Tag Archives: CT

Beyond ‘The Magic Moment’ of New Drug Marketing Approval

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“Uncontrolled clinical trials are causing havoc to human life. There are so many legal and ethical issues involved with clinical trials and the government has not done anything so far.”

This is exactly what the Supreme Court of India observed while responding to a Public Interest Litigation (PIL) on the subject in January 2013.

While Indian regulators with the active intervention of the Supreme Court are trying to grapple with, besides others, the basic ‘human rights’ aspect of the Clinical Trial (CT), many countries in different parts of the world are moving much ahead at a brisker pace. They have started thinking and putting in place more patient centric newer drug approval systems and also, in tandem, hastening the process of bringing new drugs to the market.

Current general scenario in CT:

Currently, after pre-clinical studies and before applying for regulatory approval, a new drug has to be tested on volunteers in randomized studies to prove its efficacy and safety on patients. Relatively short duration of new drug trials can hardly establish long-term safety and efficacy, which are now arrived at through extrapolation of data collected during CT period.

It is worth noting, the overall situation changes dramatically after launch of these products, as their usage expands from a relatively smaller number of CT volunteers to millions of real-world patients.

In a situation like this, unrealistic expectation of patients’ safety in perpetuity based primarily on extrapolation of very limited CT data is being increasingly questioned today.

That is why, on going post-marketing surveillance, which is also known as a Phase IV CT, is considered as a much more effective process to gauge relative superiority of the drug against the existing ones in terms of both efficacy and safety on a longer term.

That said, today one reads and hears umpteen number of accusations for almost lack of any meaningful response on the part of the pharmaceutical companies, in general, towards revelations of post-marketing surveillance data. This could, in turn, expose the patients to various types of risks, including wasteful healthcare expenditure.

The ‘Magic Moment’ in the present regulatory process:

A recent paper highlights a single “Magic Moment” between pre and post-licensing processes in the current drug-approval model in many countries. In this system, the use of a drug is tightly controlled in a narrowly defined pre-licensing population. Thus, CTs are also conducted on such pre-defined and relatively homogeneous volunteers, who are generally free from complicating conditions.

However, after ‘The Magic Moment’ of marketing approval, a large number of heterogeneous patient population, with many of them on multiple therapy, also use these new products in uncontrolled settings. Situations as these had led to post-marketing major drug withdrawals like, Vioxx and Avandia due to patients’ safety.

These grave concerns have led to a strategic shift in the drug regulatory approval scenario throwing open new ideas in the drug approval process.

Adaptive Licensing:

To find the right answer to this vexing issue the drug regulators in many countries are  reportedly seriously contemplating to imbibe a process that will continuously help analyzing information through ongoing post-marketing surveillance data. Continuous medical data analysis like this will enable the regulators to modify their earlier decisions on marketing approval and also medical reimbursements related to pricing reasons.

This new process is called ‘Adaptive Licensing (AL)’, which is expected to benefit the overall healthcare system, by not allowing medical reimbursement of treatments with those drugs, which will provide negligible benefit over existing low cost therapies.

Difference between current mechanism and AL:

According to a ‘Health Canada’ paper titled, “The Path to Adaptive Drug Regulation”, the difference between the two is as follows:

Current system:

As explained above, post-licensing i.e. after ‘The Magic Moment’ of regulatory approval, treatment population grows rapidly and treatment experiences do not contribute to evidence generation.

Adaptive Licensing:

After initial license, treated patients grow more slowly due to regulatory restrictions. Patient experience is captured to contribute to real-world information. The marketing license is also modified accordingly from time to time.

Most desirable for many drugs:

Experts in this field opine that AL will help bringing in alignment of all required processes so important for a new drug seen from patients’ perspective like, R&D, regulatory approval and market access with the active involvement of all stakeholders like, the pharmaceutical companies, the drug regulator, payors/insurance companies and also the researchers.

In the AL system, a transparent drug development process will provide enough data on risk-benefit profile of the concerned drug to satisfy the drug regulator for its quick marketing authorization on pre-determined types of patients.

Such approval will follow real-life monitoring of efficacy and safety for modification of the drug license accordingly, wherever and whenever required.

Thus, AL is expected to strike a right balance balance between timely access to new drugs for the patients and the need to evaluate real time evolving information on safety and efficacy leading to a well-informed patient centric decisions by the drug regulators.

A continuous regulatory evaluation and decision-making process:

AL intends to evaluate a drug through its entire life span.  It has been reported that during this long period, clinical and other data will “Continue to be generated on the product through various modalities, including active surveillance and additional studies after initial and full licensing. The artificial dichotomy of pre vs. post licensing stages (‘The Magic Moment’) will be replaced by graded, more tightly managed, but more timely and potentially more cost-effective market entry and market stability.”

Not necessary for all drugs in the near term:

It is worth noting that AL system may not perhaps be required for all pharmaceutical or biologic products and will not totally replace the current system of drug licensing process, at least in the near term.

AL process may immediately be followed only for those products with a favorable risk-benefit drug profile as demonstrated in the initial data and there is a robust reason for early market entry of this drug to meet unmet needs, simultaneously with ongoing studies.

The ‘Magic Moment’ freezes in India…in perpetuity:

As per the Drugs and Cosmetics Act of India, after obtaining drug marketing approval from the regulators, concerned pharmaceutical companies are required to follow the pharmacovigilance system in the country to own the responsibility and liability of the drugs as enunciated in the Schedule Y of the Act. Unfortunately, this is hardly being followed in India, ignoring patients’ safety blatantly.

With the plea that most products launched in India are already being marketed in many developed markets of the world, the concerned companies prefer to depend on clinical experiences in those markets. This attitude totally bypasses the regulatory requirement to follow a robust pharmacovigilance system in India. Indian drug regulators also do not seem to be much concerned about this important patients’ safety related requirements, very surprisingly not even for biosimilar drugs.

However, the current ground realities are quite different. As we witness today, there does not seem to be much difference in time between international and India launch of innovative products. Thus, the argument of gaining medium to long-term experience on safety and efficacy from international data related to these drugs, does not seem to hold any water at all.

On the contrary, some drugs withdrawn from the international markets on safety grounds are still available in India, despite ire and severe indictment even from the Indian Parliamentary Standing Committee.

In a situation like this, AL process of Marketing approval for selected newer and innovative drugs may be considered by the Indian Drug Regulators, just not to be more patient centric, but also to help evaluating  pricing decisions of innovative drugs failing to demonstrate significantly better treatment outcomes as compared to the existing ones.

A recent example of AL:

One of the latest drugs, which reportedly will undergo such regulatory scrutiny of USFDA is Tacfidera (dimethyl fumarate) used for the treatment of multiple sclerosis, approved in April 2013 and costing US$ 54,900 per patient per year.  Interestingly, Tacfidera, before the drug can find itself on a formulary, will need to demonstrate its effectiveness in the real world.

The report indicates, “the first six months after a drug launch are always about educating payers about its benefits, and while most large payers are likely to make a decision to reimburse the drug in the next twelve months, data collection will continue and changes in policies might be made at a later date.”

Thus, in the years ahead, whether a new drug will become a blockbuster or not will very largely be decided by the ongoing real world data. If the promise of a drug diminishes at any point of time through clinical data, it will certainly going to have consequential financial and other adverse impacts.

Another interesting recent development:

Under new pharmacovigilance legislation in Europe, the European Medicines Agency has reportedly announced the list of over 100 drugs that soon will bear the “black triangle” logo. This initiative is directed to encourage both the doctors and patients to report side effects to enable close monitoring of drug safety.

Criteria to include drugs under additional monitoring are:

  • Medicines authorized after January 1, 2011 that contain a new active substance.
  • Biologics for which there is limited post-marketing experience.
  • Medicines with a conditional approval or approved under exceptional circumstances.
  • Medicines for which the marketing-authorization holder is required to carry out a post-authorization safety study (PASS).
  • Other medicines can also be placed under additional monitoring, based on a recommendation from the European Medicines Agency’s Pharmacovigilance Risk Assessment Committee (PRAC).

Conclusion:

Global regulatory experts do believe that in the concept of AL, there are still some loose knots to be tightened expeditiously to make it a fully implementable common drug marketing authorization process.  Appropriate pilot projects need to be undertaken in this area to establish beyond any doubt that AL will be decisively more preferable to the current regulatory process.

As and when AL will become the preferred drug-licensing pathway across the world, it is expected to offer greater real benefits of new drug development to the patients for their optimal use at an affordable price.

That said, some other experts do opine as follows:

“No matter how fast the authorization process operates, the merits of innovation will not be felt until they reach patients. And the barrier between authorization and patient access remains, in most of Europe, the issue of reimbursement.”

While all these are fast developing in the global CT scenario, in the jangle of Clinical Trials‘ in India, ‘Adaptive Licensing’ has still remained a critical missing ingredient even to encourage a wider debate.

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 Innovation Absolutely Critical: But NOT Shorn from Ethics, Propriety, Compliance and Values

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Significant value added innovation is the bedrock of progress of the pharmaceutical industry and is essential for the patients. This is a hard fact.

However, this current buzzword – ‘innovation’ can in no way be shorn from soft business necessities like, ethics, propriety, compliance and values… not just for longer term sustainability of business, but more in the larger interest of patients and patient groups.

Most importantly, ‘ethics, propriety, compliance and values’ are not meant for mere display  in the corporate websites like, any other business showpieces. These should neither be leveraged to create a false positive impression in the minds of the stakeholders with frequent PR blitzkriegs.

The creators of these soft ‘X factors’ are now being increasingly hauled up for gross violations of the same by the Governments in various parts of the world .These are not just legal issues. The net impact of all such acts goes much beyond.

In this article, I shall deliberate on these continuing and annoying issues both in global and local perspectives, quoting relevant examples at random.

The sole purpose of my argument is to drive home that all such repeated gross violations, as reported in the media, go against patients’ interests, directly or indirectly. None of these incidents, in any way, can be negated with stories of great innovations or with any other make of craftily designed shields.

Under increasing scrutiny in the developed world:

Ethics, propriety and business value standards of big pharma, besides various types of legal compliance, are coming under increasing stakeholders’ scrutiny, especially in the developed markets of the world.

Very frequently media reports from across the world, highlight serous indictments of the Government and even judiciary for bribery, corrupt business practices and other unbecoming conduct, aimed at the the global mascot for healthcare.

It is indeed flabbergasting to note that more and more corporates, with all guns blazing at the same time, publicize with equal zest various initiatives being taken by them to uphold high ethical standards and business practices, if not propriety, as the juggernaut keeps on moving forward, unabated.

The scope of ‘ethics and propriety’:

The scope of ‘ethical business conducts, propriety and value standards’ of a company usually encompasses the following, among many others:

  • The employees, suppliers, customers and other stakeholders
  • Caring for the society and environment
  • Fiduciary responsibilities
  • Business and marketing practices
  • R&D activities, including clinical trials
  • Corporate Governance
  • Corporate espionage

That said, such scope should not be restricted to the top management, but must be allowed to percolate downwards in a structured manner, looking beyond the legal and regulatory boundaries.

Statistics of compliance to ‘codes of business ethics and corporate values’ are important to know, but the qualitative change in the ethics and value standards of an organization should always be the most important goal to drive any corporation and the pharmaceutical sector is no exception.

‘Business Ethics and Values’ in the globalized economy:

Globalization of business makes the process of formulating the ‘codes of ethics and values’ indeed very challenging for many organizations in many ways. This is mainly because, the cultural differences at times create a conflict on ethics and values involving different countries.

For this purpose, many business organizations prefer to interact with the cultural and religious leaders in the foreign countries, mainly to ascertain what really drives culturally diverse people to act in certain ways.

With the wealth of knowledge of the local customs and people, the cultural and religious leaders can help an organization to unify the code of ethics and values of the globalized business.

Such leaders can also help identifying the ‘common meeting ground of minds’ from a specific country perspective, after carefully assessing the cultural differences, which are difficult to resolve in the near term.

The ‘common meeting ground of minds’ within a given society, thus worked out, could form the bedrock to initiate further steps to strengthen global business standards of ethics and values of an organization.

OECD with USA started early enacting ‘Foreign Corrupt Practices Act (FCPA)’: 

To prevent bribery and corrupt practices, especially in a foreign land, in 1997, along with 33 other countries belonging to the ‘Organization for Economic Co-operation and Development (OECD)’, the United States Congress enacted a law against the bribery of foreign officials, which is known as ‘Foreign Corrupt Practices Act (FCPA)’.

This Act marked the early beginnings of ethical compliance program in the United States and disallows the US companies from paying, offering to pay or authorizing to pay money or anything of value either directly or through third parties or middlemen. FCPA currently has significant impact on the way American companies are required to run their business, especially in the foreign land.

A dichotomy exists with ‘Grease Payment’:

OECD classified ‘Grease payment’ as “facilitating one, if it is paid to government employees to speed up an administrative process where the outcome is already pre-determined.”

In the FCPA of the US, ‘Grease Payment’, has been defined as “a payment to a foreign official, political party or party official for ‘routine governmental action,’ such as processing papers, issuing permits, and other actions of an official, in order to expedite performance of duties of non-discretionary nature, i.e., which they are already bound to perform. The payment is not intended to influence the outcome of the official’s action, only its timing.”

Many observers opine, ‘Grease Payments’ is an absolute dichotomy to the overall US policy for ethical standards and against corruption.

Currently besides US, only Canada, Australia, New Zealand and South Korea are the countries that permit ‘Grease payments’.

Notwithstanding, the governments of the US and four other countries allow companies to keep doing business without undue delay by making ‘Grease Payments’ to the lower government officials, such payments are considered illegal in most other countries, in which they are paid, including India.

In India such a business practice is viewed as bribery, which is not only perceived as unethical and immoral, but also a criminal offense under the law of the land. Even otherwise, right or wrong, ‘Grease Payments’ are viewed by a vast majority of the population as a morally questionable standard of ‘business conduct’.

Many companies are setting-up the ethical business standards globally:

While visiting the website of especially the large global and local companies, one finds that all these companies, barring a very few exceptions, have already put in place a comprehensive ‘code of business ethics and values’. Some of these companies have also put in place dedicated code compliance officers across the globe.

‘Practice as you preach’:

Despite all these commendable initiatives towards establishing corporate codes of business ethics and values, the moot question that keeps haunting many times and again: “Do all these companies ‘practice what they preach’ in real life?”

Instances are too many for breach in ethics, propriety and value standards:

The media is now increasingly reporting such instances of violations both locally and globally.

Some Indian examples: (At random, not in a chronological order)

Criminal drug regulatory manipulation:

One of India’s top pharma players reportedly will pay a record fine of US$ 500 million in the US for lying to officials and selling badly made generic drugs.

The company has pleaded guilty to improper manufacturing, storing and testing of drugs, closing a year long civil and criminal investigation into the matter.

Compensation for deaths related to Clinical Trials not paid:

In 2011 the Drug Controller General of India (DCGI) reportedly summoned nine pharma companies on June 6 to question them on the amount of compensation they have decided to pay the ‘victims of their clinical trials’, which is a mandatory part of any clinical trial, or else all other trials of these nine companies going on at that time or yet to start, will not be allowed.

Clinical Trial is another area of pharmaceutical business, especially in the Indian context, where more often than not, issues related to ethics and values are being raised. In an article titled, ‘Clinical trials in India: ethical concerns’ published by the World Health Organization (WHO) following observations have been made:

“The latest developments in India reflect a concerted effort on the part of the global public health community to push clinical trials issues to the fore in the wake of several high-profile cases in which pharmaceutical companies were shown to be withholding information from regulators.”

Alleged marketing malpractices:

In 2010, the Parliamentary Standing committee on Health reportedly expressed concern that the “evil practice” of inducement of doctors by the pharma players continues.

Congress MP Jyoti Mirdha sent a bunch of photocopies of air tickets to Prime Minister Manmohan Singh to claim that doctors and their families were ‘beating the scorching Indian summer’ with a trip to England and Scotland, courtesy a pharmaceutical company.

30 family members of 11 doctors from all over the country reportedly enjoyed the hospitality of the concerned company.

Department of Pharmaceuticals reportedly roped in the Revenue Department under Finance Ministry to work out methods to link the money trail to offending companies.

Some global examples: (At random, not in a chronological order)

United States Government sues a Swiss pharma major for alleged multi-million dollar kickbacks:

The United States Government very recently reportedly announced its second civil fraud lawsuit against a Swiss drug major accusing the company of paying multimillion-dollar kickbacks to doctors in exchange for prescribing its drugs.

Fraud fines: 

Two largest drug makers of the world reportedly paid US$ 8 billion in fraud fines for repeatedly defrauding Medicare and Medicaid in the USA over the past decade.

Denigrating generics:

Another global pharma major reportedly has been recently fined US$ 52.8 million for denigrating generic copies.

Drug overcharging: 

Another global drug major reportedly stirred an ethics scandal and paid US$ 499 million towards overcharging the US government for medicines.

Bribing doctors:

  • A top global pharma player reportedly paid total US$ 60.2 million to settle a federal investigation on alleged bribing overseas doctors and other health officials to prescribe medicines. 
  • Another European pharma group reportedly was fined US$ 3bn after admitting bribing doctors and encouraging the prescription of unsuitable antidepressants to children.

 Concealment of important facts:

A judge in USA reportedly ordered a large pharma company to pay more than $1.2 billion in fines after a jury found that the company had minimized or concealed the dangers associated with an antipsychotic drug.

Off-label marketing:

  • A Swiss pharma major reportedly agreed to pay US$ 422.5 million to resolve an investigation into alleged off-label promotion of a drug, as well as civil allegations relating to five other products.
  • The U.S. Justice Department reportedly hit an American drug major with a US$ 322 million penalty for illegally promoting a drug before it received approval by the Food and Drug Administration for that condition.

Other illegal marketing practices:

Yet another European pharma group was reportedly fined USD 34 million by a court in the United States for illegal marketing practices for its medicine.

‘Illegal’ Clinical Trials: 

It was revealed on May 17, 2013 that global pharmaceutical companies reportedly paid millions of pounds to former communist East Germany to use more that 50,000 patients in state-run hospitals as unwitting guinea pigs for drug tests in which several people died.

All these are some random examples of alleged malpractices associated with ‘ethics, propriety, compliance and values’ in the pharma world, both local and global.

Middle and lower management becomes the ‘fall guy’: 

It is interesting to note that whenever, such incidents take place, the fingers are usually pointed towards the middle or lower management cadre of the corporations concerned for violations and non-compliance.

Corporate or top management ownership of such seemingly deplorable incidents still remains confined within a ‘black box’ and probably a distant reality.

Public perception is not encouraging:

In the pharmaceutical sector all over the world, many business practices have still remained very contentious, despite many well-publicized attempts of self-regulation by the industry. The flow of complaints for alleged unethical business practices have not slowed down either, across the world, even after so many years of self-regulation, penalty and severe indictments.

Government apathy in India:

Nearer home, the Government apathy, despite being pressured by the respective Parliamentary Committees and sometimes including judiciary in repose to Public Interest Litigations (PIL), has indeed been appalling, thus far.

The Department of Pharmaceuticals of the Government of India has already circulated a draft ‘Uniform Code of Pharmaceutical Marketing Practices (UCPMP)’ for stakeholders to comment on it. The final UCPMP, when it comes into force, if not implemented by the pharmaceutical players in its ‘letter and spirit’, may attract government’s ire in form of strong doses of regulatory measures. However, the moot question remains, will the UCPMP come at all?

Similar issues are there in drug regulatory areas falling under the Ministry of Health, especially in the clinical trial area. In this matter, very fortunately Supreme Court has intervened against a Public Interest Litigation (PIL). Thus, one can expect to witness some tangible steps being taken in this area, sooner than later.

Walking the talk:

The need to formulate and more importantly effectively implement ‘Codes of Business Ethics & Values’ should gain increasing relevance in the globalized business environment, including in India.

It appears from the media reports, many companies across the world are increasingly resorting to ‘unethical behavior, impropriety and business malpractices’ due to intense pressure for business performance, as demanded primarily by the stock markets.

There is no global consensus, as yet, on what is ethically and morally acceptable ‘Business Ethics and Values’ across the world. However, even if these are implemented in a country-specific way, the most challenging obstacle to overcome by the corporates would still remain ‘walking the talk’ and owning responsibility at the top.

Conclusion:

Pharmaceutical innovation will continue to remain the launch pad for the industry growth in the battle against diseases of all types, forms and severity. However, that alone should in no way deserve to receive encouragement from any corner shorn from Ethics, Propriety, Compliance and Values.

Balancing pharmaceutical innovation with Ethics, Propriety, Compliance and Values, I reckon, will in turn help striking a right balance, to a considerable extent, between pharmaceutical innovation and public health interest for everyones’ satisfaction, mostly the patients.

Being equipped with the wherewithal to bring new drugs for the global population and being the fundamental source of growth momentum for the generic drug industry of the world, the innovator companies are expected to lead by setting examples in this area too. After all, as the saying goes:

“Caesar’s wife ought to be above suspicion. ‥Caesar himself ought to be so too”.

By: Tapan J. Ray

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

 

 

New ‘Patient Compensation’ Norms on Clinical Trials in India: Overdue Action, Sharp Reaction and Ethical Issues

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Responding to the damning stricture made by the Supreme Court on January 3, 2013, the Ministry of Health, as expected, by a gazette notification of January 30, 2013 has made the norms of compensation to patients participating in Clinical Trials (CT) more stringent.

‘Patient Compensation’ will now include injury or death, even if those are not related to the drugs being tested in the CT.

It is worth mentioning that these guidelines have been reportedly worked out after due consideration of around 300 comments received from the stakeholders on the draft proposal circulated by the Ministry of Health in July 2011, couple of rounds of discussion with the members of the civil society, expert groups and against reported ‘stiff opposition from the drug companies’.

Just a day after, on February 1, 2013, the Ministry of Health also notified final regulations on the conditions under which CT sites will be authorized by the local licensing and the inspection authorities of the Central Drugs Standard Control Organization (CDSCO).

Key features of the new Government ‘Action’ on patient compensation:

Following are the key features in the new norms for patient compensation:

1. The sponsors of CTs will now be liable for injuries or deaths, which will take place during the course of a clinical trial and will be required to pay compensation to the patients or their families.

2. The investigator of the CT must inform the concerned pharmaceutical company, the Clinical Research Organization (CRO) and the Ethics Committee regarding injury or death during CT within 24 hours.

3. It will be mandatory for all CT Ethics Committees to be pre-registered with the Drug Controller General of India (DCGI), unlike the old system where this was not required and trial sponsors reportedly could staff the committee.

4. The pharmaceutical companies and the CROs will get 10 days time to submit a detailed report on related serious adverse event to the Ethics Committee, which in turn will get another 10 to 11 days to convey its evaluation on compensation to be paid to the independent expert committee. The Expert Panel will then advise the DCGI of an appropriate financial compensation within 30 days from the date of receiving the above report.

5. It will no longer require inclusion of specific amount of compensation for injury or death in the informed consent form and does not refer to insurance coverage for potential liability.

6. It requires the sponsors of CTs to provide the trial subject with free “medical management” for as long as it will require.

Will make CT more expensive in India:

Clinical Trials (CT), as we know, are of critical importance for obtaining marketing approval of any new drug and at the same time forms a major cost component in the new drug development process, across the world.

Any savings in this area, both in terms of time and money, will add significantly to the profit margin of the product. In that context the above notification will now make CT more expensive in India.

Sharp ‘reaction’ of CT related industry:

Understandably, reacting to this notification, some Clinical Research Organizations have expressed concerns in areas like:

  1. Lack of distinction between study-related injuries and non-study related injuries
  2. The use of placebos in placebo-controlled trials,
  3. Lack of any arbitration mechanism in case of disagreement on causality/quantum of compensation and the lack of clarity on who constitutes the Expert Committee and its composition.

Some other Experts related CT industry do highlight a few more troubling issues in the notification, as follows:

1. Compensation to be paid for ‘failure of an investigational product to provide intended therapeutic effect.’ This, they expressed, is intriguing as the very nature of a CT is to ascertain whether the investigational drug is efficacious or not.

2. If compensation is not paid as required, a sponsor or CRO may be banned from conducting any further trials in the country. This, they feel, provision could make India a challenging place to conduct CT.

3. There should also be clarity on the formula to determine compensation, the process for determining a compensation amount, and how an appeal process would work.

The bottom-line is, due to this new policy on ‘Patient Compensation’ CT expenses may go up considerably in India.

Other expert views:

On the other hand, some other experts opined to the International Weekly Journal on Science – ‘nature’ as follows:

“These reforms should go further to restore public confidence and the Indian government should establish special courts to deal quickly with allegations of medical misconduct, such as not fully disclosing to participants the risks involved in a clinical trial”.

Global concern on ethical issues with ‘Placebo Controlled’ studies:

In this context, though issues related to ‘Placebo Controlled’ trials have been raised by the CT related industry in India, very interestingly a paper of Research Administration of the University of California on the ethical issues with ‘Placebo Controlled’ studies’ clearly articulates that the use of a placebo in clinical research has remained a contentious issue in the medical community since long.

Some strongly argue that use of placebos is often unethical because alternative study designs would produce similar results with less risk to individual research participants. Others argue that the use of placebos is essential to protect society from the harm that could result from the widespread use of ineffective medical treatment.

However, as per the Office for Human Research Protections (OHRP) guidebook, “Placebos may be used in clinical trials where there is no known or available (i.e. US-FDA-approved) alternative therapy that can be tolerated by subjects.”

This issue also needs to be deliberated and effectively addressed by the Indian drug regulator in the debate of patient compensation for ‘placebo controlled trials’.

A perspective on CT in India:

Interestingly, in this critical area India is fast evolving as a major hub. This is vindicated by a study conducted by Ernst & Young and the Federation of Indian Chambers of Commerce and Industry of India (FICCI), which states that India now participates in over 7 per cent of all global phase III and 3.2 per cent of all global phase II trials. The key points of attraction of the global players, so far as India is concerned, were reported as follows:

1. Cost of Clinical Trial (CL) is significantly less in India than most other countries of the world

2. Huge patient pool with different disease pattern and demographic profile

3. Easy to enroll volunteers, as it is easy to persuade poor and less educated people as ‘willing’ participants.

Such opportunities, experts believe, should have ideally made the clinical research industry to demonstrate greater responsibility to ensure that patients’ safety needs are adequately taken care of. Unfortunately, despite such expectations, some important areas like ‘patient compensation’ have still remained blatantly neglected.

It has now come to light with the help of ‘Right To Information (RTI)’ query that more than 2,000 people in India died as a result of Serious Adverse Events (SAEs) caused during drug trials from 2008-2011 and only 22 of such cases, which is just around 1 percent, received any compensation. That too was with a meager average sum of around US$ 4,800 per family.

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

DCGI had hauled-up 9 companies for blatant negligence:

According to another report quoting the Drug Controller General of India (DCGI), 25 people died in clinical trials conducted by nine pharmaceutical companies, in 2010. Unfortunately, families of just five of these victims received” compensation for trial related death, which ranged from Rs 1.5 lakh (US$ 3000) to Rs 3 lakh (US$ 6000).

This report also highlighted that arising out of this critical negligence, for the first time ever, the then DCGI was compelled to summon these nine pharmaceutical companies on June 6, 2011 to question them on this issue and with a clear directive to pay up the mandatory compensation for deaths related to clinical trial by June 20, 2011, or else all other CTs of these nine companies, which were ongoing at that time or yet to start, will not be allowed.

The report also indicates that after this ultimatum all the nine companies as mentioned therein had paid the compensation to the families of the patients who had died related to the CT.

Long exploitation of the fragile CT regulations in India:

For all these reasons, the subject of CT in India has created a huge ruckus, mainly for wide spread alleged malpractices, abuse and misuse of fragile CT regulations of the country by some players in this field. The issue is not just of GCP or other CT related standards but more of ethical mind-set and reported rampant exploitation of uninformed patients, especially in case of trial related injuries or even death.

The Bulletin of the World Health Organization (WHO) in an article titled, “Clinical trials in India: ethical concerns” reported as follows:

“Drug companies are drawn to India for several reasons, including a technically competent workforce, patient availability, low costs and a friendly drug-control system. While good news for India’s economy, the booming clinical trial industry is raising concerns because of a lack of regulation of private trials and the uneven application of requirements for informed consent and proper ethics review.”

“Pharmaceutical industry seeks to run studies in countries with lower costs”:

There seems to be nothing basically wrong in this approach per se. However, a recent report does highlight as follows:

“Clinical trials conducted by global drug makers and their proxies have generated increased scrutiny in recent years as the pharmaceutical industry seeks to run studies in countries with lower costs and populations where patients are not exposed to as many medications that can confound results. India has been a prime example”.

A lesson to learn by the Indian Drug Regulator:

It is worth noting that US-FDA in a communication meant for the consumers has stated as follows:

“The Food and Drug Administration’s job is to make sure medical treatments are safe and effective for people to use. FDA staff members meet with researchers, and perform inspections of clinical trial study sites to protect the rights of participants and to verify the quality and integrity of the data.”

The above approach seems to be drastically missing with the drug regulator in India as on date.

Conclusion:

Over a long period of time, a blatant negligence on reasonable care and financial compensation was allowed to continue by the Drug Regulator and the sponsors alike on the CTs conducted in India. A perceptible intent of justice to the patients, with the enforcement of stricter compensation laws and regulations for CT though belated, could dramatically change the CT scenario in India for the better in the years ahead.

In the fine balance of national priority for this area, patients’ safety and interest, I reckon, should always weigh more than the possibility of increase in the costs of CT in India. Thus,  the new norms of Patient Compensation indeed bring with it a breath of fresh air for the concerned stakeholders.

That said, the lose knots in some areas of the new norms, as discussed above, must be properly addressed and adequately tightened for greater clarity of the CT process, for all concerned.

By: Tapan J. Ray

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

‘Havoc’ and its ‘Aftermath’: Clinical Trials in India

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Just as the New Year dawned, on January 3, 2013, in an embarrassing indictment to the Government, the bench of honorable justices R.M Lodha and A.R Dave of the Supreme Court reportedly observed that uncontrolled Clinical Trials (CT) are creating ‘havoc’ to human life causing even deaths to patients.

In an interim order, the bench directed to the Government that CTs can be conducted only under the supervision of the Health Secretary of India. Holding the Government responsible, the bench further observed, “You (Government) have to protect health of citizens of the country. It is your obligation. Deaths must be arrested and illegal trials must be stayed,”

Responding to this damning stricture by the Supreme Court, the Government has now reportedly decided that appropriate rules laying down guidelines for pharma companies and other organizations engaging in drug trials in India would be notified within January 2013. It is envisaged that thereafter, the government will also amend the Drugs and Cosmetics Act of India making any violation of prescribed rules and guidelines a punishable offense under the law.

It is worth mentioning that these guidelines have been reportedly worked out after due consideration of around 300 comments received from the stakeholders on the draft proposal circulated by the Ministry of Health in July 2011, couple of rounds of discussion with the members of the Civil Society, expert groups and against reported ‘stiff opposition from the drug companies’.

Better late than never:

In conformance to the well known saying – “better late than never”, it appears that after reportedly around 2,242 deaths related to CT and under immense pressure from the civil society and the Supreme Court, the Government has now left with no options but to bring US$ 500 million CT segment of the country, which is expected to cross US$ 1 Billion by 2016, under stringent regulations.

Experts believe that the growth of the CT segment in India is driven mainly by the overseas players for easy availability of a large patient population with varying disease pattern and demographic profile at a very low cost, as compared to many other countries across the world.

Clinical trial related deaths in India:

As per the Ministry of Health following are the details of deaths related to CTs registered in India from 2008 to August 2012:

Year Total no of deaths CT related deaths  Compensation paid to:
2012 (up to August) 272 12 NA
2011 438 16 16
2010 668 22 22
2009 737 NA NA
2008 288 NA NA

It is estimated that over the last four years, on an average, 10 persons have died every week in India related to CT.

However, looking at the above reported numbers it appears that financial compensation was paid for all registered death related cases however meager such amounts may be.

A huge ruckus:

The subject of CT in India has created a huge ruckus, mainly for wide spread alleged malpractices, abuse and misuse of fragile CT regulations of the country by some players in this field. The issue is not just of GCP or other CT related standards but more of ethical mind-set and reported rampant exploitation of uninformed patients, especially in case of trial related injuries or even death.

The Bulletin of the World Health Organization (WHO) in an article titled, “Clinical trials in India: ethical concerns” reported as follows:

“Drug companies are drawn to India for several reasons, including a technically competent workforce, patient availability, low costs and a friendly drug-control system. While good news for India’s economy, the booming clinical trial industry is raising concerns because of a lack of regulation of private trials and the uneven application of requirements for informed consent and proper ethics review.”

 Inadequate auditing:

It is unfortunate that focus on ‘Clinical Trial Registry’ and even ‘Auditing of Clinical Trials’ has been grossly lacking in India, which are considered so important not only in maintaining credibility of the studies, but also to demonstrate their scientific integrity and ethical values.

Unfortunately, there seems to be many loose knots in the current CT policy, practices, rules and guidelines. All these require to be adequately tightened by the Government to make the system efficient and transparent in the national endeavor of establishing India as a preferred destination for global CT without compromising safety and the health interest of the volunteers.

 Indian Parliament intervened:

On May 8, 2012, the department related ‘Parliamentary Standing Committee (PSC)’ on Health and Family Welfare presented its 59th Report on the functioning of the Indian Drug Regulator – the Central Drugs Standard Control Organization (CDSCO) in both the houses of the Parliament.

The PSC in its report made the following critical findings, besides many others:

  •  A total of 31 new drugs were approved in the period January 2008 to October 2010 without conducting clinical trials on Indian patients.
  • Thirteen drugs scrutinized by the panel are not sold in the United States, Canada, Britain, European Union and Australia, as instructed by their respective regulatory authorities.
  • Sufficient evidence is available on record to conclude that there is collusive nexus between drug manufacturers, some functionaries of CDSCO and some medical experts.
  • Due to the sensitive nature of CTs in which foreign companies are involved in a big way and a wide spectrum of ethical issues and legal angles, different aspects of CTs need a thorough and in-depth review.

 Jolted drug regulator initiates action: 

In response to the high-pitched conundrum and media glare, The Ministry of Health and Family Welfare of the Government of India issued a draft notification on 17th July 2012 seeking stakeholders’ views on:

  • Permission to conduct CT
  • Compensation of the CT victims

The draft notification also says that the licensing authority, only after being satisfied with the adequacy of the data submitted by the applicant in support of proposed clinical trial, shall issue permission to conduct CT, subject to compliance of specified stringent conditions.

However, some experts do apprehend that such stringent system may give rise to significant escalation in the costs of CT for the pharmaceutical players.

Similarly, to assess right compensation for clinical trial related injuries or deaths, following parameters were mooted in the document:

  • Age of the deceased
  • Income of the deceased
  • Seriousness and severity of the disease the subject was suffering at the time of his/her participation into the trial.
  • Percentage of permanent disability

Further, unlike current practices, the government is expected to set up independent registered Ethics Committees under medical institutions for effective and smooth conduct of CTs in India.

Poor patient compensation:

Absolutely unacceptable level of compensation, by any standard, paid by the concerned companies for the lives lost during CTs are mainly attributed to the lackadaisical attitude of the drug regulators to frame rules and laws for patient compensation for such cases in India.

Information reportedly gathered through the ‘Right To Information (RTI) Act’ reveals that one pharmaceutical company paid just Rs. 50,000 each to the families of two patients who died during CT of its cancer drug. Another Ahmedabad-based Clinical Research Organization (CRO) paid a compensation of exactly the same amount to another patient for a CT related death.

The report points out that in 2011 out of 438 CT related deaths in India only 16 families of such patients received any compensation, the quantum of which varied from Rs. 50,000 to Rs. L 3.0  with one exception being of Rs. L 5.

In 2012 till August, 272 more CT related deaths have already been reported.

Higher patient compensation expected:

It has been alleged that currently the pharmaceutical companies are “getting away with arbitrary payments” sometimes as meager as Rs. 50,000, as stated above, in case of loss of life during CT, as there are no set norms for calculating compensation to those patients.

It is expected that the new rules will help putting in place a transparent formula for providing a respectable compensation for CT related serious adverse events like deaths, along with a prescribed provision for minimum compensation amount to such patients.

Increasing public scrutiny:

Over the last few years, CTs in India are increasingly coming under intense public and media scrutiny. As a result, both the concerned pharmaceutical companies as well as the CROs are facing the wrath of various stakeholders including the Supreme Court.

Following are the reported numbers of registered CTs in India from 2009 to 2011:

Year Total Number
2009 181
2010 313
2011 513

Although the total number of CTs registered in India from 2007 to 2011, as per available records, was around 1875, the number of new trials registered in the country had reportedly sharply declined in 2011 over 2010, mainly due to time-consuming regulatory approvals and increasing public scrutiny on alleged unethical practices.

According to www.clinicaltrials.gov – the website of the U.S Government, out of 118,804 human trials conducted in 178 countries, less than 2,000 or 2%, are carried out in India as compared to 9,352 or 8% in China.

It appears, all concerned players now seem to be either willingly or grudgingly waiting for the CT regulatory system to function the way it should. 

Conclusion:

Although the Ministry of Health has already started taking some positive measures, as stated above, there is an urgent need for the players in this field to reassure the Civil Society, in general, and the Government in particular about the high ethical standards that the pharmaceutical companies and CROs would comply with and continuously practice, while conducting clinical research in India.

We all understand, CTs are the core of research-based pharmaceutical industry. No new drug can come into the market without CTs, which involve both potential benefits and risks to the participants. All CTs are conducted with the primary aim of bringing to patients new medicines with a favorable benefit–risk ratio.

Global CTs being relatively new to India, no wonder, there are several misconceptions on the subject. The companies conducting clinical research need to proactively publicize their commitment to protecting the rights, safety and the well being of the trial participants.

That said, the bottom line is, without any selfish interest or pressure to the Government in any form, from within the country or outside, all concerned must ensure that CTs of all types must strictly adhere to the prescribed norms and well laid down procedures of India, as soon as these are put in place.

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 and also do not contribute to any other blog or website with the same article that I post in this website. Any such act of reproducing my articles, which I write in my personal capacity, in other blogs or websites by anyone is unauthorized and prohibited.

 

 

 

Pharmaceutical R&D in India: Issues and Challenges

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Research and Development (R&D) initiatives, though very important for most of the industries, is the life blood for the pharmaceutical sector, across the globe, to meet the unmet needs of the patients. Thus, very rightly, the Pharmaceutical Industry is considered as the ‘lifeline’ for any nation, in the battle against diseases of all types.

Drugs and Pharmaceuticals not only cure diseases and improve the quality of life of patients, but also help reducing the ‘burden of disease’ significantly. A study on five illnesses like AIDS, Cardiovascular, Cancer, Alzheimer’s and Rheumatoid-arthritis showed that drug research will save more than US$ 750 Billion in the treatment costs alone [1].

Similarly, treatment with drugs for schizophrenia can save more than US$ 70,000 per patient per year, due to avoidable hospitalization [2]. All these highlight the critical role that R&D could play in the healthcare system of any country.

R&D is not a threat to cheaper generic medicines:

More number of incoming patented medicines from the R&D labs will ensure faster growth of the generic pharmaceutical industry too, after the former will go off-patent. Even in the USA, which offers the highest number of innovative medicines across the globe, has a vibrant high growth generic pharmaceutical industry in place. The market penetration of cheaper generic drugs in the US is amongst the highest in the world and stands at more than half of all prescription medicines.

R&D process:

Over the years, pharmaceutical R&D process, though has evolved into a highly sophisticated and complex science, it still calls for enormous resources in terms of money, materials and skilled manpower, besides years of precious time.

Over a period of so many years, the small-molecule blockbuster drugs business model made pharmaceuticals a high-margin industry. However, it now appears that the low hanging fruits to make blockbuster drugs have mostly been plucked.

These low hanging fruits involved therapy areas like, anti-ulcerants, anti-lipids, anti-diabetics, cardiovascular, anti-psychotic etc. and their many variants, which were relatively easy R&D targets to manage chronic ailments. Hereafter, the chances of successfully developing drugs for cure of these chronic ailments, with value addition, would indeed be a very tough call. Even in this environment, India’s investment in R&D still remains very modest by the international standard.

Global R&D investment and Asia-Pacific Region:

It has been reported that in the global pharmaceutical industry[3] 85 % of the medicines are produced by North America, Europe, Japan and Latin America and the developed nations hold 97% of the total patents worldwide.

Unlike the common perception, that China is attracting a significant part of the global investments towards R&D, latest data of MedTRACK revealed that only 15% of all drugs development is taking place in Asia-Pacific, despite the largest growth potential of the region in the world.

The key growth driver of any economy:

Innovation being one of the key growth drivers for the knowledge economy, creation of innovation friendly ecosystem in the country calls for a radical change in the mind set – from ‘process innovation’ to ‘product innovation’, from ‘replicating a molecule’ to ‘creating a molecule’.  A robust ecosystem for innovation is the wheel of progress of any nation.

It is encouraging to hear that the Government of India is working towards this direction in a more elaborate manner in its 12th Five Year Plan.

Indigenous capability for production of the country must give way to indigenous capability for innovation and discovery.  Laws and policies need to facilitate, reward, recognise, protect and encourage all those who are or could be a part of this critical process.

Striking a right balance between the cost of research and affordability of medicines:

While the common man expects newer and better medicines at affordable prices, the Pharmaceutical Industry has to battle with burgeoning R&D costs, high risks and increasingly long period of time to take a drug from the ‘mind to market’, mainly due to stringent regulatory requirements. It will indeed be a very proud moment for India, when a drug, especially, for treating Non-infectious Chronic Diseases (NCD) comes out of its home-grown R&D centers.

R&D is an arduous process:

The dynamics of Drug Discovery are shown below:

  • Despite patent life being 20 years, effective period of exclusivity for the discoverer is only 7.5 – 8.5 years.
Stages of Development No. of Years
Pre-clinical 3.5
Clinical 6.5
Regulatory 2.5 – 1.5
Total: 12.5 – 11.5
  •  Another report, as depicted in the chart below indicates the investment pattern in R&D by various countries in the developed markets of the world:

Where does the money go? (%)

US 36
Japan 19
Germany 10
France 9
UK 7
Switzerland 5
Sweden 3
Italy 3
Other 8

Where does the R&D investment go? (%)

Synthesis & Extraction 12
Screening & Testing 15
Toxicology & Safety 5
Dosage & Stability 9
Clinical Phase 1-3 26
Phase IV 6
Process Dev. & QA 10
IND & NDA 4
Bioavailability 2
Other 11

Looking at the long lead time before a new drug starts paying back and even if net profitability of 50% on sales are permitted, recovery of the entire R&D cost only from the Indian market would be virtually impossible.  Hence, if Indian R&D is to pay back, we need to have access to overseas markets.

Harmonization of regulatory standards is a must for containment of R&D costs.  Researchers in the country are currently following the ‘DRL’ or ‘Glenmark’ model of selling /out licensing the discovery for offshore development.

Strengths and weaknesses of India in Pharmaceutical R&D:

Following are the current strengths and weaknesses of the Pharmaceutical Industry of India from the R&D perspective:

Strengths:

  • Mature Industry with strong manufacturing base
  • Strengths in (innovative) process chemistry
  • Abundance of raw talent
  • Entrepreneurial spirit
  • Highly talented and skilled Indian scientists working abroad (great potential for networking)
  • Low cost of Manpower
  • Cost effective Manufacturing Facilities
  • Rich Biodiversity
  • Global Clinical Trials are now being contacted in India

Weaknesses:

  • Lack of funding and resources
  • Lack of a ready ‘talent pool’
  • Low profile of high quality work being carried out
  • Inadequate regulatory framework / infrastructure
  • Low investment in R & D
  • Missing Link between Research and Commercilisation

R&D Expenditure in India:

The following chart gives details of R&D spend of the major players of the Indian Pharmaceutical industry in 2009:

FY 2009                                  (USD=INR46)
Company Sales USD Mn. R&D USD Mn. As % of Sales
Ranbaxy Laboratories 1610 90.3 5.6
Dr. Reddy’s Laboratories 1572 83.6 5.3
Cipla 1152 51.2 4.4
Sun Pharmaceuticals 951 67.4 7.1
Lupin 847 48.4 5.7
Wockhardt 770 11.2 1.4
Piramal Healthcare 720 18.5 2.6
Cadila Healthcare 644 34.4 5.3
Aurobindo Pharma 557 24.5 4.4
Matrix Laboratories 500 46.6 9.3
Total 9324 476 5.1

(Source: Prowess: Business World, February 8, 2010)

Research Options for India:

Following are various research options available to India:

  • Basic Discovery Research:

Basic Discovery Research is capital intensive, costly and takes a long time for the return on investments.  This could be made possible only if significant (NIH-type) funding is available.

  • Genetic & Proteomic Research:

Genetic and Proteomic Research involves many of these following procedures:

- Decoding Human Genetic Code

- Identification of Genetic Markers

- Personalized cards or chips that will contain each person’s genetic structure

- Genetic Manipulation to alter a person’s susceptibility to a particular disease

- Elimination of therapies that will not work on certain genotypes

This is probably the most exciting field of Research today, where the Industry will be able to “leap-frog” given the right priority.  The International Center of Genetic Engineering and Biotechnology (ICGEB) is already a recognized center of excellence both within and outside the country.  Hence international grants and funding must be aggressively pursued.

Biotechnology & Biosimilar drugs could be yet another opportunity area for India to leapfrog.  Biotech derived products are among the fastest growing in the world. These products being more expensive, if discovered and developed locally, could be affordable to many and also highly profitable.  Immunological and DNA Vaccines could be the most cost-effective answer to healthcare problems in developing countries, including India and should, therefore, be given top priority.  Here again, collaborative and international grants will be a critical success factor, just as the success of Biotech Companies in the US was fuelled by private venture capital.

  • Process Research:

While focusing on Product Research, the Process Research should not be ignored, as India possesses considerable skill base for this type of research, even better than China.  Cost effective, more and more economical processes will always be necessary to make products more and more affordable to patients.

  • Natural Product Screening:

India’s rich bio-diversity should not go waste.  The amount of work being done today is negligible as compared to the availability of “raw material” from the natural source.  Indian bio-diversity should be captured and cataloged into a meaningful library to facilitate R&D in this area.

  • The ‘Open Innovation’ Model:

As the name suggest, ‘Open Innovation’ or the ‘Open Source Drug Discovery (OSDD)’ is an open source code model of discovering a New Chemical Entity (NCE) or a New Molecular Entity (NME). In this model all data generated related to the discovery research will be available in the open for collaborative inputs. In ‘Open Innovation’, the key component is the supportive pathway of its information network, which is driven by three key parameters of open development, open access and open source.

Council of Scientific and Industrial Research (CSIR) of India has adopted OSDD to discover more effective anti-tubercular medicines.

Other Areas:

  • Epidemiological Research: The Industry needs good reliable data on the burden of human diseases.  In the absence of this data, it will be difficult to allocate resources and predict outcomes of new therapies.
  • Clinical Research (including toxicological / animal testing):  This area needs to be made world class, sooner than the later, not only to bring down the cost of drug development, but also to ensure that the data thus produced are acceptable in other countries.  India has the potential to emerge as the most sought after global hub for pre-clinical and clinical drug development processes.

Success of Indian pharmaceutical companies in R&D:

Following are the details of success of some major domestic pharmaceutical players in their pharmaceutical R&D initiatives:

Company NCE Pipeline Key Therapeutic Area
Biocon Preclinical – 2Phase II – 2Phase III – 1 Inflammatory Diseases, Oncology, Diabetes
Piramala Healthcare 13 Compounds in Clinical Trials Oncology, Infectious Diseases, Diabetes, Inflammatory Diseases
Glenmark Discovery – 4Preclinical – 5Phase I – 1Phase II – 3 Metabolic Diseases, Infectious Diseases, Respiratory Diseases, Oncology
Suven Life Sciences Discovery – 2Preclinical – 4Phase I – 1 Neurodegenerative Diseases, Obesity, Diabetes, Inflammatory Diseases
Dr. Reddy’s Lab Preclinical – 1Phase II – 2Phase III – 1 Metabolic Disorders, Cardiac, Oncology
Advinus Preclinical – 3 Diabetes, Cardiac, Lipid Disorders
Worckhardt Preclinical – 10Phase II – 1 Infectious Diseases
Lupin Discovery – 2Preclinical – 1 Migraine, Psoriasis, T.B.

(Source: Financial Express, March 13, 2009)

Basic pre-requisites to encourage R&D in India:

  • Innovation friendly ecosystem
  • Adequate Funding
  • World class Infrastructure
  • Ready talent pool

The key elements of creating an ecosystem conducive to R&D:

  • Knowledge and learning need to be upgraded through the universities and specialist centres of learning within India.
  • Science and Technological achievement should be recognized and rewarded by the sanction of grants and the future funding should be linked to scientific achievement.
  • Indian scientists working abroad are now inclined to return to India or network with laboratories in India. This trend should be effectively leveraged.

Key role of Universities:

Most of our raw talent goes abroad to pursue higher studies.  International Schools of Science like Stanford or Rutgers should be encouraged to set up schools in India, just like Kellogg’s and Wharton who have set up Business Schools. It has been reported that the Government of India is actively looking into this matter.

R&D funding:

Access to world markets is the greatest opportunity in the entire process of globalisation and the funds available abroad are a valuable source of “funding” to boost R&D in India. Inadequacy of funding is the greatest concern.

The various ways of funding R&D could be considered as follows:

  1. Self-financing Research: This is based on (i) “CSIR Model” i.e. recover research costs through commercialization – collaboration with industries to fund research projects and (ii) “Dr Reddy’s Lab / Glenmark Model” i.e. recover research costs by selling lead compounds without taking through to development – wealth creation by the creation of Intellectual Capital.
  2. Overseas Funding:  By way of joint R&D ventures with overseas collaborators; seeking grants from overseas Health Foundations; earnings from Contract Research as also from Clinical Development and transfer of aborted leads (‘Killing Fields” of the West) and collaborative projects on Orphan Drugs.  Multinational companies could be encouraged to deploy resources, as this is where the real money is.
  3. Venture Capital & Equity Market :  This could be both via Private Venture Capital Funds and Special Government Institutions.  If regulations permit, foreign venture funds may also wish to participate. Venture Capital and Equity Financing will emerge as important sources of finance once track record is demonstrated and ‘early wins’ are recorded.
  4. Fiscal Support & Non-Fiscal Support: Will also be valuable in early stages of R&D, for which a variety of schemes are possible as follows:
  • Customs Duty Concessions: For Imports of specialised equipment, e.g. high throughput screening equipment, equipment for combinatorial chemistry, special analytical tools, specialised pilot plants, etc.
  • Income tax concessions (weighted tax deductibility): For both in-house and sponsored research programmes.
  • Soft loans: For financing approved R&D projects from Government financial institutions / banks.
  • Tax holidays: Deferral, loans on earnings from R&D.

Government funding: Government grants though available, tend to be small and typically targeted to government institutions or research bodies. There is very little government support for private sector R&D.

All these schemes need to be simple and hassle free and the eligibility criteria must be tight.

Infrastructure for R&D:

Scientific infrastructure needs of the country require to be urgently strengthened.  Many of our Research Institutions require immediate upgradation.  All research laboratories should be encouraged to be profit driven and plough back earning in modernization.

Quality of life (proximity to schooling, hospitals, recreation) and ambiance is important, particularly for scientists working abroad, who could be encouraged to return to India.

Setting up of world class Clinical Pharmacology Laboratories and Toxicology Centers must be considered.  All clinical trials carried out in India must conform to GCP standards.  At the same time, Indian registration procedures should be harmonized and simplified in order to minimize duplication of efforts and time loss.

Indian Patent infrastructure:

Indian patent infrastructure needs to be strengthened, among others, in the following areas:

  • Enhancing patent literacy both in Legal and Scientific Communities, who must be taught how to read, write and file a probe.
  • Making available appropriate Search Engines to our scientists to facilitate worldwide patent searches.
  • Creating world class Indian Patent Offices where the examination skills and resources will need considerable enhancement.
  • Advisory Services on Patents to Indian scientists to help in filing patents in other countries.

Partnering for Drug Discovery:

Many Indian pharma companies have entered into international collaborative arrangements, including R&D for development of new drugs for disease areas like cancer, diabetes, malaria and nervous system disorders.

DRL has partnered with ClinTec International for clinical trials and co-development of its anti-cancer drug. ClinTec International will possess the marketing rights for European markets while the commercialization for the rest of the world and US markets would be retained by DRL. It has also tied up with Torrent Pharma for the exclusive marketing rights of its two hypertension drugs in Russia, where Torrent has a strong market hold.

GSK and Ranbaxy set up an early-stage partnership in drug research, under which GSK will provide the Indian firm with leads, Ranbaxy will conduct lead optimization and animal trials, and GSK will take the drug through human trials. GSK will have exclusive rights to sell any resulting product in developed-world markets, and the two firms will co-promote it in India.

Conclusion:

- It is essential to have balanced policies offering equitable advantage to all stakeholders, including patients.

- Globalization brings opportunities like, access to markets, which are far more profitable than ours.  Any policy of isolation or retaliation in an increasingly more global environment, could go against the general interest of the country.

- Acceptance by the Government of the benefits of privatization, market liberalization and rationalization of Government controls, will add speed to R&D initiatives.

- The trade policy is another important ingredient of public policy which can either reinforce or retard R&D efforts.

- Empirical evidence across the globe has demonstrated that a well balanced patent regime in the country encourages the inflow of technology, stimulates research and development, benefits both the national and the global pharmaceutical sectors and most importantly benefits the healthcare system.

- The Government, academia, scientific fraternity and the Pharmaceutical Industry should get involved in various relevant Public Private Partnership (PPP) arrangements for R&D to ensure wider access to newer and better medicines in the country, providing much needed stimulus to the public health interest of the nation.

References:

  1. The Process of New Drug Discovery and Development, Second Edition, Charles G. Smith and James T. O’Donnell, 2006, p. 422, published by Informa Healthcare.
  2. Goddamn the Pusher Man, Reason, April 2001
  3. Abhinav Agrawal, Kamal Dua, Vaibhav Garg, U.V.S. Sara and Akash Taneja, 27- Challenges and Opportunities for The Indian Pharma Industry, Health Administrator vol. xx number 1&2 : 109-113
  4. “Food & Drug Administration, Generic Drugs: Questions and Answers”. Food and Drug Administration, January 12, 2010.

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.