Reverberations Around The Proposed New IPR Policy Of India

Posted on February 16, 2015 by Tapan Ray

“If the Obama administration succeeds in forcing India to strengthen its patent laws, the change would harm not only India and other developing countries; it would also enshrine a grossly corrupt and inefficient patent system in the US, in which companies increase their profits by driving out the competition – both at home and abroad. After all, generic drugs from India often provide the lowest-cost option in the US market once patent terms have expired.”

The above sharp, piercing and precise comment did not come from any health activist from India or elsewhere. It came from a team of highly credible academic experts working in the United States.

On February 10, 2015, Nobel Laureate in Economics – Joseph E. Stiglitz, who is also University Professor at Columbia University, former Chairman of President Bill Clinton’s Council of Economic Advisers and Chief Economist of the World Bank, made this comment in an article published in ‘The World Opinion Page’ of ‘Project Syndicate’.

The article is co-authored by Dean Baker, Co-Director of the Center for Economic and Policy Research in Washington DC and Arjun Jayadev, Professor of Economics at the University of Massachusetts, Boston.

The authors arrived at the above conclusion based on some sound arguments. I am highlighting below some of those important ones (may not be in the same order):

A patent that raises the price of a drug a hundred-fold has the same effect on the market as a 10,000 percent tariff.

India’s Patents and Act and policies allow drugs to be sold at a small fraction of the monopoly prices commanded by patent holders. For example, the Hepatitis-C drug Sovaldi is sold for US$84,000 per treatment in the US; Indian manufacturers are able to sell the generic version profitably for less than US$1,000 per treatment.

The threat of competition from Indian generics is partly responsible for major pharmaceutical companies’ decision to make some of their drugs available to the world’s poor at low prices. If the US compels India to tighten its patent rules substantially, so that they resemble US rules more closely, this outcome could be jeopardized.

Multilateral approach, using the World Trade Organization (WTO), has proved less effective than the major multinational pharmaceutical companies hoped, so now they are attempting to achieve this goal through bilateral and regional agreements.

In the view of America’s pharmaceutical industry, TRIPS did not go far enough. The Indian government’s desire to enhance its trade relations with the US thus provides the industry an ideal opportunity to pick up where TRIPS left off, by compelling India to make patents easier to obtain and to reduce the availability of low-cost generics.

In September 2014, during his visit to the US, Indian Prime Minister Narendra Modi agreed to establish a working group to reevaluate the country’s patent policy. The US participants in that group will be led by the Office of the US Trade Representative, which serves the pharmaceutical companies’ interests, rather than, say, the National Academy of Sciences, the National Science Foundation, or the National Institutes of Health.

Any comparable voice in favor of changes in Indian Patents Act?

I don’t seem to have heard or read as strong arguments from as credible sources as Nobel Laureate Joseph E. Stiglitz, Dean Baker and Arjun Jayadev – the authors of the above article, in favor of the changes that American pharma companies want in the Indian Patents Act.

India at the center stage in IPR debate:

In the IPR debate, India is continuously being seen at the center stage for various reasons. The key one being the size, scale and economic efficiency that the home grown Indian pharma players have attained to cater to the needs of a large number of global population, including those residing in the United States and Europe, with a wide range of high quality generic drugs at affordable prices.

Fast evolving scenario:

It is now absolutely clear that being rattled by several refusals of India’s granting product patent to very similar molecules with minor tweaking under section (3d) of the country’s Patents Act, together with the nation’s uprightness in issuing Compulsory License (CL) for an enormously expensive cancer drug reducing its price by over 95 percent, United States now intends to directly intervene into India’s IPR policy environment.

As Nobel Laureate Stiglitz wrote, keen desire of the new dispensation of the Indian government to enhance its trade relations with the US has provided a golden opportunity to American pharma companies and their paid lobbyists to jump into the fray. They have started exerting enormous pressure on their own Government to compel India, at bilateral discussions, dilute its well-balanced Patents Act, ignoring India’s sovereign right to play by the flexibilities as provided by the WTO to protect public health interest in the country.

Both the domestic and international civil society organizations, including public health activists have expressed their serious concerns on this aggressive intent of US and India’s seemingly vulnerable position in this regard.

“The US is pushing India to play by its rules on Intellectual Property, which we know will lead to medicines being priced out of reach for millions of people,” commented the Executive Director of MSF’s Access Campaign, according to media reports.

Non-pharma American Organizations reacted differently:

14 American organizations in a letter to their President Barack Obama dated January 20, 2015, just prior to his visit to India, asked him “to support India’s central role in providing high-quality, low-cost generic medicines -which are essential for health care around the world. Recent U.S. policy stances have sought to topple parts of India’s intellectual property regime that protect public health in order to advance the interests of multinational pharmaceutical corporations in longer, stronger, and broader exclusive patent and related monopoly rights. India’s laws fully comply with the WTO TRIPS Agreement. Millions around the world depend on affordable generic medicines that would disappear if India acceded to these proposals, including many beneficiaries of US-funded programs. Instead of using your trip to promote the narrow interests of one segment of the pharmaceutical industry, we ask you to support the interests of people who need affordable medicines, whether they live in the U.S., in India, in Africa or elsewhere. Our world is safer and healthier because of India’s pro-health stance and we ask you to say so publicly while you are there.”

The letter re-emphasized at the end:

“From Detroit to New Delhi, health is increasingly interconnected. Our world is safer when it is healthier, and it is healthier because India’s laws appropriately balance health and IP.”

An interesting development:

It is interesting to note that after Winter Session of the Indian Parliament, the Modi Government announced a number of important policy changes at the end of December 2014.

Interestingly, one more critical policy – National Intellectual Property Rights (IPR) Policy has been left open for public comments and the final IPR Policy is yet to be announced despite enormous American pressure on India in this regard.

Without any specifics, the first draft of the National IPR policy just states that India will “review and update IP laws, where necessary, and remove anomalies and inconsistencies, if any.” It does emphasize though, the need of “more innovation” in the country, unequivocally and quite justifiably.

I wrote on the draft National IPR Policy in my blog post of January 19, 2015, titled “New “National IPR Policy” of India – A Pharma Perspective”.

Conclusion:

It is generally believed that the National Intellectual Property Rights (IPR) Policy is undoubtedly a positive step to clarify the Government’s stand in maintaining a balanced IP regime in the country that would encourage innovation to add speed to the progress of the nation.

In just 10 years Indian IPR regime has, by and large, attracted enormous global attention mostly for balancing IP and public health interest, admirably. Experts like Nobel laureate Joseph E. Stiglitz sincerely hope that India will not change this course under pressure of any kind or form.

Be that as it may, several recent media reports also speculated, around the same time, that Government of India is probably considering putting in place ‘Data Exclusivity’ and ‘Patent Linkage’ through administrative measures, without making any amendments in the Patents Act of the country.

In my subsequent articles in this blog, I shall deliberate on these two contentious issues, keeping the evolving scenario in perspective.

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.

New “National IPR Policy” of India – A Pharma Perspective

Posted on January 19, 2015 by Tapan Ray

Whether under pressure or not, is hardly of any relevance now. What is relevant today is the fact that the new Indian Government, almost in a record time of just around two months, has been able to release a high quality first draft of an important national policy for public discourse.

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

A quick glance at the Draft IPR Policy:

The proposed ‘Mission Statement’ as stated in the draft “National IPR Policy” is:

“To establish a dynamic, vibrant and balanced intellectual property system in India, to foster innovation and creativity in a knowledge economy and to accelerate economic growth, employment and entrepreneurship.”

Specifying its vision, mission and objectives, the draft policy suggests adopting a catchy national slogan to increase IP awareness: ‘Creative India; Innovative India’ and integrating IP with “Smart cities”, “Digital India” and “Make in India” campaigns of the new Government.

The ‘Think Tank’ dwells on the following seven areas:

IP Awareness and Promotion
Creation of IP
Legal and Legislative Framework
IP Administration and Management
Commercialization of IP
Enforcement and Adjudication
Human Capital Development

In the policy document, the ‘Think Tank’ has discussed all the above seven areas in detail. However, putting all these in a nutshell, I shall highlight only three of those important areas.

1. To encourage IP, the ‘Think Tank’ proposes to provide statutory incentives, like tax benefits linked to IP creation, for the entire value chain from IP creation to commercialization.

2. For speedy redressal of patent related disputes, specialized patent benches in the high courts of Bombay, Calcutta, Delhi and Madras have been mooted. The draft also proposes creation of regional benches of the IPAB in all five regions where IPOs are already located and at least one designated IP court at the district level.

3. The draft concludes by highlighting that a high level body would monitor the progress of implementation of the National IP Policy, linked with performance indicators, targeted results and deliverables. Annual evaluation of overall working of the National IP Policy and quantification of the results achieved during the period have also been suggested, along with a major review of the policy after 3 years.

Although the National IPR policy cuts across the entire industrial spectrum and domains, in this article I shall deliberate on it solely from the pharmaceutical industry perspective.

Stakeholders’ keen interest in the National IPR Policy – Key reasons:

Despite full support of the domestic pharmaceutical industry, the angst of the pharma MNCs on the well-balanced product patent regime in India has been simmering since its very inception, way back in 2005.

A chronicle of recent events, besides the seven objectives of the IPR policy as enumerated above, created fresh general inquisitiveness on how would this new policy impact the current pharmaceutical patent regime of India, both in favor and also against.

Here below are examples of some of those events:

At a Congressional hearing of the United States in July 2013, a Congressman reportedly expressed his anger and called for taking actions against India by saying:

“Like all of you, my blood boils, when I hear that India is revoking and denying patents and granting compulsory licenses for cancer treatments or adopting local content requirements.”

This short video clipping captures the tone and mood of one such hearing of the US lawmakers.

On April 30, 2014, the United States in its report on annual review of the global state of IPR protection and enforcement, named ‘Special 301 report’, classified India as a ‘Priority Watch List Country’. Placement of a trading partner on the ‘Priority Watch List’ or ‘Watch List’ indicates that particular problems exist in that country with respect to IPR protection, enforcement, or market access for persons relying on IP.

It further stated that USTR would conduct an Out of Cycle Review (OCR) of India focusing in particular on assessing progress made in establishing and building effective, meaningful, and constructive engagement with the Government of India on IPR issues of concern. An OCR is a tool that USTR uses on adverse IPR issues and for heightened engagement with a trading partner to address and remedy in those areas.

“India misuses its own IP system to boost its domestic industries,” commented the US Senator Orrin Hatch while introducing the 2014 report of the Global Intellectual Property Centre (GIPC) of US Chamber of Commerce on ‘International Intellectual Property (IP) Index’. In this report, India featured at the bottom of a list of 25 countries, scoring only 6.95 out of 30. The main reasons for the low score in the report were cited as follows:

- India’s patentability requirements are (allegedly) in violations of ‘Trade Related Aspects of Intellectual Property Rights (TRIPS)’ Agreement.

- Non-availability of regulatory data protection

- Non-availability of patent term restoration

- The use of Compulsory Licensing (CL) for commercial, non-emergency situations.

Based on this report, US Chamber of Commerce urged USTR to classify India as a “Priority Foreign Country”, a terminology reserved for the worst IP offenders, which could lead to trade sanctions.

In the midst of all these, international media reported:

“Prime Minister Narendra Modi got an earful from both constituents and the US drug industry about India’s approach to drug patents during his first visit to the US last month. Three weeks later, there is evidence the government will take a considered approach to the contested issue.”

Washington based powerful pharmaceutical industry lobby group – PhRMA, which seemingly dominates all MNC pharma trade associations globally, has reportedly urged the US government to continue to keep its pressure on India in this matter. According to industry sources, PhRMA has a strong indirect presence and influence in India too. Interestingly, as reported in the media a senior representative of this lobby group would be India when President Obama visits the country later this month.

In view of all these concerns, during Prime Minister Narendra Modis’s visit to the United States in September 2014, a high-level Indo-US working group on IP was constituted as a part of the Trade Policy Forum (TPF), which is the principal trade dialogue body between the two countries.

Almost immediately after the Prime Minister’s return to India, in October 2014, the Government formed a six-member ‘Think Tank’ to draft ‘National IPR Policy’ and suggest ways and legal means to handle undue pressure exerted by other countries in IPR related areas. The notification mandated the ‘Think Tank’ to examine the current issues raised by the industry associations, including those that have appeared in the media and give suggestions to the ministry of Commerce and Industry as appropriate.

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

A perspective of National IPR Policy in view of Pharma MNCs’ concerns:

I shall now focus on four key areas of concern/allegations against India on IPR and in those specific areas what has the draft National IPR Policy enumerated.

- Concern 1: “India’s patentability requirements are in violations of ‘Trade Related Aspects of Intellectual Property Rights (TRIPS)’ Agreement.”

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

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

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

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

It is envisaged that this new development at the IPO would prompt entry of a good number of generic equivalents of Sovaldi. As a result, the price of sofosbuvir (Sovaldi) formulations would further come down, despite prior licensing agreements of Gilead in India, fetching huge relief to a large number of patients suffering from Hepatitis C Virus, in the country.

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

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

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

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

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

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

- Concern 4: “Non-availability of patent term restoration, patent linkage, use of compulsory licensing (CL) for commercial, non-emergency situations”.

Draft IPR Policy: Does dwell on these issues.

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

Conclusion:

Overall, the first draft of the outcome-based model of the National IPR Policy appears to me as fair and balanced, especially considering its approach to the evolving IPR regime within the pharmaceutical industry of India.

The draft policy though touches upon the ‘Utility Model’, intriguingly does not deliberate on ‘Open Source Innovation’ or ‘Open Innovation’.

Be that as it may, the suggested pathway for IPR in India seems to be clear, unambiguous, and transparent. The draft policy understandably has not taken any extreme stance on any aspect of the IP. Nor does it succumb to high voltage power play of the United States and its allies in the IPR space, which, if considered, could go against the public health interest.

It is heartening to note, a high level body would monitor the progress of implementation of the National IPR Policy, which will be linked with performance indicators, targeted results and deliverables. Annual evaluation of the overall working of the policy and the results achieved will also be undertaken. A major review of the policy will be done after 3 years.

That said, pharma MNCs in general, don’t seem to quite agree with this draft policy probably based purely on commercial considerations, shorn of public health interest. It is quite evident, when a senior lobbyist of a powerful American pharma lobby group reportedly commented to Indian media on the draft National IPR Policy as follows:

“Real progress will only be achieved when India demonstrates through policy change that it does indeed value the importance of intellectual property, especially for the innovative treatments and cures of today and tomorrow”.

It appears, India continues to hold its stated ground on IPR with clearly enunciated policy statements. On the other hand MNCs don’t stop playing hardball either. Though these are still early days, the question that floats on the top of mind: Who would blink first?…India? Do you reckon so?

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.

Pharma Outlook 2015: A Glimpse Of Some Drivers and Barriers

Posted on January 5, 2015 by Tapan Ray

Looking ahead, the brand new year 2015 appears quite interesting to me both from the global and also from the local pharmaceutical industry perspective. In this article I shall try to give a glimpse of some of the important drivers and barriers for success of the industry as the year unfolds, based on recent and ongoing developments.

Let me start with the global outlook of 2015, where in the midst of all gloom and doom of the past years, I notice formation of a distinct and new silver lining, mainly due to the following two reasons:

1. Record number of new drugs approval in 2014 spanning across10 therapy areas:

As indicated in its website, USFDA has approved 41 novel medicines in 2014, which is 14 more than the previous year and is the second highest after 1996 that witnessed 53 approvals. Many of these new drugs are with blockbuster potential.

According to another report, the European Medicines Agency (EMA) has also recommended 82 new medicines in 2014, which though includes generic drugs in its list. However, this number too shows an increase from 79 in 2013 and 57 in 2012.

According to January 02, 2014 report from Forbes, very interestingly, infectious diseases dominated with 12 approvals (27 percent), cancer with 8 approvals (18 percent), followed by rare diseases with 5 (11 percent). Just two of these new approvals are for Hepatitis treatment and the rest are for bacterial, fungal, viral, and parasitic infections.

AstraZeneca received the highest number of 4 approvals followed by Eli Lilly with 3.

2. Patent expired blockbuster drugs in 2015 would have low generic impact:

Though drugs worth sales turnover of US$ 44 billion would go off patent in 2015, patent expiries will have minimal impact on the top line as 2015 sales will grow close to four times that of patent losses. Following are the top 10 drugs among those:

No.	Brand	Company	Disease	Sales2013 (US$ Bn)	Patent Expiry
1.	Lantus	Sanofi	Diabetes	7.9	Feb 2015
2.	Abilify	Otsuka/Bristol-Myers Squibb	Schizophrenia/ Other neurological conditions	7.8	April 2015
3.	Copaxone	Teva	Multiple sclerosis	4.33	Sept 2015
4.	Neulasta	Amgen	Infection reduction in cancer patients on chemotherapy	4.4	Oct 2015
5.	Tracleer	Actelion	Pulmonary arterial hypertension	1.57	Nov 2015
6.	Namenda	Actavis	Alzheimer’s disease	1.5	April 2015
7.	Avodart/Jalyn	GSK	Benign prostatic hypertrophy	1.34	Nov 2015
8.	Zyvox	Pfizer	Gram-positive bacterial infections	1.35	May 2015
9.	AndroGel	Abbvie	Low testosterone	1.03	Early 2015
10.	Synagis	AstraZeneca	Monoclonal antibody to prevent respiratory syncytial virus infection in infants	1.1	Oct 2015

(Compiled from FiercePharma data)

As a significant number of these drugs are biologics, such as Lantus, Abilify, Neulasta and Synagis, the generic impact on those large brands, post patent expiry, would be minimal, at least, for several more years.

However, Lantus sales could soon be impacted, as its biosimilar versions from Boehringer Ingelheim and Eli Lilly have already received approval in Europe, and may be launched in the United States, as well.

Biosimilar versions of other drugs that will go off patent in 2015, do not seem to be anywhere near launch soon to make immediate dent in the sales of the original biologics. I had deliberated on various possible reasons for delay in biosimilar entry, especially in the US, in my earlier blog post of August 25, 2014, titled “Scandalizing Biosimilar Drugs With Safety Concerns”

Taking all these into consideration, EvaluatePharma has estimated that out of patent expiry related sales turnover of US$44 billion, just around US $16 billion would get impacted in 2015 by their generic equivalents.

Global market outlook 2015:

According to IMS Health, spending on medicines will reach nearly $1,100 billion in 2015 with a growth rate of 3-6 percent over the last five-year period.

According to EvaluatePharma, the overall outlook of the global pharma industry in 2015 and beyond is expected to be as follows:

A dozen products launched in 2015 are forecast to achieve blockbuster sales by 2020

Drugs treating high cholesterol and heart failure will dominate the field with a combined 2020 sales forecast of US$8 billion

Sovaldi and its combination product Harvoni will take the number one worldwide seller spot with forecasted sales of $15.3 billion in 2015

Patent expiries will have minimal impact on the top line as 2015 sales will grow close to four times that of patent losses

Financing climate appears friendly and deals will continue at a steady pace but M&A activity unlikely to match the frenzy of 2014

Moreover, Oncology therapy area brings a huge promise with novel immuno-oncology drugs. As Reuters have reported, Merck & Co’s Keytruda and Bristol-Myers Squibb’s Opdivo, which work by blocking a protein called Programmed Death receptor (PD-1), are the first in a coming wave of immuno-therapies that analysts believe could generate annual sales of more than US$30 billion a year.

Indian pharma industry outlook 2015:

Indian pharmaceutical industry, dominated by branded generic drugs, is estimated to register a turnover of around US$ 33.8 billion with an average growth of 10.3 percent in 2014 – 2018 period, according to Deloitte. Increasing number of diagnosis and treatment of chronic ailments, fuelled by ascending trend in the per capita income, would be the key factors to drive this double-digit growth rate.

In 2013-14, pharma exports of the country with a turnover of US$ 14.84 billion grew at a meager 1.2 percent, which is the slowest growth in nearly the last 15 years. Pharmexcil attributed its reason to USFDA related regulatory issues and increasing global competition. India still stands exposed in this area, unless meaningful corrective measures are taken forthwith. It is worth noting, although India exports drugs to over 200 countries in the world, the United States (US) alone accounts for about 25 percent of India’s pharma exports.

Key issues and challenges in ‘The Exports Front’:

Generic drugs currently contribute over 80 percent of prescriptions written in the US. Around 40 percent of prescriptions and Over The Counter (OTC) drugs that are sold there, come from India and account for around 10 per cent of finished dosages in the US.

Almost all of these are cheaper generic versions of patent expired drugs, which are mainly produced in around 200 USFDA approved drug-manufacturing facilities located in India. Hence, India’s commercial stake in this space is indeed mind-boggling.

Indian drug exports were taking place satisfactorily without any major regulatory hitches since quite some time. Unfortunately, over the last few years, mostly the Federal Drug Administration of the US (USFDA) and the United Kingdom (UK)’s Medicines and Healthcare Products Regulatory Agency (MHRA) have started raising serious doubts on the quality of medicines manufactured in India, creating an uncertainty on drug exports in those countries.

To overcome this critical issue and keep marching ahead with distinction in the drug exports front, Indian pharma would require to successfully dealing with the following two areas:

A. Data integrity:

Since quite a while, USFDA has been raising serious concerns on ‘Data Integrity’ in their previously approved production facilities of a large number of Indian pharma players. The details of each of these concerns are available in the USFDA website.

This worrying development is now posing a huge threat to future growth potential of Indian drug exports, as in this area the Indian government had set an objective, in its strategy document, to register a turnover of US$ 25 billion in 2014-15. In all probability, it would fall far short of this target at the end of this fiscal, predominantly for related reasons. However, the good news is, considering the criticality of the situation, the Indian government is now working with the USFDA to resolve this problem.

I discussed a part of this area in my Blog Post of September 29, 2014 titled “Make in India…Sell Any Where in The World”: An Indian Pharma Perspective

B. Credibility of Clinical Trial Data from India:

Credibility of ‘Clinical Trial Data’ generated by the domestic players in India, has also become a cause of great concern, as the regulators in France, Germany, Belgium and Luxembourg suspended marketing approval for 25 drugs over the genuineness of clinical trial data from India’s GVK Biosciences.

Key issues and challenges in ‘The Domestic Front’:

Though 2015 would also witness the following important issues and challenges, meeting with this challenge of change should not be difficult with a proper mindset and right strategies:

A. The Drug Price Control Order 2013 (DPCO 2013):

Change in the mechanism of drug price control from earlier ‘cost based’ to newer ‘market based’ one and the specified provisions to neutralize inflationary impact of the input costs on the bottom line, based on the WPI, have already been considered as welcoming changes for the industry. As a result, despite implementation of the DPCO 2013, the pharma shares continued to do well in 2014 despite doomsayers’ predicaments, not just in the past, but even today.

I believe, the DPCO 2013 would not cause any significant negative impact further in 2015 on the performance of pharma companies, as the price controlled drugs would in all probability continue to be around 20 percent of the total pharma market. Moreover, now annual price increases are linked to the WPI for the controlled products and the companies can increase prices of remaining 80 percent of decontrolled products, upto 10 percent every year, irrespective of inflationary trend.

That said, due to huge inter-brand price differences, in July 2014 the National Pharmaceutical Pricing Authority (NPPA) had brought under price control 50 more cardiovascular and anti-diabetic drugs in addition to 348 drugs that featured under price control in the DPCO 2013.

If the pharma players do not take note of such abnormal inter-brand price variation of the same drugs without meaningful reasons, there could possibly be further move by the NPPA in this direction.

Additionally, any mechanism for patented products’ pricing, if announced in 2015, would have far-reaching impact, especially on the MNCs marketing such drugs.

B. Unethical practices in Clinical trial:

In the Clinical Trial arena of India, responding to a Public Interest Litigation (PIL), the Supreme Court of the country and separately the Parliamentary Standing Committee had indicted the drug regulator and charted out some action areas. The Parliamentary Committee in its report had even mentioned about a nexus existing between the drug regulator and the industry in this area.

Driven by the directives of the Apex Court of the country, the union ministry of health of the government of India has already strengthened some areas of past laxity in drug regulatory control, such as mandatory registration of clinical trials, constitution of committees to oversee the trial approval, its execution and above all ethical treatment of patients, including compensation.

Although, these are all requisite measures to create an appropriate longer-term eco-system for clinical trials in India, it has reportedly ruffled many feathers, such as CROs in the country who work mainly for pharma MNCs and some global pharma players too. This is mainly because of inordinate delays in drug approvals during the regulatory rectification process, besides cost of clinical trials going up. An orderly drug regulatory environment must prevail, instead of allegedly ‘free for all’ clinical trial environment in the country, costing many innocent lives and livelihoods. Responding to this changing clinical trial environment, some MNCs have already articulated that they are reconsidering their drug trial strategy in India and some Indian players, possibly with vested interests and echoing similar sentiments, are also saying that they would shift their clinical trial projects out of India, which would adversely impact the country’s clinical trial industry.

Be that as it may, it appears now that under the directive of the Supreme Court of the country, the decisions taken by the government in clinical trial area are irreversible, for the long-term interest of the country.

C. Intellectual Property (IP) issues:

Reacting to some well-justified measures taken by India in the IP area to make healthcare affordable to all, the US and its some key allies, continuously pressured by their powerful pharma lobby groups, continue to push India hard to broaden the IP protections. ‘Big Pharma’ lobbyists are reportedly trying to compel India to amend its IP laws that would suit their business interest at the cost of patients.

Fortunately, many stakeholders, including media, have started raising their voices against such strong-arm tactics, further fueling the credibility erosion of ‘Big Pharma’ and creating important pressure groups for the government.

Simultaneously, concerned pharma MNCs are also seeking legal recourse over issues mainly related to the section (3d) and Compulsory Licensing of the Indian Patents Act. However, most of the judicial verdicts vindicate the quality of decisions taken by the Indian Patent Office (IPO) in these areas.

Though very unlikely, any amendment or tweaking of the existing patent laws of India in 2015 would provide an unfair advantage to MNCs with negative impact on public health interest.

D. Uniform Code of Pharmaceutical Marketing Practices:

Compared to the actions that are now being taken by the law enforcers overseas against pharmaceutical marketing malpractices, India has been showing a rather lackadaisical attitude in these areas, until recently. It astonishes many that unlike even China; no pharmaceutical company has been investigated thoroughly and hauled up by the government for alleged bribery and other serious allegations of corrupt practices.

However, frequent reporting by the Indian media had triggered a debate in the country on the subject. A Public Interest Litigation (PIL) on this subject is now pending before the Supreme Court for hearing in the near future. It is worth noting that in 2010, ‘The Parliamentary Standing Committee on Health’ also had expressed its deep concern by stating that the “evil practice” of inducement of doctors by the pharma companies is continuing unabated as the revised guidelines of the Medical Council of India (MCI) have no jurisdiction over the pharma industry.

The Government, until recently, has shown no active interest in this area either, though the new Union Health Minister, J.P. Nadda decried the unethical nexus between the doctors and pharma companies, amounting violations of medical ethics in the country. He reportedly has stated that in majority of the cases, the pharma companies are luring the doctors by giving gifts and other benefits for prescribing the brand of medicines of their choice to the patients.

As the saying goes, ‘better late than never’, on December 12, 2014, the Department of Pharmaceuticals (DoP) of the Government of India announced details of the ‘Uniform Code of Pharmaceutical Marketing Practices (UCPMP)’, which would be effective across the country from January 1, 2015 for all pharma players to implement, across India.

However, I reckon, the document in its current form is rather weak in its effective implementation potential. Meaningful and transparent deterrent measures to uphold public health interest are also lacking. The entire process also deserves a well-structured monitoring mechanism and digital implementation tools that can be operated with military precision. I discussed this issue in my Blog Post of December 29, 2014, titled “India’s Pharma Marketing Code (UCPMP): Is It Crafted Well Enough To Deliver The Deliverables?”

On UCPMP a survey done by E&Y has highlighted the following points, besides other areas:

More than 50 percent of the respondents are of the opinion that the UCPMP may lead to manipulation in recording of actual sampling activity.

Over 50 percent of the respondents indicated that the effectiveness of the code would be very low in the absence of legislative support provided to the UCPMP committee.

90 percent of the respondents felt that pharma companies in India should focus on building a robust internal controls system to ensure compliance with the UCPMP.

In my view as well, the self-regulatory measures prescribed in the UCPMP of the DoP are unlikely to make any significant impact in 2015, unless pharma companies start focusing on building robust internal controls system to ensure compliance with the UCPMP.

Conclusion:

I would now put on the balance of probabilities, the new ‘Silver Linings’ of the Global pharmaceutical industry as discussed above, the issues and challenges of 2015 for the Indian pharma and also other important factors that I have not been able to discuss in this article. The overall emerging picture depicts that the pharma industry, both global and local, would fare much better than what it did in the recent past, provided the industry, as a whole, does not continue to ignore the storm signals outright.

Thus, based on the available data, the year 2015, as appears to me, would provide an enormous opportunity with promises of an interesting time ahead that the pharmaceutical industry should try to leverage on…and then cherish it for a long while…most probably as a turning point of the same ball game with different success requirements.

By: Tapan J. Ray

Would ‘Regenerative Medicine’ Shape The Future Of Global Healthcare?

Posted on December 22, 2014 by Tapan Ray

Just the last week, on December 19, 2014, international media broke the news of regulatory approval of the first stem cell treatment by the European Medicines Agency (EMA).

The Agency reportedly has recommended an Orphan Drug – Holoclar of the Italian pharmaceutical company Chiesi Farmaceutici S.p.A for the treatment of moderate-to-severe Limbal Stem Cell Deficiency (LSCD) caused due to physical or chemical burns to the eyes in adults. LSCD can lead to blindness, where Holocar works in around 80 percent of cases.

The EMA decision to approve Holoclar will now be sent to the European Commission for market authorization.

As reported, this new generation treatment takes a small sample of the patients’ healthy cornea, removes the stem cells and grows them until there are sufficient numbers to put back into the eye. The cells themselves then repair the damage.

Experts consider this development as very significant step forward, as stem-cell therapies are now being tried mostly in the laboratory environment and clinical trials.

Treatment with Stem Cells – A new paradigm:

A stem cell is defined as an undifferentiated cell of a multicellular organism that is capable of giving rise to indefinitely more cells of the same type, and from which certain other kinds of cell arise by differentiation.

Stem cells are, therefore, immature cells that can be induced to transform into tissue or organ-specific cells and are classified as per their source, such as Embryonic Stem Cells (ES) from early human embryos, fetal stem cells from aborted fetus; adult stem cells from tissues, skin and bone marrow; cord blood cells from umbilical cord and even fatty tissues.

In human developmental biology, extensive scientific research over many years has led to the discovery of human stem cells.

Regenerative Medicine:

This terminology is generally used for new medical advances in which an understanding of the human genome allows the use of the body’s own mechanism to heal it. This may include new pharmaceuticals and the ability to create new cells that could be implanted into patients to replace diseased or missing tissues.

The science of ‘Regenerative Medicine’ is increasingly being considered as an emerging medical space aimed at the treatment of those diseases that are usually classified as degenerative, incurable and irreversible. As it appears today, this science would unfold a new paradigm, where patients can expect cure for many serious ailments, such as, spinal injuries, heart disease, Parkinson’s, Alzheimer’s disease and even diabetes, besides many others.

Some promising developments:

Besides the recently EMA approved new treatment, as mentioned above, examples of just a few more promising developments in research with the stem cells, are as follows:

- Possible cure for Type 1 diabetes:

According to an international report of October 9, 2014, for the first time, after 23 years of research, Harvard University has been able to manufacture millions of beta cells required for transplantation. It could mean a cure for diabetes and the end of daily insulin injections for patients living with Type 1 diabetes. Around 10 per cent of all diabetes is Type 1, but it is the most common type of childhood diabetes.

The report indicated, the stem cell-derived beta cells are presently undergoing trials in animal models, including non-human primates, where they are still producing insulin after several months.

Another report of April 2014 indicates that for the first time, scientists have successfully replaced the damaged DNA of a type 1 diabetes sufferer with the healthy genetic material of an infant donor. When these cells are injected back into the diabetic patient, it is expected that they will begin to produce insulin on their own.

- Transplant of embryonic human stem cells on patients with macular degeneration partially restored vision:

Another study published in ‘The Lancet’ in October 2014 stated that scientists in the United States have announced that single transplant of stem cells has helped restore the sight of patients suffering from incurable forms of blindness due to Age-related Macular Degeneration (AMD). Currently no effective treatments exist for this eye disorder, which can cause complete blindness due to the loss of light-receiving photoreceptor cells in the retina.

To recreate a type of cell in the retina that supports those photoreceptors, the new treatment uses stem cells derived from embryos that are only a few days old and have the ability to develop into any kind of tissue in the body. However, the transplants have proved controversial because they use stem cells derived from spare human embryos left over from IVF treatment.

- A cure for heart failure could be just a few years away:

Yet another international report of May 01, 2014 states, by injecting human stem cells into the organs of macaque monkeys, scientists have been able to regenerate their damaged hearts by up to 40 per cent in just a few weeks. Thus, it appears now that a cure for heart failure could be just a few years away and would mean that even people who are “bed-bound” with heart failure could be “up and about” again within a few weeks.

As on date, the heart muscle cannot be repaired, making people with severe heart failure necessarily wait for heart transplant. Of course, if the patients are willing and can afford so.

Debate around stem cell research:

Like many other research areas involving biological science, a raging debate has also commenced globally on several sociopolitical, cultural and ethical issues involving the use of stem cells as therapy.

Many clinical research related issues too are now surfacing on the use of human embryos, manipulations and modifications in stem cells research.

Apprehension of misuse, especially through cloning, had prompted many governments, India included, to ban reproductive cloning, keeping therapeutic cloning open for research.

However, arriving at a broader consensus in this area does not seem to be an insurmountable problem, in any case, as things stand today.

Research on stem cells and regenerative medicine in India:

Though it may sound almost unbelievable, India is now considered to be in the forefront of stem cells research and its use in a limited manner.

Indian Government under Indian Council for Medical Research (ICMR) and the Department of Biotechnology (DBT) has already set up a number of stem cell research institutions across the country. These institutions have already commenced valuable research in this area. DBT had granted more than Rs 300 Crore over the previous five years to be used in basic and applied research in stem cell technology.

According to one August 2014 report from ‘Business Insider’, several stem cells research initiatives are ongoing both in public and the private sectors in India.

A few examples, as reported, are as follows:

Public initiatives:

The National Centre for Cell Research (NCCR), Pune, has worked on stem cell trans differentiation into pancreatic islets.

Research at All India Institute of Medical Science (AIIMS) and Postgraduate Institute of Medical Education & Research (PGIMER), is ongoing on retinal degeneration and stroke.

National Institute of Immunohematology (NIIH) has been able to differentiate umbilical cord-derived mesenchymal stem cells into cardiomyocytes or cardiac muscles.

The National Centre for Biological Sciences (NCBS) in Bangalore, part of the Tata Institute of Fundamental Research, also works closely with the government on stem cells research.

The Government of India had set up The Centre for Stem Cell Research (CSCR) in 2008 in collaboration with Christian Medical College, Vellore, with the intention of using stem cell science for understanding human diseases and development of stem cell-based therapies. Interestingly, it also runs a training program for scientists and students of stem cell research. CSCR will also carry out clinical trials with stem cells produced under current good manufacturing practice (GMP) conditions.

Private initiatives:

Reliance Life Sciences obtained permission to use on large-scale stem cells sourced from the patient’s body for therapy.

The LV Prasad Eye Institute, Hyderabad, has developed corneal limbal stem cells.

Sankara Nethralaya Stem Cell Research Center, Chennai, is working on retinal and corneal stem cell application and immunoregulatory properties of stem cells.

Hospitals such as Dr KM Cherian’s research facility in Medville have used stem cells from bone marrow to help regenerate the heart.

Besides, Indian rules and law permit the usage of one’s own banked stem cells. Several storage facilities such as Life Cell, Reliance Life Sciences, Cryobanks International and Stemade for dental stem cell storage have also come up.

Stem cells research guidelines in India:

In India, ICMR-DBT Guidelines for Stem Cell Research are in place. These guidelines have been laid down to ensure that research with human stem cells is conducted in a responsible and ethically sensitive manner and complies with all regulatory requirements pertaining to biomedical research in general and stem cell research in particular.

Since it is a rapidly evolving field of science, the recommendations may change with time.

All types of research and clinical trials in stem cells would require to be registered with and obtain prior permission and approval of the National Apex Committee (NAC) and the Institutional Committee (IC-SCRT) for Stem Cell Research.

It is notably important that the guidelines categorically states that only stem cell research, basic and translational, is permitted but not therapy.

NAC- IC-SCRT permits therapy usage in patients only through approved and fully monitored clinical trials. Stem cells cannot be used as therapy without appropriate regulatory approvals in India.

Conclusion:

Currently, most treatments for non-infectious chronic ailments only delay the disease progression and associated complications. There is virtually no cure for most of these diseases, which include, spinal injuries, heart diseases, Parkinson’s, Alzheimer’s disease or even hypertension, asthma or diabetes.

Regenerative Medicine would not just bring down the cost of healthcare and the disease burden significantly, but would also help increasing the economic productivity of a nation considerably.

Currently, medical research of the highest order in this area is mostly being conducted by various academia of global repute along with the industry. This emerging trend sends a clear signal that ‘Regenerative Medicine’ is now strongly poised to give an altogether new shape to the future of global healthcare, adding unique dimensions.

Consequential paradigm shift in the field of healthcare, I reckon, would herald the dawn of a brand new era, setting in place a whole new commercial ball game, the like of which the world has never witnessed, ever before.

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.

Paying For The Best Health Outcomes At The Lowest Possible Cost

Posted on December 8, 2014 by Tapan Ray

“Bayer CEO Dr. Marijn Dekkers is happy to have fair Outcomes-Based Pricing”, reported ‘PharmaTimes’ on December 3, 2014.

Dr. Dekkers was quoted saying, “It is okay to be tested on that in the process of price-setting, that is fine, we should only be paid for the value we bring”. However, at the same time he also reminded, “When we have a new drug that is significantly better than the previous drug but the previous drug just went generic, we are compared to the 20% price, not the 100% price”.

I reckon, the above statement of the Bayer CEO sounds quite amazing, if not bizarre, especially considering the legality in the prevailing global pharma patent regime. Thus, any discontentment in this area, howsoever intense these are, would unlikely to be able to attract any unbiased favorable ear, across the world.

Another aspect of the aggressive patented drug pricing trend, I deliberated in one of my earlier blog posts titled, “An Aggressive New Drug Pricing Trend: What It Means To India?” of October 27, 2014.

What is it really?

As many would know, another common terminology of Outcome-Based Pricing (OBP) is Value-Based-Pricing (VBP). This approach for pricing is basically intended to offering the best value for the money spent in healthcare. It is ‘the costs and consequences of one treatment compared with the costs and consequences of alternative treatments’. For pharmaceutical players, VBP/OBP would mean not charging more than the actual real value of the product offerings.

As we shall find below, this concept is gaining ground now in the developed markets of the world, prompting the pharmaceutical companies generate requisite ‘health outcomes’ data using similar or equivalent products. Cost of incremental value that a product will deliver is of key significance. Some independent organizations such as, the ‘National Institute for Health and Clinical Excellence (NICE)’in the United Kingdom (UK) has taken a leading role in this area.

An evolving scenario:

It would be worthwhile to note that over a period of time, while pricing new pharma products, manufacturers have been traditionally considering the costs of all inputs of various kinds incurred to bring these drugs into the market and thereafter adding hefty mark-ups on those medicines in a non-transparent manner to arrive at the market price.

This absolutely opaque process of patented drugs pricing is increasingly making the stakeholders, such as patients’ groups, payors, including the governments and insurers much concerned about the differential value offerings of these high priced new drugs over the existing ones for commensurate improvement in the actual health outcomes for the patients.

The relevance:

In the past decade, there has been a clear trend in the price negotiation of new and complex pharma based on health outcomes models as the pharma players are coming under increasing pressure from the payors/patients to improve the treatment cost-effectiveness.

In an article published in the Harvard Business Review of October 2013, Michael Porter and Thomas Lee had cautioned, “ In healthcare, the days of business as usual are over…it is time for a fundamentally new strategy. At its core is maximizing value for patients: that is, achieving the best outcomes at the lowest cost.”

They elucidated the relevance of value based pricing, supporting very strongly the idea of paying for “value” in healthcare.

Thus, if this trend were not checked, the healthcare spending would keep going up, as it is happening today globally, impacting access of these drugs to patients significantly due to spiraling cost pressure.

A recent vindication:

‘Gallup’ in an articles titled, “Cost Still a Barrier Between Americans and Medical Care” published in December 5, 2014, has reported that in U.S., 33% of Americans have put off medical treatment because of cost. Interestingly, more of them put off treatment for serious conditions than non-serious and more with private insurance had put off treatment in 2014 than 2013.

Thus, to address this issue, as we shall see below, various governments either have or in the process of developing regulatory policies to rationalize new drug prices based on the Outcome/Value-Based Pricing (OBP/VBP) Models of different kinds.

In this backdrop, Bayer CEO’s acceptance of OBP/VBP is indeed a welcoming development. This process is undoubtedly one of the most reasonable ways to arrive at a patented drug price.

For a large majority of stakeholders, treatment outcomes and differential value offerings of new medicines are the most critical factors to monitor the value pathway of patients’ medical care, irrespective of types of illnesses.

The move has already commenced:

Deloitte Center for Health Solutions in a study on Value-Based Pricing for

Pharmaceuticals, has highlighted that unlike the United States, many countries, where the government plays a decisive role in pricing and price negotiations of pharmaceuticals, have focused on reducing costs through value-based pricing agreements.

The article gives examples of Denmark, where Bayer entered into a “no cure, no pay” initiative on Levitra (vardenafil) for erectile dysfunction in 2005. Patients not satisfied with the treatment were eligible for a refund. Similarly, in 2007, after the National Institute for Health and Clinical Excellence (NICE) of the United Kingdom (UK) initially concluded that Velcade (bortezomib) was too expensive as compared to its estimated benefits to the population, Johnson & Johnson offered to forgo charges for patients who did not have an adequate medication response.

Further, according to the Burrill Report of October 2013, as part of an effort to regain market share for its statin Zocor, which had been losing ground to then Warner Lambert’s Lipitor, Merck had reportedly offered an out of box proposition to consumers and insurers in 1998. Merck’s “Get to Goal” guarantee offered refunds to any takers who failed to reach target cholesterol levels set by their doctors within six months of using Zocor and adjusting their diet.

Could serve the purpose of global pharma too:

The above Burrill Report also states, “The performance-based pricing also serves a simpler purpose for drug makers. It allows them to provide discounts that may be necessary to establish acceptable value in one market without affecting the price for a drug in other markets around the world as a number of payers peg the price they will pay for a drug to what price a specific country may negotiate with the drug maker.”

Following this trend it appears that like Dr. Dekkers, other head honchos of global pharma majors would ultimately be left with no option but to willy-nilly toe this line in most of the countries across the world for their patented products.

This would be necessitated due to increasing product-pricing pressure based on quantification of differential benefits of the new medicines over already existing ones, as would be reflected in the analysis of intensive cost-effectiveness data.

Defining a measure of cost-effectiveness:

One of the several other methods to measure the cost-effectiveness of a new drug, as reported in a case study published by ‘2020 Public Services Trust at the RSA’, is as under:

“The efficiency of new products can be captured through incremental cost-effectiveness ratios (ICER). These are usually based on quality-adjusted life-years (QALY), which are a measure of how many extra months or years of reasonable quality life a patient might gain as a result of treatment, based on average life expectancy. Life expectancy is usually extrapolated from the results of clinical trials whilst the quality adjustment is based on patients’ experiential response to the level of pain, mobility and general mood which are usually expressed as a weighted utility value of between 0 and 1. The final calculation of the ratio is based on the difference in the cost to QALY ratio between the new drug and the standard available treatment. However, to make sense of the ICERs it has been necessary to establish thresholds beyond which drugs are no longer deemed cost-effective.”

As the above case study highlights, “NICE had established a notional upper limit of £20-30,000 per QALY above which a drug will generally not be recommended, although in exceptional circumstances this can be increased as was the case for beta-interferon, where it was raised to £36,000.”

The Indian perspective:

In developing countries such as India, expenditure towards medicines is considered as an investment made by patients to improve their health and productivity at work. Maximizing benefits from such spending will require avoidance of those medicines, which will not be effective together with the use of lowest cost option with comparable value and ‘health outcomes’.

For this reason, as stated above, many countries have started engaging the regulatory authorities to come out with head to head clinical comparison of similar or equivalent drugs keeping ultimate ‘health outcomes’ of patients in mind.

A day may come in India too, when the regulatory authorities will concentrate on ‘outcomes/value-based’ pricing models, both for patented and high price branded generics, where low priced equivalents are available.

However, at this stage it appears, this would take some more time. Till then for ‘health outcomes’ based medical prescriptions, working out ‘Standard Treatment Guidelines (STG)’, especially for those diseases, which are most prevalent in India, should assume high importance.

Standard Treatment Guidelines (STG):

STG is usually defined as systematically developed statements designed to assist practitioners and patients in making decisions about appropriate cost-effective treatment in specific disease areas.

For each disease area, the treatment should include “the name, dosage form, strength, average dose (pediatric and adult), number of doses per day, and number of days of treatment.” STG also includes specific referral criteria from a lower to a higher level of the diagnostic and treatment requirements.

In India, the medical experts have already developed STGs for some disease areas. However, formulation of STGs covering all major disease areas and, more importantly, their effective implementation would ensure cost-effective healthcare benefits to a vast majority of population.

The Ministry of health of the respective states of India should encourage the medical professionals/institutions to lay more emphasis on ‘health-outcomes/value based’ prescription of medicines, ensuring more cost effective treatment for their patients.

Conclusion:

The medical practitioners in their part should ideally volunteer to avoid prescribing expensive drugs offering no significant improvement in ‘health outcomes’, against the cheaper equivalents. The Government should initially encourage it through ‘self-regulation’ and if it does not work, stringent regulatory measures must be strictly enforced, within a reasonable time frame.

Be that as it may, it clearly emerges today that in the healthcare arena, effective implementation of ‘Outcomes/Value-Based-Pricing-Models’ would ensure paying for the best health outcomes at the lowest possible cost, especially for those who deserve it the most, not just in India, but across the world too.

By: Tapan J. Ray

It Took 90 Years To Accept The Dreaded Disease Discovered In A Mental Asylum

Posted on December 1, 2014 by Tapan Ray

In 1908 Dr. Alois Alzheimer discovered a memory erasing, attitude destroying and human dignity stealing deadly disease coined after his name, researching on a patient in a mental asylum.

The disease, in the absence of still any effective treatment, converts a lively human being gradually into a vegetative state, ruthlessly, though the life keeps ticking erratically before it finally extinguishes.

Despite advancement of medical science at a break neck speed, is it not quite surprising that it took 90 years, from 1908 to 1998, to formally accept the root cause of Alzheimer’s disease in the medical science?

Still the greatest mystery of this disease is why it strikes mostly at an advancing age. Other risk factors include ailments such as, diabetes, depression, cardiac conditions and sedentary life style.

I deliberated on this issue in one of my earlier blog posts titled, “Alzheimer’s Disease: Robs Memory: Steals Dignity: Escapes Treatment” of August 11, 2014, though on a different perspective.

A flash back on the disease:

A September 2014 article of Dr. Rod Tanchanco, published in the ‘History News Network’, elucidates how Dr. Alzheimer discovered this deadly disease in a Mental Asylum.

As Dr. Rod Tanchanco narrated, the germination of this discovery started with an orderly and industrious homemaker Auguste, a 50 year old housewife, who started making uncharacteristic mistakes in preparing home meals – a task in which she had been quite proficient for long.

With the progress of time, Auguste gradually started wandering aimlessly around the apartment, leaving many unfinished work in the house. Her attitude and behavioral pattern also started changing noticeably. Concerned with these changes, her husband Carl had no other choice but to take her to the local mental asylum.

The physician’s in the asylum described her as suffering from a weak memory, persecution mania, sleeplessness, and restlessness that rendered her unable to perform physical or mental work. However, the psychiatrist sensed that there was something special about Auguste and Dr. Alois Alzheimer decided that he should see Auguste for himself. The limited treatments included the use of sedatives and warm baths.

After thorough examination, what struck Dr. Alzheimer was Auguste’s relatively young age (51) as he had seen many cases of mental deterioration in much older patients that prompted him to theorize that age-related thickening of the brain’s blood vessels led to brain atrophy.

After about five years of progressive mental and physical decline, Auguste died in 1906. The official cause of death was stated as blood poisoning due to bedsores. However, Dr. Alzheimer suspected that behind her mental illness was a strange disease and perhaps examining her brain would offer some clues.

Discovery of the disease:

When Dr. Alzheimer examined Auguste’s brain sections under the microscope, his inkling was proved to be a reality. He described changes in the neurofibrils – the protein filaments found in brain cells. He also saw peculiar deposits that he referred to as “millet seed-sized lesions.” These pathologic findings, which are now known as neurofibrillary tangles and amyloid deposits, characterize the brains of patients suffering from Alzheimer’s Disease.

Skeptical initial response:

As Dr. Rod Tanchanco highlights, Dr. Alzheimer’s discovery was not immediately well received, as correlating mental or neurologic disorders with histopathologic findings was not firmly established nor accepted by his peer groups at that time.

Acceptance after long 90 years:

Ninety years later, in 1998, researchers re-examined Auguste’s original brain sections and confirmed the presence of neurofibrillary tangles and amyloid plaques. There is still no cure of this life-threatening disease, and the burden on the afflicted continue to remain mind-boggling.

According to Dr. Tanchanco, one of the most prominent psychiatrists in the early 1900s called Emil Kraepelin, first mentioned the term ‘Alzheimer’s Disease’ in the 1910 edition of his textbook on psychiatry. The disease was still poorly understood, but one of the most famous medical eponyms was born with it.

Where are we today?

All current treatments for Alzheimer’s cannot stop the underlying decline and death of brain cells. Thus, as more cells die, Alzheimer’s continues to progress.

Experts are cautiously hopeful about developing Alzheimer’s treatments that can stop or significantly delay the progression of Alzheimer’s. A growing understanding of how the disease disrupts the brain has led to potential Alzheimer’s treatments that short-circuit fundamental disease processes.

A laudable initiative has come to the fore recently in this arena. Having experienced something like the ‘law of diminishing return’ in pursuit of high resource intensive R&D projects aimed at critical disease areas such as Alzheimer’s, 10 big global pharma majors reportedly decided in February 2014 to team up with the National Institutes of Health (NIH) of the United States in a ‘game changing’ initiative to identify disease-related molecules and biological processes that could lead to future medicines.

This Public Private Partnership (PPP) for a five-year period has been named as “Accelerating Medicines Partnership (AMP)”. According to the report, this US federal government-backed initiative would hasten the discovery of new drugs in cost effective manner focusing first on Alzheimer’s disease, Type 2 diabetes, and two autoimmune disorders: rheumatoid arthritis and lupus. The group considered these four disease areas among the largest public-health threats, although the span of the project would gradually expand to other diseases depending on the initial outcome of this project.

New drug development concepts:

A. Two new treatment approach strategies:

The protein beta-amyloid (plaques) has long been considered a sign of Alzheimer’s disease. Some of the new Alzheimer’s treatments in development target microscopic clumps of plaques.

According to Mayo Clinic, beside other studies, following are the two newer strategies aimed at beta-amyloid (plaques):

Immunization strategies:

Most current immunization studies focus on administering antibodies against beta-amyloid from outside sources instead of enhancing a person’s immune system.

One large research effort is exploring the value of intravenous (IV) infusions of a product derived from donated blood. This product contains naturally occurring anti-amyloid antibodies from the donors.

Some other studies are investigating laboratory-engineered (monoclonal) antibodies.

Production blockers:

This may reduce the amount of beta-amyloid formed in the brain. Research has shown that beta-amyloid is produced from a “parent protein” in two steps performed by two different enzymes. Several experimental drugs aim to block the activity of the two enzymes.

B. The concept of heart-head connection:

Another interesting area, among many, that the Mayo Clinic highlights is the concept of heart-head connection.

Growing evidence suggests that brain health is closely linked to heart and blood vessel health. Our arteries nourish our brain. The risk of developing Alzheimer’s appears to increase as a result of many conditions that damage the heart or arteries. These include high blood pressure, heart disease, stroke, diabetes and high cholesterol.

In addition, a strong genetic Alzheimer’s risk factor is one form of a gene for a protein that carries cholesterol in the blood (apolipoprotein E). Strategies under this concept include:

- Available drugs for heart disease risk factors: Researchers are investigating whether drugs now used to treat high blood pressure, diabetes and high cholesterol may also help people with Alzheimer’s or reduce the risk of developing the disease.

- Drugs aimed at new targets: Additional projects are looking more closely at how the connection between heart disease and Alzheimer’s works at the molecular level to find new drug targets.

- Lifestyle choices: Researchers have explored whether lifestyle choices with known heart benefits, such as exercising on most days and eating a heart-healthy diet, may help prevent Alzheimer’s disease or delay its onset.

A large new database of Alzheimer’s disease patients:

Meanwhile, the Coalition Against Major Diseases (CAMD), which is a formal consortium of pharmaceutical companies, research foundations and patient advocacy/voluntary health associations, with advisors from federal agencies, has released a new database of more than 4,000 Alzheimer’s disease patients who have participated in 11 industry-sponsored clinical trials.

According to the Critical Path Institute, which oversees the coalition, this is the first database of combined clinical trials to be openly shared by pharmaceutical companies and made available to qualified researchers around the world. It is also the first effort of its kind to create a voluntary industry data standard that will help accelerate new treatment research on brain disease, as patients with other related brain diseases are expected to be added.

A large number of researchers believe that sharing these data from more than 4,000 study participants will speed development of more-effective therapies.

CAMD is funded by a cooperative agreement with the USFDA and a matching grant from the Science Foundation Arizona.

Conclusion:

It took 90 years to accept the cause of this memory erasing, attitude destroying and human dignity stealing deadly disease that was first discovered in a mental asylum by Dr. Alois Alzheimer.

Thereafter, discovering a safe an effective medicine for the treatment of Alzheimer’s disease has rather been very slow, if not frustrating, especially for the afflicted patients and their families. Some global pharma majors have even announced jettisoning research initiatives in this area.

Even with the application of modern day’s cutting edge science and technology, it is still difficult to fathom, how many years would still remain in waiting for a breakthrough treatment option for Alzheimer’s disease.

In a scenario like this, even today, the very thought of becoming a victim of this life-threatening disease sends shivers down the spine of many.

By: Tapan J. Ray

Is The Core Purpose of Pharma Business Much Beyond Profit Making?

Posted on November 10, 2014 by Tapan Ray

Dr. Margaret Chan, the Director General of the World Health Organization (WHO), at a briefing to discuss the Ebola outbreak in West Africa at the UN Foundation in Washington on September 3, 2014 said:

“Big Pharma’s greed for profits, not lack of funding, delaying Ebola treatment development.”

Highlighting that the disease has already taken lives of 4,951 people in West Africa, Dr. Chan castigated the pharmaceutical industry for failing to develop an effective treatment for the deadly virus Ebola since 1976. “Though the Ebola crisis has become the most severe acute public health emergency seen in modern times, a profit-driven industry does not invest in products for markets that cannot pay”, Dr. Chan added.

That said, the Big Pharma has now initiated some efforts in this area, as the disease currently poses a significant threat to non-African countries, including America.

The sentiment reverberates:

Echoing similar sentiment, an article published in the BBC News on November 7, 2014 reiterated:

“Big pharma companies are in the business to make money, so will generally develop those drugs that offer the greatest potential for profit. This means a number of important drugs are neglected – the current Ebola crisis being a case in point.”

The profit oriented approach isn’t restricted just to the diseases of Africa:

The above article also points out that, besides diseases of the developing world, the Big Pharma has been slow to develop newer and multi-drug resistant antibiotics, as well.

This is mainly because, it is lot more difficult for the pharma companies to make huge quantum of profit from discovery of newer antibiotics for acute infections having limited use for around 7 to 10 days, as compared to the medicines for chronic illnesses that people will have to necessarily take every day, for life.

It appears today that the ongoing public opinion and pressure are possibly not adequate enough to trigger even a slightest change in the fetish for profit-making incentives of the Big Pharma companies.

Despite high profitability, the fetish for even more profit continues:

The pharma industry that basically exists to help saving lives of patients of all types, status and color in various ways, now seems to focus mostly on generation of more and more profit than ever before.

- The following table would vindicate the point of profitability of the industry:

Highest and Lowest Profit Margins of 5 key Industrial Sectors, 2013 (Profit Margin in %)

No.	Sectors	Highest	Lowest
1.	Pharmaceuticals	42	10
2.	Banks	29	5
3.	Carmakers	10	3
4.	Oil & Gas	24	2
5.	Media	18	6

NB: Highest and lowest margins achieved by individual company (Source: Forbes, BBC News)

To generate mind boggling profits, many of the Big Pharma constituents have reportedly resorted to various types of gross misconduct and malpractices too, the Chinese saga being the tip of the iceberg.

- The following are some recent examples to help fathom the enormity of the problem:

In September 2014, GlaxoSmithKline was reportedly fined US $490m by China for bribery.

In March 2014, the antitrust regulator of Italy reportedly fined two Swiss drug majors, Novartis and Roche 182.5 million euros (U$ 251 million) for allegedly blocking distribution of Roche’s Avastin cancer drug in favor of a more expensive drug Lucentis that the two companies market jointly for an eye disorder.

Just before this, in the same month of March 2014, it was reported that a German court had fined 28 million euro (US$ 39 million) to the French pharma major Sanofi and convicted two of its former employees on bribery charges.

In November 2013, Teva Pharmaceutical reportedly said that an internal investigation turned up suspect practices in countries ranging from Latin America to Russia.

In May 2013, Sanofi was reportedly fined US$ 52.8 Million by the French competition regulator for trying to limit sales of generic versions of the company’s Plavix.

In August 2012, Pfizer Inc. was reportedly fined US$ 60.2 million by the US Securities and Exchange Commission to settle a federal investigation on alleged bribing of overseas doctors and other health officials to prescribe medicines.

In April 2012, a judge in Arkansas, US, reportedly fined Johnson & Johnson and a subsidiary more than US$1.2 billion after a jury found that the companies had minimized or concealed the dangers associated with an antipsychotic drug.

Many more of such instances are regularly being reported by the international media, unabated.

More profit through high drug pricing – The key argument in favor:

The Big Pharma argues that high drug pricing is absolutely necessary to generate a kind of profit, that is essential to fund heavy investments for drug innovation to meet the unmet needs of patients. Moreover, only 3 out of 10 drugs launched are profitable, on an average.

This argument really goes over the top. It does not hold much water either, as the Big Pharma reportedly spends more on the process of drug marketing than on innovation (R&D) of new drugs.

The following table would paint a different picture altogether, marketing expenditure being far more than the R&D costs:

R&D and Marketing Spend of World’s largest Pharmaceutical Companies

Company	Total Revenue (US$ Bn.)	R&D Spend (US$ Bn.)	Marketing Spend (US$ Bn.)	Profit (US$ Bn.)	Profit Margin (%)
J & J (US)	71.3	8.2	17.5	13.8	19
Novartis (Swiss)	58.8	9.9	14.6	9.2	16
Pfizer (US)	51.6	6.6	11.4	22.0	43
Roche (Swiss)	50.3	9.3	9.0	12.0	24
Sanofi (France)	44.4	6.3	9.1	8.5	11
Merck (US)	44.0	7.5	9.5	4.4	10
GSK (UK)	41.4	5.3	9.9	8.5	21
AstraZeneca(UK)	25.7	4.3	7.3	2.6	10
Eli Lilly (US)	23.1	5.5	5.7	4.7	20
AbbVie (US)	18.8	2.9	4.3	4.1	22

(Source: GlobalData, BBC News)

Thus, it is difficult to fathom why are numbers of drugs, such as, Sovaldi and others costing as much as US $ 84,000 and above for a treatment course, when the cost of manufacturing is no more than an insignificant fraction of that treatment cost?

Considering all these and looking at the published profit and loss accounts of various pharma companies, it appears that, the line between ‘making reasonable profit’ and ‘profiteering’ is getting increasingly blurred in the pharma world.

Why is the marketing cost so high?

Since about the last decade and half, despite reasonably high expenditure on R&D there does not seem to have been many reports on breakthrough innovations. According to an expert of the World Health Organization (WHO), “of the 20 or 30 new drugs brought to the market each year, typically 3 are genuinely new, with the rest offering only marginal benefits.”

In a situation like this, when the challenge mostly is of generating targeted revenues with the new products of ‘me-too values’ rather than with those having intrinsic ‘unmet values’, marketing costs to generate doctors’ prescription would obviously escalate disproportionately. Even the process followed to generate these prescriptions, often cross the red line of regulatory, ethics and compliance standards, as have been cited above.

The following questions come up consequently:

- Are these exorbitant avoidable marketing expenditures adding any tangible or intangible values to the ultimate consumers – the patients?

- If not, why burden the patients with these unnecessary costs?

India is no different against similar parameters:

Back home in India, the deep anguish of the stakeholders over similar issues is now being increasingly reverberated with every passing day, as it were. It has also drawn the attention of the patients’ groups, NGOs, media, Government and even the Parliament.

The quality of the pharmaceutical sales and marketing process in India has touched a new low and continues to go south, causing suffering to a large number of patients. Well documented unethical drug promotion is increasingly becoming an emerging threat to the society.

Even today, the Ministry of Health and the Department of Pharmaceuticals of the Government of India provide few checks and balances on unethical drug promotion in India and prefer to keep the eyes meant for vigilance, closely shut.

Despite deplorable inaction of the government on the subject and frequent reporting by Indian media, the national debate on this issue is yet to attain a critical mass. A related Public Interest Litigation (PIL) is now pending before the Supreme Court for hearing, hopefully in the near future. Its judicial verdict is expected to usher in a breath of fresh air around a rather stifling environment for healthcare in India.

I deliberated on a similar issue in one of my earlier blog posts of September 1, 2014, titled, “Pharma And Healthcare: Mounting Trust deficit In Post Halcyon Days”

Conclusion:

While it is well-acknowledged that pharma industry has contributed immensely for the development of a large number of life saving new drugs to save precious lives all over the globe, none can also deny that for such efforts the companies concerned have not been hugely profited either…and, as we have been witnessing, not necessarily through legitimate means, always.

That said, in the backdrop of all the above examples, the core issue that emerges today as raised by many, including the World Health Organization (WHO), is the growing inherent conflict between predominantly the profit driven business goals of the pharma players and the public health interest of a nation.

Considering a number of recent serious public outbursts of the global thought leaders and also from the international media on the ‘profit dominating goals’ of the pharma industry, in general, the following questions need to be addressed with all seriousness:

- Is there a need to define afresh the core purpose of pharmaceutical business for all?

- Does the core purpose go much beyond profit making?

- If so, how would the industry plan to engage the stakeholders for its credible public demonstration?

Meanwhile, taking a serious note of it and learning from the past examples, India should initiate experts’ debate on the subject soon, to effectively resolve the conflict of two different mindsets, not resting on the same page in many ways.

By: Tapan J. Ray

“Make in India…Sell Anywhere in The World”: An Indian Pharma Perspective

Posted on September 29, 2014 by Tapan Ray

In his Independent Day speech from the ramparts of the Red Fort on August 15, 2014, Indian Prime Minister Modi gave a clarion call to all investors of the world, “Come, make in India”, “Come, manufacture in India”, “Sell in any country of the world, but manufacture here”.

The Prime Minister did not stop there. In his inimitable style, following it through on September 25, 2014 he gave an official status to ‘Make in India’ slogan and launched a global campaign.

“My definition of FDI for the people of India is First Develop India. This is also a responsibility for the people of India,” he further clarified.

An Indian perspective:

If I juxtapose this vision of the Prime Minister in the Indian pharmaceutical industry perspective, one finds that many small, medium and large size local domestic manufacturers are currently manufacturing drugs not just for the domestic market, but are also exporting in large quantities to various countries of the world, including, North America, South America and Europe.

The United States (US) is one of the most critical markets for majority of the Indian drug exporters. This transaction was taking place without any major regulatory hitches since quite some time. Unfortunately, over the last few years, mostly the Federal Drug Administration of the US (USFDA) and the United Kingdom (UK)’s Medicines and Healthcare Products Regulatory Agency (MHRA) have started raising serious doubts on the quality of medicines manufactured in India, making a significant impact on the drug exports of the country.

Most of these quality issues are related to ‘Data Integrity’ in the dug manufacturing and its documentation processes.

The impact:

According to industry data, in 2013-14, Indian drug exports registered the slowest growth in nearly the last 15 years. In this fiscal year, pharma exports of the country with a turnover of US$ 14.84 billion grew at a meager 1.2 percent. Pharmexcil attributed its reason to USFDA related regulatory issues and increasing global competition.

US accounts for about 25 percent of India’s pharma exports and its Federal Drug Administration (USFDA) has been expressing, since quite a while, serious concerns on ‘Data Integrity’ at the agency’s previously approved production facilities of a large number of Indian pharma players.

The issue is causing not just a serious concern to USFDA and some other overseas drug regulatory agencies, but also posing a huge threat to future growth potential of Indian drug exports.

It is worth noting that Indian government had set an objective, in its strategy document, to register a turnover of US$ 25 billion for pharma exports in 2014-15. In all probability, it would fall far short of this target at the end of this fiscal, predominantly for related reasons.

Why is so much of ‘fuss’ on ‘Data Integrity’?

Broadly speaking, ‘Data Integrity’ in pharmaceutical manufacturing ensures that finished products meet pre-established specifications, such as, for purity, potency, stability and sterility. If data integrity is breached in any manner or in absence of credible data, the product becomes of dubious quality in the eyes of drug regulators.

Manufacturing related ‘Data Integrity’ is usually breached, when data from a database is deliberately or otherwise modified or destroyed or even cooked.

Over the last several years, ‘Data Integrity’ related issues in India are attracting enormous attention of both the USFDA and the MHRA, UK. As a result, concerned pharma manufacturing facilities are receiving Import Alerts/Warning Letters from the respective overseas drug regulators, refusing entry of those medicines mostly in the United States and some in the UK.

Recent warning letters:

Just over a year – from May 2013 to July 2014, around a dozen ‘Warning Letters’ have been sent to the Indian drug manufacturers by the USFDA on ‘Data Integrity’ related issue, as follows:

	Recent ‘Warning Letter’ issued to:	Date of issue
1.	Marck Biosciences Ltd.	08. 07. 2014
2.	Apotex Pharmachem India Pvt Ltd.	17. 06. 2014
3.	Sun Pharmaceutical Industries	07. 05. 2014
4.	Canton Laboratories Private Limited	27. 02. 2014
5.	USV Limited	06. 02. 2014
6.	Wockhardt Limited	25. 11. 2013
7.	Agila Specialties Private Limited	09. 09. 2013
8.	Posh Chemicals Private Limited	02. 08. 2013
9.	Aarti Drugs Limited	30. 07. 2013
10.	Wockhardt Limited	18. 07. 2013
11.	Fresenius Kabi Oncology Ltd	01. 07. 2013
12.	RPG Life Sciences Limited	28. 05. 2013

(Source: RAPS, 19 August 2014)

Another report states that USFDA has, so far, banned at least 36 manufacturing plants in India from selling products in the US.

Importance of US for Indian generic players:

Generic drugs currently contribute over 80 percent of prescriptions written in the US. Around 40 percent of prescriptions and Over The Counter (OTC) drugs that are sold there, come from India. Almost all of these are cheaper generic versions of patent expired drugs. Hence, India’s commercial stake in this area is indeed mind-boggling.

The ‘Data Integrity’ issue is not restricted to just US or UK:

A report quoting researchers led by Roger Bate, an American Enterprise Institute scholar and funded by the The Legatum Institute and the Humanities Research Council of Canada, concluded that many Indian pharma companies follow double manufacturing standards, as they are sending poor quality drugs to Africa compared to the same pills sold in other countries. This study was based on tests of 1,470 samples produced by 17 Indian drug manufacturers.

Besides India, the researchers took drug samples from pharmacies in Africa and middle-income countries, including China, Russia and Brazil.

According to this paper, the researchers found that 17.5 percent of samples of the tuberculosis therapy rifampicin sold in Africa tested substandard, which means the drug has less than 80 percent of the active ingredient than what it should otherwise. Against this number, in India, 7.8 percent of the medicine sampled was found substandard.

Moreover, Almost 9 percent of samples of the widely used antibiotic ciprofloxacin sold in Africa tested substandard, as compared to 3.3 percent in India.

Thorny issues around golden opportunities:

Much reported breach in manufacturing ‘Data Integrity’ detected at the manufacturing sites in India, are throwing fresh doubts on the efficacy and safety profile of generic/branded generic medicines, in general, produced in the country and more importantly, whether they are putting the patients’ health at risk.

A new analysis by the U.S. National Bureau of Economic Research pointed out some thorny issues related to ‘Data Integrity’ of drugs produced by the Indian pharmaceutical companies, which supply around 40 percent of the generic drugs sold in the United States, as stated above.

The researchers examined nearly 1,500 India-made drug samples, collected from 22 cities and found that “up to 10 percent of some medications contained insufficient levels of the key active ingredients or concentrations so low, in fact, that they would not be effective against the diseases they’re designed to treat.”

The report also highlighted that international regulators detected more than 1,600 errors in 15 drug applications submitted by Ranbaxy. The Bureau Officials commented that these pills were “potentially unsafe and illegal to sell.”

Frequent drug recalls by Indian pharma majors:

The above findings came in tandem with a series of drug recalls made recently by the Indian pharma companies in the US.

Some of the reported recent drug recalls in America, arising out of manufacturing related issues at the facilities of two well-known Indian pharma majors, which are going to merge soon, are as follows:

Sun Pharmaceuticals recalled nearly 400,000 bottles of the decongestant cetirizine (Zyrtec) and 251,882 of the antidepressant venlafaxine (Effexor) this May, because the pills failed to dissolve properly. The drugs were distributed by the drug maker’s US subsidiary Caraco Pharmaceutical Laboratories, but were manufactured in India.

In the same month – May, Ranbaxy recalled 30,000 packs of the allergy drugs loratadine and pseudo-ephedrine sulphate extended release tablets because of manufacturing defects in packaging.

In March, Sun Pharma recalled a batch of a generic diabetes drug bound for the US after an epilepsy drug was found in it. A patient discovered the error after noticing the wrong medication in the drug bottle.

Again in March, Ranbaxy recalled nearly 65,000 bottles of the statin drug atorvastatin calcium (Lipitor) after 20-milligram tablets were found in sealed bottles marked 10-milligrams. A pharmacist in the U.S. discovered the mix up.

Indian media reinforces the point:

Indian media (TNN) also reported that there is no quality control even for life-saving generic drugs and the government is apathetic on ensuring that the quality protocol of these drugs is properly observed.

This happens, as the report states, despite government’s efforts to push generic drugs, as they are more affordable. The report gave an example of a life-saving drug, Liposomal Amphotericin B, which is used to treat fungal infections in critically ill patients.

Are all these drugs safe enough for Indian Patients?

Though sounds awkward, it is a fact that India is a country where ‘export quality’ attracts a premium. Unintentionally though, with this attitude, we indirectly accept that Indian product quality for domestic consumption is not as good.

Unfortunately, in the recent years, increasing number of even ‘export quality’ drug manufacturing units in India are being seriously questioned, warned and banned by the overseas drug regulators, such as USFDA and MHRA, UK, just to ensure dug safety for the patients in their respective countries.

Taking all these into consideration, and noting increasing instances of blatant violations of cGMP standards and ‘Data Integrity’ requirements for ‘export quality’ drugs, one perhaps would shudder to think, what could possibly be the level of conformance to cGMP for the drugs manufactured solely for the consumption of local patients in India.

A cause of concern, as generic drugs are more cost effective to patients:

It has been widely recognized globally that the use of generic drugs significantly reduces out-of-pocket expenditure of the patients and also payers’ spending.

The findings of a study conducted by the Researchers from Brigham and Women’s Hospital (BWH), Harvard Medical School and CVS Health has just been published in the Annals of Internal Medicine on September 15, 2014. In this study the researchers investigated whether the use of generic versus brand name statins can play a role in medication adherence and whether or not this leads to improved health outcomes. The study concluded that patients taking generic statins were more likely to adhere to their medication and also had a significantly lower rate of cardiovascular events and death.

In this study, the mean co-payment for the generic statin was US$10, as against US$48 for brand-name statins. It is generally expected that the generic drugs would be of high quality, besides being affordable.

I deliberated on a related subject in one of my earlier blog posts of November 11, 2013 titled, “USFDA” Import Bans’: The Malady Calls For Strong Bitter Pills”.

Conclusion:

According to USFDA data, from 2013 onwards, about 20 drug manufacturing facilities across India attracted ‘Import Alerts’ as against seven from China, two each from Australian, Canadian and Japanese units and one each from South African and German facilities.

Unfortunately, despite intense local and global furore on this subject, Indian drug regulators at the Central Drugs Standard Control Organization (CDSCO), very strangely, do not seem to be much concerned on the ‘Data Integrity’ issue, at least, not just yet.

In my view, ‘Data Integrity’ issues are mostly not related to any technical or other knowledge deficiency. From the “Warning Letters” of the USFDA to respective Indian companies, it appears that these breaches are predominantly caused by falsification or doctoring of critical data. Thus, it basically boils down to a mindset issue, which possibly pans across the Indian pharma industry, irrespective of size of operations of a company.

Indian Prime Minister’s passionate appeal aimed at all investors, including from India, to “Make in India” and “Sell Anywhere in The World”, extends to pharma industry too, both local and global. The drug makers also seem to be aware of it, but the ghost keeps haunting unabated, signaling that the core mindset has remained unchanged despite periodic lip service and public utterances for corrective measures by a number of head honchos.

Any attempt to trivialize this situation, I reckon, could meet with grave consequences, jeopardizing the thriving pharma exports business of India, and in that process would betray the Prime Ministers grand vision for the country that he epitomized with, “Make in India” and “Sell Anywhere in The World”.

By: Tapan J. Ray

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A Tapan Ray Website

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