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Even Smaller Countries Now Question Indian Drug Quality Standard

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India has over 135 US-FDA approved pharmaceutical manufacturing units, at present. This number is very significant ranking second behind the United States, and was driving the growth of generic drug exports in the top pharma market of the world. Riding on the wave of such stellar progress, a hubris seems to have set in the related operational areas of many Indian pharma players, especially the drug exporters.

This incredible ride continued, until a first major jolt shook all concerned in this business. It came first in the form of an unprecedented hefty fine for wrong doing, followed by the US- FDA ‘import bans’ of several drugs, manufactured around 44 different Indian drug-making facilities, since over the last five years.

The first major jolt:

Not so long ago, just in 2013, quality related concerns with generic drugs exported from India came to the fore, after Ranbaxy reportedly pleaded guilty and paid a hefty fine of US$ 500 million for falsifying clinical data and distributing ‘adulterated medicines’ in the United States.

Thereafter, US-FDA banned drug imports from Ranbaxy and Wockhardt, manufactured in all those facilities that failed to conform to its cGMP quality standards.

Those are the stories for generic formulations. It then covered the Active Pharmaceutical Ingredients (API) too. On January 23, 2014, USFDA notified Ranbaxy Laboratories, that it is prohibited from manufacturing and distributing APIs from its another Indian manufacturing facility in Toansa. With this step, erstwhile Ranbaxy had virtually no access to the top pharmaceutical market of the world.

Was it for raising the bar of quality norms?

Many of us felt and expressed that ‘import bans’ of Indian drugs due to failing quality parameters, manufactured in certain facilities of largely Indian pharma companies, are mostly due to higher stringent quality norms of the US-FDA, the European Medicines Agency (EMA) and the Medicines and Healthcare products Regulatory Agency (MHRA). Nevertheless, this argument does not carry much weight, as an exporter will always have to conform to the set quality standards of the importers, whatever these are. 

Indian drug regulator too made a much avoidable remark:

Unfortunately, amid such a scenario, instead of taking appropriate transparent and stringent measures, the Drug Controller General of India (DCGI) was quoted by the media saying, “We don’t recognize and are not bound by what the US is doing and is inspecting. The FDA may regulate its country, but it can’t regulate India on how India has to behave or how to deliver.”

The DCGI made this comment as the then US-FDA Commissioner Margaret Hamburg was wrapping up her a weeklong maiden trip to India, in the wake of several ‘Import Bans’ arising out of repeated cGMP violations by some large domestic generic drug manufacturers. Whereas, Hamburg reiterated the need for the domestic drug manufacturers conform to the USFDA quality standards ensuring health and safety for American patients, the DCGI’s above comment appears rather arrogant, out of tune, and was avoidable, to say the least. Instead, some serious corrective regulatory measures should have followed.

On the above comments of the DCGI, the American Enterprise Institute reportedly reacted by saying, “Indian drug regulator is seen as corrupt and colliding with pharma companies…”.

Smaller countries initiated similar action:

It now appears that this situation is going from bad to worse and malady is much deeper. Smaller countries, such as Vietnam, have recently banned products of a sizable number of domestic pharma exporters.

On September 5, 2016, a leading business daily of India reported: “Close on the heels of Prime Minister Narendra Modi’s visit to Vietnam to strengthen bilateral ties, including defense, security and trade, the ministry of commerce and industries is planning to set up a committee, along with the Central Drugs Standard Control Organization (CDSCO), to inspect Indian pharmaceutical companies which have been banned from Vietnam for exporting sub-standard drugs.”

In 2014, the Drug Regulatory Authority of Vietnam ‘red-listed’ about 50 pharma companies for alleged regulatory non-compliance in their manufacturing practices. The names included, some big names of Indian pharma industry.

Overall pharma market size of Vietnam is estimated over US$ 2 billion, and expected to grow to US$ 8 billion by 2020. A significant chunk of Vietnam’s pharmaceutical market comprises of generic drugs, where India used to be a major exporter. In the recent years, however, Indian pharmaceutical product exports to Vietnamese market have dipped considerably, reflecting the effects of the ban, with exports declining by 12 percent to US$ 146 million in 2015-16 from US$ 165 million in the previous fiscal year, the report said.

It was envisaged, especially after the Prime Minister’s visit to Vietnam, this situation will improve notably. However, just as what happened with the USFDA on related issues, there has been no change in the overall situation in this case, either.

Further, on November 23, 2016, yet another Indian Business news daily reported that 39 Indian drug companies have been blacklisted by Vietnam for quality standard violations, along with some others in Bangladesh and South Korea. The Vietnamese regulator has listed the names of all blacklisted companies on its website, without specifying in detail the exact reason behind the bans. The Indian products include, antibiotics and anti-rabies vaccine, among others. The latter was also reportedly banned by the World Health Organization (WHO), in January 2016.

What is more intriguing, despite the Union Ministry of Health and the Ministry of Commerce and Industries of India being aware of it, the issue seems to have drifted beyond reasonable control of the Indian regulators.

Some local companies still not acting:

On Feb 24, 2016, the US and the EU drug regulators reportedly called upon India’s pharmaceutical sector to step up efforts to improve manufacturing standards, and ensure the reliability of data, if it wishes to maintain its dominance in the generic drug industry. In the report, the director of the office of surveillance at the USFDA – Russell Wesdyk was quoted saying, “some Indian companies are still not taking enough steps to identify risks and failures at their firms.”

“Data integrity really sounds-off alarm bells for us. If you see data integrity on the surface, there is likely a lot going on underneath,” the foreign drug regulators reportedly commented.

These comments are profound, especially considering that India supplies about 33 percent of medicines sold in the United States, and nearly a quarter sold in the UK. Similar Indian drug quality related issues are now being raised by even smaller countries.

How safe are drugs for domestic consumption?

Many reasons may be attributed to quality concerns on Indian generics in the United States. Nonetheless, another question that surfaces alongside, if cGMP violations can take place for drug exports, despite rigorous compliance checks by the foreign drug regulators, what could possibly happen when the same system is so tardy in India? Are we consuming safe and effective drugs, whenever required, even within the country?

No one seems to have the right answer to this question, be because of various reasons. One such reason, out of various others, could well be how robust is data quality generated by the contract manufacturing companies? These are the core quality related issues, and can’t just be wished away, under any pretext.

Some examples:

On November 12, 2013, the DCGI was quoted saying that the investigative team of the drug regulator concluded that all the data submitted by Puducherry-based contract drug manufacturer ‘GuruFcure’, while seeking approval for manufacturing seven fixed dose combination drugs, are ‘fabricated’ and not ‘authentic’.

‘GuruFcure’, which started operations in 2007, and calls itself “one of the leading pharmaceutical formulation manufacturers in India”, reportedly used to manufacture drugs for some leading pharma MNC and Indian companies, such as: Abbott, Alkem, Glenmark, Wockhardt, Unichem, Intas Pharma, among others.

Though, as per the above media report, Wockhardt and Glenmark said that they were no longer associated with ‘GuruFcure’ at that time, the fact remains, they did market drugs produced by this contract manufacture in the past, and the patients consumed those drugs against doctors’ prescriptions. The saga continues unabated, even today.

On November 28, 2016, a major national English daily reported with a video clip that, following a crackdown since March this year, the drug regulators of seven states have alleged that 27 medicines, sold by 18 major drug companies in India, including Abbott, GSK, Sanofi, Sun Pharma, Cipla, Torrent, Alkem, Emcure and Glenmark Pharma, are of substandard quality, citing grounds such as false labelling, wrong quantity of ingredients, discoloration, moisture formation, failing dissolution test and failing disintegration test. Such allegations, though supported by laboratory test results, needs to brought to their logical conclusion. This is mainly because, media reports of this nature fuel lurking apprehension on the overall drug quality standards in India, leading to serious compromise with patients’ health and safety.

Conclusion:

Against this rather gloomy backdrop, a ray of hope comes from a report that CDSCO has started training Indian drug manufacturers in good manufacturing practices, as it tries to address concerns of the USFDA, and other drug regulators, effectively.

Quoting the DCGI, who has now apparently resolved to put together proper practices and regulation in place for the pharma industry, the report says that CDSCO has hired 500 personnel, and is expected to further train employees of other units, to ensure that high quality medicines are manufactured in the country.

These officials will visit drug manufacturing hubs of the country over the next three to four years and train employees in producing quality medicines, following proper procedures and maintaining records. I hope, this will include contract manufacturers too. The question would remain: What happens when these regulatory lapses do not take place out of ignorance or lack of experience or expertise, but are purely intentional to cut corners?

Alleged dubious quality of many drugs manufactured in India is a critical issue, both within the country and with several foreign drug regulators, such as US-FDA, EMA and MHRA, among others. It affects all those who consume such drugs.

Today, even smaller countries are questioning Indian drug quality to protect their patients’ health interest. Thus, everything, when clubbed together, sends a strong signal to the Indian drug regulator to come out of its denial mode, walk the talk, and act decisively to safeguard the interest of Indian patients too.

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.

 

Nutraceuticals: Still An Oasis Amidst Well-Regulated Pharmaceuticals

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On November 24, 2016, the food-safety watchdog of India announced that health supplements or Nutraceuticals cannot be sold as ‘medicines’ anymore. This new regulatory standard has been set for the manufacturers of Nutraceuticals and food supplements, and is aimed at controlling mislabeling of such brands. The fine prints of the notification are yet to be assessed.

On the face of it, this new announcement seems to be a good step, and would largely address a long-standing issue on the such products. Prevailing undesirable practices of labeling some pharma brands as food supplements or Nutraceuticals, with some tweaking in the formulations, mainly to avoid the risk of price control, is also expected to be taken care of by the food-safety authority of India, while granting marketing approval.

Nevertheless, it is often construed that off-label therapeutic claims, while promoting these products to the doctors, help achieving brand positioning objective as medicines, though indirectly. Appropriate authorities in India should probably resolve this issue, expeditiously.

In this article, I shall focus on the rationale behind different concerns over the general quality standards, claimed efficacy and safety profile of Nutraceuticals and food supplements, in general, and how the regulatory authorities are responding to all these, slowly, albeit in piecemeal, but surely.

The ‘gray space’ is the issue:

The close association between nutrition and health has assumed a historical relevance. Growing pieces of evidence, even today, suggests that nutritional intervention with natural substances could play an important role, especially in preventive health care. The World Health Organization (WHO) has also highlighted that mortality rate due to nutrition related factors in the developing countries, like India, is nearly 40 percent.

However, as one of the global consulting firm of repute has aptly pointed out, “At one end of this natural nutrition spectrum, are functional foods and beverages as well as dietary supplements, aimed primarily at maintaining health. On the other, more medical end of the spectrum, are products aimed at people with special nutritional needs. In the middle, is an emerging gray area of products that have a physiological effect to reduce known risk factors, such as high cholesterol, or appear to slow or prevent the progression of common diseases such as diabetes, dementia or age related muscle loss.”

This gray space between Pharmaceutical and Nutraceuticals, therefore, holds a significant business relevance, from various perspectives.

An Oasis amidst highly-regulated pharmaceuticals:

Mostly because of this gray space, several pharma companies and analysts seem to perceive the Nutraceutical segment virtually an oasis, lacking any transparent regulatory guidelines, amidst well-regulated pharma business. This perception is likely to continue, at least, for some more time.

Such pattern can be witnessed both within the local and global pharma companies, with some differences in approach, that I shall deliberate later in this article.

However, regulators in many countries, including India, have started expressing concerns on such unfettered manufacturing, marketing and other claims of Nutraceuticals. Many of them even ask, do all these Nutraceuticals deliver high product quality, claimed effectiveness and safety profile to their consumers, especially when, these are promoted by several pharma companies, though mostly off-label, to generate physicians’ prescriptions for various disease treatments?

Not just domestic pharma companies:

This concern is not restricted to the domestic companies in India.

Global pharma players, who generally believe in scientific evidence based medicines, have been reflecting an iffiness towards Nutraceuticals. For example, whereas both Pfizer and Novartis reportedly hived off their nutrition businesses, later Pfizer invested to acquire Danish vitamins company Ferrosan and the U.S. dietary supplements maker Alacer. Similarly, both Sanofi and GlaxoSmithKline also reportedly invested in mineral supplements businesses that could probably pave the way of the company’s entry into medical foods.

However, it is worth underscoring that generally the consumer arms of global pharma companies focus on OTC, and Nutraceuticals do not become an integral part of the pharma business, as is common in India.

Interestingly, not very long ago, Indian pharma industry witnessed a global pharma major virtually replicating the local marketing model involving Nutraceuticals. It also became an international news. On August 24, 2011, ‘Wall Street Journal (WSJ)’ reported that ‘Aventis Pharma Ltd. (now Sanofi India) agreed to buy the branded nutrition pharmaceuticals business of privately held Universal Medicare Pvt. Ltd for an undisclosed amount, as its French parent Sanofi looks to expand in the fast-growing Indian market.’

Universal Medicare, which posted about US$ 24.1 million revenue in the year ended March 31, 2011, will manufacture these branded Nutraceutical products and Aventis will source them from Universal Medicare on mutually agreed terms. Around 750 of the Universal Medicare’s employees also moved to the French Company along with its around 40 Nutraceutical brands, the report said.

If all these acquired brands, do not fall under the new FSSAI guidelines related to the required composition of food supplements and Nutraceuticals in India, it would be worth watching what follows and how.

Nutraceuticals are also promoted to doctors:

Let me reemphasize, India seems to be slightly different in the way most of the pharma companies promote Nutraceuticals in the country. Here, one can find very few standalone ‘Over the Counter (OTC)’ pharma or Nutraceutical product company. For this reason, Nutraceutical brands owned by the pharma companies, usually become an integral part of their prescription product-portfolio. Mostly, through off-label promotion Nutraceuticals are often marketed for the treatment or prevention of many serious diseases, and promoted to the doctors just as any other generic pharma brand.

Need to generate more scientific data based evidences:

A 2014 study of the well-known global consulting firms A.T. Kearney titled, “Nutraceuticals: The Front Line of the Battle for Consumer Health”, also recommended that ‘a solid regulatory framework is crucial for medical credibility, as it ensures high-quality products that can be relied on to do what they say they do.’

This is mainly because, Nutraceuticals are not generally regarded by the scientific community as evidence based medicinal products, going through the rigors of stringent clinical trials, including pharmacokinetics and pharmacodynamics studies, and is largely based on anecdotal evidence. Besides inadequacy in well-documented efficacy studies, even in the areas of overall safety in different age groups, other side-effects, drug interactions and contraindications, there aren’t adequate scientific evidence based data available to Nutraceutical manufacturers, marketers, prescribers and consumers.

There does not seem to be any structured Pharmacovigilance study is in place, either, to record adverse events. In this scenario, even the ardent consumers may neither realize, nor accept that Nutraceuticals can cause any serious adverse effects, whatsoever.

From this angle, the research study titled, “Emergency Department Visits for Adverse Events Related to Dietary Supplements”, published in the  New England Journal of Medicine (NEJM) on October 15, 2015, becomes very relevant. The paper concluded as follows:

“More than 23,000 emergency department visits annually in the United States from 2004 through 2013 were for adverse events associated with dietary supplements. Such visits commonly involved cardiovascular adverse effects from weight-loss or energy herbal products among young adults, unsupervised ingestion of micronutrients by children, and swallowing problems associated with micronutrients among older adults. These findings can help target interventions to reduce the risk of adverse events associated with the use of dietary supplements.”

Fast growing Nutraceutical industry continues to remain largely unregulated. It persists, even after several previous studies had revealed dangerous levels of harmful ingredients, including amphetamine, in some Nutraceuticals.

Indian regulatory scenario:

In India, the ‘Food Safety and Standards Authority of India (FSSAI)’, established under the Food Safety and Standard Act of 2006, is the designated Government body responsible for the regulation and approval of Nutraceuticals in the country.

In July 2015, FSSAI proposed draft regulations for Nutraceuticals, Functional Foods, Novel Foods and Health Supplements for comments from all stakeholders within the stipulated time limit. This draft regulation defines Nutraceuticals as follows:

“Nutraceuticals means a naturally occurring chemical compound having a physiological benefit or provide protection against chronic disease, isolated and purified from food or non-food source and may be prepared and marketed in the food-format of granules, powder, tablet, capsule, liquid or gel and may be packed in sachet, ampoule, bottle, etc. and to be taken as measured unit quantities.”

In this draft FSSAI also proposed that therapeutic claims of Nutraceuticals and all such foods are required to be based on sound medical and nutritional evidence, backed by scientific as well as clinical evidence.

In 2011, FSSAI constituted a product approval committee, whose members were supposed to use similar parameters as drugs, to assess Nutraceuticals for this purpose. However, FSSAI had to jettison this idea, in compliance with the order dated August 19, 2015 of the Supreme Court questioning the procedure followed for approvals by the food regulator.

In April 2016, FSSAI restricted enforcement activity against Nutraceuticals and health supplement companies to only testing of products till new standards are notified.

The latest regulatory developments:

There are, at least, the following two recent developments reflect that the regulatory authorities, though trying, but are still grappling with the overall product quality, efficacy and safety concerns for Nutraceuticals:

  • Responding to the growing demand for regulatory intervention in this important matter, on November 30, 2015, by a gazette notification, the Government of India included phytopharmaceutical drugs under a separate definition in the Drugs & Cosmetics (Eighth Amendment) Rules, 2015, effective that date.
  • Again, on November 24, 2016, FSSAI reportedly announced that health supplements or Nutraceuticals cannot be sold as ‘medicines’ anymore. This new regulatory standard set for the manufacturers of Nutraceuticals and food supplements is aimed at controlling mislabeling of such brands. On its enforcement, every package of health supplement should carry the words ‘health supplement’ as well as an advisory warning ‘not for medicinal use’ prominently printed on it.

It further added: “The quantity of nutrients added to the articles of food shall not exceed the recommended daily allowance as specified by the Indian Council of Medical Research and in case such standards are not specified, the standards laid down by the international food standards body namely the Codex Alimentarius Commission shall apply.”

However, these regulations will be enforced from January 2018.

Curiously, in September 2016, National Institutes of Health in United States announced plans to put some more scientific eyes on the industry, the NIH reportedly announced plans to spend US$ 35 million to study natural products, ranging from hops to red wine’s resveratrol to grape seed extract. The new grants, reportedly, are expected to fathom the basic science behind many claims that Nutraceuticals can improve health.

The market:

The August 2015 report titled, ‘Indian Nutraceuticals, Herbals, and Functional Foods Industry: Emerging on Global Map,’ jointly conducted by The Associated Chambers of Commerce and Industry of India (ASSOCHAM) and the consulting firm RNCOS, estimates that the global Nutraceuticals market is expected to cross US$ 262.9 billion by 2020 from the current level of US$ 182.6 billion growing at Compound Annual Growth Rate (CAGR) of about 8 percent.

Driven by the rising level of awareness of health, fitness and changing lifestyle pattern, increasing co-prescription with regular drugs, and focus on preventive health care, India’s Nutraceuticals market is likely to cross US$ 6.1 billion by 2020 from the current level of US$ 2.8 billion growing at CAGR of about 17 percent, the report states.

The United States (US) has the largest market for the Nutraceuticals, followed by Asia-Pacific and European Union. Functional food is the fastest growing segment in the US Nutraceutical market, followed by Germany, France, UK and Italy in Europe.

Conclusion:

Today, both manufacturing and marketing of Nutraceuticals keep charting in a very relaxed regulatory space, in India. There are no robust and transparent guidelines, still in place, for product standardization and scientifically evaluate the safety and efficacy of all these products on an ongoing basis. Neither is there any stringent requirement for conformance to the well-crafted cGMP standards.

The reported discussions within the Union Ministry of Ayush for setting up a structured regulatory framework, within the CDSCO, for all Ayush drugs and to allow marketing of any new Ayurvedic medicine only after successful completion of clinical trials to ensure its safety and efficacy, are indeed encouraging. This may be followed for all those Nutraceuticals, which want to be promoted as medicines, claiming direct therapeutic benefits.

Be that as it may, November 24, 2016 announcement of FSSAI, that health supplements or Nutraceuticals cannot be sold as ‘medicines’ anymore to control mislabeling of such brands, is a step in the right direction.

Another major issue of many pharma brands being put under Nutraceuticals with some tweaking in formulations and labelled as food supplements, would also probably be largely addressed, as FSSAI would continue to be the sole authority for marketing approval of Nutraceuticals.

However, it is still not very clear to me, as I am writing this article, what happens to those Nutraceutical brands, which are already in the market, with compositions not conforming to the new FSSAI norms. Fairness demands reformulation and relabeling of all those existing Nutraceuticals, strictly in conformance to the new guidelines, and obtain fresh approval from FSSAI. This will help create a level playing field for all Nutraceutical players in India.

While there is a pressing need to enforce a holistic regulatory discipline for the Nutraceuticals to protect consumers’ health interest, the commercial interest of such product manufacturers shouldn’t be ignored, either. This is primarily because, there exists enough evidence that proper nutritional intervention with the right kind of natural substances in the right dosage form, could play an important role, especially in the preventive health care.

As the comprehensive regulatory guidelines are put in place, Nutraceuticals not being essential medicines, should always be kept outside price control, in any guise or form. In that process, the general pharma perception of Nutraceutical business, as an ‘Oasis’ amidst well-regulated and price-controlled pharmaceuticals, would possibly remain that way, giving a much-needed and well-deserved boost to this business.

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.

Escalating Antibiotic Resistance, And Thwarting Ban Of Irrational FDCs

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September 2016 ‘Fact Sheet’ of the World Health Organization (W.H.O) raised a red flag on fast increasing incidence of Antimicrobial Resistance (AMR). It poses a serious threat to global public health, more than ever before. Consequently, effective prevention and treatment of an ever-increasing and complex range of infections caused by bacteria, parasites, viruses and fungi are becoming more and more challenging.

In this situation, various medical procedures, such as, organ transplantation, cancer chemotherapy, diabetes management and major surgery like, caesarean sections or hip replacements, invite much avoidable a very high element of risk.

Further, a July 2014 paper titled ‘Antibiotic resistance needs global solutions’, published in ‘The Lancet’ reports increase of incidences of drug-resistant bacteria at an alarming rate. In fact, antibiotic resistance is one of the most serious threats in the history of medicine, and new antibiotics and alternative strategies should be sought as soon as possible to tackle this complex problem.

Another more recent paper titled ‘Fixed-dose combination antibiotics in India: global perspectives’, published in ‘The Lancet’ on August, 2016 finds that nowhere in the world this problem is as stark as in India. It emphasizes that the crude infectious disease mortality rate in India today is 416.75 per 100,000 persons, which is twice the rate prevailing in the United States. Misuse, or rather abuse, of Antibiotics is a major driver of resistance. In 2010, India was the world’s largest consumer of antibiotics for human health, the paper says.

Thus, this critical issue calls for urgent action across all government sectors and the society, in general, as W.H.O cautions.

The Devil is also in irrational antimicrobial FDCs:

The reasons for the fast spread of antimicrobial resistance are many, and each one is well documented. One such factor is the use of irrational antimicrobial FDCs. Some of these have already been banned by the Union Government of India, though continue to be manufactured, promoted, prescribed, sold and consumed by the innocent patients unknowingly.

In this article, I shall focus on the banned FDCs of such kind, highlighting how the consequential serious threat to public health and safety is repeatedly getting lost in the cacophony of protracted court room arguments against these bans.

Irrational FDCs and antimicrobial resistance:

That ‘irrational’ FDCs of antibiotics very often hasten the spread of antimicrobial resistance, is now a well-documented fact.

The ‘National Policy for Containment of Antimicrobial Resistance in India 2011’ clearly recognizes that: “Antimicrobial resistance in pathogens causing important communicable diseases has become a matter of great public health concern globally including our country. Resistance has emerged even to newer, more potent antimicrobial agents like carbapenems.” The Policy also recommends removal of irrational antibiotic FDCs from the hospital drug list.

‘The Lancet’ article of August, 2016, as mentioned above, also reiterates, while citing examples, that “Studies of several antibiotic combinations, such as meropenem and sulbactam, have reported no additional advantage over their individual constituents, and have been reported to cause toxic reactions and promote resistance. Despite repeated investigations into the shortcomings of some FDCs, such drugs are still being manufactured and promoted on the Indian drug market.”

Why does it matter so much?

Corrective regulatory measures to contain the spread of antibiotic resistance are absolutely necessary in India, for the sake of the patients. According to a paper titled ‘Antibiotic Resistance in India: Drivers and Opportunities for Action’, published in the PLOS Medicine on March 2, 2016: “Out of around 118 antibiotic FDCs available in the Indian market, 80 (68 percent) are not registered with the Central Drugs Standard Control Organization (CDSCO). Moreover, 63 (19 percent) of around 330 banned FDCs are antibiotics.”

The global relevance:

Such regulatory bans of antimicrobials FDCs in India are important from a global perspective too, as ‘The Lancet’ article of August 2016 observes.

The article recapitulates that the ‘New Delhi metallo-β-lactamase’ – an enzyme that causes bacteria to be resistant to antibiotics, was first reported in India in 2008 and is now found worldwide. The growth of worldwide trade and travel has allowed resistant microorganisms to spread rapidly to distant countries and continents. In addition, some of these banned FDCs in India are reported to be exported to African and Asian countries too.

That said, each country will also need to play a significant role to curtail the abuse or misuse of antibiotics, locally. I find a glimpse of that in England, besides a few other countries.

A research paper of Antibiotic Research UK and EXASOL dated November 12, 2015, concluded that overall antibiotic prescriptions are coming down across England. However, the same paper also articulated that in the deprived areas of the country, such as Clacton-on-Sea, antibiotic prescribing rates are almost twice the national average.

Some big MNCs are no different:

In the Government’s ban list of irrational FDCs even some top brands of pharma MNCs feature, including antibiotic FDC of antibiotics. For example, on Mar 14, 2016, Reuters reported that one of the largest pharma MNCs operating in India – Abbott Laboratories, was selling a FDC of two powerful antibiotics Cefixime and Azithromycin, without approval of the DCGI. This could possibly be a legacy factor, arising out of its acquisition of a good number of branded generic drugs, together with their management, from a domestic pharma company. Abbott, otherwise is well regarded by many as a distinguished global institution, practicing high standards of business ethics and values, across the world.

Be that as it may, this powerful antibiotic cocktail that poses huge health risk to patients has reportedly not received marketing approval in the major global pharma markets, such as, the United States, the United Kingdom, Germany, France or Japan.

The Reuters report also elaborates that the drug ‘had been promoted and administered as a treatment for a broad array of illnesses, including colds, fevers, urinary tract infections, drug-resistant typhoid and sexually transmitted diseases.’ It also found chemists who were selling the drug to prevent post-operative infection and for respiratory problems. After the ban, the company has reportedly stopped manufacturing and sales of this antibiotic FDC.

Irrational FDC ban – a significant corrective measure:

Keeping all this in perspective, the regulatory ban on irrational FDCs of antibiotics on March 10, 2016, along with products falling in several different therapy areas, was a significant regulatory measure, among many others, to contain the menace of AMR in India.

Unfortunately, quite a lot of these formulations are still in the market, actively promoted by their manufacturers and widely prescribed by the doctors, till date. This is mainly because, to protect the revenue and profit generated from these brands, concerned pharma companies have obtained an injunction from various high courts against the ban, which was notified by the Government, earlier.

Thwarting FDC ban – a key issue:

Looking back, 294 FDCs were banned by the DCGI in 2007. At that time also, the same important issue of patients’ health, safety and economic interest got caught in an intriguing legal quagmire. As a result, implementation of the Government’s decision to ban of these irrational FDCs got delayed, indefinitely.

Added to this, irrational antimicrobial FDCs featuring in the ban list of March 10, 2016, got trapped in exactly the same legal battle, yet again. Thus, repeated stalling of Government ban on irrational FDCs, including antibiotics, continue to remain a key health and safety issue in India.

The latest development:

In September 2016, the Union Government has reportedly moved the Supreme Court of India in defense of its March 2016 ban on irrational FDCs.

In its petition, the Union Government has reportedly urged that all cases against the orders related to ban of ‘irrational’ FDCs, now being heard in various High Courts across the country, be transferred to the apex court and heard as a single case. The move is expected to cut any ambiguity that could arise from differing verdicts between high courts.

In case of a verdict favoring the ban of all the notified irrational FDCs, scores of patients will be benefited by not just falling victims to possible health menace arising out of such unjustifiable drugs, as the Government argues, but also due to expected containment of rapid spread of deadly antimicrobial resistance in the country.

Conclusion:

With the ban of irrational FDCs, the Union Ministry of Health has taken one of the much-needed steps to restrict antibiotic resistance in India, besides addressing other health and financial menace caused by such drugs.

The support of the Apex court of India to urgently resolve this legal jig-saw-puzzle, would also help control, though not in a holistic way, the scary antibiotic resistance challenge in India. In that process India would possibly be able to contribute its little bit towards the antibiotic resistance challenge, across the world, if we consider the ‘New Delhi metallo-β-lactamase’ case as a glaring example in this area.

It is, therefore, widely expected that for the greater public interest, the honorable Supreme Court may view this important health and safety issue accordingly, while pronouncing its final verdict. If and when it happens, hopefully soon, the prevailing industry practice in the country to make profits with dubious drug cocktails sans any robust medical rationale, basically at the cost of patients, can’t possibly be thwarted any longer, and will be effectively implemented on the ground.

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.

Millennial Generation Doctors And Patients: Changing Mindset, Aspirations, And Expectations

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The term ‘Millennial Generation’ normally refers to the generation, born from 1980 onward, brought up using digital technology and mass media. According to ‘Millennial Mindset’ – a website dedicated to helping businesses understand millennial employees and new ways of working, the key attributes of this generation are broadly considered as follows:

  1. Technology Driven:
  2. Socially Conscious
  3. Collaborative

The millennial mindset:

The publication also indicates that the overall mindset of the millennial generation is also vastly different from the previous generations, which can fall into four categories:

  1. Personal freedom, Non-hierarchical, Interdependent, Connected, Networked, Sharing
  2. Instant gratification, Wide Knowledge, Test and learn, Fast paced, Always on, Innovative
  3. Fairness, Narcissistic, Purpose driven
  4. Balance, Eco-friendly and Experience focused

Seeks different professional ecosystem:

In the professional arena too, this new generation’s expectations from the professional ecosystem are often seen to be distinctly different, as they are generally seen to be:

  • Willing to make a meaningful professional contribution, mostly through self-learning
  • Seek maintaining a reasonable balance between work and personal life
  • Prefer flexible work environment, unwilling to be rigidly bound by convention, tradition, or set rules
  • Impatient for fast both personal and organizational growth, often on the global canvas

The ‘Millennial Generation’ in India:

The millennium generation with a different mindset, aspirations and value system, already constitutes a major chunk of the Indian demography. According to the 2011 Census, out of estimated 1.2 billion population, around 701 million Indians (60 percent) are under 30 years of age, which also very often referred to as ‘demographic dividend’ of India.

Currently, a large number of Indians belonging to the millennial generation are entering into the work stream of both national and International companies operating in the country.

The challenge in healthcare arena:

In the healthcare sphere too, we now come across a fast increasing number of technology savvy and digitally inclined patients and doctors of this generation. Accurately gauging, and then meeting with their changing expectations has indeed been a challenging task for the pharma companies, and the related service providers.

Their expectations from the brands and other services, as provided by the pharma companies, don’t seem to be quite the same as before, either, so are the individually preferred communication formats, the way of processing, and quickly cross-verifying the product and other healthcare information. Before arriving at any decision, they were found to keenly observe the way brands are marketed, their intrinsic value, type and the quality of interface for engagement with them by the companies, whenever required.

Thus, from the pharma business perspective, qualitatively different strategic approaches, to both the millennial doctors and patients, would be of increasing importance and an ongoing exercise. The goal posts would also keep moving continuously. Achieving proficiency in this area with military precision, I reckon, would differentiate the men from the boys, in pursuit of business performance excellence.

In this article, I shall primarily discuss on the changing mindset and needs of the patients and doctors of the ‘millennial generation’.

A. Treating millennial patients differently:

Around 81 percent of millennial doctors, against 57 percent of older generation doctors think that millennial patients require a different relationship with their doctors than non-millennial patients. About 66 percent of millennial doctors actually act upon this and change their approach, as the survey reported.

The difference:

The key differences on millennial doctors’ treating millennial patients, are mainly in the following areas:

  • Expects more, doesn’t get swayed away: Millennial doctors are more likely to advise the millennial patients to do additional research on their own for discussion. 71 percent of millennial doctors believe it’s helpful for patients to do online research before their appointment. However, they don’t get swayed by requests from more-informed patients, as only 23 percent of millennial doctors say they are influenced by patient requests when it comes to prescribing a treatment, whereas 41 percent of non-millennial doctors report finding those requests influential.
  • Gets into the details: The millennial doctors are more likely to simplify and streamline explanations for older patients, whereas non- millennial doctors were more likely to simplify explanations for millennial patients too, treating them exactly the same way.
  • Relies on digital resources: Millennial doctors rely mostly on using digital resources for treating millennial patients, but only around 56.5 percent of them do so for non-millennial patients.

B. Treating millennial doctors differently:

For effective business engagement and ensure commensurate financial outcomes, pharma companies will first require to know and deeply understand the changing mindset, expectations, and aspirations of the millennial doctors, then work out tailor-made strategic approaches, accordingly, to achieve the set objectives.

Top 3 expectations from the pharma industry:

According to a June 2016 special survey report on Healthcare Marketing to Millennials, released by inVentive Health agencies, the top 3 expectations of millennial and non-millennial doctors from the pharma industry, are as follows:

Rank Millennial Doctors % Rank Non- Millennial Doctors %
1. Unbranded Disease Information 67 1. Unbranded Disease Information 58
2. Discussion Guides 48 2. Latest Specific News 46
3. Adherence Support 40 3. Healthy Life Style Information 42

Pharma players, therefore, can provide customized offerings and services, in various innovative platforms, based on these top 3 different expectations of millennial and non-millennial doctors, to achieve much needed critical competitive edge for a sustainable business performance.

Brand communication process needs a relook:

The above report also noted a number of the interesting trends related to the millennial doctors. I am quoting below just a few of those:

  • Only 16 percent of millennial doctors found pharma promotional materials to be influential when considering a new treatment compared to 48 percent of non-millennial doctors who do.
  • 79 percent of them refer to information from pharmaceutical companies only after they’ve found that information elsewhere.
  • 65 percent of these doctors indicated, they did not trust information from pharmaceutical companies to be fair and balanced, while only 48 percent of their older peers shared that sentiment.
  • 50 percent found educational experiences that are driven by their peers to be the most relevant for learning and considering about new treatments, against 18 percent of non-millennial physicians.
  • 52 percent of them, when learning about new treatment options, favor peers as their conversation partners.
  • They are much more likely to rely on a third-party website for requisite product or treatment information
  • 60 percent of millennial doctors are more likely to see a pharma rep, if they offer important programs for their patients, compared to only 47 percent of non-millennial doctors. This also reflects greater patient centric values of the millennial doctors.
  • However, an overwhelming 81percent of millennial doctors believe that any type of ‘Direct To Consumer (DTC)’ promotion makes their job harder, because patients ask for medications they don’t need.
  • 41 percent of millennial doctors prefer a two-way and an in-person interaction, against just 11 percent of them with online reps. Here, it should be noted that this has to be an ‘interaction’, not just predominantly a monologue, even while using an iPad or any other android tablets.

Redesigning processes to meet changing expectations and needs:

Thus, to create requisite value, and ensure effective engagement with millennial doctors, the pharma companies may consider exploring the possibility of specifically designing their entire chain of interface with Millennials, right from promotional outreach to adherence tools, and from medical communications to detailing, as the survey report highlights. I shall mention below just a few of those as examples:

Communication platforms:

For personal, more dynamic and effective engagement, non-personal digital platforms – driving towards personal interactions with company reps, together with facilitating collaboration between their professional peer groups, came out as of immense importance to them.

Adherence and outcomes:

There is a need for the pharma companies to move the strategic engagement needle more towards patient outcomes. This is mainly because, medication adherence is a large part of the patient outcome equation. It involves a wide range of partnerships, such as, between patients and physicians, and also the physicians and pharma players. This particular need can be best met by offering exactly the type of collaborative approach that millennial doctors favor.

Medical communication:

Redesigning the core narrative of medical communication around a disease state and product, engaging the wisdom and enthusiasm of scientific, clinical, and educational leaders primarily to serve a well-articulated noble cause, are likely to fetch desired results, allaying the general distrust of millennial doctors on the pharma companies, in general.

Medical representative:

Earning the trust of the millennial doctors by respecting, accepting, and appealing to their value systems, is of utmost importance for the medical reps. To achieve this, drug companies would require to equip their reps with tools and programs that offer value in terms of patient support and adherence, while demonstrating compelling outcomes with a positive patient experience, and greater efficiency in treatment decisions.

Building reputation:

The “Purpose Generation” – that’s how millennials are often referred to. In that sense, to build a long lasting business reputation among them, pharma companies need to be in sync with this new generation.

Weaving a trusting relationship with them involves meeting all those needs that these doctors value, such as, adherence solutions, innovative patient support programs, and creating shared value for communities. This would mean, for many drug companies, charting an almost uncharted frontier, where there aren’t many footsteps to follow.

Need to induct younger generation to top leadership positions faster:

To capture these changes with precision, and designing effective engagement strategies for millennial patients and doctors accordingly, an open, innovative and virtually contemporary mindset with a pair of fresh eyes, are essential. As against this, even today, many ‘Baby Boomers’ (born approximately between 1946 and 1956), who have already earned the status of senior citizens, meticulously nursing a not so flexible mind with traditional views, still keep clutching on to the key top leadership positions in the pharma industry, both global and local.

This prevailing trend encompasses even those who are occupying just ornamental corporate leadership positions, mostly for PR purpose, besides being the public face of the organization, sans any significant and direct operational or financial responsibilities. Nevertheless, by pulling all available corporate levers and tricks, they hang-on to the job. In that way, these senior citizens delay the process of change in the key leadership positions with younger generation of professionals, who understand not just the growing Millennials much better, but also the ever changing market dynamics, and intricate customer behavior, to lead the organization to a greater height of all round success.

I hasten to add, a few of the younger global head honcho have now started articulating a different vision altogether, which is so relevant by being a community benefit oriented and patient centric, in true sense. These icons include the outgoing GSK chief Sir Andrew Witty, who explains how ‘Big Pharma’ can help the poor and still make money, and the Allergan CEO Brent Saunders promising to keep drug prices affordable. Being rather small in number, these sane voices get easily drowned in the din of other global head honchos, curling their lips at any other view point of less self-serving in nature. Quite understandably, their local or surrounding poodles, toe exactly the same line, often displaying more gusto, as many believe.

Conclusion:

The triumph of outdated colonial mindset within the drug industry appears to be all pervasive, even today. It keeps striving hard to implement the self-serving corporate agenda, behind the façade of ‘Patient Centricity’. When the demography is changing at a faster pace in many important countries, such as India, a sizeable number of the critical decision makers don’t seem to understand, and can’t possibly fathom with finesse and precision, the changing mindset, aspirations and expectations of the millennial generation doctors and patients.

Expectedly, this approach is increasingly proving to be self-defeating, if not demeaning to many. It’s affecting the long term corporate performance, continually inviting the ire of the stakeholders, including Governments in various countries.

From this perspective, as the above survey results unravel, the millennial doctors and patients, with their changing mindset, aspirations, expectations and demands, look forward to an environment that matches up with the unique characteristics and values of their own generation.

To excel in this evolving scenario, especially in India – with one of the youngest demographic profiles, proper understanding of the nuances that’s driving this change, by the top echelon of the pharma management, is of utmost importance. Only then, can any strategic alignment of corporate business interests with the expectations of fast growing Millennials take shape, bridging the ongoing trust deficit of the stakeholders, as the pharma industry moves ahead with an accelerated pace.

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.

 

Relevance of Artificial Intelligence In Creative Pharma Marketing

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Keeping pace with the challenge of change globally, the macro environment in the pharma business is also undergoing a metamorphosis. This includes areas, such as, strong product pricing pressure, dwindling new product pipelines, increasing operating expenses, stringent regulatory requirements, rising stakeholder expectations, and several others. All these developments collectively, are making the drug companies, both global and local, feel the tailwind of various intensities, in their efforts to achieve the corporate financial goals, more than ever before.

Despite this continuous change, most pharma players’ overall strategic business models to meet with the increasing economic expectations of the shareholders, other investors and the stock markets, have hardly undergone any path breaking, radical, or disruptive advancement, just yet. This includes even the most critical interface between an organization and the consumers – pharma sales and marketing.

That said, it is not uncommon, either, to witness some sporadic initiatives of major business process reengineering with sophisticated digital applications. Interestingly, all these measures are mostly replacements or for realignment of the same age old, and traditional strategic pharma sales and marketing models. Most of these are aimed at adding more speed and accuracy to the same business core process, along with ensuring greater management information and control to support the decision making process.

Despite this palpable environmental shift, general inertia within the pharma industry to respond to all these, with commensurate strategic game plans of surgical accuracy, is glaring. Currently, the general response to this transformation is mostly reactive and traditionally defensive in nature, rather than proactive, as the overall business environment around the industry keep becoming increasingly demanding. Most pharma players may not, but the time keeps galloping ahead, offering a mind boggling rapid advances in disruptive technological innovations – the potential game changers for its several business domains.

In the midst of such all-embracing changes, yet another disruptive technology – ‘Artificial Intelligence (AI)’, is prompting many business leaders to step on to a brand new paradigm, making use of AI to the extent required, especially, while preparing a detail strategic roadmap for the business with high precision.

A clear intent to seize this moment is now visible in many industries, though in varying degrees and scale, but surely it is happening. This is vindicated by the gradual increase in demand for AI, across a wide variety of its application areas.

Marketing to turn upside down?

On October 26, 2016 an article published in ‘The Huffington Post’ on how AI could ‘Turn the Marketing World Upside Down’ indicated its disruptive impact on the way innovative marketing strategies are conceived, created and implemented on the ground.

The article gave an interesting example of how paradigm shift follows a predictable pattern of development that starts with substitution, followed by augmentation, modification, and finally redefinition.

For example, the evolution of today’s smartphones also followed the same pattern, as follows:

  • First replaced simpler landline phones
  • Then adapted with the addition of a camera
  • And finally redefined “phone” altogether, not just by replacing cameras, pagers, and many functions of personal computers, but by being able to perform with great precision an incredible number of various other serious requirements, well supported by related digital apps.

With the application of AI in marketing, the conventional ball game right from conception, to charting out and execution of marketing strategies, will be catapulted to a new and fascinating orbit altogether. I have no intent to romanticizing it. This is going to happen sooner than later, as we move on.

Artificial Intelligence (AI):

In a simple and commonly understandable way ‘Artificial Intelligence (AI)’ can be explained as the theory and development of computer systems, which are able to perform tasks normally requiring human intelligence, such as, machine learning, visual perception, image processing, speech recognition, decision-making, and language processing, besides many others.

In the Hollywood film industry, several sci-fi movies have already been made, based on AI as the core theme. Some of these international blockbuster films are ‘The Terminator’, ‘Transcendence’, ‘The Matrix’, ‘Ex Machina’, ‘Ex Machina’ or even ‘2001: A Space Odyssey’, among many others.

Some concern, but…:

Alongside, a serious concern has also been expressed by some global icons, that the evolution of AI could reach a dangerous threshold, where mankind will no longer remain in control of the creation of its own progeny, besides other living beings. This could, as they believe, jeopardize the continuity of an entire civilization, at least, in its present form.

In 2014, globally acclaimed Professor Stephen Hawking commented in an  interview with the BBC: “Humans, limited by slow biological evolution, couldn’t compete and would be superseded by A.I.”

In fact, in July 2015, Professor Hawking reportedly joined Elon Musk, Steve Wozniak, and many others, warning that AI can potentially be more dangerous than nuclear weapons.

In the same year, even Bill Gates, co-founder of Microsoft, reportedly expressed his concerns, saying, “I am in the camp that is concerned about super intelligence…”

On the other hand, despite such apprehensions, AI based technology keeps evolving at a rapid pace, with the funding in AI research taking giant leaps forward. The technology has already found its cutting edge extensive applications in several warfare. We now hear almost every day about unmanned drones not just doing defense surveillance, but destroying strategic targets with jaw-dropping precision. Or for that matter, use of robots has become rather common to diffusive explosive devices of various kinds, intensity, and planted in important places to kill people. As reported by the media, ‘autonomous and self-aware robots to diminish the need for human soldiers to risk their lives.’

Google’s driverless cars also use similar AI technology offering advanced analytics-based algorithms, machine learning and deep learning processes, which could well be another game changing example in this area.

The benefits far outweigh the risks?

Be that as it may, the benefits of AI seem to far outweigh the risks, in various areas. This includes its strategic applications in the pharma industry.

This gets vindicated by the February 2016 research report of ‘Markets and Markets’ (claimed as the world’s second largest firm in publishing premium market research reports, per year), which estimated that AI market would record a turnover of around US$ 5.05 Billion by 2020, growing at a CAGR of 53.65 percent between 2015 and 2020. This market is currently dominated by the ‘Machine Learning’ technology, as it provides the computers with the ability to learn without being explicitly programmed, and are capable of updating themselves when exposed to new data.

Some of the key players operating in the artificial intelligence market are IBM Corp. (U.S.), Microsoft Corp. (U.S.), Google Inc. (U.S.), IPsoft (U.S.), FinGenius Corp. (U.K.), Rocket Fuel Inc. (U.S.), Mobileye N.V. (Israel), Kensho Technologies, Inc. (U.S.), Sentient Technologies (U.S.), and Zephyr Health (U.S.), the report revealed.

AI in pharma:

Over the last decade, AI is being increasingly used by various industries, as a key support to the strategic decision making process, in various areas of business. Understandably, in pharma its use has been rather limited, as on date. Nevertheless, there are several key domains within the pharma industry, where effective use of AI has the potential to be a critical performance enhancer. These areas include, not just in discovery research, or in clinical trials, or in sales and marketing, but also in setting the right strategic direction for the company.

However, in this article, I shall focus mainly on the application of AI in pharma marketing.

AI in pharma marketing:

Although AI is now being sparsely used, it is expected to be more widely used in pharma research and development. It also shows tremendous potential in developing creative sales and marketing strategies, with great accuracy.

So far, pharma marketing strategies are based more on the qualitative data, some traditional quantitative data, and a huge dose of marketers ‘gut feel’. It continues to happen, when the world, including India, is moving towards innovative data driven decision models. If one chooses to, now a pharma marketer also can make effective use of an abundantly available wide variety of quality data to feel the pulse of the markets, consumers and any identified issues, with great precision. Thereafter, based on these real life hard facts, the team needs to put in place for implementation, with an open and innovative mind, a creative sales and marketing game plan, to achieve the set goals.

Would that mean, a pharma marketer should necessarily be an expert in a huge volume of data analysis? I don’t guess so. ‘Machine Learning’, ‘Deep Learning’ and other analytics-based processes of AI can help them enormously to do so.

AI based analytics has now been proved to be far more reliable than any human analysis of the humongous volume of different kinds of quality data. Doing so is even beyond the capacity of any conventional computers that a marketing professional generally uses for this purpose.

The prime requirement for this purpose, therefore, is not just huge volume of data per se, but good quality of a decent volume of data, that a state of the art analytics would be able to meaningfully deliver, that is tailor made to meet the specific requirements of pharma marketers to create a cutting edge marketing strategy.

Areas of AI use in pharma – some examples:

AI will be extremely useful to arrive at the most effective strategic options available, with pros and cons, to achieve the core sales and marketing objectives of the organization, both long and short term.

It can also add immense value right at the decision making stages to determine the key ingredients of an effective strategic plan in a number of critical areas, such as:

  • Arriving at the optimal product-portfolio-mix with the right expense tag attached to each brand
  • Deep learning about market dynamics, customer behavior and their interplay
  • Matching unmet customer needs with enhanced and differentiated value offerings – both tangible and intangible
  • Effective bundling of brand offerings and associated services for each patient segment
  • Selecting the right mix of communication channels, including social media, to ensure maximum productivity in reaching each category of the target audience
  • Detailed strategic blueprint for each type of stakeholder engagement, along with related value offerings
  • Arriving at the best possible resource-mix with the available budget
  • Real-time monitoring of each strategic action steps, consistently, making quick changes on the run, if and when required

Pharma AI platforms are already available:

There are a number of AI platforms now available for the pharmaceutical companies, across the world. For example, in September 2015, by a Press Release, Eularis – a leading provider of next-generation advanced marketing analytics to the Pharma industry, announced the release of the E-VAI, the latest development in sophisticated machine learning technology delivering next-generation analytics and decision making for Pharma marketers globally.

Another recent example of AI in this area, as well, is ‘Salesforce Einstein’. It delivers advanced AI capabilities in sales, service, and marketing, and enables anyone to build AI-powered apps that get smarter with every interaction. According to Salesforce, it will enable everyone in every role and industry to use AI to be their best.

Conclusion:

The use of AI in pharma is still in its nascent stage today. However, for a sustainable business excellence in its various domains, AI is increasingly proving to be of great relevance, now and also in the future. Sales and marketing is one such domains.

With the passage of time, both the macro and micro pharma business operating environments are changing fast, primarily driven by changing expectations of stakeholders, the public at large, and disruptive algorithmic technical innovations, based on advanced science, statistics and mathematics.

The scope to effectively utilize the full potential of advanced algorithmic technical tools, is huge. It is easier now to capture a massive volume of pharma related high quality raw data of different kinds, for tailor-made innovative analysis, with the help of AI based analytics, while creating cutting-edge strategic game plans.

Nonetheless, pharma players apparently continue to chart the same strategic frontier where there are many footsteps to follow. Many of them have restricted themselves to no more than digitally re-engineering the same overall business processes that they have been already following, since long. Just a few of them are making use of the leading edge analytics involving AI, such as ‘Machine Learning’, ‘Deep Learning’, ‘Visual Perception’, ‘Image Processing, besides many others, which can be more ‘patient-centric’ and at the same help deliver a strong business performance.

Thus, quicker adaptation, and thereafter continuous scaling up applications of high quality AI based analytics in creative pharma marketing, are not just of immense relevance today, they also bring with them the commensurate potential for sustainable excellence in financial performance of the organization, fueled by critical early mover advantage.

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. 

Reticence Around Unveiling Clinical Trials

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While scanning through various publications, we now get to know, almost at regular intervals, about new clinical trials capturing the newer ways of treating different ailments. Such information instils an invigorating hope in the minds of doctors and the patients alike, to more successfully and predictably fight the battle against diseases in the ongoing pursuit for a better quality of life.

However, for independent and impartial assessment of any new drug before it comes to the market, an ethical and transparent process of unveiling clinical trials, sans any reticence whatsoever, are absolutely essential. Only this process would be able to satisfactorily establish, beyond an iota of doubt, the safety and efficacy levels of, especially, the new drugs. To move in that direction, the fundamental requirements will be diligently recording and publishing all types of data – positive, not so positive, and also negative, arising out of all clinical trials, conducted anywhere in the world, for the same drug.

Thus, there should be a system of open access to all clinical trial data, as each trial is completed. Otherwise, pharma companies’ publication bias, overwhelmingly on positive results, would continue, as alleged by many across the world. It is worth noting that over 60 percent of all clinical trials for new drugs are sponsored by the pharma and biotech companies.

There isn’t any dearth of examples of new drugs’ getting not just the required regulatory approval, riding on the back of robust ‘positive’ clinical trial data on safety and efficacy, but also becoming highly dependable money-spinners for the companies, and in no time, as it were. These cash churning new brands would also get well protected for monopolistic pricing all through their respective patent life, and sometimes even after that, in various different ways.

Nevertheless, at a later date, mostly post patent expiry, not all pre-launch new drug trials could be universally accepted as robust and conclusive, especially on their efficacy and safety claims. On the contrary, a number of detailed and deep-stick independent studies indicate that some new drugs are, in fact, much less effective, if not ineffective, and cause more serious side effects than what were published earlier.

Hence, some critical questions are now being asked by many stakeholders, with greater assertiveness than ever before and backed by solid evidence, in this arena. Although it has now started creating a snowballing effect, still, nothing much seems to have changed on the ground, just yet.

Why aren’t all clinical trial results, and for all new drugs not still published, or otherwise made available for public scrutiny, unveiled, and of course after protecting any reasonable commercial interest? Does business consideration, then continue to prevail over the need for transparency in clinical trial data disclosure for patients’ health and safety? The sneaking fear behind the reasons of this reticence of pharma players, in general, continues to torment many. I shall discuss this point in this article backed by recently published data.

Not a recent trend:

This isn’t a recent trend either, and continuing for decades, without any effective remedial measures by the appropriate authorities. I would give just a couple of examples, one from 1998 and the other from 2014, to drive home this point.

A  British Journal of Clinical Pharmacology (BJCP) article, published way back in August 1998 would vindicate this point. This study revealed the following on clinical trial data:

“Substantial evidence of selective reporting was detected, since trials with positive outcome resulted more often in submission of final report to regulatory authorities than those with inconclusive or negative outcomes.”

Another study published on September 10, 2014 in the Journal of American Medical Association (JAMA) states as follows:

“Thirty-five percent of published reanalysis led to changes in the findings that implied conclusions different from those of the original article about the types and number of patients who should be treated.”

That said, I shall now focus on a very recent controversy in this area, related to a blockbuster drug that has now gone off-patent.

A contemporary example:

Statin class of drugs, especially, Atorvastatin is one of many such examples.

Pfizer launched Atorvastatin with the brand name Lipitor in early 1997. At that time, it was the fifth in the statin class of drugs for the treatment of hyperlipidemia.

It was launched on the back of a 1996 clinical study that concluded, Lipitor reduces bad cholesterol significantly more than the other statins, from the very onset of treatment to as long as the treatment continues. After that it’s a history in the pharma industry, Pfizer marketing turned it into the best-selling drug ever, in the history of pharmaceuticals, so far.

Over 14.5 years, Lipitor reportedly made over US$ 125 billion in sales, and provided up to a quarter of Pfizer Inc.’s annual revenue for years.

Product claim – then:

Claiming that in ‘one year alone, statins reduced numerous cases of cardiovascular-related complications and saved thousands of lives’, a Pfizer Paper on “The Value of Statin”, reiterated the drug’s role both in the treatment and prevention of Coronary Artery Diseases (CAD). I am quoting below from this paper to cite just one example each – treatment and prevention:

  • In a study of patients with Coronary Artery Disease (CAD) statin therapy reduced the relative risk of mortality by 50 percent in those > 80-years-old, 44 percent in those 65- to 79-years-old, and 30% in those < 65 years old, compared to CAD patients in the same age group not taking statin therapy (Ref. Chloe, Allen A., et al. ‘Statin Therapy Is Associated With Reduced Mortality Across All Age Groups of Individuals With Significant Coronary Disease, Including Very Elderly Patients’. JACC. 40: 10; 1777-1785)
  • An analysis of 18 trials, including 56,934 patients, primarily without CVD, demonstrated statins conferred a relative risk reduction (RRR) in all-cause mortality by 14 percent and stroke by 22 percent (Ref. Statins for the primary prevention of cardiovascular disease. Cochrane Database System Review. 2013 Jan 31; 1:CD004816).

Research findings for the same drug – now:

Among several other publications on statins, a July 26, 2015 article, published in the ‘World Journal of Cardiology’ concludes as follows:

“History has proven otherwise, and the global prevalence of Coronary Heart Disease (CHD), despite worldwide statin usage and cholesterol lowering campaigns, has reached pandemic proportions. Coronary heart disease is an extremely complex malady and the expectation that it could be prevented or eliminated by simply reducing cholesterol appears unfounded. After twenty years we should concede the anomalies of the cholesterol hypothesis and refocus our efforts on the proven benefits of a healthy lifestyle incorporating a Mediterranean diet to prevent CHD.”

To give one more example, let me quote from a contemporary study, published on June 12, 2016 in the ‘BMJ Open’, which also comes to a similar conclusion, as follows:

“High LDL-C (Low-Density Lipoproteins – Cholesterol) is inversely associated with mortality in most people over 60 years. This finding is inconsistent with the cholesterol hypothesis (i.e., that cholesterol, particularly LDL-C, is inherently atherogenic). Since elderly people with high LDL-C live as long or longer than those with low LDL-C, our analysis provides reason to question the validity of the cholesterol hypothesis. Moreover, our study provides the rationale for a re-evaluation of guidelines recommending pharmacological reduction of LDL-C in the elderly as a component of cardiovascular disease prevention strategies.”

Examples of other drugs:

Lipitor should not stand out as a solitary example, in this field. To establish this point, let me now put forth, just as illustrations, a few more examples of similar bias on positive results in clinical trial publications, besides many others.

An October 4, 2016 article titled, “Big Pharma’s Role in Clinical Trials”, published in the ‘Drug Watch’, quotes several other companies sailing in the same boat, as follows:

  • The Cochrane Collaboration, a nonprofit organization based in London that reviews health care information, concluded that unlike its promotional claims, Roche’s Tamiflu only shortened symptoms of influenza by one day, and it did not prevent hospitalizations or complications from influenza.
  • AstraZeneca reportedly paid US$ 647 million in lawsuit settlements for failing to inform the public of Seroquel’s side effects.
  • Takeda Pharmaceuticals reportedly settled lawsuits claiming the company’s anti-diabetic drug Actos caused bladder cancer, for US$ 2.37 billion.
  • In July 2012, GlaxoSmithKline reportedly pleaded guilty and agreed to pay US$ 3 billion to settle charges brought by the U.S. Department of Justice for failing to report clinical data on its anti-diabetic drug Avandia.
  • Johnson & Johnson was reportedly accused of hiding some dangerous side effects like, diabetes, substantial weight gain, stroke and gynecomastia – or breast development in boys for its product Risperdal – used to treat schizophrenia and bipolar disorder in adults and adolescents and autism spectrum disorders in children and adolescents.  The company reportedly settled claims in Kentucky, Texas and Montana for a total of more than US$ 340 million and settled multiple cases in Pennsylvania for undisclosed amounts.
  • As reported by ‘Financial Times’ on February 03, 2015, Novartis was accused of manipulating trial data in favor of its anti-hypertensive drug – Diovan, and concealing side-effects associated with its Tasigna – for leukemia treatment. As a result, the company reportedly faced a temporary suspension of its business in Japan, as punishment for alleged manipulation of clinical trial data.

Possible reasons:

The above ‘Drug Watch’ article attributed several reasons to positive data bias in publications, as follows:

  • Researchers publish positive findings more often than negative findings as a result of human bias. Scholars want their work to contribute to medical advancement and not deter it.
  • Researchers do not want to put their time and energy into writing studies about negative results.
  • Journals seek positive results, and publish them more quickly to increase publicity.
  • Trial sponsors want to publish positive results to increase profit.

The article emphasized, “Big Pharma funds 60 percent of all clinical trials, and takes advantage of its power to persuade researchers and influence institutions.  The result is an under-informed, and misinformed medical community giving advice to patients with false or incomplete data. The byproducts of industry cover-ups are scores of deaths and millions of dollars in industry profits.”

Indian scenario:

India is also not immune from such alleged wrongdoings. Indian clinical trial organizations have also been accused of trial related scams, and that too on a mega scale, reaching beyond the shores of the country. I am quoting below two such recent examples:

  • In August 2015, the European Union reportedly banned the marketing of around 700 generic medicines for alleged manipulation of clinical trials conducted by the domestic research company GVK Biosciences. This was reported as the largest EU-wide suspension of sales and distribution of generic drugs ordered by the European Commission that was applicable to all its 28 member nations.
  • In July 2016, the European Medicines Agency (EMA) reportedly recommended suspending the sale of dozens of generic medicines over concerns about “flawed” studies that were conducted by the Semler Research Center, located in Bengaluru. Many of these drugs are sold by Novartis and Teva Pharmaceuticals.
  • In September-October 2015, US-FDA also found “significant instances of misconduct and violations of federal regulations by the same research center, which includes substitution and manipulation of study subject samples.”
  • This year, the World Health Organization (WHO) also had issued a notice to Semler for the same reasons. After, examining the company’s computer servers, early and late last year, WHO reportedly found a spreadsheet file containing detailed instructions for manipulating drug samples that were used in clinical trials for its clients. 

It is even more unfortunate that such malpractices are continuing, even after the Supreme Court of India’s widely reported observation in early 2013 that ‘Uncontrolled clinical trials are causing havoc to human life.’ The apex court of the country made this remark in response to a petition filed by the human rights group Swasthya Adhikar Manch (SAM).  

The upshot:

Recent scrutiny of all original clinical trial findings of many new drugs by the independent experts, including statins, even if taken just as raising controversies, the question would still remain, why did such controversies not surface much earlier, or during the product patent life? No company would possibly be willing to unveil the fact behind this raging debate.

The good news is, pharma companies operating in Europe and the United States have decided to share trial data with qualified researchers, effective 2014, presumably in response to mounting pressure from clinical trial transparency campaigners, for quite some time.

The European Federation of Pharmaceutical Industries and Associations (EFPIA) and the Pharmaceutical Research and Manufacturers of America (PhRMA) have jointly released a set of principles detailing plans to allow greater access to information from clinical trials. However, it fell short of public availability of all clinical trial data. Let’s wait, watch and hope that this seemingly good intent would be translated into reality by all their member companies.

Some pharma companies and their trade associations continue to raise issues of the various legalities against related to public disclosures of all trial data. Nevertheless, it is worth noting that in April 2014, a legislation was approved in Europe by the European Parliament to increase transparency in clinical trials by making the trial results publicly available. EMA was commissioned by the European Parliament to create a database where all interested parties could view comprehensive data from clinical trials. The transparency rules for the European Clinical Trial Regulation entered into force on January 1, 2015 and apply to clinical trial reports contained in all marketing authorization applications submitted on or after this date. On March 3, 2016, EMA announced the detailed guidance on the requirements for pharmaceutical companies to comply with the agency’s policy on publication of clinical trials data for all medicines. Chapter Three of this publication gives guidance to companies on how to anonymize clinical reports for the purpose of publication.

The EMA initiative of transparency of clinical trial data  aims at ensuring that drug companies are aware of what is expected of them, and that they are ready for the publication of these critical data.

Besides Europe, in the United States too, though there is a clear mandate of the federal government that all clinical trial results related to serious or life-threatening diseases require to be published and uploaded on ClinicalTrials.gov – the database of the Government covering all clinical trials in America. However, this government mandate also seems to be hardly followed, both in its letter and spirit, according to reports. Similar scenario, reportedly, still prevails in most other developed countries, as well. India does not seem to be any different in this matter, either.

Intriguingly, the whole issue continues to remain polemical, with more number of initial clinical trial conclusions reportedly turning out to be not as transparent as these ought to be, carrying a significant bias towards positive treatment outcomes.

As a result, prevailing reticence around unveiling all clinical trials, including those of blockbuster drugs, is eventually pushing many patients to the brink of much avoidable and unforeseen serious health risk.

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.