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‘Indian Drug Control World’s Weakest: Pharma Trade Bodies Working At Cross Purposes’

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“In the entire world, I think our drug control system probably is the weakest today. It needs to be strengthened,” said the Secretary of the Department of Pharmaceuticals (DoP) – V K Subburaj at an event in New-Delhi on April 19, 2016. 

In his speech, the Secretary also singled out the pharma industry associations for working in opposite directions, adding that “if we take one decision, it is appreciated by one but the other one criticizes us”.

This is indeed an irony. Such scathing comments from an important and a top Government official indeed stand out. This is primarily because, in the midst of the prevailing scenario, where a large section of the Government is saying ‘we are the best’ or ‘best among the worst’ or, at least, ‘fast improving’, a seemingly helpless key decision maker for the pharma industry was constrained to publicly say, what he had said, as above.

Nonetheless, public expressions, such as these, coming from a top Government official well-captures the sad and pathetic scenario of the systemic failure of pharma industry regulators to bring order in the midst of continuing chaos. Virtually free-for-all business practices, blatantly ignoring the patients’ health and safety interest in the country, continue to thrive in a self-created divisive environment.

Unsparing remarks in two critical areas:

As reported by the ‘Press Trust of India (PTI)’, the DoP Secretary, with his unsparing remarks, publicly expressed his anguish for the delay in taking remedial measures, at least in the two critical areas of the pharma industry in India, as follows:

  • Questionable quality of drugs
  • Questionable pharma marketing practices 

He also highlighted, how just not some Government Departments, but the pharma trade associations, which are formed and fully funded by the pharma players, both global and local, are working at cross-purposes to perpetuate the inordinate delay in setting a number of things right, to satisfy the healthcare needs of most patients.

I briefly dwelled on this critical conflict in my article in this blog of March 28, 2016 titled, “Ease of Doing Pharma Business in India: A Kaleidoscopic View”

A. Questionable quality of drugs:

There wasn’t enough debate in the country on the questionable drug quality in India. It began when the US-FDA started banning imports of a number of medicines in the United States from several drug manufacturing facilities in India. These pharma plants are of all sizes and scales of operations – large, medium, small and micro.

Almost on a regular basis, we now get to know, both from the national and international media, one or the other pharma manufacturing facility in the country, has received the ‘warning letter’ from the US-FDA on its ‘import ban’.

Dual drug manufacturing quality standards?                                            

The spate of ‘Warning Letters’ from the US-FDA have brought to the fore the existence of two different quality standards of drug manufacturing in India:

  • High quality plants dedicated to exports in the well-regulated markets of the world, such as, the United States, following the US-FDA regulations.
  • Other plants, with not so stringent quality standards of the Drug Controller General of India (DCGI), cater to the needs of the Indian population and other developing non-regulated markets. 

In this situation, when many Indian manufacturers are repeatedly faltering to meet the USFDA quality standards, the following two critical questions come up:

  • Are the US-FDA manufacturing requirements so stringent that requires a different compliance mindset, high-technology support, greater domain expertise and more financial resources to comply with, basically for protection of health and safety of the American patients?
  • If so, do the Indian and other patients from not so regulated markets of the world, also deserve to consume drugs conforming to the same quality standards and for the same reason? 

Answers to these questions are absolutely vital for all of us.

Pharma associations working at cross-purposes? 

Considering this from the patients’ perspective, there lies a huge scope for the pharma associations, though with different kind of primary business priorities, to help the Government unitedly in resolving this issue.

It appears from the deliberation of the DoP Secretary that the health ministry is already seized of the matter. The concerned departments are also apparently batting for quality, and trying to strengthen some specific capacity building areas, such as, increasing the number of inspectors and other drug control staff.

Reports also keep coming on the poor quality clinical trial data in India, including data fudging, as was recently detected by the foreign drug regulators. Intriguingly, nothing seems to be changing on the ground. In these areas too, the industry can unitedly try to protect the innocent patients from the wrongdoers, demonstrating enough credible and publicly visible real action.

From the anguish of the DoP Secretary on the critical quality related issue, it appears, there is a huge task cut out for the Indian drug regulators to ensure uniform and high drug quality standards for health and safety of all Indian patients’, just as their counterparts in America.

It is unfortunate to note from his observation that pharma industry associations are not visibly working in unison on many such issues in India.

B. The UCPMP:

The Edmund J. Safra Center for Ethics of Harvard University, while deliberating on “The Pharmaceutical Industry, Institutional Corruption, and Public Health” dwelled on the legal, financial, and organizational arrangements within which the pharmaceutical industry operates. It said, this situation sometimes creates incentives for drug firms and their employees, that conflict with the development of knowledge, drug safety, the promotion of public health, and innovation. More importantly, they also make the public depend inappropriately on pharmaceutical firms to perform certain activities and this leads to institutional corruption.

Illustrating from Professor Marc Rodwin’s project, the article said pharma players provide substantial discretionary funding for important medical activities, such as, continuing medical education, medical research, medical journals, and professional medical societies, which can encourage unwanted and undesirable compromise and bias in favor of their interests.

The same sentiment was also well-captured in an editorial of the well-reputed international medical journal BMJ of June 25, 2014. It unambiguously articulated, “Patients everywhere are harmed when money is diverted to the doctors’ pockets and away from priority services. Yet this complex challenge is one that medical professionals have failed to deal with, either by choosing to enrich themselves, turning a blind eye, or considering it too difficult.”

The editorial underscored the point that success in tackling corruption in healthcare is possible, even if it is initially limited, as anti-corruption bodies in the United Kingdom and US have shown to a great extent. With this, BMJ planned to launch a campaign against ‘Corruption in Medicine’, with a focus on India.

The DoP initiative:

Initiating a step in this direction, on December 12, 2014, the DoP announced details of the ‘Uniform Code of Pharmaceutical Marketing Practices (UCPMP)’, which became effective across the country from January 1, 2015. The communique also said that the code would be voluntarily adopted and complied with by the pharma industry in India for a period of six months from the effective date, and its compliance would be reviewed thereafter on the basis of the inputs received.

Not a panacea:

It is worth noting, since the last three and a half decades, ‘Code of Pharmaceutical Marketing Practices’, prepared by various global pharma trade associations and most of the large global pharma companies individually, have come into existence purported for strictest voluntary adherence. These are being relentlessly propagated by them and their trade associations, as panacea for all marketing malpractices in the drug industry. Squeaky clean ‘pharma marketing codes’ for voluntary practices can be seen well placed in the websites of almost all large global pharma players and their trade associations.

The concept of a pharma marketing code and its intent are both commendable. However, the key question that follows: are all those working in practice? If the answer is yes, why then mind boggling sums in billions of dollars are being paid as settlement fees by a large number of global pharma companies for alleged colossal marketing malpractices in different countries of the world?

Mandatory UCPMP:

As happens with any other voluntary pharma marketing code of a global drug company or their trade associations, however mighty they are, similar non-compliance was detected by the DoP with voluntary UCPMP.  This gross disregard on the code, apparently prompted the DoP making the UCPMP mandatory, with legal implications for non-compliance, which could possibly lead to revocation of marketing licenses. 

A move in this direction, obviously necessitated meaningful discussion of the DoP with all stakeholders, especially the pharma trade associations. According to the Secretary, the discussions got unduly protracted, crippling his decision making process to put the mandatory UCPMP in place, soon.

Divergent views of pharma associations?

Thus, it is now quite clear that one of the reasons for the delay in making the UCPMP mandatory is the divergent views of various pharma trade associations.

In the Secretary’s own words, “To take an example of uniform marketing code, we thought we could arrive at a common solution. But even after 7-8 meetings, we failed to come to a conclusion. It’s only now that we have arrived at a code.” 

However, the bottom-line is, as on date, we don’t know when would the mandatory UCPMP come into force in India.

Conclusion:

The reverberation of virtual helplessness in the recent utterances of the Secretary of the DoP, has naturally become a cause of great concern, especially for the patients. There is still no sign of early resolution of the critical issue of dubious quality, both in the drug manufacturing and clinical trials in India.

The concerned ministries would require to demonstrate unwavering will and unflagging zeal for good governance with accountability, to set things right, without any further delay. When US-FDA can, why can’t the DCGI succeed in doing so? The Government is expected to ensure that justice prevails in this area, for the patients’ sake, soon enough.

Similarly, wrong doings in pharma marketing practices also need to be addressed by the DoP, initially making the UCPMP mandatory having strong legal teeth, to start with, notwithstanding the fact that the trade associations mostly work at cross-purposes, in this area too.

As I hear from the grapevine, especially the MNC trade associations, both inside and outside the country, are trying hard to take, especially, the owners of the large Indian pharma companies on board, in several ways, basically to further their crusade on various self serving issues, such as dilution of Indian Patents Act.

That said, taking serious note of the observation of the DoP Secretary that the Indian drug control is the “weakest in the world”, together with the challenges that he is facing in containing pharma marketing malpractices, I hope, the honorable Prime Minister’s Office (PMO) may wish to intervene soon, in order to promptly contain these snowballing public health menace.

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.

Clinical Trials: Critical Need To Improve Patient Participation With Informed Consent

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On April 13, 2016, an article in the Wall Street Journal (WSJ) titled, “Clinical Trials Need More Subjects” underscored an important point that the rate at which the clinical researchers are able to recruit and retain patients for ‘Clinical Trials (CT)’, has now hit an all-time low. This is vindicated by studies that indicate less than 10 percent of Americans now participate in clinical trials, and only 3 to 5 percent of patients sign up for trials of new cancer therapies, in the largest CT market of the world.

As a result, about 40 percent of CTs do not recruit enough patients to meet their goals, the article highlights. Consequently, a large number of pharma industry sponsored CTs are now, reportedly, moving away from the United States. India should, therefore, take note of this development and pull up the socks.

If similar situation gets replicated in other countries too, and persists, it would be very unlikely that critical and credible medical and scientific knowledge that can significantly improve the treatment outcomes in many serious disease conditions could be meaningfully gathered and put to practice. Its other serious fallouts too, are also not terribly difficult to imagine.

A key medical research tool: 

In pursuit of the advancement of medical knowledge and patient care, CT of drugs is universally considered to be a key medical research tool, as it is the best way to learn what works best in treating various types of diseases. It goes without saying that drugs for all new types of treatments would need to be discovered first through a long and painstaking process of discovery research. These are then purified, and tested in preclinical studies, before a final decision is taken for commencement of CT on human against preset parameters, as deemed necessary.

While going through this stringent process some drugs are found to be safe and effective on human subjects and some others are not, on the contrary may be harmful.

There lies the crucial importance of CT for all scientific evidence based medicines. According to the Department of Health & Human Services of the United States, Clinical research is done only if doctors don’t know:

  • whether a new approach works well with people and is safe and
  • which treatments or strategies work best for certain illnesses or groups of people 

CT, though a small part in the important and lengthy process of developing newer treatments, significantly helps the health care decision makers to decide on the treatments that work best for any patient.

Broad types: 

Pharmaceutical companies usually sponsor CT for new drugs and treatments, which are carried out by the designated research teams, consisting of doctors and other related professionals in different specialized areas.

There are 4 phases in any CT, which are broadly as follows:     

  • Phase I: Here, for a new treatment, an investigational drug is tested for the first time in small numbers, usually between 20 and 100, on healthy volunteers, to identify the proper dosage ranges for drug administration, while critically monitoring its method of absorption, adverse effects and toxicity profile.
  • Phases II: This phase, just as Phase I studies, also tests the drug on, usually between 100 and 300 patients, suffering from the targeted disease conditions. Safety is the main goal of this phase of CT and is programmed towards adjusting treatment doses, monitoring the common side effects, and whether patient’s disease condition improve as a result of the drug. These studies are usually randomized and double-blinded, where neither the patient nor the researchers would know whether a patient is receiving the investigational drug, or a placebo, or a standard treatment.
  • Phase III: In this phase, the investigational new drug goes through rigorous testing of safety, efficacy, and proper dosage levels in a large group of subjects, which may even exceed several thousand, with a specific illness or disease. The key objective is to enable the doctors to evaluate the safety and effectiveness of the treatment for various groups of patients, such as, men versus women, elderly versus young, besides many others. 
  • Phase IV: Such studies are done after the drug receives the marketing approval from the drug regulator. The basic objective of these trials is usually to monitor whether the treatment offers desired benefits or gives rise to long-term side effects, which were not seen in the phase II and III trials. This phase may involve even several hundreds and thousands of patients.

It is worth noting that CT is essential to obtain marketing approval for any new treatment, as required by the drug regulators in the different countries, and takes around 6 to 8 years.

The role of patients:

Patients play a critical role in the entire scientific value chain of any drug evaluation process, especially on human. It is absolutely necessary, particularly in the regulated markets of the world, that all medicines are fully vetted through highly regulated, stringently monitored and well-scrutinized CTs, to ensure safety and effectiveness of each new drug and treatment for the patients.

No CT can take place sans the willingness and informed consent for participation of thousands of patients for any such studies held across the world. Without adequate patient participation in a CT, the drug performance data may also not be credible and thus acceptable to the drug regulator. This would, consequently, make it impossible to bring any new drug for prevention or treatment of various, often life threatening, disease conditions. 

Major reasons for not enough patient participation:

There are many reasons for not enough patients volunteering to participate in the CT, even in India. Some of the major reasons have been identified as follows:

  • Patients often are not aware that such trials also offer a treatment option. In many cases, their doctors too may not be explaining it effectively to them, as a part of their professional discourse. Several studies conclude that trust in a physician is a main reason patients decide to participate in CT.
  • Some patients, after reading media reports, interacting with some NGOs and also from word of mouth, mistrust the CT process and suffer from fear of being a guinea pig.
  • At times, complicated protocols, and eligibility requirements may also be discouraging.
  • Many patients, especially in India, are not very clear about the exact insurance (financial) cover the study provides for them, along with other payments for the care that they would receive during the trial, or for any drug-related long term untoward incident even after completion of the CT.

All these need to be effectively addressed. 

India attractiveness for CT:

The number of CT conducted in India had increased with a rapid pace till 2012, driven by cost arbitrage, treatment-naïve patient population, qualified English speaking medical research professionals that the country offers. According to available reports, in 2009, outside the United States, India was the second most preferred country to conduct CT. Incidentally, at that time, the CT guidelines in India were too loose, quite discretionary, patient-unfriendly and with many gaping holes. This scenario has changed dramatically since 2013, with consequent adverse impact on the number of CT in India.

A 2009 study conducted by Ernst & Young and the Federation of Indian Chambers of Commerce and Industry of India (FICCI), states that India participates in over 7 percent of all global phase III and 3.2 percent of all global phase II trials. The major reasons of India attraction of the global players to conduct CT in the country, were highlighted as follows:

  • Cost of Clinical Trial (CL) is significantly less in India than most other countries of the world
  • Huge treatment-naïve patient pool with different disease pattern and demographic profile
  • Easy to enroll volunteers, as it is not very difficult to persuade poor and less educated people as ‘willing’ participants. This may not be so easy now with the recent amendment of CT guidelines. 

However, there is an urgent need for a world class capacity building in this area to reap a rich harvest.

Improving CT regulations in India:

Not so long ago, it came to light with the help of ‘Right To Information (RTI)’ query that more than 2,000 people in India died as a result of Serious Adverse Events (SAEs) caused during drug trials from 2008-2011 and only 22 of such cases, which is just around 1 percent, received any compensation. That too was a meager average sum of around US$ 4,800 per family.

It has been widely reported that pharmaceutical companies often blame deaths, that occur during trials, on a person’s pre-existing medical condition, and not related to CT.

This gloomy situation is now gradually improving. According to an August 2015 research article titled “Impact of new regulations on clinical trials in India”, published in International Journal of Clinical Trials, 2015 Aug; 2 (3): 56-58, there was a need of strict vigilance and regulations for conducting CT in India, which was much easier than in North America or Europe. In India, the trial participants were exploited because of illiteracy, poverty and lack of awareness of their basic rights in this area. The Central Drugs Standard Control Organization (CDSCO) has now taken a noteworthy step by launching online Clinical Trial Registry-India (CTRI) ensuring accountability, transparency and information sharing on clinical trials in the public domain.

Followed by a tough intervention of the Supreme Court in 2013, Indian Government brought in amendments to the CT guidelines of Schedule Y, in December 2014 which came into force effective June 2015. These long-overdue amendments are expected to strengthen the CT process in India and effectively protect the rights, desired safety and general well-being of the participating subjects, while generating authentic clinical data for new drugs or treatment.

Informed consent:

Obtaining informed consent of the participating patients, is absolutely necessary for the researchers. This has recently been made stringent in India effective June 07, 2013. From that date, to make the sCT process transparent and ensure requisite confidentiality, an audio-visual recording of the ‘informed consent’ process has been made mandatory in the country.

A valid consent would mean that the participants have well understood the risks and benefits of the treatment during the CT period and after, along with the general procedures that he or she would need to undergo during the given time-frame.

However, the question that is still being debated, primarily because of the continuing challenge in defining in each case, beyond any scope of doubt, what should be universally considered as an adequate level of information given to the patients to obtain consent of participation in the CT. 

Financial compensation process:

Currently, the calculation of financial compensation, wherever applicable, is based on a well-defined formula. This system has been made mandatory for the sponsor in India for any trial related injuries or death. Such compensation has to be paid, even when the trial related injury is discerned after the completion of the CT. The concerned participants would receive this compensation over and above the free medical management of injury, which in any case has to be provided by the sponsor.

Hence patient safety and compensation related issues pertaining to CT in India have, to a great extent, been addressed, though there is still more scope for improvement on an ongoing basis.

Another major issue still to be addressed:

It is generally expected that when CT of a new drug is conducted by the global pharma players in India with the participation of Indian patients, the same drug when launched in other countries would also be made available in India for the benefit of Indian patients. 

Unfortunately, the situation is not so, as indicated by a paper titled, “A critical appraisal of clinical trials conducted and subsequent drug approvals in India and South Africa”, published in the BMJ Open on August 31, 2015.

The objective of this study was to assess the relation between the number of clinical trials conducted and respective new drug approvals in India and South Africa.

The study found that out of CTs with the participation of test centers in India and/or South Africa, 39.6 percent (India) and 60.1 percent (South Africa) CTs led to market authorization in the EU/USA, without a New Drug Application (NDA) approval in India or South Africa. 

The paper concluded, despite an increase in CT activities, there is a clear gap between the number of trials conducted and market availability of these new drugs in India and South Africa. Hence, the drug regulatory authorities, investigators, institutional review boards and patient groups should direct their efforts to ensuring availability of new drugs in the market that have been tested and researched on their population, the article suggested. 

I hope, the CDSCO would take remedial measures to address this situation, soon.

Indian pharma players should get their act together:

In view of the international media reports on alleged ‘CT data fudging’ by some of the larger Indian players in the pharma and relator sectors, there is an urgent need of the Indian pharma players to get their acts together, without any further delay.

On April 15, 2016, Reuters reported, “India’s Alkem Laboratories has been accused by Germany’s health regulator of fudging data on clinical trials of an antibiotic and brain disorder drug, becoming the third Indian firm to be scrutinized since 2014 for suspected manipulation of trial data.” However, a day later Alkem said that it was submitting suitable clarifications to the European Medical Agency (EMA).

Be that as it may, if the allegation for such gross violations of basic ethical standards is true, it would bring shame not just to the companies concerned, but also to India as a trusted source for pharma products and services. Such alleged foul play has the potential to ultimately shatter the stakeholders’ confidence, including patients, on CTs done by the Indian players, both for the local and global markets. 

Conclusion:

At the long last, after a grueling experience and tough intervention of the Supreme Court of India, CTs conducted in India are now reasonably well regulated and generally seem to comply with ethical requirements and standards. The question of human ‘guinea pigs’ and its associated concerns have also been adequately addressed by the CDSCO now.

Gradually improving the CT regulatory environment in India, barring some avoidable aberrations, offers some significant direct and indirect benefits to all concerned. Indian pharma is, therefore, expected to handle this sensitive opportunity with great care and following the highest ethical standards. 

This, in turn, would help bring to the market robust evidence-based new drugs and treatment for many types of diseases, and at the same time could facilitate their early access to many patients, at a time of dire need.

Through increasing access to CT, the participating patients would be able to avail several important benefits, such as, new and still unavailable treatment options, especially for those serious ailments, where other existing drugs either are not working effectively with satisfactory results, not affordable to many, or not working at all. In that sense, CT could offer to a sizeable number patients several other treatment options to choose from, especially, for many life-threatening diseases. This important benefit needs to be explained to the patients from credible sources, and thus merits serious consideration by the practicing medical professionals.

However, it is also a fact, particularly, in India that some people are lured to, or voluntarily enroll themselves for CT with an objective to make some extra money. Let me hasten to add that there are many other patients for whom the compensation for participation in the CT is no more than just an extra bonus.

Hence, improved patient participation with informed consent, to avail an important medical option in the disease treatment process, encouraged by the doctors without having any vested interest, has a great potential to create a win-win situation, for all concerned.

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: Make The Fragile Regulatory Space Robust, Soon

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In the space between drugs and nutrition, there is an intriguing ‘gray area’ with significant business relevance, especially in India.

In a related publication, A.T. Kearney – a leading global management consulting firm has elaborated it as below:

“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.”

Falling in the middle of the spectrum, a large number of Nutraceuticals clearly blur the line between food and drugs, in many cases. In India, there is no clearly defined legal and regulatory status for such Nutraceuticals, just yet.

Why a robust regulation required for Nutraceuticals? 

The scholarly article of S.H. Zeisel (Professor of Nutrition, University of North Carolina at Chapel Hill Nutrition) titled, “Regulation of Nutraceuticals,” Science 5435, 1853–1855 (1999) highlighted that in many cases when the dosages of food supplements exceed those of a normal diet, there could well be a drug-like bioactivity of a nutrient.

An example of the nutrient tryptophan may suffice to illustrate this point briefly. At higher dosage tryptophan can exhibit drug-like activity, as it is the precursor of serotonin, which is extensively used to treat insomnia. Many of such points are yet to draw the regulators’ attention in India as much as it should, as yet.

Marketing drugs as ‘food supplements’?

Marketing drugs as food supplements to evade Drug Price Control Order (DPCO) by some pharma players, of all sizes and scale of operation, is not an uncommon practice in India. The National Pharmaceutical Pricing Authority (NPPA), reportedly, pointed it out sometime around 2009.

Not just for pricing reason, but more importantly for consumers’ health and safety, the Central Drugs Standard Control Organization (CDSCO) should address this issue now with a greater sense of urgency, as the market for Nutraceuticals and health supplements is reportedly growing at a brisk pace today. According to a Frost & Sullivan report, the total Indian Nutraceuticals market in 2015 was expected around US $ 5 billion. 

In the absence of any clear and robust regulatory guidelines, most Nutraceutical products, with a spectrum of therapeutic claims, are virtually self-categorized as food supplements, which are not covered under the Drugs and Cosmetics Acts in India.

Currently in the country, Nutraceuticals and functional foods are covered under the definition of ‘food’ as per Section 22 of Food Safety & Standards Act (FSSA), 2006. These food products have been categorized as Non-Standardized/Special Food Products. Accordingly, Food Safety and Standards Authority (FSSAI) of India have described Nutraceuticals as:

“Naturally occurring chemical compound having a physiological benefit or provide protection against chronic disease, isolated and purified from food or non-food source.”

Though categorized as nutritional supplement, the product packs of such Nutraceuticals usually do not carry any “FSSAI’ logo, which signifies conformance to the food safety standards of India, for the benefit of consumers.

Recommendations are many, but no comprehensive action yet:  

To give an example, many Nutraceuticals contain vitamins in varying quantity. However, most of these products seem to carefully avoid Schedule V guidelines for vitamin content to avoid being categorized as drugs, and thereby coming under strict regulatory requirements. Self-categorizing these products as ‘food supplement’, helps bypassing this issue, as on date.

Such ongoing practices related to Nutraceuticals need to be viewed keeping in perspective, some of the recent key recommendations made by the Drugs Technical Advisory Board (DTAB) of the CDSCO, on Schedule V related formulations.

The minutes of the 70th. meeting of the Drugs Technical Advisory Board (DTAB) held on August 18, 2015, recorded the acceptance of the report of its sub-committee on vitamins, which recommended, among others, some of the following guidelines:

  • Ingredients which are covered under the range as prescribed under schedule “V” of the Drugs and Cosmetics Rules for Tablets, capsules, granules are 18 classified as a drug, while those powders like Farex, Oats and Cereal fortified vitamins are exempted from the provisions of chapter IV under schedule K of Drugs and Cosmetics Rules.
  • Ingredients which fall below the range as prescribed under schedule “V” shall be classified as food. However, if there is a claim for treatment, mitigation or prevention of any diseases or disorder, then it will be classified as a drug. 
  • Ingredients which are within Recommended Daily Allowance (RDA) levels, but fall under the range as prescribed under schedule V Drugs and Cosmetics Rules shall be classified under drug as it is already mentioned in the rules. 
  • Products containing ingredients which are neither covered under Schedule V nor fall within RDA, these can be classified as unprovable products under Drugs and Cosmetics Rules, unless otherwise specifically permitted by the Licensing Authorities of drugs based on major purpose of the item (like food/drug).
  • Whenever there are additional ingredients than those given in schedule V, including some of herbal ingredients, a separate and conscious view has to be taken about the safety and efficacy of the drug
  • Any product containing herbal ingredients shall be dealt with by the food or drug authority based on the above principles. 

The same subcommittee, on June 12, 2015, after discussing each of some specified products, with a claim of falling in non-drug category, as per directions of the Hon’ble High Court of Patna, recommended categorization of some of the well-known brands brands, such as, Revital (Ranbaxy) and A to Z capsules (Alkem) as drugs. The sub-committee report was then uploaded in the CDSCO website for stakeholders’ comment.

Could there be ‘irrational FDC ban’ like an issue with Nutraceuticals?

The answer to this question is anybody’s guess at this point of time. However, such a possibility can be just wished away either.

This lurking fear stems from the recent notification of FSSAI dated March 30, 2016, which states as follows:

“It has been decided that till the standards of Nutraceuticals, food supplements and health supplements are finally notified, the enforcement activities against such food business operators may be restricted to testing of these products with respect to requirements given in the draft notification on such products of September 9, 2015″.

However, it clarifies that the companies will get an exemption, if such products were available in the market before the Food Safety and Standards Act came into effect in 2011, or if product approval was pending on August 19, 2015.

The key objective of the above September 9, 2015, FSSAI draft notification was to ensure that Nutraceuticals, health and food supplements and other such products are not sold as medicines with therapeutic claims. Thus, asking the industry players to send their suggestions and objections to the proposal, this draft notification indicates, among others, that all such products should: 

  • Adhere to the proposed permissible limits of various minerals, vitamins, plant or botanical-based ingredients, among others.
  • Adhere to the proposed list of food additives used in all these categories of products, besides labelling norms, every package must carry the words “Food” or “Health Supplement” and prominently display “Not for Medicinal Use” on the label. 
  • Give a disclaimer on the package that the food or health supplement should not be used as a substitute for a varied diet.
  • Clearly indicate on the label that “this product is not intended to diagnose, treat, cure or prevent any disease”, besides information on recommended dosages, among others.

As this notification is expected to cover all products, which are marketed as food supplements, many Nutraceuticals manufacturers, reportedly, fear that it could effectively mean a ban on virtually all those brands, self-categorized as food or nutritional supplement, and launched post 2011.

If it happens, the saga of ban of a large number of irrational Fixed-Dose Combinations (FDCs) of drugs, that includes some top-selling pharma brands and is now sub judice, could get extended to the Nutraceuticals sector too. 

Nonetheless, the bottom-line is that a robust mechanism to effectively regulate and monitor Nutraceuticals in India, is yet to see the light of the day. 

Crazy marketing of Nutraceuticals: 

Despite regulatory and marketing restrictions to the therapeutic claims for this category of drugs, Nutraceuticals are mostly promoted to the doctors, just as any other ethical pharma products in India.

Consequently, these are widely prescribed by the medical profession, not just as nutritional supplements, but also for the treatment of disease conditions, ranging from obesity to arthritis, osteoporosis, cardiovascular conditions, diabetes, anti-lipid, gastrointestinal conditions, dementia, age-related muscle loss, pain management and even for fertility. All these are generally based on off-label therapeutic claims of the respective manufacturers.

Being advertised in the mass media too:

To illustrate this point, I would give an example of a well known brand in India. As I see from the Government records, i.e. from the minutes of the 68th meeting of the DTAB sub-committee held on June 12, 2015 that it had recommended Revital’s (Ranbaxy) categorization under drug.

As we all know that, as per drugs and Cosmetics Act of India, drugs cannot be advertised in the mass media, except Schedule K drugs, such as Aspirin and paracetamol. In that sense, I find it difficult to fathom, how is Revital then, which highlights a naturally occurring substance fortified with vitamins and minerals, advertised even on the Television, along with a top celebrity endorsement?

A recent notification on phytochemicals:

As I mentioned in my article in this Blog on December 21, 2015, titled “Nutraceuticals: A Major regulatory Step That Was Long Overdue”, partly 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.

This regulatory action followed the rapidly growing use of these drugs in India, which includes purified and standardized fraction with defined minimum four bio-active or phytochemical compounds.

On the ground, this significant regulatory measure would require the pharma players to submit the specified data on phytopharmaceutical drugs, along with necessary applications for conduct clinical trial or import or manufacture of these products in the country. 

However, this is no more than half-measure in this direction. Hopefully, this will be followed by final action on the DTAB recommendations on vitamins, and final notification of FSSAI on standards of Nutraceuticals, food and health supplements. A well-integrated action of the CDSCO and FSSAI, would possibly help to contain the unregulated proliferation of various types of Nutraceutical products coming into the Indian market, prescribed by the doctors and consumed by the people, sans any scientific evidence based efficacy, safety and quality standards.

Manufacturers’ business interest also can’t just be ignored:

While there is a pressing need to enforce regulatory discipline for claimed efficacy, safety and high quality standards for the Nutraceuticals to protect consumers’ health interest, commercial interest of such drug manufacturers can’t also just be ignored. If that happens, it will be unfair.

Thus, one of the ways to encourage the manufacturers to expand this market, I reckon, could well be categorizing the Nutraceuticals offering health benefits, under a separate category altogether, which will be kept out of any form of drug price control.

Conclusion:

The manufacturers of Nutraceuticals still keep charting in a very relaxed regulatory space. Currently, there is no robust and transparent process in place to standardize and scientifically evaluate safety and efficacy of these products on an ongoing basis. This scenario should not be allowed to continue, any longer.

Appropriate control of standardized Nutraceutical manufacturing, regular monitoring of the same and scientific evidence-based marketing approval process of all such products, therefore, require to be well-well regulated. The requirement for stringent conformance to the set cGMP standards would ensure desired safety, efficacy and high quality of nutraceutical products for the consumers.

The recent decisions of 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.

Just as Ayurvedic products, all Nutraceuticals, not being essential medicines, should always be kept outside price control in any form. It should happen in tandem with the Government’s taking a bold step to make the prevailing fragile regulatory space for the Nutraceuticals a robust one, creating a win-win situation for all. 

By: Tapan J. Ray

Disclaimer: The views/opinions expressed in this article are entirely my own, written in my individual and personal capacity. I do not represent any other person or organization for this opinion.

Biosimilar Drugs: First Indian Foot Print In An Uncharted Frontier

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A homegrown Indian biologic manufacturer is now about to leave behind its first foot-print, with a ‘made in India’ biosimilar drug, in one of the largest pharma market of the world. This was indeed an uncharted frontier, and a dream to realize for any Indian bio-pharma player.                                                      

On March 28, 2016, by a Press Release, Bengaluru based Biocon Ltd., one of the premier biopharmaceutical companies in India, announced that the Ministry of Health, Labour and Welfare (MHLW) of Japan has approved its biosimilar Insulin Glargine in a prefilled disposable pen. The product is a biosimilar version of Sanofi’s blockbuster insulin brand – ‘Lantus’.

The Company claims that Glargine is a high quality, yet an affordable priced product, as it will reportedly cost around 25 percent less than the original biologic brand – Lantus. This ‘made in India’ biosimilar product is expected to be launched in Japan in the Q1 of 2017. Incidentally, Japan is the second largest Glargine market in the world with a value of US$ 144 Million. Biocon will co-market this product with its partner Fujifilm.

Would it be a free run? 

Although it is a very significant and well-deserved achievement of Biocon, but its entry with this biosimilar drug in Japan’s Lantus market, nevertheless, does not seem to be free from tough competition. This is because, in 2015, both Lilly and Boehringer Ingelheim also obtained Japanese regulatory approval for their respective biosimilar versions of Lantus. In the same year, both these companies also gained regulatory approval from the US-FDA, and the European Medicine Agency (EMA) for their respective products.

Moreover, Sanofi’s longer acting version of Lantus – Lantus XR, or Toujeo, to treat both Type 1 and Type 2 diabetes, has already been approved in Japan, which needs to be injected less, expectedly making it more convenient to patients.

Key barriers to a biosimilar drug's success: 

Such barriers, as I shall briefly outline below, help sustaining monopoly of the original biologic even after patent expiry, discourage investments in innovation in search of biosimilars, and adversely impacts access to effective and much less expensive follow-on-biologics to save patients’ precious lives. 

These barriers can be broadly divided in two categories: 

A. Regulatory barriers:

1. Varying non-proprietary names:

A large number of biosimilar drug manufacturers, including insurers and large pharmacy chains believe, just as various global studies have also indicated that varying non-proprietary names for biosimilars, quite different from the original biologic, as required by the drug regulators in the world’s most regulated pharma markets, such as, the United States, Europe, Japan, and Australia, restrict competition in the market for the original biologic brands. 

However, the innovator companies for biologic drugs hold quite different views. For example, Roche (Genentech), a developer of original biologic, reportedly explained that “distinguishable non-proprietary names are in the best interest of patient safety, because they facilitate Pharmacovigilance, and mitigate inadvertent product substitution.”

Even, many other global companies that develop both original biologic and also biosimilar products such as, Amgen, Pfizer and others, also reportedly support the use of ‘distinguishable nonproprietary names’.

That said, the Biosimilars Council of the Generic Pharmaceutical Association argues that consistent non-proprietary naming will ensure robust market formation that ultimately supports patient access, affordability, Pharmacovigilance systems currently in place and allow for unambiguous prescribing, 

2. Substitution or interchangeable with original biologics:

Besides different ‘non-proprietary names’, but arising primarily out of this issue, automatic substitution or interchangeability is not permitted for biosimilar drugs by the drug regulators in the major pharma markets of the world, such as, the United States, Europe and Japan.

The key argument in favor of interchangeability barrier for biosimilar drugs is the fact that the biological drugs, being large protein molecules, can never be exactly replicated. Hence, automatic substitution of original biologic with biosimilar drugs does not arise. This is mainly due to the safety concern that interchangeability between the biosimilars and the original biologic may increase immunogenicity, giving rise to adverse drug reactions. Hence, it would be risky to allow interchangeability of biosimilar drugs, without generating relevant clinical trial data.

On the other hand, the Generic Pharmaceutical Association (GPhA) and the Biosimilars Council, vehemently argue that a biosimilar drug has a lot many other unique identifying characteristics “including a brand name, company name, a lot number and a National Drug Code (NDC) number that would readily distinguish it from other products that share the same nonproprietary name.”

Further, the interchangeable status for biosimilar drugs would also help its manufacturers to tide over the initial apprehensions on safety and quality of biosimilar drugs, as compared to the original ones.

3. 12-year Data Exclusivity period for biologics in the United states:

Currently, the new law for biologic products in the United States provides 12 years of data exclusivity for a new biologic. This is five years more than what is granted to small molecule drugs. 

Many experts believe that this system would further delay the entry of cost-effective biosimilar drugs, restrict the biosimilar drug manufacturers from relying on the test data submitted to drug regulator by the manufacturers of the original biologic drugs while seeking marketing approval.

A rapidly evolving scenario in the United States:

The regulatory space for approval of biosimilar drugs is still evolving in the Unites States. This is vindicated by the fact that in March 2016, giving a somewhat positive signal to the biosimilar drug manufacturers, the US-FDA released another set of a 15-page draft guidelines on how biosimilar products should be labeled for the US market. Interestingly, it has come just around a year of the first biosimilar drug approval in the United States – Zarxio (filgrastim-sndz) of Novartis.

The US-FDA announcement says that all ‘comments and suggestions regarding this draft document should be submitted within 60 days of publication in the Federal Register of the notice announcing the availability of the draft guidance.’ Besides labeling issues, this draft guidance document, though indicates that the ‘interchangeability’ criteria will be addressed in the future, does not still throw enough light on how exactly to determine ‘interchangeability’ for biosimilar drugs.

That said, these key regulatory barriers are likely to continue, at least in the foreseeable future, for many reasons. The biosimilar drug manufacturers, therefore, would necessarily have to work within the set regulations, as applicable to different markets of the world.

I deliberated a related point in my article of August 25, 2014, titled “Scandalizing Biosimilar Drugs With Safety Concerns” 

B. Prescribers’ skepticism:  

Initial skepticism of the medical profession for biosimilar drugs are, reportedly, due to the high voltage advocacy of the original biologic manufacturers on the ‘documented variability between original biologic and biosimilars. Which is why, any substitution of an original biologic with a related biosimilar drug could lead to increase in avoidable adverse reactions.

‘The medical platform and community QuantiaMD’, released a study just around September 2015, when by a Press Release, Novartis announced the launch of the first biosimilar approved by the US-FDA – Zarxio(TM) (filgrastim-sndz). However, in 2006, Novartis after suing the US-FDA, got the approval for its human growth hormone – Omnitrope, which is a biosimilar of the original biologic of Genentech and Pfizer. At that time a clear regulatory guideline for biosimilar drugs in the United States, was not in place.

The QuantiaMD report at that time said, “Only 12% of prescribing specialists are ‘very confident’ that biosimilars are as safe as the original biologic version of the drug. In addition, a mere 17% said they were ‘very likely’ to prescribe a biosimilar, while 70% admitted they were not sure if they would.” 

Since then, this scenario for biosimilar drugs is changing though gradually, but encouragingly. I shall dwell on that below.

The major growth drivers:

The major growth drivers for biosimilars, especially, in the world’s top pharmaceutical markets are expected to be:

  • Growing pressure to curtail healthcare expenditure
  • Growing demand for biosimilar drugs due to their cost-effectiveness
  • Rising incidences of various life-threatening diseases
  • Increasing number of off-patent biologics
  • Positive outcome in the ongoing clinical trials
  • Rising demand for biosimilars in different therapeutic applications, such as, rheumatoid arthritis and blood disorders. 

This in turn would probably usher in an unprecedented opportunity for the manufacturers of high quality biosimilar drugs, including in India.

Unfolding a huge emerging opportunity with biosimilars: 

This unprecedented opportunity is expected to come mainly from the world’s three largest pharma market, namely the United States, Europe and Japan, due to very high prices of original biologic drugs, and simultaneously to contain rapidly escalating healthcare expenditure by the respective Governments. 

Unlike in the past, when the doctors were apprehensive, and a bit skeptic too, on the use of new biosimilars, some new studies of 2016 indicate a rapid change in that trend. After the launch of the first biosimilar drug in the US, coupled with rapidly increasing incidences of various complex, life-threatening diseases, better knowledge of biosimilar drugs and their cost-effectiveness, doctors are now expressing much lesser concern, and exhibiting greater confidence in the use of biosimilars in their clinical practice.

Yet another, March 2016 study indicates, now only 19.5 percent of respondents feel little or no confidence in the use of biosimilar monoclonal antibodies compared to 61percent of respondents to a previous version of the survey undertaken in 2013 by the same market research group. The survey also shows that 44.4 percent of respondents consider that the original biologic and its biosimilar versions are interchangeable, as compared with only 6 percent in the 2013 survey.

As a result of this emerging trend, some global analysts of high credibility estimate that innovative biologic brands will lose around US$110 billion in sales to their biosimilar versions by 2025.

Another March, 2016 report of IMS Institute for Healthcare Informatics states that lower-cost biosimilar versions of complex biologic, could save the US and Europe’s five top markets as much as US$112 billion by 2020,

These encouraging developments in the global biosimilar arena are expected to encourage the capable Indian biosimilar drug players to invest in this high-tech format of drug development, and reap a rich harvest as the high priced blockbuster biologic brands go off-patent.

Conclusion:

Putting all these developments together, and considering the rapidly emerging scenario in this space, it now appears that challenges ahead for rapid acceptance of biosimilar drugs though are still many, but not insurmountable, at all.

The situation necessitates application of fresh and innovative marketing strategies to gain doctors’ confidence on biosimilar medicines, in total conformance with the regulatory requirements for the same, as they are, in the most important regulated markets of the world.

It goes without saying that success in the generation of enough prescriptions for biosimilar drugs is the fundamental requirement to benefit the patients, which, in turn, would lead to significant savings in health care cost, as estimated above, creating a win-win situation for all, in every way.

As more innovator companies start joining the biosimilar bandwagon, the physicians’ perception on these new varieties of medicines, hopefully, would also change, sooner.

Biocon’s grand announcement of its entry with a ‘made in India’ biosimilar drug in one of the word’s top three pharma markets, would probably be a great encouragement for all other Indian biosimilar drug manufacturers. It clearly showcases the capabilities of an Indian drug manufacturer to chart in an uncharted and a highly complex frontier of medicine.

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.

Ease of Doing Pharma Business in India: A Kaleidoscopic View 

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Ensuring ease of doing any ethical business activity in India, is a new focus area of the Government and is very rightly so. Creating ease of doing ethical pharma business too, falls under this overall national objective.

In this article, restricting myself to the drug sector, I shall deliberate on various aspects, which are now being considered by the pharma industry, related to the ‘ease of doing pharma business in India’. My discussion would cover all subsets of pharma players, irrespective of whether they fall under Multinational (MNC) or purely homegrown Indian companies, with different scales of operations – large, medium, small, or micro. 

To help the Government facilitating the ‘‘ease of doing pharma business in India’, it is just not enough to make the business models for all subsets of the Indian pharma sector looking ethical, conforming to all relevant laws, policies, rules and norms. Each pharma player need also to maintain an ongoing strict internal vigil, religiously, to ensure that the requirements of high quality clinical development, manufacturing and selling practices for effective, safe and rational medicines, are properly understood and strictly followed by all the employees within the organization.

A Kaleidoscopic View:

The above situation is something that ought to happen, as the Government keeps striving to improve the ‘ease of doing pharma business’ in India. However, while looking through a Kaleidoscope, as it were, the colors of industry expectations in this area keep changing rapidly, as the new contentious issues keep emerging. Consequently, the ground reality of assessing the same, by a large section of the pharma players in India, seems to veer only around different types of just self-serving demands, expecting those to act as a powerful tailwind pushing their business interests rapidly forward.

Such expectations keep surfacing, rather frequently, from all the subsets of the pharma industry, be they MNCs and their trade associations or the Companies of purely Indian origin and their trade bodies. The accusation to the Government pertaining to all these issues, is a common one: ‘Where is the ease of doing pharma business in India?’

Citing even some recent incidents, they are voicing with equal gusto, that the root causes of all these problems lie miles outside the pharma industry. The causative factor, they indicate, is rooted at the very doorsteps of the Government, as its ministries initiate tough action to root out corruption in the pharma industry as concurrent measures, disturbing their business comfort zones, and upsetting the apple carts. 

The Government has its task cut out:

I hasten to add that I have no intention to paint it as a confrontation between the Government and the pharma industry, in any way. The Government is also facing the brunt from the various stakeholders, relentlessly, for its utter negligence of public health care, and public expenditure over it.

The impact of this Government indifference, though also comes on the patients, the industry does not seem to have much to crib over it as a direct impediment to the ‘ease of doing pharma business’ in India.

Probably as a diversionary tactic, the industry keeps using this critical Government inaction in the hope of diverting the public, or media attention from its own alleged business malpractices, even at a time when these are being covered both by the national and international media, regularly. Nevertheless, the industry credibility on these issues, seems to have started waning fast, as the genie is out of the bottle.

A common punching bag of all industry dissatisfaction on the Government:

It is worth noting that despite some key differences between the MNC and Indian pharma companies, which I shall discuss later, the common punching bag of the industry dissatisfaction on various Government decisions, always has been the lack of ‘ease of doing pharma business’ in the country.

This discontentment may be well justified. I have no qualms about it. However, when this dissatisfaction gets tagged with some recent Government action, taken to protect public health interests and does not have much to do with the ‘ease of doing ethical pharma business’, many eyebrows are obviously raised.

Against some of these critical patient-centric actions, the industry continues to express its annoyance in unison, while for some other Government decisions, it speaks in different voices – some are happy ones, and the others are not so. However, the common thread of expression of all such dissatisfactions is always linked with the lack of ‘ease of doing business’ in India.

A. Where the pharma Industry in India speaks in unison: 

I shall now give two major examples of the key Government decisions, that have irked the entire pharma industry immensely, and makes it voicing that those Government actions grossly violate the fundamental requirements of its smooth running of business. Is that fair? Let me analyze that below with these two examples:

1. Drug price control:

The industry, by and large, opines that individual drug company should be allowed to decide the way it would price any drug, as the market forces, especially for generic drugs, would determine its price.

Indian Parliament, the Supreme Court of India, the Government in power at different times, most of the independent experts and the NGOs, on the contrary, consider drug price control is necessary in India, especially for essential drugs. It makes high quality essential medicines affordable and accessible to the general population.

National Pharmaceutical Pricing Authority (NPPA) has also announced and explained that the competition does not work on controlling prices for pharma products, where the consumers are not the decision makers. The key prescribing decision makers for the patients are the doctors, who are mostly and unethically influenced by the drug companies having vested interest in making such decisions. This unholy nexus has been widely alleged globally, and also established through umpteen number of studies of high credibility.

Nevertheless, the doctors, from across the globe, including in India, have long disputed that any payments, if and when they receive from pharmaceutical companies, have no relationship to how they prescribe drugs.

A March 17, 2016 study of ProPublica has conclusively established that: “The more money doctors receive from drug and medical device companies, the more brand-name drugs they tend to prescribe. Even a meal can make a difference.” This study may be in the context of the Unites States, but India in this in this regard is no exception, as captured even in the parliamentary Committee reports.

Thus, conceding to high voltage pharma advocacy, made on the pretext of ‘encouraging innovation’ and ‘ease of doing business in India’, if any Government contemplates the abolition of drug price control in India is, it would make not just essential drugs inaccessible to a large section of society, but encourage blatant corrupt practices. This caution has come, besides many others, also from a Parliamentary Committee report, unambiguously. Incidentally, the present Government too strongly speaks against corruption, in any form.

Thus, I reckon, if the industry believes that the price control of essential drugs, which are for public health interest, goes against ease of doing pharma business in India, so be it.

2. Manufacturing and selling of irrational FDCs:

A Fixed Dose Combination (FDC) drug may appear irrational to drug regulators and well-qualified experts, after necessary scientific scrutiny, for various reasons. This may happen, primarily because of the following reasons:

  • When the medical rationale of the FDC along with the ingredient details, submitted to the regulatory authority for marketing approval, are considered scientifically inappropriate.
  • When the evolving medical science establishes the irrationality of the FDC after a period of time.
  • When the analysis of ‘Adverse Drug Event’ reports from the ongoing Pharmacovigilance studies signals a red alert.
  • Widespread uncontrolled misuse or abuse of FDCs, where the consumers’ health risks far outweigh the drug benefits, as provided in the drugs Act, for public health interest.
  • Some regulatory loopholes were misused by the drug manufacturers in the past to get the irrational FDCs approved by the State Drug Authorities, violating the new FDC regulatory approval Policy.

Any irrational FDC so identified by the drug regulators and experts, by putting a system of scrutiny in place, must be banned forthwith, in public health interest. There should not be any scope of negotiation with drug manufacturer to make the bans effective.

Incidentally, realizing the gravity of public health risks posed by irrational FDCs, even the NPPA has reportedly decided to review afresh all new applications for price fixations of FDC and examine their safety and efficacy profile.

Moving towards this direction, the NPPA Chairman, has reportedly sent back more than 200 applications for price fixation of FDCs, instructing the concerned manufacturing and marketing companies to apply again with a declaration that their formulations are not “irrational.” It was also reported that the price regulator has also brought under the lens third-party drug makers and pharma companies that outsource to them, to check illegal sales of irrational FDCs and spurious drugs.

Two key questions being raised now:

Despite all these, the industry keeps repeating, especially, the following two questions, which are worth looking at, one by one: 

1.  Why is the ban now?

I discussed the issue of FDC ban in my previous article in this Blog on March 21, 2016 titled, “The Recent Ban On Irrational FDCs: History Repeats Itself”.

In the above article, I also argued that large section of the industry and its associations are protesting against the Government ban of 344 irrational FDCs, and questioning vigorously, even outside the Delhi High Court – ‘why is the ban now?’

The point ‘why now’ is absolutely irrelevant, as not taking any action ever, against a wrong doing ignored over a long period time for whatever reasons, does not confer any regulatory legitimacy to an irrational FDC formulation to be considered as a rational one for all time to come, and thereby, exposing patients to serious health risks, knowingly.

2.  Why is this ban so sudden, and in some cases after decades?

Sudden banning of drugs, which are in the market for a long time, is not a recent Indian phenomenon in India. In 2011, according to a report, in the world’s largest pharma market – the United States, the FDA banned 500 prescription drugs that had been on the market and working for decades. USFDA ban also happened suddenly, and that includes cough syrups too.  Thus, it is intriguing, why is this fuss created by the Industry in India now? 

In the midst of it, one odd, knee-jerk, apparently ‘spoon-fed’ and ill-informed editorial in some Indian business daily, raises more questions about its real intent, rather than help finding answers to the poorly sketched problems.

I would hope, the Government would stay firm and be able to convince the Delhi High Court today, i.e. on March 28, 2016, with its robust data-based arguments, accordingly.

Be that as it may, in my perspective, if the industry still believes that bans of irrational FDCs to protect public health interest, as decided by the independent experts after long and structured deliberations, would go against ‘ease of doing pharma business’ in India, so be it. 

B. Where the pharma industry in India speaks in different voices:

As stated above, there are several other key areas, where the MNC and Indian Pharma players have sharp differences in their perspectives. Despite these differences, the aggrieved section does not even blink a bit to attribute those Government actions to the lack of ‘ease of doing pharma business’ in the country.

 In this area, I shall give just the following three examples: 

1. The Patents Act:

MNCs say that section 3 (d) of the Indian Patents Act 2005, which is aimed at curbing patent ever-greening or frivolous inventions, is against the ease of doing business in India. However, the Indian Pharma players, do not think so, at all. Similar disagreement also exists in other critical areas too, such as, ‘Data Exclusivity (DE)’ and ‘Compulsory Licensing (CL)’.

Thus, in my opinion, if some ‘public health interest’ related provisions of the robust Indian Intellectual Property (IP) Act, such as, section 3 (d), DE and CL, are considered as going against the ‘ease of doing pharma business in India’ by the MNCs, so be it.

2. Mandatory Uniform Code of Pharma Marketing Practices (UCPMP):

Need to have a mandatory UCPMP, though, is reportedly supported by the MNCs, Indian pharma players do not seem to be quite in sync with this idea. I am not sure, whether the delay in the announcement of mandatory UCPMP, almost in every 3 months, has any coincidence with it or not. However, the reality is, no one still knows clearly, when would it definitely come, if at all.

Media reports on pharma MNC support to mandatory UCPMP, and repeated reiteration that its members in India rigidly follow the IFPMA Code of Marketing Practices, though commendable, seem to grossly lack in credibility.

Interestingly, despite the existence of this code and high-decibel vouch for its rigid conformance, maximum number of MNCs have been fined billions of dollars, by the Government in various countries, for alleged gross marketing and other business malpractices. It has been happening over a long period of time, and is being reported by the international media, frequently.

What is really happening, especially, on the so called total support of ethical marketing practices by the MNCs? Are they trying to create just good optics by craftily framing and supporting such showpiece codes, and blatantly defying these to achieve self-serving goals? The voice gets shriller, even when they are being levied hefty fines, after getting caught red handed, as reported by the global media? I guess, the future would ultimately unfold the reality. But would it, at all?

The Indian Scenario: 

Even in India, such alleged marketing malpractices involving even a top pharma MNC have often been reported by the media. Just to illustrate, “Prescribe a drug maker’s medicine and get a free vacation”, reported a news article. There are several other similar reports too. Hence, the credibility of pharma MNC statements regarding strict conformance to ethical marketing codes, ably formulated by the well-known pharma trade associations, such as, IFPMA, appears to be very low, if exists at all.

The well-reputed medical Journal BMJ in one of its articles titled, “Corruption ruins the doctor-patient relationship in India”, published on May 8, 2014, expressed serious concern on this issue.

It concluded that corruption, kickbacks and the nexus between doctors and pharmaceutical firms are rampant India. This eventually prompted the BMJ, in June 2014, to launch a campaign reportedly called ‘Corruption in Medicine’.

On this issue, way back in May 08, 2012, even the Indian Parliamentary Standing Committee on Health and Family Welfare in its 58th Report, placed before the Parliament on May 08, 2012, expressed its serious concern.

Indian lawmakers, recommended in the report that the Department of Pharmaceuticals (DoP) should take decisive action, without further delay, in making the UCPMP mandatory, so that effective checks could be ensured on ‘huge promotional costs’ and the resultant add-on impact on medicine prices. Unfortunately, despite a change in the Government in 2014, UCPMP has still not been mandatory.

It is anybody’s guess, despite all these reports, what type of external pressure, if at all, the DoP is still facing to put in place a robust mandatory UCPMP with strong deterrent measures.

Under this backdrop, in my view, if mandatory UCPMP having enough teeth, to curb ongoing blatant marketing malpractices to protect patients’ health interest in India, is considered by any as going against the ‘ease of doing pharma business in India’, so be it. 

3. Drug manufacturing quality:

Enough discussions have already been made on import ban of USFDA from over 45 drug manufacturing facilities of Indian Companies, of all sizes and scale of operations, on the ground of drug quality standards. USFDA considered drugs manufactured in those banned facilities are unsafe for the consumption of American patients. Some other foreign drug regulators, from the developed countries, have also taken similar action.

Taking advantage of this development, it was reported that attempts are indirectly being made to establish that MNC marketed generic drugs are superior to similar ones, manufactured even by the large Indian drug producers.

The fact, apparently, is quite different. MNCs operating in India has not come under the USFDA scanner in this regard as much, probably not because of their far superior drug manufacturing quality standards in India, as compared to even the best of their Indian counterparts. I reckon, it is mainly because, very few MNC drug manufacturing facilities in India export India manufactured drugs for consumption in the United States. 

It may not, therefore, make any real sense to conclude that MNC marketed generic drugs in India, either manufactured my themselves or under loan & license or under a third party, are generally better in quality than the similar ones manufactured even by the large Indian manufacturers. 

In any case, I feel that there is a huge scope for Indian drug regulators to ensure uniformly high drug quality standards. This is necessary for Indian patients’ health and safety. There also should be stringent regular quality audits in all drug manufacturing facilities in India, where non-conformance with prescribed standards would attract serious punitive measures. The Union Ministry of Health, together with the State Governments would require increasing the number of auditors accordingly.

However, the reality is, many Indian drug manufacturers have expressed that maintaining stricter drug manufacturing standards (cGMP) would involve huge expenditure, which they will not be able to afford. Consequently, this would go against the ‘ease of doing pharma business’ in India.

Again, in my view, if the stringent regulatory requirements for maintaining high drug manufacturing standards in India to protect public health interest, is considered as going against the ‘ease of doing pharma business’ in India, so be it.

Conclusion:

Improving ‘ease of doing pharma business’ in India is an absolute necessity, just as all other businesses. Pharma sector deserves it very badly too, as it has been experiencing excruciating delay in multiple regulatory clearances. Single window clearances of all applications, with a much greater sense of urgency, without bureaucratic red tapes and avoiding other unnecessary delays, is certainly the way forward for India. It would require urgent policy reforms, maintaining a right balance between, public, consumers and business interests.

Pharma sector is not all villain, either, by any yardstick. It is instrumental in saving and improving the quality of lives of so many people across the globe, since a very long time, with its both innovative and generic medicines. All must acknowledge it, and the Government does it too, openly, several times. 

That said, the space of focus of the pharma industry appears to be getting increasingly narrowed down to more of its self-serving acts, and in their hard selling, through hugely expensive advocacy campaigns, even at the huge cost of attracting frequent self-defeating scathing criticisms, across the world.

At the same time, the Governments in different times hugely disappointed its citizens, in charting a clear road map for quality and affordable health care for all in India, along with appropriate budgetary allocations and policy reforms, and thereafter, in its implantation with military precision.

However, that doesn’t mean, in any way, while facilitating ‘ease of doing pharma business’ in India, the Government would turn a blind eye on the rapidly breeding corruption in the pharma business practices, and give in to unjustified industry muscle-flexing, sacrificing the health interest of its citizens in the country.

While looking through this Kaleidoscope, it appears to me, if the pharma sector considers the appropriate Government actions to protect public health interest, against the unacceptable industry practices, would also go against the ‘ease of doing pharma business’ in India… Well, so be it.

By: Tapan J. Ray

Disclaimer: The views/opinions expressed in this article are entirely my own, written in my individual and personal capacity. I do not represent any other person or organization for this opinion.

 

The Recent Ban On Irrational FDCs: History Repeats Itself

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The recent regulatory ban on a large number of irrational Fixed Dose Combination (FDC) drugs is not a new incident in India. A similar mega ban was announced even before, about nine years ago. Intriguingly, the saga continues, for various reasons, without any tangible outcome for the patients on the ground.

On March 11, 2016, the latest ban, again on a large number of irrational FDCs, was notified. It caused a flutter and an immediate sharp adrenaline rush to the impacted drug companies and was soon followed by an interim stay order, again by an honorable High Court of the country.

Thus, when I connect the past dots with the latest one, on mega ban of irrational FDCs in India, a similar sequence of events gets unfolded, following each of such ban notifications of the Government.

Looking back, 294 FDCs were banned by the DCGI in 2007. At that time too, the important issue of patients’ health, safety and economical interest, got converted into a legal quagmire. Many adversely affected FDC drug players chose to go to the court of law to protect their business interest, and also successfully managed to obtain a ‘Stay’ order from the Madras High Court.

Consequently, those 294 irrational FDCs, banned by the Union Ministry of Health on health and safety grounds, continued to be promoted, prescribed and sold to patients across India, without any hindrance, whatsoever.

The matter continues to remain sub judice, as we deliberate the issue here. Thus, whether the recent gazette notification on the ban of irrational FDCs would immediately be implemented, unlike the past ban, or the history would repeat itself, is indeed a big question mark, at this juncture.

Would this ban have similar outcome?  

As discussed, close to a decade after the serious legal fall-out of the ban of 294 irrational FDCs in 2007, another mega ban of 344 irrational FDCs has been announced by the Government, through a Gazette Notification dated March 11, 2016. Some well known brands, such as, Corex, Phensedyl, Crocin Cold and Flu, D-Cold Total, Nasivion and Vicks Action 500 Extra, among others, reportedly come under this ban now. Here is the complete list of 344 banned FDCs.

According to the Government, the reason for banning these drugs is that ‘they involve risk to humans and safer alternatives were available.’

Nevertheless, manufacturers of some of these mega brands have again obtained an interim injunction on the ban for their respective products, from the Delhi High Court.

Sometime during the day, i.e. on March 21, 2016, the honorable Delhi High Court is expected to take up this patient-centric issue. It apparently smacks a blatant self-serving interest of the concerned irrational FDC manufacturers, that defeats the core purpose and value of pharma products for their users.

Like most other issues, the Court directive on this issue, as well, would ultimately prevail, without any shade of doubt.

Is it a ‘bolt from the blue’ for the pharma industry? 

Many industry watchers feel that this recent ban has not come as a ‘bolt from the blue’ for the pharma players, at all, as is being claimed by a section of the pharma industry. Even the Union Ministry of Health has, reportedly, clarified the following points on the recent notification:

  • “We have tried to bring objectivity to the issue by roping in the best of scientists to study the effects of these FDCs.”
  • “Show cause notices were also issued to more than 344 companies and they were given time to make further representations after the expert committee gave their recommendations. Some of them did not even care to respond. Everybody was given ample opportunity. After that, the move was initiated. It was done after much examination.”
  • “It is necessary and expedient in the public interest to regulate by way of prohibition of manufacture for sale, sale and distribution for human use, of the said drugs in the country.”

It is worth noting, at least, one of these well known pharma brands was, reportedly, banned in one of our neighboring countries – Sri Lanka, in 2012, for wide-spread drug misuse, long after its marketing approval in the country.

Some key events leading to the recent ban: 

Besides the above articulation by the Union Ministry of Health, it is worth noting, especially, the following key developments to ascertain, whether this ban came suddenly to the irrational FDC manufacturers, and without any prior warning or appropriate communication:

  • The issue of manufacturing licenses being granted by some states for FDCs without prior approval of Central Drugs Standard Control Organization (CDSCO), was first discussed by the Drugs Technical Advisory Board (DTAB) in the year 2000, though without any major tangible outcome till 2007. 
  • In 2007, Government banned 294 FDCs, and the consequent court proceedings had ‘Stayed’ this ban.
  • Expressing huge concern on pharma malpractices related to irrational FDCs, the Parliamentary Standing Committee on Health and Family Welfare in its 59th report (2012) also had flagged this issue. The lawmakers observed in the report that manufacturing licenses for large numbers FDCs were being issued by the State Drug Authorities, without prior approval of the Central Drugs Standard Control Organization (CDSCO), in violation of rules. The committee also noted that multiple FDCs, which are available in India had been rejected by the drug regulators in Europe, North America, and Australia, while for many others never had marketing approval applications submitted outside India (Section 7 of [6]).
  • Subsequently, in June 2013, CDSCO  announced the “Policy Guidelines for Approval of Fixed Dose Combinations (FDCs) In India.”
  • According to CDSCO, just 1193 FDCs were approved by the DCGI, since 1961 till November, 2014. Thus, all drug manufacturers should clearly know, which FDC has been approved by the DCGI, and when, leaving no scope for any ambiguity in this area. Thus, there should be no problem in total conformance to the above ‘FDC Policy Guidelines’ by these drug producers.
  • In the same year – 2013, a public notice was also, reportedly, issued, calling all those drug players manufacturing FDCs to apply with the requisite fee, in the prescribed form to the DCGI office, providing the required details.  
  • In 2014, a six-member committee, chaired by Prof. (Dr.) Chandrakant Kokate, Vice Chancellor, KLE University, Jawaharlal Nehru Medical College, Belgaum, Karnataka, was formed to expedite the review process of the applications. 
  • The Kokate Committee has, reportedly, reviewed about 6,600 FDCs, so far, and classified them under four categories – irrational, require further deliberations, rational and require additional data generation. 
  • According to a report, 963 FDCs were found under the irrational category, providing reasons in detail for each. 
  • In 2016, the Government finalized its action, based on the Report of Kokate Committee and also the response received (or still not received despite requests) from the concerned FDC manufacturers.
  • The March 11, 2016 Gazette Notification banned 344 ‘irrational’ FDCs, ruffling many feathers, but understandably to protect patients’ health interest.
  • On March 14, 2016, in response to an appeal against this ban through a writ petition, first by Pfizer, the Delhi High Court reportedly granted the company a stay, pending the next court hearing on March 21, 2016. Subsequently, several such stay orders by the honorable Delhi High Court have been issued with the same date of hearing. 
Adverse health and economic impact on patients:

Besides serious health risks, the patients also suffer from a huge adverse economical impact, in rupee value terms, by consuming much avoidable irrational FDC formulations, which are generally more expensive than single ingredient drugs, if taken separately at times of necessity or convenience.

The ban of 344 FDCs is estimated to cover over 2,500 brands, in different therapy categories, including chronic diseases, where medicines are taken for a long period of time. Thus, a large number of patients were consuming these irrational formulations for a long period of time without any inkling of their necessity and more importantly serious adverse health impact that these irrational FDCs could cause.

To quantify how much have the patients collectively spent on these banned medicines, in the rupee value terms, I shall quote from the estimates of one of the well reputed and much quoted pharma retail audit and market research organization of India – AIOCD Pharmasofttech AWACS Pvt. Ltd.

According to its report of March 13, 2016, Indian Pharmaceutical Industry would lose Rs. 3,838 Crore (MAT), which is 3.1 percent of the turnover of the Indian Pharmaceutical Market (IPM), when calculated based on the retail sales of these FDCs in the last 12-month period.

Paraphrasing the same finding, one can logically conclude that Indian patients withstood an adverse economic impact of Rs. 3,838 Crore in a 12-month period, by spending on these unnecessary and irrational FDCs of dubious value, besides health risks. 

To my surprise, some of the MNC pharma players contribute a major chunk to this avoidable expenditure of the patients, besides associating and avoidable health risks.

Quoting similar credible data, it is also possible to give company-wise break-up in this area, which, in my view, may not be meaningful here.

Two Critical issues to address:

Although, a lot of water has since flown down the bridges, a large number of irrational FDCs are still in the market, exposing patients to possible health hazards and economical hardship.

In this blog, I discussed this core issue in two of my articles, one on July 15, 2013 titled, “FDC Saga: Defiant Manufacturers, Sloppy Regulators and Humongous Inaction”, and the other on May 18, 2015 titled, “Booming Sales Of Unapproved Drugs: Do We Need ‘Safe In India’ Campaign For Medicines?”.

I reckon, the following two would still remain the critical issues, which need to be addressed, expeditiously, once and for all, for patients’ sake: 

  • Stringent compliance with the latest CDSCO requirements by all the manufacturers of FDCs in India must be ensured. Any non-conformance should attract strong punitive measures, through a transparent process.
  • Whether such drugs are being widely misused, creating a grave risk for health and other safety hazards, must be ascertained periodically, based on credible data.
An important example:                         

Just the other day, Reuters reported that one of the largest pharma companies operating in India, was selling a FDC of the antibiotics cefixime and azithromycin, without approval of the DCGI.

Interestingly, this particular FDC has reportedly not received marketing approval in the major global pharma markets, such as, the United States, the United Kingdom, Germany, France or Japan.

After the ban of this irrational FDC, the company was compelled to stop manufacturing and sales of this powerful antibiotic cocktail that poses huge health risk to patients.

This Reuters report also states, 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.

Many doctors and health experts have been saying that the spread and misuse of antibiotic combinations may be contributing to antibiotic resistance in India.

FDC approval must be hard evidence-based:

Since all pharmaceutical products, whether available as a single ingredient, or FDC formulations, are globally considered as ‘Evidence-Based Medicines’. Such evidences are established through robust, stringent and well regulated clinical trials for obtaining marketing approval from the drug regulators, unlike most ‘traditional medicines’.

Following this well-established global norm, and as recommended by even the World Health Organization (WHO), all irrational FDCs must be identified through a transparent and medical science-based process, and banned forthwith by the Government.

Establishing safety and efficacy for all FDCs through clinical trials, just like any other single ingredient drug, introduced for the first time in India, whenever it happens or had happened in the past, inadvertently or otherwise, should be a ‘must happen’ regulatory requirement, for all time to come.

Profit making interest through introduction of a plethora of irrational FDCs, should never be allowed to overshadow patients’ health and economical interest.

The bogey of even ‘25 to 30-year-old FDCs’ now being banned: 

Some section of the industry is also raising this point, vociferously, protesting against the bans of their respective old and top-selling FDC brands, which have now been considered by the Government as irrational, and questioning: ‘why now?’

This point is irrelevant, as not taking action ever, against a wrong doing allowed over a long period time, does not make an irrational FDC formulation a rational one, for all time to come.

Moreover, this recent action of the drug regulator can not be considered as unique either. With the advancement of medical science, in the past years too, the DCGI issued banned notifications, covering many old FDCs, considering those ‘irrational combinations’ at a given point of time, such as, analgin + pitofenone, vitamins B1 + B6 + B12, cyproheptadine + lysine, just to name a few.

Conclusion:

As is known to many, pharmacovigilance is still at a very nascent stage in India. Consequently, ‘Adverse Drug Reactions (ADR)’ or ‘Adverse Drug Events’ reporting are still abysmally poor in the country. No information on ‘Adverse Drug Events’, as claimed by the manufacturers of these irrational FDCs, should, therefore, in no way mean that these drugs are safe and efficacious and beyond any reasonable doubt.

Although the laxity of the drug regulator in this area can’t also be condoned, in any way, the enormity of the risks posed by irrational FDCs to the innocent patients, is indeed mind boggling.

If the manufacturing and sale of all irrational FDCs are not legally stopped, even after a long and rigorous scientific and medical scrutiny by the experts, the patients in the country would, unfairly, continue to remain exposed to huge health and economic risks, without any fault of theirs. This is exactly what happened in 2007 also, when, after the stay order of the ban notification for 294 irrational FDCs by the honorable Madras High Court, all those FDCs continued to be promoted, prescribed and sold to patients across India, unhindered… but at whose cost?

Yet again, the gazette notification of the Government on the recent ban on 344 FDCs, has gone for judicial scrutiny, at least, for some money spinning key brands of the large pharma players.

This time, however, there is one significant difference, the Government seems to be far more assertive and committed to ensure that only safe medicines are available in the market, despite reported intense advocacy by the industry. This commitment on the part of the Government is also evident from the media report that the (DGCI) has again sent a new list of additional 1,200 FDCs for a probe to the panel, which recommended the ban of 344 irrational FDCs in the last week, and that too, after the court stay order on the latest ban.

Further, a senior a senior official in the Health Ministry has, reportedly, reiterated that the Government will stand firm on its decision, and will support the ban with robust data, in the Delhi High Court.

Would history repeat itself, this time now? We, at least, would get a sense of it, as the proceeding of the honorable Delhi High Court commences today, on this issue.

Either way, it will possibly send a clear signal, whether the triumph of commercial profit motive with irrational FDCs would continue, unabated, over patients’ health, safety and economic interests, at least in the foreseeable future. 

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.

 

For Drug Safety Concern: “Whistleblower’s Intention Should Be Nationalistic”

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In the recent weeks, three significant developments related to the Pharmaceutical Industry in India, have triggered rejuvenated concerns in the following critical areas: 

A. Overall drug safety standards in the country

B.  Self serving interest, rather than patients’ interest, dominate the prescribing decisions

C. Government assurance to American Trade Organization on ‘Compulsory License (CL)’ in India. 

These important issues fall under three key regulatory areas of India, as follows:

  • The Central Drugs Standard Control Organization (CDSCO)
  • The Medical Council of India (MCI)
  • The Indian Patent Office

It is worth mentioning here that the Department Related Parliamentary Committee on Health and Family Welfare in its 59th Report, placed before both the houses of the Parliament on May 08, 2012, on the functioning of the Central Drug Standards Control Organization (CDSCO), begins with the following observations:

Medicines apart from their critical role in alleviating human suffering and saving lives have very sensitive and typical dimensions for a variety of reasons. They are the only commodity for which the consumers have neither a role to play nor are they able to make any informed choices except to buy and consume whatever is prescribed or dispensed to them, for the following reasons:

  • Drug regulators decide which medicines can be marketed
  • Pharmaceutical companies either produce or import drugs that they can profitably sell
  • Doctors decide which drugs and brands to prescribe
  • Consumers are totally dependent on and at the mercy of external entities to protect their interests.

Most importantly, all these concerns, if not properly clarified and appropriately addressed by the Government, soon enough, have the potential to create an adverse snowballing impact on the uniform access to affordable quality medicines, for all sections of the society in India.

Under this backdrop, I shall discuss in this article briefly, my perspective on each of these critical areas, as they are today, and not just the drug safety concerns.

The headline of this article is expected capture not only the prevailing mood of some key regulators, but also their inertia to address critical healthcare concerns and above all how the core public health related issues are getting lost, and the trivial ones are gradually occupying the center stage.

A. Overall drug quality and safety  standards in India:

A Public Interest Litigation (PIL) suit, filed against the Drugs Consultative Committee and the Central Drugs Standard Control Organization (CDSCO), was listed on the Supreme Court website for hearing on March 11, 2016.

The PIL has been filed by one Dinesh Thakur, requesting the Supreme Court to lay down guidelines by which manufacturers could be made liable for violating drug standards and also give a direction to the government to set up a ‘Drug Approvals Review Committee’ for examining criminality in the manner in which faulty drug approvals were granted. 

Many may recall that the same Dinesh Thakur worked for Ranbaxy from 2003 for two years, and is now the Chief Executive of MedAssure Global Compliance based in Florida, US. Thakur’s Company now advises pharma manufacturers on drug safety and quality standards.

As reported by Reuters, Thakur had earlier exposed how the erstwhile largest drug maker of India, Ranbaxy Laboratories, failed to conduct proper safety and quality tests on drugs and lied to regulators about its procedures. Consequently, USFDA fined Ranbaxy US$500 million for violating federal drug safety laws, and making false statements to the US regulator.

This news report further states: “Indian Parliamentary Committee, thereafter, reportedly demanded an investigation and the drugs regulator committed to one in 2013. Thakur received a statement from the health ministry last year, seen by Reuters, showing no inquiry had begun.”

On the last Friday, however, the Supreme Court of India refused to entertain this PIL of Dinesh Thakur, saying it does not have time to adjudicate academic issues, such as, need for guidelines to regulate quality of medicines.                                                  

The core issue:

The core issue here is not at all the above PIL, not at the very least. The issue is the much reported concern being expressed, over a period of time, regarding the drug safety standards in India. The reasons include breach of of data integrity, and gross violation of the ‘Good Manufacturing Practices’ standards. Such instances are being detected, almost regularly, by the foreign drug regulators, in several manufacturing facilities run by many large and small Indian drug producers.

It is well vindicated by the fact that around 45 Indian drug manufacturing plants have been banned by the USFDA alone, from shipping generic drugs to the United States, as these were considered unsafe for consumption of patients in the US. Some other foreign regulators too had taken similar action, citing similar reasons. The USFDA website specifies the details of gross violations made in each of these cases.

Ironically, all such facilities can manufacture and sell their drugs in India, as they conform to the quality requirements of the Indian drug regulator. Consequently, the Indian patients consume even those medicines, which are considered unsafe by the USFDA for American patients, innocently, as and when prescribed by the doctors.

Arising out of these incidents, when asked about the drug safety standards in India, and the public health-safety, instead of giving credible and action oriented answers for public reassurance, some of the apparently brazen replies of the DCGI are quite stunning for many stakeholders, both within and outside the shores of India.

I would now quote below just a few of those replies, just as examples. 

“…Whistleblower’s Intentions Should Be Nationalistic” -  DCGI:

According to Reuters, it has received the following response from the Drug Controller General of India (DCGI), on the above PIL related to the drug safety standards in India:

“We welcome whistleblowers, we have got great respect, but their intentions should be genuine, should be nationalistic… I don’t have any comment on this guy.”

Thus, many industry watchers feel that in a situation like this, the honorable Supreme Court of India would possibly require to intervene, just as what it did on alleged ‘Clinical Trial’ malpractices in the country or for drug price control, solely for public health interest.

The same attitude continues:

Such brazen response of the Central Drug Regulator, and that too on a serious subject, is indeed bizarre. It becomes increasingly intriguing, as the same attitude continues without any perceptible meaningful intervention from the Ministry of Health.

For example, on February 22, 2014, in the midst of a more intense scenario on a similar issue, instead of taking transparent and stringent measures, the DCGI was quoted by the media commenting:

“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.”

On February 26, 2014, presumably reacting to the above remarks of the DCGI, the American Enterprise Institute reportedly commented, “Indian drug regulator is seen as corrupt and colliding with pharma companies…”

Such apparently irresponsible and loose comments keep continuing, despite the 2012 report of the Parliamentary Committee of India alleging collusion between some pharmaceutical companies and officials of the CDSCO, which oversees the licensing, marketing and trials of new drugs. The report also commented that the agency is both chronically under-staffed and under-qualified.

Some possible remedial measures:

As the saying goes, “better late than never”, considering all these continuing developments, it is about time to reconsider some of the key recommendations of Dr. R. A. Mashelkar Committee on a similar subject and make amendments in the relevant Act accordingly, soon, to facilitate creation of a robust with high accountability ‘Central Drugs Authority (CDA)’. It would introduce a centralized licensing system for drug manufacturing, along with stringent drug safety standards; besides, sale, export and distribution of drugs. Perhaps, the draft bill on CDA is now lying in the heap of archival documents with the change in Government.

Why does India need CDA?

I believe, the formation of a robust CDA with high accountability, besides meeting with drug safety concerns, would provide the following significant benefits, both to the Industry and also to the Government:

  • Achieving uniform interpretation of the provisions of the Drugs & Cosmetics Act & Rules
  • Standardizing procedures and systems for drug control across the country
  • Enabling coordinated nationwide action against spurious and substandard drugs
  • Upholding uniform quality standards with respect to exports to foreign countries from anywhere in India
  • Implementing uniform enforcement action in case of banned and irrational drugs
  • Creating a Pan-Indian approach to drug control and administration
  • Evolving a single-window system for pharmaceutical manufacturing and research undertaken anywhere in the country.

B.  Self serving interest dominates the prescribing decision: 

That the self serving interest, rather than patient interest, dominate the prescribing decision, was vindicated by a key announcement of the Medical Council of India (MCI) last month.

In February 2016, apparently succumbing to continuous and powerful external pressure, the MCI announced an amendment in a clause of its Code of Ethics Regulations 2002, exempting doctors’ associations from the ambit of its ethics code, as applicable to doctors now across the country. Prior to the amendment, this section used to read as: “code of conduct for doctors and professional association of doctors in their relationship with pharmaceutical and allied health sector industry”.                      

In other words, it means that the professional associations of doctors will no longer come under the ambit of ethics regulations, legitimizing their indulgence in the identified unethical and corrupt practices, by receiving gifts in cash or kind from the pharma or healthcare industry.

A large section of the key stakeholders believes that this amendment would help creating an additional large space for the pharmaceutical marketing malpractices to thrive, unabated, at the cost of patients.

The latest report of the Parliamentary Standing Committee on MCI:

In its 92nd Report, the Department-Related Parliamentary Standing Committee on Health and Family Welfare titled, “The Functioning of Medical Council of India”, presented to the Rajya Sabha and laid on the Table of Lok Sabha on 8th March, 2016, the Committee observed on this amendment as “an action that is ethically impermissible for an individual doctor cannot become permissible, if a group of doctors carry out the same action in the name of an association.”

The report also noted the failure of MCI to instill respect for a professional code of ethics in the medical professionals and take disciplinary action against doctors found violating the code of Ethics, etc.

The Committee called for a complete restructuring of the MCI, since it believes that the Council has failed as a regulator of medical education and the profession. Casting serious aspersions on the functioning of the MCI, the house panel of the Parliament recommended that the Act under which the MCI was set up be scrapped and a new legislation be drafted “at the earliest”. 

The report castigated the health ministry:

The lawmakers castigated the Health Ministry in this report saying, “The committee also finds it intriguing that instead of intervening to thwart attempts of MCI at subverting the system, the ministry meekly surrendered to MCI.”

While summing up, the report states, “the Committee exhorts the Ministry of Health and Family Welfare to implement the recommendations made by it in this report immediately and bring a new Comprehensive Bill in Parliament for this purpose at the earliest.”

How will it pan out now?

I reckon, it will now be immensely interesting now for all concerned to follow, how does the Government deal with this report to curb, among others, the strong interference of mighty and powerful vested interests to continue with the rampant pharma marketing malpractices, at the cost of patients in India.

C. Reported Government assurance on ‘Compulsory License’: 

On March 3, 2016, a media report quoted a submission by the US Chamber of Commerce to the office of the US Trade Representative (USTR) as follows:

“While the Government of India has privately reassured (American) industry that it would not use compulsory licenses for commercial purposes, a public commitment to forgo using (this) would enhance legal certainty for innovative industries.”

This is an interesting development, primarily because there are a number of legal provisions for granting Compulsory Licenses (CL) in the Indian Patents Act 2005, including, when a drug is not widely available, extremely expensive and some other situation. In some these provisions, law should follow its own course and there is no legally permissible scope for Government’s administrative interference. Grant of CL for Nexavar of Bayar is one such example, and incidentally, that’s the sole CL that India has granted, so far, from the date of amendment of the country’s Patents Act in 2005. 

Thus, a blanket assurance of not invoking any of the provisions of the CL, as provided in the Indian Patents Act 2005, if true, would possibly require to pass through intense legal scrutiny, as that would adversely impact the access to key medicines in a necessary situation, for the public health interest.

So far, India has amply demonstrated to all, time and again, that the country does not grant a CL at the drop of a hat. That situation should continue to encourage and protect innovation. 

Nevertheless, “a written public commitment to forgo using the CL provisions for enhancing legal certainty for innovative industries,” as demanded by the US Chamber of Commerce, appears to be unreasonable, goes against the spirit of India’s Patents Act, and perhaps is not legally tenable either, unless the IP Act is amended accordingly in the Parliament.

Conclusion:

All these three areas, as discussed above, are critical from the healthcare perspective of the country.

Ironically, while deliberating on the subject, the capability, credibility and competence of some of the key regulators of the country, are being repeatedly questioned. These doubts emanate not just from Tom, Dick and Harry, but from an illustrious spectrum of constitutional institutions of India, spanning across the lawmaking Parliament, through its various committee reports, to the ultimate legal justice provider – the Supreme Court of India, through is various orders and key observations.

Regrettably, in this specific space, which is primarily related to healthcare, nothing seems to be changing on the ground, since long. The same tradition continues, without any visible sense of urgency, even from the Government.

On the contrary, we now read a new genre of comments, even from a key regulator, on the stakeholder concerns. For example, reacting to concern on drug safety standards, instead of articulating tangible actions to usher in a perceptible change, the chief action taker reportedly specified a totally judgmental and an outlandish requirement: “…Whistleblower’s intentions should be Nationalistic.”

Together with these incidents, the key public healthcare concerns of India too, are now apparently getting drowned in the high decibel ‘Nationalistic’ versus ‘Anti-nationalistic’ cacophony. But, the hope still lingers… for a change…for our nation’s sound health!

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.

Healthcare: Unwrapping The Union Budget (2016-17)

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February 29, 2016 was the day of high expectations for many, especially to get to know the focus areas of public resource allocations of the incumbent governments in its third year of office. Healthcare sector too awaited eager to see something substantial in the resource allocation, that would make a fundamental difference in the public health systems and services in India.

The general expectation was high, as its main ruling party had promised to deliver a robust healthcare reform in its Election Manifesto 2014, when it will be voted to power. Some of those critical promises are as follows:

  • “India needs a holistic health care system that is universally accessible, affordable and effective and drastically reduces the out of pocket spending on health.
  • NRHM has failed to meet the objectives and will be radically reformed.
  • The Party accords high priority to health sector, which is crucial for securing the economy.
  • The overarching goal of healthcare would be to provide, ‘Health Assurance to all Indians and to reduce the out of pocket spending on health care’, with the help of state governments.
  • The current situation calls for radical reforms in the healthcare system with regards to national healthcare programs and delivery, medical education and training and financing of healthcare.”
  • The manifesto then went into the details of each reform areas, after stating, “the last healthcare policy dates back to 2002; India now needs a comprehensive healthcare policy to address the complex healthcare challenges, keeping in view the developments in the healthcare sector and the changing demographics. The party will initiate the New Health Policy.”

Over three years have passed since then, unfortunately even the new and comprehensive healthcare policy is not in place, just yet.

In that backdrop, we all witnessed in the budget presentation, a well-wrapped package for healthcare in India. The ‘attractive’ packaging label, listing each element of its broad content, was outwardly impressive and attracted almost instant eulogy from a number of industry commentators.

In this article, I shall first present before you, the healthcare measures announced by the Finance Minister Mr. Arun Jaitely in his Budget speech (2016-17), and then would unwrap the package to discuss briefly the implications of each of these three key elements, and the possible impact.

Union Budgetary Proposals on healthcare:

While proposing his Union Budget Proposal (2016-17), the Minister mostly covered ‘healthcare’ in points 52, 53, 54 and 55 of his speech, as follows:

A. Improving access to healthcare: 

While proposing a key measure to improve access to healthcare, the Minister acknowledged before the Parliament:

  • Catastrophic health events are the single most important cause of unforeseen out-of-pocket expenditure which pushes lakhs of households below the poverty line every year. 
  • Serious illnesses of family members cause severe stress on the financial circumstances of poor and economically weak families, shaking the foundation of their economic security.

In the above backdrop, the Minister proposed that, in order to help such families, the Government will launch a new health protection scheme, which will provide health cover up to Rs. One lakh (Rs. 100,000) per family. For senior citizens, age 60 years and above, belonging to this category, an additional top-up package up to Rs. 30,000 will be provided.

B. Availability of quality medicines at affordable prices:

Acknowledging the fact that making quality medicines available at affordable prices has been a key challenge for the country, the Minister reiterated that the Government will reinvigorate the supply of generic drugs. Moving towards this direction, 3,000 Stores under Prime Minister’s Jan Aushadhi Yojana will be opened during 2016-17. 

C. Addressing an important need of end-stage renal disease patients:

The Minister informed the Parliament that around 2.2 lakh new patients of End Stage Renal Disease gets added in India every year, resulting in additional demand for 3.4 crore dialysis sessions. With approximately 4,950 dialysis centers in India, largely in the private sector and concentrated in the major towns, the demand is only half met. Every dialysis session costs about Rs. 2,000 – an annual expenditure of more than Rs. 3 lakhs. Besides, most families have to undertake frequent trips, often over long distances, to access dialysis services, incurring heavy travel costs and loss of wages.

To address this situation, the FM proposed to start a ‘National Dialysis Services Program’. Funds will be made available through PPP mode under the National Health Mission, to provide dialysis services in all district hospitals. To reduce the cost, he proposed to exempt certain parts of dialysis equipment from basic customs duty, excise/CVD and SAD.

Unwrapping the healthcare budget proposal: 

Let me hasten to add at this stage that I have not seen the fine prints of each of these proposals, as yet. My analysis is solely based on the budget speech. 

A. Improving access to healthcare:

At Rs. 19,037 crores, the budgetary allocation for the ‘National Health Mission (NHM)’ remains almost the same as the previous year. Overall investments to improve healthcare infrastructure still remaining absolutely meager, the ad hoc strategy of the Government to improve access to healthcare is an insurance-centered, rather than universal, free and cashless health services, as was earlier suggested by the ‘High Level Expert Group (HLEG)’ constituted earlier by the Government. 

According to the analysis of National Sample Survey (NSS) data for 2014, published in the Economic&PoliticalWeekly dated August 15, 2015, only 13.1 percent of rural and 12 percent of urban residents are covered by government-funded insurance schemes, though the official data states 25 percent coverage. The NSS data also shows an increase in the out-of-pocket expenditure in these areas.

This has happened, even after the promotion of the Governments own insurance-based schemes, such as, the RSBY by the Central Government and also similar schemes by the State Governments, such as, Arogyasri in Andhra Pradesh, over a decade.

Additionally, there are many other reports, which clearly highlight that just pushing for increased insurance coverage, does neither help the poorest of the poor of society, nor does it ensure better and more efficient financial protection.  

A paper of October 9, 2013 titled, “Universal Health Coverage – Why health insurance schemes are leaving the poor behind” reiterates that funding through progressive taxation is the key to achieving ‘Universal Health Coverage’. Even the poorest countries can raise more revenue for health through taxes. Oxfam estimates that improving tax collection in 52 developing countries could raise an additional US$269 billion, which is enough to double health budgets in these countries.

The world over, and mostly in the OECD countries, serious doubts are still being expressed about the effectiveness of targeted insurance-based health schemes, instead of public funded focus on ‘Universal Health Care’. 

Looking in isolation, while the measure of incremental health insurance coverage, as proposed by the Minister, seems to be a good intent to improve access to healthcare to some people, but is devoid of a clearly charted holistic pathway, based on the lessons learnt from the past. Just the announcement of intent may, therefore, not be effective on the ground. 

Currently, India has the Rashtriya Swasthya Bima Yojana (RSBY), launched by the Labor and Employment Ministry on April 1, 2008, to provide health insurance coverage to ‘Below Poverty Line (BPL)’ families. RSBY coverage extends to five members of a family-head of the household, spouse and up to three dependents, who are entitled to hospitalization coverage of up to Rs 30,000 for most diseases. In this insurance scheme, the beneficiaries require to pay only Rs 30 as registration fee, while Central and state governments pay premium to the insurer.

It is still not clear to me, whether, the newly announced insurance coverage is a separate scheme all together with details to be announced later or a part of RSBY initiative.

Besides all these, the fundamental question, however, that would still keep haunting, how would the existing mostly rickety rural brick and mortar healthcare infrastructure; non-availability of right medicines at the right time and at the right places; acute shortages of medics and paramedics, satisfactorily address the incremental needs, thus created? 

B. ‘Pradhan Mantri Jan-Aushadhi Scheme’: 

This does not seem to be a new initiative, at all. Jan-Aushadhi is an ongoing campaign launched by the Department of Pharmaceuticals in 2008, in association with Central Pharma Public Sector Undertakings (PSU), to provide quality medicines at affordable prices to the masses. Jan Aushadhi Stores (JAS) are being set up to provide generic drugs, which are available at lesser prices, but are equivalent in quality and efficacy as expensive branded drugs. 

The Department of Pharmaceuticals had proposed to open at least one JAS in each of the 630 districts of the country, so that the benefit of “quality medicines at affordable prices” is available to at least one place in each district of India. If the initiative becomes successful, depending on the cooperation of all stakeholders, the scheme was to be extended to sub divisional levels as well as major towns and village centers by 2012. However, after 5 years, i.e. up to February, 2013, only 147 JAS were opened, and out of those only 84 JASs are functional.

More recently, according to a June 02, 2015 report, “under the new business plan approved in August 2013, a target of opening 3,000 Jan Aushadhi stores during the 12th plan period i.e. from 2013-14 to 2016-17 was fixed. As per the Standing Committee on Chemicals and Fertilizers report in March 2015, till date only 170 Jan Aushadhi stores have been opened, of which only 99 are functional.” 

The tardy progress of the scheme was largely attributed to:

  • A lackluster approach of State governments
  • Poor adherence to prescription of generic drugs by doctors,
  • Managerial/ implementation failures of CPSU/ BPPI.
  • Only 85 medicines spread across 11 therapeutic categories were supplied to the stores and the mean availability of these drugs was found to be 33.45 percent, with wide variations across therapeutic categories.

With all the available information, it appears that the same old and unsuccessful scheme, even during the tenure of the present Government, since the last 3 years, has been repackaged and announced with a new name “Pradhan Mantri Jan Aushadhi Scheme” in the Union Budget 2016-17. 

There is no doubt, however, the intent of ‘Pradhan Mantri Jan-Aushadhi Scheme’ of 2016 is as laudable as the “Jan-Aushadhi Scheme”, launched by the Department of Pharmaceuticals in 2008, was at that time, but will it start working now, all of a sudden, despite sustained failure?

Besides strong support required from the State Governments, and other factors as enlisted above, making the doctors prescribe drugs in generic names would be a critical factor to make the “Pradhan Mantri Jan-Aushadhi scheme’ a success and primarily to extend desirable benefits to a sizeable section of both the urban and rural poor. The question, thus, remains, how would the Government ensure that the doctors prescribe drugs in generic names?  

C. National Dialysis Services Program: 

The proposal for the ‘National Dialysis Services Program’ to provide dialysis services in all district hospitals, especially, due to a staggering number of around 2.2 lakh patients of ‘End Stage Renal Disease’ in India every year, is yet another laudable intent in isolation, though it emerges just as an ad hoc measure in the healthcare space of the country, sans the new National Health Policy.

Conclusion:

In my article last week titled, “Healthcare In India (2016-17): Whither Goest Thou?”, I wrote, as the new ‘National Health Policy’ is still not in place, we may, at best see in the Union Budget Proposals (2016-17), some ad hoc measures for healthcare.

While unwrapping this budget speech of the, it appears that on a broader perspective the measures proposed in the budget have turned out exactly that way.

Nonetheless, the proposal of the Finance Minister for a special patent regime with a 10 percent rate of tax on income from worldwide commercialization of patents, which are developed and registered in India, is an excellent one, by any standard, for the innovators.

With frugal public health expenditure of just around 1 percent of GDP, as compared to 3.5 percent of China and 5 percent of Brazil, with larger GDP base, successive Governments of India has been blatantly neglecting public healthcare, for far too long, which continues even today.

At a time, when the Government is mulling making health a fundamental right for Indian citizens, similar to education, and making denial of health an offense, besides its earlier other promises, these budgetary measures are disappointing to many.

Overall, the Union Budget Proposals, made by the Finance Minister for 2016-17, falls far too short of reasonable expectations of any deserving citizen of the country. Neither does any such healthcare measure appear holistic to me, besides being sustainable, as I unwrap the Minister’s healthcare package and take a closer look at it.

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.