiful locale of the world, when one focuses the fine print at the end as a disclaimer, which reads: “This reporter was in (name of the country) on an invitation by (name of the global company)…, do the readers arrive at the same conclusion on ‘gratification’, as above, and its consequent possible outcome on pharma related writings of these reporters?

Can the concerned members of the ‘Fourth Estate’ possibly claim desired intellectual independence in their analysis of a situation involving such companies or their trade associations, even after the above disclaimer? Or for that matter, related publications too, which allow acceptance of such avoidable ‘gratis’ by its reporters? Shouldn’t such incidences, whenever these happen, irrespective of who availed these, be perceived in the same light?

In the current scenario, this issue is something for us to seriously ponder. This is mainly because, for following similar practices, why should there be two different yardsticks to gauge the quality of professional independence of two different otherwise highly respectable professions?

This reminds me of a great pharma reporter, writing for an internationally acclaimed business daily, mainly on the drug industry and healthcare. I met him in India a few years back on his invitation. Although, I shall not take either his or his paper’s name. This is to show respect to our free and frank interaction. He flew down to India with his employer paying all the pharma reporting work related expenses. He met with all those in the Indian drug industry that he wanted to, primarily to capture the nuances of the thought pattern of large and small Indian pharma players. I was so impressed with his intellect, and independent professional outlook, like all those who met him during his that specific visit to India. Even now, I can feel his independent perspective, as I read his articles. It would be great to experience similar feelings, while reading pharma related articles and editorials, in various publications of my own country. At the same time, I shall be delighted to be proved wrong regarding any such possibilities in this area.

That said, I shall now move on to the relevance of drug price control in India.

Any relevance of drug price control in a ‘Free Market Economy’?

No doubt, this is a very pertinent question. Equally pertinent answers are also available in a 2014 paper titled, “Competition Issues in the Indian Pharmaceuticals Sector” of Delhi School Economics (DSE). The paper deals with issues related to failure of ‘Free Market Economy’, despite intense competition, especially for branded generic drugs in India.

Quoting a practicing surgeon, the DSE article states: “Sometimes it could be just plain ignorance about the availability of a cheaper alternative that makes doctors continue to prescribe costlier brands. But one cannot ignore the role of what is euphemistically called marketing “incentive”, which basically mean the inappropriate influence pharmaceutical companies exert on doctors. This runs deep. Hospitals choose to stock only certain drugs in their in-house pharmacies and insist that hospitalized patients buy drugs only from the hospital pharmacy. Drug companies sell drugs to hospitals at a price much lower than what the patient is charged, further incentivizing the hospital to stock their products. The cheaper brands often get left out in this game.”

Further, in an ideal free-market economic model, for all approved branded generics with exactly the same formulation, having the same claimable efficacy, safety and quality standards, though marketed by different pharma companies, competitive forces should prompt some parity in their pricing.

Any generic brand with exactly the same formulation as others and offering the same therapeutic value, but costing significantly more, should ideally attract a lesser number of customers, if and where purchase decisions are taken by the consumers directly. However, for prescription medicines it’s not so. The well proven process of consumers exercising their own choice to select a brand, mostly influenced by advertising or word of mouth, does not happen at all.

The Government attributes ‘Market Failure’ for pharmaceuticals:

In its price notification dated July 10, 2014, the NPPA has categorically stated the following:

  • There exist huge inter-brand price differences in branded-generics, which is indicative of a severe market failure, as different brands of the same drug formulation, which are identical to each other in terms of active ingredient(s), strength, dosage, route of administration, quality, product characteristics, and intended use, vary disproportionately in terms of price.
  • It is observed that, the different brands of the drug formulation may sometimes differ in terms of binders, fillers, dyes, preservatives, coating agents, and dissolution agents, but these differences are not significant in terms of therapeutic value.
  • In India the market failure for pharmaceuticals can be attributed to several factors, but the main reason is that the demand for medicines is largely prescription driven and the patient has very little choice in this regard.
  • Market failure alone may not constitute sufficient grounds for government intervention, but when such failure is considered in the context of the essential role of pharmaceuticals play in the area of public health, which is a social right, such intervention becomes necessary, especially when exploitative pricing makes medicines generally unaffordable and beyond the reach of most and also puts the huge financial burden in terms of out-of-pocket expenditure on health care.

Civil Society echoed the same sentiment:

In this context, it is important to note that seven large Civil Society Organizations in a letter of August 20, 2014 addressed to Mr. Ananth Kumar, the present Minister of Chemicals and Fertilizers with a copy to Prime Minister Modi, articulated similar views, as follows:

“Limiting all price regulation only to a list of 348 medicines and specified dosages and strengths in the DPCO 2013 goes against the policy objective of making medicines affordable to the public. The National List of Essential Medicines, a list of 348 rational and cost-effective medicines, is not the basis for production, promotion and prescription in India. In reality the most frequently prescribed and consumed medicines are not listed in the NLEM.”

Last week, AIDAN has also indicated that the reported Government move to curtail the power vested on the NPPA for drug price, affects an ongoing case at the Supreme Court over various aspects of the drug price control.

Are medicines cheapest in India…really?

It is often highlighted that medicines cost much cheaper, if not the cheapest, in India. This is too simplistic a view on this subject. It compares the prevailing Indian drug prices in Rupee, against the prices of similar drugs in other countries, just by simple conversion of the foreign currencies, such as, US$ and Euro into Rupee. To make the comparison realistic and credible, Indian drug prices should be compared against the same in other countries, only after applying the following two critical parameters:

  • Purchasing Power Parity and Per Capita Income
  • Quantum of per capita ‘Out of Pocket Expenditure’ on drugs

The Department of Pharmaceuticals (DoP) with the help of academia and other experts had earlier deliberated on this issue in one of its reports on patented drug pricing. The report established that post application of the above two parameters, medicines in India are virtually as expensive as in the developed world, causing great inconvenience to the majority of patients in the country.

Hence, common patients expectedly look for some kind of critical intervention by the Government, at least, on the prices of essential drugs in India.

‘Cannot do away with Drug Price Control’ – said the New Government:

On August 24, 2015 in an interview with a national business daily, V K Subburaj, the Secretary of the Department of Pharmaceuticals commented, “Price control on drugs a shot in the arm for health care” and “the Government cannot do away with it.”

He argued, “A large section of the population is poor. Suddenly, your system is disturbed if you have to spend more on drugs. Drugs are an important component of health care expenditure.”

Accepting the fact that in India, big and small companies investing in research would need more money, Mr. Subburaj said, “In India, we can’t afford to remove controls as the burden of disease is high.”

All stakeholders expect that there is some predictability in what the Government says. Can the stand taken by the policymakers change in just a year’s time, probably wilting under industry pressure?

Conclusion:

The drug price control in India is in vogue since 1970, uninterruptedly. The retail audit data continue to indicate that the growth of the Indian pharma industry, over the last four and half decade long price control regime, has been nothing less than spectacular. This would consequently mean, increasing consumption of drugs, leading to improved access to medicines in India, including its hinterland, though may still not be good enough. Sir Andrew Witty of GSK also articulated the same view, just the last week. It’s a different story altogether that some of the industry sponsored expensive market surveys attempt to wish it away.

Coincidentally, at the commencement of drug price control regime in India in 1970, almost all the players in the ‘Top 10’ pharma league table of the country, were multi-national drug companies. Today the situation has just reversed. Out of ‘Top 10’, about seven are home grown drug companies. Many of these companies were born post 1970. Without frequent M&As by the pharma MNCs, this number could have been probably higher today.

By the way, what’s the span of drug price control in India really – just about 18 percent of the total domestic pharma market now? Around 80 percent of the local drug market continues to remain in the ‘free-pricing’ and ‘high-profit’ zone.

When it comes to profitability, it is worth mentioning, the promoter of the so called ‘low margin’ generic pharma company – Sun Pharma, is the second-richest person in India. He created his initial wealth from India, despite ostensible ‘growth stunting’ price control.

Keeping this in perspective, is it not baffling to fathom the reason behind a local business publication’s apparently endorsing the advocacy initiatives of pharma industry against drug price control through an editorial, when a well-regarded global pharma CEO expresses a strong favorable view in this regard?

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.

Counterfeit Drugs In India: A Malady Much Deeper

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Many debates and discussions continue being lined up in India almost regularly, generally by the pharma trade associations, besides a few others, on the issue of counterfeit drugs. A good number of these events are sponsored by the global and local anti-counterfeit product manufacturers and the related service providers, presumably to get a captive pharma audience. By and large, these gatherings are well publicized, and very rightly so, to focus for a while on this growing menace in the country.

One of the key objectives of such proceedings, I reckon, besides recommending the immediate action steps for the government in saddle, is to encourage the manufacturers of high quality drugs to protect their brands from the onslaught of counterfeiters through anti-counterfeit measures. Several of these involve a state of the art non-cloning technology. The core message that gets filtered-through, in most of these occasions is, if the suggested steps are followed by the drug companies with the related products and services, these won’t just help protect the patients’ health interest, but also provide a boost to the top and bottom lines in the pharma business, significantly.

There are no qualms about this initiative, not at all. Nonetheless, can this be considered a holistic approach to tackle the menace of counterfeit drugs, especially by the pharma players in India, and considering various other different ways the menace keep striking the patients, so surreptitiously?

Thus, in this article, my point of focus will be on a critical question, which is not asked with the same vigor always in many of the above events: Hasn’t the malady of counterfeit drugs in India spread much wider, and taken its root considerably deeper?

Counterfeit drugs and what it includes?

According to the World Health Organization (W.H.O), there is currently no universally agreed definition among its member states in what is widely known as ‘Counterfeit medicines’. Nevertheless, W.H.O does indicate that the term ‘counterfeit’ is widely used to include falsified, unlicensed, falsely packaged, stolen and substandard medical products. Jurisdictions across the world define counterfeit medicines in many different ways.

It’s worth noting here, according to W.H.O, substandard medical products also belong to this category. In 2009, W.H.O defined ‘substandard’ drugs as “genuine medicines produced by the manufacturers authorized by the NMRA (national medicines regulatory authority) which do not meet quality specifications set for them by national standards”.

Hence, notwithstanding whatever will be accepted as the general consensus of the W.H.O members on the definition of counterfeit drugs, from the patients’ perspective, any drug failing to meet with the claimed efficacy, safety and quality standards, should come under the same ‘category definition’, including substandard drugs.

Controversy over the term ‘Counterfeit’:

Many W.H.O member countries believe that the term counterfeit is closely associated and legally defined within the Intellectual Property (IP) legislation, and concentrates on trademark protection. Consequently, usage of this terminology has been perceived to have reduced the focus from what is first and foremost a public health issue. Thus, it has become quite important for W.H.O to separate the different categories of what is widely used as ‘counterfeit drug’, for the purpose of analysis and identifying strategies, to effectively address the issue of the public health menace that such activities give rise to.

Types of counterfeit drugs:

A Review Article titled “Anti-counterfeit Packaging in Pharma Industry” dated February 17, 2011, published in the “International Journal of Pharmacy and Pharmaceutical Sciences”, divided the types of counterfeit mechanisms into five categories, in which drugs are manufactured or distributed without proper regulatory clearance, and do not meet the determined standards of safety, quality, and efficacy:

  • No active ingredient (43 percent)
  • Low levels of active ingredient (21 percent)
  • Poor quality drugs (24 percent)
  • Wrong ingredients (2 percent)
  • Wrong packaging or source (7 percent)

This particular article will dwell mainly on a very important segment in this category – the substandard or poor quality drugs.

The magnitude of the problem:

On May 17, 2016, a Research Article titled, “Public Awareness and Identification of Counterfeit Drugs in Tanzania: A View on Antimalarial Drugs”, published in ‘Advances in Public Health’ – a peer-reviewed, open access journal that publishes original research articles, highlighted something that should cause a great concern not just for the Indian drug regulators, but also the Indian pharma manufacturers, in general.

The research paper, besides other points, underscored the following:

“Currently, it is estimated that 10–15 percent of the global drugs supplied are counterfeit. The prevalence is higher in developing countries in Africa and in parts of Asia and Latin America where up to 30–60 percent of drugs on the market are counterfeit. India is a major supplier of poor quality drugs whereby 35–75 percent of fake/counterfeit drugs globally originate from India.”

Another report of ‘Pharmexcil’ dated October 04, 2010 also states: “According to the Organization for Economic Cooperation and Development (OECD), 75 percent of fake drugs supplied world over have origins in India, followed by 7 percent from Egypt and 6 percent from China. India is also a leading source of high quality generic and patent drugs in the legitimate commerce worldwide. Since drugs made in India are sold around the world, the country’s substandard drug trade represents a grave public health threat that extends far beyond the subcontinent.”

Substandard drugs: a potential crisis in public health:

An article with the above title, published in the British Journal of Clinical Pharmacology on November 29, 2013 cautioned on the potential crisis in public health with substandard drugs, as follows:

“Poor-quality medicines present a serious public health problem, particularly in emerging economies and developing countries, and may have a significant impact on the national clinical and economic burden. Attention has largely focused on the increasing availability of deliberately falsified drugs, but substandard medicines are also reaching patients because of poor manufacturing and quality-control practices in the production of genuine drugs (either branded or generic). Substandard medicines are widespread and represent a threat to health because they can inadvertently lead to health care failures, such as antibiotic resistance and the spread of disease within a community, as well as death or additional illness in individuals.”

Hence, the potential of health crisis with various substandard drugs is quite similar to other types of counterfeit drugs.

Substandard drugs and small pharma players:

As I said before, the malady of counterfeit, fake and substandard drugs are spreading much wider and deeper in India. What’s happening around today in this area prompts us to believe, it may no longer be proper to keep all the large pharma manufacturers away from the ambit of discussion on substandard or counterfeit drugs. This apprehension is raising its head, as it is generally believed that only small, unknown, or fly-by-night type of drug manufacturers, are responsible for substandard, fake or counterfeit drugs. Whereas, the reality seems to be different. There are now ample reasons to believe that even some large drug manufacturers, both local and global, who have been caught by the regulator for the same wrongdoing, are also equally responsible for causing similar adverse health impact on patients.

Substandard drugs and large pharma players:

That the issue of substandard drugs is quite widespread in India, involving both global and local pharma players – small and large, is also quite evident from the following report, published in the May 14, 2016 edition of the well-reputed national daily – Hindustan Times:

“A day after French major Sanofi announced a recall of some batches of its popular painkiller Combiflam, India’s drug regulator said over 102 medicines have been highlighted for quality concerns and withdrawal in the last five months. The list includes several popular painkillers.”

The report also indicated that these are generic medicines, both with and without brand names, such as, CIP-ZOX of Cipla, Orcerin of MacLeod Pharma, Zerodol-SP of Ipca Laboratories, Pantoprazole of Indian Drugs and Pharmaceuticals Ltd and Norfloxacin of Karnataka Antibiotics & Pharmaceutical Ltd. According to the public notices of the Central Drugs Standard Control Organization (CDSCO), these batches were manufactured in June 2015 and July 2015, and carried expiry dates of May 2018 and June 2018.

The CDSCO also reportedly said that in notices posted on its website in February and April, 2015, it found some batches of Combiflam to be “not of standard quality” as they failed disintegration tests. The point to note is, according to the US-FDA, disintegration test is used to assess the time it takes for tablets and capsules to break down inside the body and are used as a quality-assurance measure.

“All drugs listed under the drug alert list should be recalled with immediate effect. We have found some serious problems with the making of the drug because of which we have highlighted quality concerns. Hence, recall is necessary for all companies,” GN Singh, the Drug Controller General of India (DCGI), reportedly told the above newspaper.

Should the ‘intent behind’ be considered as the key differentiating factor?

This takes me to another question: What’s the ‘intent behind’ manufacturing substandard drugs? It is not difficult to make out that the only ‘intent behind’ manufacturing substandard drugs by illegal, some small or fly-by-night type of drug operators would be to make quick money, by cutting corners, and criminally falsifying the entire process.

Until recently, I used to strongly believe that those large manufacturers who are getting caught for releasing substandard drugs to the market, have made sheer mistakes, and these are no more than minor aberrations. However, recent findings by the US-FDA, after rigorous manufacturing quality audit of several production facilities of large and small generic drug producers of India, make me wonder whether this thin differentiating line of ‘intent behind’ manufacturing substandard drugs, though still exists, has started getting blurred. The foreign regulators have imposed import ban on drugs produced in those facilities on the ground of willingly compromising drug quality, and grossly falsifying data.

I am not going into those much discussed details here, once again, as the drugs involved in the above cases are meant for exports and the import bans, by the foreign regulators were aimed at protecting the health and safety of citizens of those countries. In this article my focus is on India, and health interest of the local Indian population.

Thus fathoming a different ‘intent behind’ manufacturing substandard drugs, especially by the large and well-known manufacturers, is the real challenge. What sort of anti-counterfeit events will be able to possibly address this perturbing issue, that is now getting revealed much faster than even before?

Who in India ensures that all drugs are safe?

Possibly none, not even the drug regulators and the enforcers of the drug laws, as a number of national and international media reports reveal. General public doesn’t get any assurance from any authorities that the medicines sold by the drug retail outlets, pan India, are all standard quality and genuine.

At the same time, it is equally challenging for anyone to ascertain, with absolute certainty, that it’s a counterfeit, substandard or a fake drug, in whatever name we call it, is responsible for avoidable suffering or even death of an individual. In such a sad eventuality, one has no other choice but to accept that the causative factor was either a wrong diagnosis of the disease, or delayed onset of treatment.

Is CDSCO still in a denial mode?

It’s an irony that the government sources often highlight that the incidence of substandard, spurious or fake drugs in India has declined from around 9 percent in the 1990s, to around 5 percent in 2014-15, quoting the CDSCO sample survey findings.

Nevertheless, while looking at the same CDSCO survey results of the last four years – from 2011-12 to 2014-15, the incidence of spurious and substandard drugs in India appears to be static, if not marginally increased, as follows:

Year Tested Samples Substandard Samples Spurious or Adulterated samples % Failed
2011-12 48,082,00 2,186.00 133.00 4.82
2012-13 58,537.00 2,362.00 70.00 4.15
2013-14 72,712.00 3,028.00 118.00 4.32
2014-15 74,199.00 3,702.00 83.00 5.10

Source: Central Drugs Control Organization (CDSCO)

In my view, these CDSCO results should be taken perhaps with dollops of salt, not merely the sample size for these surveys is too small, but also the complexity involved in the collection of the right kind of samples that will always pass the acid test of independent experts’ scrutiny.  Right representational sample size – state-wise, is so important, primarily considering that India is the world’s third-largest pharmaceutical market by volume, consumes 383 billion medicines per annum, according to a 2015 Government report, and is quite a heterogeneous pharma market.

A September 06, 2016 media report well captured the palpable hubris of the Government on this worrying subject. It quoted the Drug Controller General of India (DCGI) – Dr. G N Singh as saying: “This is an encouraging trend when it comes to comparing Indian made generics with that produced in regulated markets. This will help us dispel the myth that India is a source of substandard drugs as compared to any other regulated market.”

Interestingly, other studies and reports do indicate that this menace could well be, at least, thrice as large.

Be that as it may, according to an October 22, 2016 media report, CDSCO is expected to release the findings of the latest survey on ‘spurious drugs’ in India by end October 2016.

Two recent good intents of CDSCO:

Apparently, as a response to the widespread public criticism on this issue, despite being in a denial mode earlier, CDSCO has recently expressed two good intents to address this issue, as follows:

  • As reported on October 18, 2016, it has sent a recommendation to the Union Ministry of Health to amend the Drugs & Cosmetics Act to facilitate implementation of bar coding and Unique Identification Number (UIN) on every pack of domestic pharma products.
  • To ensure consistency and uniformity in the inspection process, on May 26, 2016, by a Public Notice, it issued a new draft checklist of ‘Risk Based Inspection of the Pharma Manufacturing Facilities’ for verification of GMP compliance as per the provisions stated under Schedule M of Drugs and Cosmetics Rules, 1945, and sought suggestions from the stakeholders. This checklist would be used by drug regulatory enforcement agencies as a science based tool. It also envisaged that the pharma industry would find this checklist useful for self-assessment.

Let’s now wait and watch, to get to know the timeline of translating these good intents into reality on the ground, and the impact that these decisions will make to reverse the current worrying trend of counterfeit and substandard drugs in India.

Conclusion:

The malady of counterfeit or substandard drugs is not just India centric. Various credible sources have estimated that around a million people fall victim to such so called ‘medicines’, each year. However, unlike many other countries, India still doesn’t have any structured and effective regulatory or other mechanisms, not even any spine-chilling deterrent, in place to address this public health menace of humongous implications.

That said, besides serious health hazards, the adverse financial impact of substandard drugs on patients is also significant. Such drugs, even when non-fatal, are much less effective, if not ineffective or trigger other adverse reactions. Thus, a longer course of treatment, or switching over to a different medication altogether, may often be necessary, multiplying the cost of treatment.

In that sense, substandard, spurious, fake or counterfeit drugs, in whatever name one describes these, increase the disease burden manifold, besides being life-threatening. This issue assumes greater significance in India, where 58.2 percent of the total health expenditure is incurred out-of-pocket by a vast majority of the population. Medicines alone, which are mostly purchased from private retail outlets, across India, account for between 70 and 77 per cent of the individual out of pocket health spending, according to a W.H.O report.

High decibel campaigns on various anti-counterfeit technology solutions for fast selling, or expensive brands of large pharma companies, whether sponsored by placing the commercial interest at the top of mind, or even otherwise, are welcome, so are the two recent good intents of the Union Government, in this area.

However, the desirable proactive focus on curbing the menace of substandard medicines in India, which cause similar health risks as any other type of counterfeit drugs, does not seem to be as sharp, not just yet, barring the pharma export sector. Nor does this issue attract similar zest for a meaningful discourse related to patients’ health and safety within the country, as associated with various other anti-counterfeiting technology solution oriented events. The anomaly remains intriguing, especially when the malady spreads, with its root reaching deeper.

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. 

What Happens To Pharma’s Incredible Ride On The ‘Gravy Train’?

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India continues to be one of the fastest growing pharmaceutical market of the world with its over 40 percent of the total pharmaceutical produce is exported around the world. Over half of the total exports constitute of formulations, and the balance comprises of bulk drugs. India has been consistently maintaining its supremacy in the formulation exports since my salad days.

According to Export Statistics (2014-15) published by the Pharmaceutical Export Promotion Council of India (Pharmexcil), United States (US) is the largest market for the India’s pharmaceutical exports with a share of 27 percent of the total, followed by the United Kingdom (UK), South Africa, Russia, Nigeria, Brazil and Germany.

A red flag raised: 

Up until recently, it has almost been like walking over a bed of roses in this front for Indian pharma exporters. However, it does not seem to be so now, and at least in the foreseeable future, for a number of reasons.

The Press Release of ‘CRISIL Research’ dated May 17, 2016 has also raised a red flag in this area. The report foresees growth in pharma formulations (in US dollar terms) declining sharply to 10-12 percent annually over the next 5 years, as compared with a growth of ~19% seen in the last decade.

This adverse impact will be felt mostly in the US – the largest export destination of India, followed by the UK.

I reckon, there are three basic reasons for this changing scenario, namely, pricing, quality and lesser number of branded small-molecule blockbuster drugs going off patent.

The ride on the ‘gravy train’:

Pharma companies across the world consider that doing business in the US market would provide them a lot of money without facing any head wind, fundamentally driven by the drug pricing freedom in the country, as compared to any other market of the world.

This unfettered freedom of charging a hefty price premium in the largest pharma market of the world, on an ongoing basis, has been a critical factor of attraction for many pharma players to do business in the US, coming from various corners of the globe, including India, just as honey attracts the bees, as it were.

Thus far, it has been an incredible ride on the ‘gravy train’, as it were, for most of them.

However, ongoing activities of a large number of drug companies, dominated by blatant self-serving interests, have now given rise to a strong general demand for the Government to initiate robust remedial measures, soon. The telltale signs of which indicate that this no holds barred pricing freedom may not be available to pharma, even in the US, any longer.

In this article, I shall focus mainly on this point, drawing both global and local examples, as this development has a strong potential to add more to the existing miseries of many Indian drug exporters, of course in tandem with many other large MNCs.

Some recent developments: 

The April 21, 2016 issue of ‘The Financial Times’ quoted Joe Jimenez, the Global Chief Executive (CEO) of Novartis, where he said that pharma companies can no longer count on the “hockey-stick” trajectories for new products in the US. This is primarily due to the aggressive control of the drug expenses by the insurers and other healthcare payers, besides lawmakers and the public at large, of this most lucrative pharma market of the world.

As Jimenez said in the report, yesterday’s business model that pharma companies have followed since long, has now changed, slowing the pace of growth of innovative patented products in the US.

This trend is now heading north, primarily driven by the consolidation among the US insurers and healthcare providers. Consequently, the payers are making effective use of their greater bargaining power over the drug companies, especially to avail new incentives for cost savings, as provided in President Barack Obama’s Affordable Care Act, the article highlights.

To give a feel of it, I am quoting the example of a Novartis drug from the same ‘Financial Times’ article. It states, “Entresto, a treatment for heart failure, launched last year on the back of stellar clinical trial results, has so far sold more quickly in Europe than the US, marking a reversal of usual patterns in the pharma industry.”

A key differentiator in global ranking:

In this emerging scenario, all global companies will be adversely impacted for increasing pricing pressure in the US market.

This factor remaining the same for all the pharma players in the world, one of the key differentiating factors that would now play even more important role, is the richness of the advanced stage R&D pipeline of each innovator company.

For example, according to ‘Evaluate Pharma World Preview 2016, Outlook to 2022’ report, the overall R&D pipeline value of Roche is US$ 43.2 billion, far ahead of the same of Novartis’ US$ 24.1 billion and AstraZeneca’s at US$ 23.2 billion, followed by Eli Lilly, AbbVie, Pfizer, Sanofi, Celgene, Biogen and J&J and in that order. As a result, Roche is expected to overtake Novartis and Pfizer in the ranking by 2022, just when the global pharma industry would possibly cross as US$ 1Trillion mark.

Currently Novartis, though quite a small player in the Indian Pharmaceutical Market (IPM) holding the rank of 23 (AIOCD Pharmasofttech AWACS retail audit report, MAT August 2016), is number three in the global ranking, just ahead of Roche.

Indian generic players to feel the heat:

According to the Reuters report of September 11, 2016, US Department of Justice has sent summons this month to the US arm of Sun Pharma – Taro Pharmaceutical Industries Inc. and its two senior executives seeking information on generic drug prices. In 2010, Sun Pharma acquired a controlling stake in Taro Pharmaceutical Industries.

On September 14, 2016, quoting a September 8, 2016 research done by the brokerage firm IIFL, ‘The Economic Times’ reported that some large Indian generic drug manufacturers, such as, Sun Pharma, Dr. Reddy’s, Lupin, Aurobindo and Glenmark have also hiked the prices of some of their drugs between 150 percent and 800 percent in the US. This invites even more apprehensions in the prevailing scenario.

As I wrote in this Blog on September 12, 2016, the subject of price increases even for generic drugs has also reverberated in the ongoing Presidential campaign in the US.

The Democratic Party’s presidential nominee – Hillary Clinton has already promised, if elected in November 2016, she would constitute an ‘Oversight Panel’ to protect the consumers of her country from hefty price increases for long-available life-saving drugs.

Import bans:

In the midst of all this, import bans of a large number of formulations and bulk drugs by the US-FDA from several manufacturing facilities of Indian drug manufacturers of various scales and sizes, have further compounded the future risk potential of Indian pharma business growth in the US.

As investors are raising concerns, the following comment of the Co-Chairman and Chief Executive of Dr. Reddy’s Laboratories, reported by ‘Financial Express’ on August 24, 2015, well captures the pharma business risks in this area:

“The U.S. market is so big that there is no equivalent alternative. We just have to get stronger in the U.S., resolve our issues, build a pipeline and be more innovative to drive growth.”

However, this still remains a good intent. It is worth noting, for most Indian pharma exporters, the US is the single largest export market, with a stake, as high as nearly half of most of these companies’ annual revenue, and probably much more in profit, both of which are now showing a declining trend.

Price control coming in the UK:

On September 15, 2016, the Department of Health of the United Kingdom (UK) reportedly introduced a new Bill in Parliament to use its statutory power to limit the price of generic medicines where competition in the market fails, and pharma companies charge the NHS unreasonably high prices.

The Bill would also allow the government to apply penalties for non-compliance and to recover any payments owed through the courts following a right of appeal to a tribunal. The penalties can be a single penalty not exceeding £100,000 or a daily penalty not exceeding £10,000.

UK drug regulatory authorities had also announced import bans of APIs and formulations from some manufacturing facilities of a couple of leading Indian drug manufacturers, but on a lesser scale as compared to the USFDA.

Action in EU:

As reported by Bloomberg on July 22, 2016, The European Medicines Agency (EMA) has called for a halt to sales of hundreds of medicines that were tested in India, after an inspection of a research site found “substitution and manipulation” of the study samples. The affected companies include both large Indian and multi-national players.

According to a PTI report of July 27, 2015, after this incident Pharmexcil estimated that exports worth US$ 1-1.2 billion are likely to be affected, if cancellation of 700 generic drugs by the EU stands.

Conclusion:

All these developments, particularly on pricing and mostly in the US, could have a retarding effect on the business growth trend of a large number of global and local pharma companies.

Focusing nearer home, the evolving scenario in the world’s top pharma market, viewed together with what’s happening in Europe, both on pricing and the data integrity fronts, send a strong cautionary signal to the Indian drug exporters, in general.

Inadequate remedial measures could unleash this pressure to reach a dangerous threshold, impacting sustainable performance of the concerned companies. On the other hand, adequate remedial action, both strategic and operational in nature, could lead to significant cost escalation, with no space available for its neutralization through price increases, gradually squeezing the margin.

As I see it, ease of doing pharma business in these top export markets will no longer be quite the same as in the past. Many believe, pharma industry has invited these measures sans perceptible self-control, over a long period of time.

Is it mostly a self-inflicted injury of the industry players? The drug companies, in general, don’t believe so. Will this change be irreversible?  Only the future could unravel this. However, regarding the possibility of future US Government legislation on drug pricing, it’s now a wait and watch game for the stakeholders. On a shorter time-frame, the ghost in this area, would keep haunting globally, primarily for business in the US market, at least, till the end of this year.

However, for the Indian pharma exporters, pricing appears to be just one among several other critical issues, especially, in the two most lucrative markets of the world. The overall situation in this area, by and large, remains unchanged till today, besides expression of a plethora of good intents.

Thus, pharma analysts’ quest to ferret out an answer to the Gordian knot on the continuity of Indian pharma exporters’ incredible long ride on the ‘gravy train’, has also not been plain sailing, so far. Further mired by the local manufacturers’ prolonging errors of judgement, the status quo ante is expected to still remain elusive, at least, for now.

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. 

Leveraging 3D Printing In Pharma, For Cost Containment And Patient-Centricity

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Today, although a number of new and state of the art drugs is regularly being developed, and brought to the market at a reasonably rapid pace, their access to the majority of the global population has still remained a huge challenge. One of the key access barriers continue to remain exorbitant prices of these drugs.   

Keeping commensurate pace with gradual improvement in the pinpointed diagnosis of various diseases with modern diagnostics, processes, devices and techniques, fueled by increasing health awareness within a sizeable section of the population, more patients are now aspiring for access to a better quality of life, and greater productivity at work. This is happening all over the world, though with varying degree and magnitude. 

Consequently, there has been a sharp increase in the demand for healthcare, which has caused a huge bottleneck in the overall healthcare delivery process, for various reasons. The huge gap between the availability of high-tech drugs/healthcare services, and their access to the general population, mostly due to affordability reasons, is going north at a rapid pace. 

Two-pronged cost containment pressure:

This unfettered ascending trend is creating primarily the following two types of cost containment pressure: 

  • Being driven purely by the economical reasons, the Governments and other payers have started taking stringent cost-containment measures, bringing huge pricing pressure, especially on the drugs and medical device manufacturers.
  • In countries, such as, India, where the ‘Out of Pocket’ expenditure on healthcare in general, and the medicines in particular, is hovering around 70 percent, the patients, several Governments have started announcing drug price control policy to protect the health interest of patients. 

However, currently, only some piecemeal measures are being initiated, including in India, where a holistic approach for all, such as, Universal Health Care (UHC) and several other similar options, are long overdue.

Three different remedial measures:

In my view, consideration of either of these three following approaches, or an innovative blend of these, would enable the Governments to address this pressing issue, remove the existing bottle neck, and thereby bridge the healthcare access gap, holistically:

A. Fast implementation of Universal Health Care (UHC).

B. Closer look at the entire Pharmaceutical Value Chain with a resolve to work out innovative, game-changing solutions to reduce cost of each of its critical components, significantly.

C. Effectively addressing the emerging need of Patient-Centricity.

A. Fast implementation of Universal Health Care (UHC):  

I have already discussed UHC in one of my articles titled, “Universal Health Coverage: The Only Alternative To Drug Price Control in India?”, published in this Blog on November 9, 2015.

B. Cost containment with 3D printing:

A report of IMS Health, published on November 18, 2015, forecasts the increase of  total global spend for pharmaceuticals by US$ 349 billion on a constant-dollar basis, compared with US$182 billion during the past five years. It also indicated, more than half of the world’s population will live in countries where the use of medicine will exceed one dose per person per day by 2020, up from 31 percent in 2005, as the “medicine use gap” between the developed and the emerging markets narrows. 

This steep ascending trend would eventually affect the pharma ‘Value Chain’ in a significant way, throwing open several path-breaking high-technology based options, with impressive favorable impact on the general costs of medicines. 3D-printing technology is expected to play a significant role in this initiative.

Before proceeding further, let me zero-in on a few critical components, as follows, of the pharma ‘Value Chain’, as I see visualize these: 

  • Drug innovation (R&D)
  • Manufacturing
  • Marketing
  • Supply Chain

According to my understanding, at least in 3 of the above 4 ‘Value Chain’ components, there is an immense potential of leveraging 3D printing technology effectively, and in a big way.

In my article of January 11, 2016, published in this Blog, titled “3D Printing: An Emerging Game Changer in Pharma  Business”, I have already discussed the game changing impact of 3D Printing technology on the drug discovery process, drug manufacturing strategy, and supply Chain effectiveness in the pharma business. 

Hence, I prefer not to dwell on those areas, yet again, here. Instead, I shall briefly deliberate on the application of 3D Printing technology to effectively address the emerging need of ‘Patient-Centricity’ with an interesting and a very recent example. 

C. Improving ‘Patient-Centricity’ with 3D printing: 

At this stage, there is a need to understand what exactly is the ‘’Patient-Centricity’. It seems to be a popular buzzword now with the health care related companies, primarily to give an impression that they are really focusing on ‘Patient-Centricity’.

However, there does not seem to exist any universally accepted definition of this terminology, just yet. Nevertheless, one appropriate definition could well be: “A focused and transparent approach to providing maximum possible benefits to a patient from a drug, device, technology, or health care services.” 

I briefly focused on a part of this basic issue in my article titled, “‘Disease Oriented Treatment’ to ‘Patient Oriented Treatment’- An evolving trend’, published in this Blog on January 7, 2013.

As I said before, in this article, to explain ‘Patient-Centric’ approaches with 3D printing, I would quote from a very recent, and a path-breaking work in this area.

On May 25, 2016, ‘The Straits Times’ reported, the researchers at the National University of Singapore have found a way to use 3D printers to create low-cost tablets. With the help of this technology a tablet can be so personalized to respond to individual patient’s needs that the drug can be customized to take on different release profiles, such as, constant release, pulsed release, increasing or decreasing release, and any arbitrary interval as required by the patient. However, the most striking is, different drugs with different release profiles can also be combined in a single pill.

Once administered, the tablet dissolves layer by layer over a period of time, releasing the drug at a controlled rate. The duration can be altered by changing the chemical composition of the liquid.

It is worth noting here that the conventional tablets are only capable of a constant rate of release, requiring the patient to manually control the dosage and release rate, by taking doses according to a prescribed schedule, given by the doctor. In this scenario, if a patient requires different drugs with different dosages and intervals, it can become inconvenient to keep track and potentially dangerous, especially when the patient misses a dose, the report highlighted. 

The commercially available printer used in the project costs just S$2,000.

The Assistant Professor Soh Siow Ling, who leads the project, reportedly, expects that the low cost will allow it to be used in hospitals and neighborhood clinics. He further explained, “Every single person is different, based on many factors such as genetics, age, body mass and so on. Different people also have different activity levels and consumption habits, which affect their needs. It is, (therefore), not desirable to use the same drug to treat different illnesses which have similar apparent symptoms.”

The report indicated that in October, 2015, these findings were published in an issue of Advanced Materials, which is a peer-reviewed materials science journal.

A patent for the tablets was filed last year, and they are currently in talks with multinational corporations, and medical professionals to identify potential applications, the article highlighted. 

Changing role of doctors:

From the above developments, it appears that unleashing the full potential of 3D printing technology in the pharma industry, would also enable the medical profession to move further towards ‘Patient-Centricity’, in its true sense.

This technology would empower them offering to each patient, the right drug or drug combinations, with most suitable drug delivery system, and exactly the way individual patients would prefer, with a very high degree of precision.

Thus, from overall disease treatment perspective, especially with medicines, this approach offers a great potential to be significantly more effective, and convenient to individual patients, as compared to the conventional approaches. 

I reckon, over a period of time, professional competitiveness would drive the doctors further honing their effectiveness in the disease treatment process, and that too with a high degree of precision. In that situation, many doctors may decide to setup on-demand 3D drug-printing facilities even at their clinics.

The gradual embodiment of this brilliant technology by the doctors, is expected to throw open new vistas of opportunity, also to personalize the shapes, colors and flavors of any medicine, according to individual patient’s choice. This, in turn, would improve patient compliance, ensure a predictable relief from the disease, and demonstrate ‘Patient-Centricity’ of a high order by the medical profession, in general. 

Conclusion:

For the first time ever, with Aprecia Pharmaceuticals in the United States getting approval of the US-FDA on August 3, 2015 for the market launch of a 3D printed prescription drug for oral use by the epilepsy patients, dawns a new paradigm in the global pharma business horizon.

Effective application of this ‘disruptive innovation’ could well be a game changer not just in the ‘value chain’ of conventional pharma business models, across the world, but also for taking a giant leap towards ‘Patient-Centricity’. The doctors are also expected to be very much an integral part of this process. 

Besides all the above benefits, 3D printing can also encourage low-volume production, whenever required, and a wide variety of Active Pharmaceutical Ingredients, to meet any immediate demand, mostly for use in research and developmental work. 

Thus, noting the ongoing significant progress in this area, I reckon, leveraging 3D printing technology in pharma, not just to address the cost containment pressure, effectively, but also to ensure a tangible and visible move towards ‘Patient-Centricity’, in true sense. All-round success in the innovative application of this cutting-edge technology in the global pharma industry, would eventually separate men from boys in pursuit of business excellence. 

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.