Tag Archives: drugs

Global API manufacturers are poised to penetrate the Indian market in a bigger way – will the API ‘marketing warfare’ be even more intense, in future?

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India currently plays a relatively dominant role in the Global Active Pharmaceutical Ingredient (API) Market with China being ahead of India. While this is the current scenario, many experts in this field contemplates that important players from the regulated markets will soon start making significant inroads in India.Current API Market situation in India:In 2007 the API output value in India was around US $4.1 billion registering a 5 year CAGR of around 19% and ranking fourth in the world API output. According to the Tata Strategic Management Group, Indian API export value is expected to increase to US $12.75 billion in 2012.

Currently in India about 400 different types of APIs are manufactured in around 3000 plants, Ranbaxy Laboratories, Lupin, Shasun Chemicals, Orchid Chemicals, Aurobindo Pharma, Sun Pharmaceuticals Ipca Laboratories and USV being the top API manufacturers of the country. Indian domestic companies source almost 50 percent of their API requirements from China, because of lower cost in that country.

In terms of global ranking, India is now the third largest API producers of the world just after China and Italy and by 2011 is expected to be the second largest producer after China. However, in Drug Master File (DMF) filings India is currently ahead of China.

In addition, India scores over China in ‘documentation’ and ‘Environment, Health and Safety (EHS)’ compliance. All these have contributed to India having around 100 US FDA approved world class manufacturing facilities, which is considered the largest outside the USA.

Indian API manufacturers are facing a cut throat competition from their Chinese counterparts mainly because of lower costs in China. Considerably higher economies of scale and various types of support that the Chinese API manufacturers receive from their Government are the main reasons for such cost differential.

Growing competiton from the regulated markets:

We now observe a new trend within the API space in India. Many of the global innovators and generic companies are keen to enter into the API space of India.

It is known that API manufacturers from the regulated markets are already selling their products in India. However, at present, the numbers of Indian registrations for API applied by some of the large global companies, as reported by ‘Thomson Reuters Newport Horizon Premium’, are quite significant, which are as follows:

1. Novartis, Switzerland:20
2. Pfizer, USA:16
3. Sanofi-Aventis, France: 26
4. Teva, Israel: 45
5. Schering-Plough, USA:39
6. BASF: 37
7. DSM: 26
8. E.ON AG: 16
9. Kyowa Hakko: 23

All these companies who are entering into the API business space in India, I am sure, have worked out a grand design to compete not only with the the low cost domestic API manufacturers, but also with the cheaper imports, particularly from China.

What will then be the competitive edge of these companies in India?

It appears that each of these companies has weighed very carefully the existing strategic opportunities in the API sectors of India, both in terms up technology and also in terms of domestic demand.

Strategic gap in API manufacturing technology:

India, undeniably, is one of the key global hubs in the API space, with competitive edge mainly in ‘non-fermentation technology’ product areas. This leaves a wide and perceptible technological gap in the areas of products requiring ‘fermentation technology‘.

Significant demand from domestic formulations manufacturing :

India is much ahead of China in pharmaceutical formulations manufacturing, especially in the area of exports to the regulated markets like, the USA and EU. Over 25 domestic Indian companies are currently catering to exports demand of the U.S market. However, it is interesting to note that the global manufacturers like Sandoz, Eisai, Watson, Mylan have already set up their formulations manufacturing facilities in India and some more are expected to follow suit over a period of time. Hence, fast growing domestic demand for APIs, especially for exports, will drive the business plan of the global API players for India.

Is the cost advantage in India sustainable?

Indian API manufacturers although currently have a cost advantage compared to their counterparts in the regulated market, this advantage is not sustainable over a period of time because of various reasons. The key reason being sharp increase in cost related to more stringent environmental and regulatory compliance, besides spiralling manpower and other overhead costs.

Indian regulatory requirements for the global API players:

To sell their APIs into India, global companies are now required to obtain the following regulatory approvals from the Indian authorities:

1. Foreign manufacturing sites for the concerned products
2. APIs which will be imported in the country

The Drug Controller General of India (DCGI) has stipulated a fee of U.S$1,500 to register the manufacturing premises and U.S$1,000 to register each individual API. Since January 2003, around 1,200 registration certificates have been issued in India. Large number of Indian registrations is attributed by many to the strategic technology gap in India, as stated above, demand of high-quality API for finished formulations required by the regulated markets like the U.S and EU, and relatively cheaper product registration process.

As we see above Teva has gone for maximum number of Indian registrations, so far and most probably selling the APIs to their contract formulations manufacturers in India. Similarly, Schering-Plough and Sanofi-Aventis, if not Pfizer are perhaps catering to the API demand of their respective formulations manufacturing plants in the country.

Whatever may be the reasons, these global players are now exporting APIs at a much larger scale to India and in that process have started curving out a niche for themselves in the Indian API market. Impressive growth of the domestic pharmaceutical formulations manufacturing market fueled by increasing domestic consumption and exports to the regulated markets, coupled with gradual improvement in the regulatory environment of the country, is expected to drive the growth of API business of the global players.

However, the moot question is how significant will this competition be?

By Tapan 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.

With significant competitive edge should Global Biotech Companies consider entry into high potential ‘Biosimilar drugs’ business?

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‘Biosimilar drugs’ – rapid future growth potential:
In most of the developed countries of the world, besides regulatory issues, ‘Biosimilar drugs’are considered a threat to the fast growing global biotech industry. However, many believe that innovative biotech companies can have a head start with all wherewithals at their disposal, compared to generic pharmaceutical companies, to convert this seemingly significant threat into a bright emerging opportunity and derive the best possible mileage out of such changing environment.

Sandoz (Novartis) – first to launch a ‘Biosimilar drug’ in the USA:

In mid 2006, US FDA approved its first ‘Biosimilar drug’; Omnitrope of Sandoz (Novartis) following a court directive in the U.S. Omnitrope is a copycat version of Pfizer’s human growth hormone, Genotropin. Interestingly, Sandoz (Novartis) had taken the U.S FDA to court as the regulatory approval of Omnitrope was kept pending by them, in absence of a defined regulatory pathway for ‘Biosimilar drugs’ in USA.

The CEO of Sandoz had then commented, “The FDA’s approval is a breakthrough in our goal of making high-quality and cost-effective follow-on biotechnology medicines like Omnitrope available for healthcare providers and patients worldwide.” Despite this event, no one at that time expected the U.S FDA to start commencing approval of other ‘Biosimilar drugs’ within the country.

‘Biosimilar drugs’ – emerging global interest:

Thereafter, many developments are fast taking place in the space of ‘Biosimilar drugs’, the world over. To fetch maximum benefits out of this emerging opportunity, India is also taking steps to tighten its regulatory reform process for ‘Biosimilar drugs’ to allay general fear and apprehensions regarding safety of such drugs, in absence of adequate clinical data for the specific protein substance.

Merck’s entry in ‘Biosimilar drugs’ business is through an acquisition:

In the west Merck announced its entry into the ‘Biosimilar drugs’ business on February 12, 2009, while announcing its acquisition of Insmed’s portfolio of ‘Biosimilar drugs’ for U.S$130 million in cash. Rich pipeline of follow-on biologics of Insmed is expected to help Merck to hasten its entry into global ‘Biosimilar drugs’ markets.

Current status of ‘Biosimilar drugs’ in the USA:

The new administration of President Barak Obama has expressed its strong intent to pave the way for regulatory guidelines for ‘Biosimilar drugs’ in the USA. To facilitate this process, the new draft legislation titled, “Promoting Innovation and Access to Life Saving Medicine Act” has already been introduced by the legislators of the country. This legislation, when will come into force would help define guidelines for approval of ‘Biosimilar drugs’ in the USA with just a five year exclusivity period to the innovative products, against a demand of 14 years by the global biotechnology industry.

Lucrative Global market potential for ‘Biosimilar drugs’:

It is estimated that only in the top two largest pharmaceutical markets of the world, USA and EU, sales of ‘Biosimilar drugs’ will record a turnover of U.S$ 16 billion in next two years and around U.S$ 60 billion by year 2010, when about 60 biotech products will go off-patent.

Opportunity for the Indian biotech companies:

Such a lucrative business opportunity in the west will obviously attract many Indian players, like, Biocon, Dr. Reddy’s Labs, Ranbaxy, Wockhardt etc, who have already acquired expertise in the development of ‘Biosimilar drugs’ in India like, erythropoietin, insulin, monoclonal antibodies, interferon-alfa. Domestic Indian biotech players are not only marketing these products in India but also exporting them to other non/less-regulated markets of the world.

Indian Companies are fast preparing to take a sizable share of the global pie of ‘Biosimilar drugs’ market:

Ranbaxy in collaboration with Zenotech Laboratories is engaged in global development of Granulocyte Colony-Stimulating Factor (GCSF) formulations. Wockhards is expected to enter into the Global ‘Biosimilar drugs’ market by 2010. Dr. Reddy’s Laboratories and Biocon are also preparing themselves for global development and marketing of insulin products, GCSF and streptokinase formulations.

Government of India funding for development of ‘Biosimilar drugs’ in India:

It has been reported that the Department of Biotechnology (DBT) of the Government of India has a proposal for funding of U.S$ 68 million through public private partnership (PPP) initiatives, where soft loans at the rate of interest of just 2% will be made available to the Indian biotech companies for development of ‘Biosimilar drugs’. Currently DBT spends around U.S$200 million annually towards biotechnology related initiatives.

Advantage India:

Experience in conforming to stringent U.S FDA manufacturing standards, having largest number of U.S FDA approved plant outside USA; India has acquired a great advantage in manufacturing similar high technology products in India. Significant improvement in conformance to Good Clinical Practices (GCP) standards in India offers additional advantages.

Two available choices for the innovator companies:

With increasing global cost-containment pressures within the healthcare space, emergence of a lucrative global ‘Biosimilar drugs’ market with appropriate defined regulatory pathway in place is inevitable now.

Major global research based companies will now have two clear choices in the fast evolving situation. The first choice is the conventional one of competing with the ‘Biosimilar drugs’ in all important markets of the world. However, the second choice of jumping into the fray of ‘Biosimilar drugs’ business keeping focus on R&D undiluted, appears to be more prudent to me and perhaps will also make a better business sense. Only future will tell us, which of these two business senses will prevail, in the long run for the global biotech companies.

By Tapan 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.

Growing menace of counterfeit drugs in India: why is the domestic pharmaceutical industry still so apprehensive with the new Amendments of the ACT?

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The growing menace of Counterfeit drugs has remained a serious threat to the healthcare space of India.
Do we have any credible data to assess the magnitude of this menace in India?

No we do not have, as yet. At this stage, the magnitude of the problem is anybody’s guess. Earlier a study sponsored by the World Health Organization (WHO) and conducted by SEARPharm reported that only 0.3% drugs were spurious and 3% of drugs were counterfeits.

Government of India has initiated the largest study in the world to quantify the problem:

To scientifically assess the magnitude of the problem in terms of real size of counterfeit drugs market in India , the Drugs Controller General of India (DCGI) India’s, for the first time ever, has initiated one of the largest studies in the world, as reported by the Times of India May 14, 2008.

The study has already identified 61 popular drug brands from nine therapeutic categories for testing 24000 samples. These include drugs prescribed for tuberculosis, malaria, allergic disorders, diabetes cardiovascular conditions, vitamins etc. This study is expected to cost 50 million rupees or about U.S$1.0 million and is expected to be published, soon.

Making provisions for stricter penalties through amendment of the Drugs and Cosmetics Act, 1940:

To bring into effect stricter penalties for those involved in counterfeit drugs, the process of amendment of the Drugs and Cosmetics Act, 1940 was proposed by the Ministry of Health in October, 2007. These amendments are expected to make the drug-related offences, cognisable and non-bailable.

The latest amendment to the Drugs and Cosmetics Act, 1940 became a law in 2008. The punishment for selling or distributing spurious drugs, which are likely to cause death and grievous hurt to the patients, is now imprisonment for a term not less than 10 years and fine not less than Rs 10 lakh or three times the value of drugs confiscated, whichever is more.

The Minister of Health of India announced in November 2008, that with this amendment the Government of India will “go all out to do away with spurious drugs.”

India working closely with WHO Anti-counterfeiting Taskforce:

India being a part of ‘International Medical Products Anti-Counterfeiting Taskforce’ (IMPACT), established under WHO in 2006, decided to work together to combat the growing menace of counterfeit medicines.

The Drugs Controller General of India (DCGI) was reported to have several discussions with the convenor of the IMPACT to effectively address the issue of such serious threats to the patients at large. Many people believe that China and India are the main source of counterfeit drugs in the world.

Apprehensions of the Indian Pharmaceutical Industry with new Amendments in the Law:

Indian Pharmaceutical Industry although welcomed the stricter punitive provisions in the law, expressed its apprehensions due to lack of clear demarcation between the definitions of spurious drugs and those which can lose their original potency because of improper transportation and storage.

If the law-enforcing authorities pick up such medicines from retail outlets, those can easily get categorised as spurious medicines under Section 17A and 17B of the Drugs and Cosmetics Act, 1940. Consequently the concerned manufacturers could be put behind bars with, presumably, no fault at their end.

While stringent punishment is essential for those involved in such heinous crime, the Government should take enough measures to ensure that genuine drug manufacturers are not harassed by the law enforcing authorities, as the courts will have no judicial discretion to award less than minimum punishment, as prescribed under this Act.

Need for clear guidelines for implementation of the amended ACT:

To allay the major apprehension of the industry regarding possible misuse of some provisions of the Act, the Ministry of Health is expected to work out and quickly announce clear guidelines for implementation of the act by the law enforcement agencies in different parts of India.

Will this amendment help to win the fight against counterfeit drugs?

Only time will be able to give that answer. However, by amending the Act, the Government of India has demonstrated its resolve to address the threat of counterfeit drugs with iron hand. Through enunciation of above guidelines, all concerned are expected to be taken on board to effectively curb, if not totally eliminate this growing menace, for the sake of humanity.

By Tapan 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.

Fixed Dose Combination’ drugs market in India is growing faster – are there enough regulatory checks and balances to prevent market entry of ‘irrational combinations’ to ensure patients’ safety?

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The WHO Model of FDCs:The 2005 ʹProcedure to update and disseminate the WHO Model List of Essential Medicines, Criteria for Selection‘ includes the following statement regarding fixed dose combination products (FDCs):ʺMost essential medicines should be formulated as single compounds. Fixed‐dose combination products are selected only when the combination has a proven advantage over single compounds administered separately in therapeutic effect, safety, and adherence or in delaying the development of drug resistance in malaria, tuberculosis and HIV/ AIDS.ʺ

FDCs need to demonstrate clinical efficacy and safety beyond that for the individual drugs given alone. They would also need to ‘demonstrate bioequivalence of the single combined dose unit with the components administered in the same doses separately but concomitantly’.

‘Adherence’ aspect of WHO Model for FDCs is also important. Problems with ‘adherence’ could lead to inadequate and inconsistent dosing, which in turn could lead to development of drug resistance. FDCs, therefore, are expected to improve compliance reducing the risk of development of drug resistance.

However, one of the major disadvantages with the FDCs is lack of flexibility in adjusting dose of individual ingredients, even if it is required for some patients. Internationally, most popular example is the FDCs of antiretroviral drugs for HIV infected patients like, Combivir, Trzivir, Kaletra etc. Besides, there are FDCs for various other disease areas, like, infections, respiratory and cardiovascular disorders etc.

New FDCs are patent protected in the USA:

In the western world, like the USA, new FDCs may also get patent protection. A company may obtain marketing exclusivity for a new FDC even when individual active ingredients go off patent. However, in India FDCs cannot be patented as per Patent Acts of India 2005.

Market attractiveness for FDCs in India:

In India the market for FDCs is very large and growing much faster, in sharp contrast to the western world. Because of growing market demand, pharmaceutical companies in India tend to market FDCs of all different permutations and combination, at times even crossing the line of a ‘sound medical rationale’. For this reason, we find in the website of ‘Central Drugs Standard Control Organization’ (CDSCO), the banned list of so many FDCs.

Lack of regulatory compliance has created a messy situation with FDCs in India:

Introduction of new FDCs does not only warrant a ‘sound medical rationale’ but also ‘strict conformance to all prescribed regulatory requirements’ for the sake of patents’ safety.

To check unfettered market introduction of potentially harmful FDCs, the Ministry of Health issued a Notification in September 1988, including FDCs in Rule 122 E of the Drugs & Cosmetics Rules (D&CR) 1945. In effect, it removed the powers of the State FDAs to give manufacturing or marketing approval of FDCs. After the notification was issued, all manufacturers/marketers of all FDCs are required to apply only to the Drug Controller General of India (DCGI) under Rule 122E of the D&CR 1945 as a new drug, along with the stipulated fees by way of a Treasury Challan.

Since this entire process entails relatively more regulatory data generation, besides the time and expenses involved, the above Rule was continuously and deliberately broken and manufacturing and marketing approvals were routinely sought and obtained from the State FDAs. Many believe that the State FDAs were equally responsible for knowingly flaunting the Law, as were the pharmaceutical companies.

Patients’ safety – the key concern:

This complicity resulted in the market being flooded with ‘irrational combinations’ which posed a real threat to patients’ safety. The state FDAs were reminded of the Notification by the earlier DCGI. 294 FDCs got caught in this dispute. The important issue of patients’ safety in that process got converted into a legal issue, as many FDC manufacturers chose to go to the court of law to redress their grievances in this matter.

Untangling the messy knot:

As the issue got trapped into various prolonged litigations, the current DCGI took initiative of resolving this contentious issue with the help of an expert committee, involving the manufacturers.

This subcommittee cleared 48 FDCs under ‘similar FDCs already approved’, after discussing the merits and demerits, including pharmacodynamics, pharmacokinetics, side effects, dosage, medical rationale etc. of each ingredient and the combinations. The decision of the Sub Committee was then submitted to the Drug Technical Advisory Board (DTAB).

After formal approval of DTAB, a notification is expected to be issued subsequent to which each of these combinations will be construed to be a new drug and any company wishing to market/manufacture the formulation will require submitting its Application in Form 44 to the DCGI to get approval in Form 45. The process will be completed after the balance 142 FDCs, which need further examination, are individually approved.

This issue sends a clear signal to all concerned that resorting to any form of shortcuts to bypass strict adherence to prescribed regulatory requirements, could seriously jeopardise the patients’ safety. The number of FDCs banned by CDSCO and also ban of those FDCs agreed and accepted by the industry without any challenge during the above process, will vindicate this point.

Solving the current logjam is not enough:

Solving the current logjam on FDCs by the DCGI is a onetime exercise and will perhaps clear a serious mess-up created over a long period of time. It can definitely not be an ongoing process. Neither will it be desirable. There is an absolute and urgent need to follow the WHO Model for FDCs, in India, as indicated above, through appropriate regulatory processes. At the same time, the DCGI should ensure strict compliance of the Notification issued by Ministry of Health on FDCs, in September 1988. Otherwise, unchecked entry of FDCs of all possible permutations and combinations could pose a serious threat to patients’ interest and safety.

Meeting unmet needs of the patients with high quality drugs of scientifically proven high efficacy and safety profile should always define the purpose of existence of the pharmaceutical industry. Any patients’ safety related issue deserves no scope for any compromise.

By Tapan 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.

From ‘Blockbuster Drugs’ to ‘Personalized Medicines’ – will it revolutionize the way the patients will be treated tomorrow?

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Financial Times quoted Jeff Kendler, the CEO of Pfizersaying, “the era of dependence on a single or a couple of blockbuster drugs should be over. Lipitor sells U.S$ 12 billion a year. You can’t build a company predicted on the belief that you are going to find such a drug.”The argument is robust, what then are the alternatives?Rapid strides in pharmacogenomic bring in a promise of radically different way of treating diseases, as major pharmaceutical companies of the world make progress in developing much more effective medicines designed to target smaller populations. These medicines are termed as ‘personalized medicines’ and are expected to be an effective alternative to now quite unwieldy ‘blockbuster drugs’ business model.

In what way ‘Personalized Medicines’ will be different?

With ‘Personalized Medicines’ the health of a patient will be managed based on personal characteristics of the individual, including height, weight, diet, age, sex etc, instead of defined “standards of care”, based on averaging response across a patient group. Pharmacogenomic tests like, sequencing of human genome will determine a patient’s likely response to such drugs.

These are expected to offer more targeted and effective treatment with safer drugs, and presumably at a lesser cost. Such medicines will also help identify individuals prone to serious ailments like, diabetes, cardiovascular diseases and cancer and help physicians to take appropriate preventive measures, simultaneously. ‘Personalized medicines’ in that process will focus on what makes each patient so unique, instead of going by the generalities of a disease.

To give a quick example, genetic differences within individuals determine how their bodies react to drugs such as Warfarin, a blood thinner taken to prevent clotting. It is of utmost importance to get the dosing right, as more of the drug will cause bleeding and less of it will not have any therapeutic effect.

‘Personalized medicines’, therefore, have the potential to bring in a revolutionary change the way patients are offered treatment by the medical profession. Genomic research will enable physicians to use a patient’s genetic code to arrive at how each patient will respond to different types of treatments.

In the field of cancer, genetic tests are currently being done by many oncologists to determine which patients will be benefitted most, say by Herceptin, in the treatment of breast cancer.

What is then the aim of ‘Personalized Medicines’?

The aim of ‘personalized medicines’ is to make a perfect fit between the drug and the patient.
It is worth noting that genotyping is currently not a part of clinically accepted routine. However, it is expected to acquire this status in the western world, by 2010.

Expected benefits from ‘Personalized Medicines’:

1. More Accurate dosing: Instead of dose being decided based on age and body weight of the patients, the physicians may decide and adjust the dose of the medicines based on the genetic profiling of the patients.

2. More Targeted Drugs: It will be possible for the pharmaceutical companies to develop and market drugs for patients with specific genetic profiles. In that process, a drug needs to be tested only on those who are likely to derive benefits from it. This in turn will be able to effectively tailor clinical trials, expediting the process of market launch of these drugs.

3. Improved Health care: ‘Personalized Medicines’ will enable the physicians to prescribe ‘the right dose of the right medicine the first time for everyone’. This would give rise to much better overall healthcare.

Role of Pharmaceutical and Biotech companies:

Many research based pharmaceutical and biotechnology companies have taken a leading role towards development of ‘personalized medicines’ in line with their key role as healthcare enterprises. India is also taking keen interest in this science.

Some important issues:

However, there are some ethical and social issues in the development of ‘personalized medicines’ primarily in the area of genetic testing and consideration of race in the development of such medicines, which need to be effectively addressed, sooner.

Can it replace the‘Blockbuster Drugs’ business model?

Realization of deficiencies in the economics of ‘block buster drugs’ R&D business model, has made ‘personalized medicines’ a reality today.

Improved efficacy and safety of treatment with ‘personalized medicines’ will prove to be cost-effective in healthcare systems. Smaller and exclusive markets for ‘personalized medicines’ are expected to be profitable for the pharmaceutical companies. But such smaller segmentation of the market may not leave enough space for the conventional ‘blockbuster model’, which is the prime mover of the global pharmaceutical industry, today.

Reports indicate that some renowned global pharmaceutical companies like, Roche, AstraZeneca, GlaxoSmithKline are making good progress towards this direction through collaborative initiatives.

Approximate cost of ‘Genome Sequencing’:

When human genome was first sequenced, the reported cost was staggering U.S$ 3 billion. However, with the advancement of technology, it came down to U.S$ 1 million, last year. Currently, the cost has further come down to U.S$ 60,000. With the rapid stride made in the field of biotechnology, combined with the economies of scale, cost of such genetic tests is expected to be around U.S$ 1,000 in near future, making it possible for people to obtain the blue print of their genetic code.

Savings on cost of Clinical trials with ‘Personalized Medicines’:

Genome sequencing will help identifying a patient population, which will be far more likely to respond positively to the new treatment. In that process, if it reduces costs of clinical trial by even 5%, expected net savings for the industry towards clinical trial have been reported to be around U.S$ 5 billion.

With ‘personalized medicines’ the innovator companies will be able to significantly reduce both time, costs and the risks involved in obtaining regulatory approvals and penetrating new markets with simultaneous development of necessary diagnostic tests. Such tests will be able to identify patients group who will not only be most likely to be benefitted from such medicines, but also will be least likely to suffer from adverse drug reactions.

Therefore, considerable cost advantages coupled with much lesser risks of failure and significant reduction in the lead time for clinical trials are expected to make ‘personalized medicines’ much more cost effective, compared to conventional ‘blockbuster drugs’.

Innovative and cost effective way to market ‘Personalized Medicines’:

With ‘personalized medicines’ the ball game of marketing pharmaceuticals is expected to undergo a paradigm shift. Roche’s model of combining necessary diagnostic tests with new drugs will play a very important role in the new paradigm.

Roche is ensuring that with accompanying required diagnostic tests, the new oncology products developed at Genentech can be precisely matched to patients.

Can ‘Personalized Medicines’ be used in ‘Primary Care’ also?

To use ‘personalized medicines’ in a ‘primary care’ situation, currently there is no successful model. However, it has been reported that in states like, Wisconsin in the U.S, initiative to integrate genomic medicines with ‘primary care’ has already been undertaken. Scaling-up operations of such pilot projects will give a big boost to revolutionize the use of ‘personalized medicines’ for precision and targeted treatment of the ailing population.

In my view, there does not seem to be any possibility of looking back now. The robust business model of ‘personalized medicines’, is now the way forward, as much for the industry as for the patients. It is a win-win game.

By Tapan 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.

Simmering discontentment in the functioning of the Indian Patent Office (IPO) – urgent need to tighten the ‘loose knots’ in the system.

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Indian Patent office (IPO) though is headquartered at Kolkata, because of some unknown reason, the office of the Controller General of Patents, Designs and Trade Marks (CGPDTM)is located in Mumbai with other two offices at New Delhi and Chennai. Moreover, the office of the ‘Patent Information System’ is located at Nagpur. Scattered location of the IPO, many believe, could be an impediment in ensuring uniformity in operations between all its units. Such an opinion is debatable though, I shall not deliberate on this issue in this article.The point that I shall argue upon is the crying need in the IPO to tighten 15 identified ‘loose knots’in its operation, which are causing considerable concern within stakeholders, who are casting serious aspersions in its efficiency.There are some areas where our IPO is doing quite well. I shall also dwell upon those areas before highlighting the areas of improvements.

The new IPR regime came into force from January 1, 2005. Even 4 years down the line, the IPO still remains grossly understaffed. Growing dissatisfaction with the current functioning of the IPO is fast sapping initial enthusiasm of the innovators on the new IPR regime in the country. ‘The glass’ now perpetually looks as ‘half empty’, as it were and will continue to do so, if corrective measures are not taken, forthwith.

The information available from the IPO website indicates that all the four centers put together, there are just 134 Examiners, 31 Assistant Controllers, 4 Deputy Controllers and 1 Joint Controller. Staff attrition rate within the IPOs has been reported to be reasonably high, which incidentally appears to be one of the key issues of their inefficiency. These trained IPO personnel are being poached mainly by the private sector enterprises, offering significantly higher remuneration. At the same time, there appears to be 3 times increase in the number of applications filed in the last five years, complicating the situation further.

The silver lining is, despite all these, the performance of IPO quantitatively speaking, is really not as poor. Around 11,000 patents were granted by the IPOs in 2007-08. This number, when translated into average number of patents granted per day, works out to be 50. This figure, when viewed in terms of number of patents granted against the number of applications made, compares reasonably well with the developed nations of the world like, USA and EU. It is worth noting that in those countries the product patent regime is in place, since long.

Indian Patent Act 2005 is believed to be more stringent than the prevailing Patent Acts in the USA or EU. It is good to note that quoting the Department of Industrial Policy and Promotion (DIPP) it has been reported that each Indian Patent Examiner examines about 100 applications per annum against 50 to 80 in the USA and the EU. This is indeed laudable.

Indian Patent Office is currently going through ‘capacity building’ exercises. The efforts being made towards this direction are expected to make the IPOs more efficient, hopefully, in pursuit of excellence.

India has recently been approved as an International Searching and Preliminary Examining Authority under the Patent Cooperation Treaty (PCT). This, in turn, will significantly increase the workload of the IPO.

When we are mentioning about the PCT, perhaps it will not be out of place to say that some section in India argues in favour of the need to include the International Nonproprietary Names (INN) in the title of pharmaceutical patent applications by the IPO. However, as INNs are not required in the title of patent applications under Article 27(1) of the PCT, such a requirement, in my view, could appear to conflict with the PCT.

Thus, it has now become more essential that the Controller General of Patents, Designs and Trade Marks (CGPDTM) tightens the ‘loose knots’ in the IPO system, immediately, to make it efficient and effective.

In this article I shall not go into much debated and discussed, ‘Indian Patent Manual’ issue. I shall only submit the following 15 suggestions towards achieving the above objective:

1. To effectively cope with its growing workload, the Patent office should upgrade its IT facilities and ensure that patent examiners are trained to handle the filing and prosecution of patent applications.

2. Electronic-filing of patent applications has been introduced, but there is no facility of paying the fees online by credit card. This facility should be introduced to make it more convenient for applicants to file patent application online. This will also add speed to the process.

3. Electronic prosecution of patent applications should be introduced to make the patent prosecution paperless and more efficient.

4. To encourage applicants to file applications electronically, incentives such as reduced fees should be offered to applicants who file their applications electronically.

5. The Patent Office has in the past experienced problems in locating and managing physical application files. It is therefore recommended that the Patent Office introduce systems for better management and storage of physical files. Using a system of bar codes on the physical files could be one such system.

6. The Patent Office should digitize all of its physical files so that file histories of each application will be available online.

7. The Indian Patents Database and the Indian Designs Database to be released without further delay.

8. An efficient system to be introduced to ensure timely publication of all patent applications and proceedings that are eligible for publication in the technical journal of the IPO. Currently there is inordinate delay, for example Delhi Patent Office is now publishing applications for 2005

9. Patent applications that are published in the official gazette have minimal information. It is therefore recommended that the official gazette include more details of the applications in order to avoid any frivolous or unnecessary oppositions being filed.

10. The Patent office does not have any centers, which provide assistance to applicants for filing or prosecuting applications. It is therefore recommended that assistance centers should be established to help applicants to file and prosecute applications in India.

11. Clear guidelines to be issued for conducting pre-grant and post grant opposition proceedings. Presently they are being handled in an arbitrary manner

12. In order to avoid any frivolous pre-grant opposition during the prosecution of the application, the Patent Office should introduce a fixed fee that has to be paid to the Patent Office at the time of filing of a pre-grant opposition. This will help to avoid frivolous delays in the grant of the patent.

13. In order to introduce an efficient system of patent prosecution, it is recommended that the Patent Office adjust patent term to compensate patentees for any delay in the grant of the patent that reduces the term of the patent, when such delay is caused solely by the Patent office.

14. Decision making and its communication to all concerned to be made faster at the IPO. A system to be instituted for issuing the operative part of the decision first, followed by details of the decision taken. These should be advertised immediately in the technical journal to close proceedings at the earliest. Delays are leading to extensive delays in the grant of patents even if the proceedings have been concluded (opposition or otherwise) attracting serial and frivolous pre-grant oppositions. Such delays are also preventing the patent applicants to get their grants and are, therefore, unable to initiate infringement proceedings against infringers quickly, defeating the very purpose of the patent and trademark system.

15. The timeline for an application to be taken up for examination to be clearly defined. Currently, there is no time defined for taking up the applications for examination.

It will indeed be great, if the DIPP and the IPO take note of these suggestions and formalize a process within the IPO to address these issues. A growing discontentment in several areas of operation within the IPO is brewing, both in India and abroad. If such discontentment increases further, it may have serious impact on the credibility of the new IPR regime in India.

Will the Government of India want that to happen? I hope not.

By Tapan Ray

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

The heated debate on WHO IMPACT definition of Counterfeit Drugs is now on a ‘pause’ – A time to evaluate the reasons for supporting and opposing it.

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The World Health Organisation (WHO), in December 2008, proposed the following new definition, as prepared by the International Medical Products Anti-Counterfeiting Taskforce (IMPACT):“A medical product is counterfeit when there is a false representation in relation to its identity and/or source. This applies to the product, its container or other packaging or labeling information. Counterfeiting can apply to both branded and generic products. Counterfeits may include products with correct ingredients/components, with wrong ingredients/components, without active ingredients, with incorrect amounts of active ingredients, or with fake packaging.”This definition, indeed, created a furor in India. The Ministry of Health of the Government of India initiated discussions, on this issue, with the stakeholders and by mid-January, 2009 a consensus was arrived at between the Drug Controller General of India (DCGI) and the generic industry on much debated definition of counterfeit drugs. It was reported that the Government had decided to place this definition before the World Health Organisation (WHO) in its next meeting on the subject. The consensus definition, after the above meeting, was reported as follows:

“A medical product (medicine, vaccine, diagnostics and medical implants/devices) is counterfeit when it is deliberately and fraudulently mislabelled with respect to its identity and/or source. Counterfeit can apply to components with wrong ingredients/components without active ingredients, with incorrect amounts of active ingredients, or with fake package”

In end-January 2009, although it was reported that under pressure from the developing countries like, India, WHO has dropped this new definition, it is very likely that the initiative is now just on a ‘pause’ mode.

Let us now try to explore the ‘Eye’ of this stormy debate and its relevance to India. The ‘eye’ of the storm lies mainly within the following 3 key concerns of the opponents of the definition:

1. False representation of identity and source applies not only to labeling but also to the ‘product,
its container or other packaging’
2. The new definition could include Intellectual Property Right (IPR) issues and as a cosequence of
which, Indian generics could run into the risk of being branded as counterfeit
3. Removal of the words ‘fraudulent and deliberate’ from the original definition and replacing them
with ‘false representation’ will shift the burden of proof

In India, the share of voice of those opposing this definition was undoubtedly much more than those who were supporting it. However, the rationale for supporting the definition, in Indian context, appears to be much stronger than opposing it.

While arguing on this point, I am of the view that most of the apprehensions expressed above have been abundantly clarified in the definitions of Misbranded drugs (section 17), and Spurious drugs (Section 17 B) of the Indian Drugs and Cosmetics Act, 1940.

Let us now have a quick look at the Section 17 and Section 17 B of the Drugs and Cosmetics Act to find out whether the WHO IMPACT definition is way off the definitions for Misbranded and Spurious drugs as indicated in the above Act.

“Section 17. Misbranded drugs – For the purposes of this Chapter, a drug shall be deemed to be misbranded –

(a) If it is so coloured, coated, powdered or polished that damage is concealed or if it is made to appear of better or greater therapeutic value than it really is; or

(b) If it is not labelled in the prescribed manner ; or

(c) If its label or container or anything accompanying the drug bears any statement, design or device which makes any false claim for the drug or which is false or misleading in any particular.”

Does Section 17 of the Drugs and Cosmetics Act, 1940 answer the ‘concern 1’ above?

“Section 17B. Spurious drugs – For the purposes of this Chapter, a drug shall be deemed to be spurious

(a) If it is manufactured under a name which belongs to another drug; or

(b) If it is an imitation of, or is a substitute for, another drug or resembles another drug in a manner likely to deceive or bears upon it or upon its label or container the name of another drug unless it is plainly and conspicuously marked so as to reveal its true character and its lack of identity with such other drug; or

(c) If the label or container bears the name of an individual or company purporting to be the manufacturer of the drug, which individual or company is fictitious or does not exist; or

(d) If it has been substituted wholly or in part by another drug or substance; or

(e) If it purports to be the product of a manufacturer of whom it is not truly a product.”

Does Section 17B of the Drugs and Cosmetics, 1940 Act answer the ‘concern 2′ above?

The ‘concern 3’ above deals with shifting the ‘burden of proof’ with replacement of the words ‘fraudulent and deliberate’ by ‘false representation’. Many legal experts opine that this change will only mean that “criminal intent (fraudulent and deliberate) shall be considered during the legal procedures for the purpose of sanctions.”

What could then possibly be the reasons for opposing the revised WHO IMPACT definition of Counterfeit Drugs in India, especially when we have similar definition in place in our own Drugs and cosmetics Act, 1940? Does it make sense for the Government to reinvent the wheel? Who knows?

By Tapan Ray

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

Biosimilar Drugs -A raging scientific debate with mounting global commercial interest

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On December 11, 2008, Reuters reported that two days after Merck & Co. announced a major push into generic versions of biotechnology medicines, Eli Lilly & Co. signaled similar aspirations. This report raised many eyebrows in the global pharmaceutical industry, in the midst of a raging scientific debate on this issue. Be that as it may, many felt that this announcement ushered in the beginning of a new era. An era of intense future competition with Biosimilar drugs in the world market with immense commercial interest.Globally, the scenario for generic versions of biotechnology medicines, which are called Biosimilars, Biogenerics or follow-on Biologics, started heating up when Merck announced that the company expects to have atleast 5 follow-on biologics in the late stage development by 2012. The announcement of both Merck and Eli Lilly surprised many, as the largest pharmaceutical market of the world – the U.S.A is yet to approve the regulatory pathway for generic biologic medicines. In the developed world, European Union (EU) has taken a lead towards this direction by already having a system in place for regulatory approval of Biosimilar drugs in 2003.What then prompts the research based global pharmaceutical companies like Merck and Eli Lilly to step into the arena of Biosimilar medicines? Is it gradual drying up research pipeline together with skyrocketing cost of global R&D initiatives?

The future business potential of Biosimilar medicines:

Currently, over 150 different biologic medicines are available in the Global Pharmaceutical market. However, the low cost Biosimilar drugs are available in just around 11 countries of the world, India being one of them. Supporters of Biosimilar medicines are indeed swelling as time passes by. At present, the key global players are Sandoz (Novartis), Teva, BioPartners, BioGenerix (Ratiopharm) and Bioceuticals (Stada). This market is expected to develop slowly because of regulatory hurdles in the major countries of the world.

Very recently, the EU has approved Sandoz’s (Novartis) Filgrastim (Neupogen brand of Amgen), which is prescribed for the treatment of Neutropenia. With Filgrastim, Sandoz will now have 3 Biosimilar products in its portfolio.

Raging debate on Biosimilar Drugs still continues:

The debate is centered on the argument that like small chemical molecules is it possible to replicate large biological molecule of the innovator? It is widely believed that a protein cannot be absolutely replicated. How could possibly then Biosimilar drugs be considered equivalent to the original product by a regulator and marketing approval be granted to them without full scale clinical trials ignoring safety concerns of the patients? In favor of this argument some refer to the problem of red cell aplasia that affected many patients administering Johnson & Johnson’s Exprex (Epoetin) after only a minor change made in its manufacturing procedure.

Hurdles to cross for future Market entry of Biosimilar Drugs:

Emergence of second generation branded biosimilar products such as PEGylated products Pegasys and PegIntron (peginterferon alpha) and Neulasta (pegfilgrastim), and insulin analogs etc. have the potential to reduce the market size for first generation Biosimilar drugs creating significant entry barrier.

Even otherwise, the barriers to market entry of Biosimilar drugs are much higher than any small molecule generic drug. In the markets within EU, many companies face the challenge of higher development costs for biosimilar drugs because of stringent regulatory requirements and greater lead time for product development. Navigating through such a tough regulatory environment will demand a different type of skill sets from the generic companies not only in areas of clinical trials and pharmacovigilance, but also in areas of manufacturing and marketing. Consequently, the investment needed to take Biosimilar drugs from clinical trials to launch in the developed markets, will indeed be quite significant.

Current Scenario in the U.S:

Recently in the U.S.A, the new, widely reported, biotechnology policy of President Barak Obama has become one of the most closely watched healthcare policy initiatives of the country. It is expected that such a policy will help facilitate regulatory approval process of Biosimilar drugs in the USA by end 2009. This new policy initiative could have a major impact on many biotech companies who will face new generic competition, rather quickly. On the other hand, it will prove to be a boon to the new entrants in this market like, Merck and Eli Lilly, besides the existing ones.

Global Market Potential of Biosimilar Drugs:

The biosimilar drug market in the world is estimated to be around U.S. $ 16 billion by 2011. Currently, off-patent biologic blockbusters including Erythropoietin offer an excellent commercial opportunity in this category of drugs. By 2013, about 10 branded biologics with a total turnover of around U.S. $ 15 billion will go off-patent.

Biosimilar Drugs in India:

Sales of biosimilar drugs in India are estimated to be around U.S. $ 4 billion by 2011.

Biosimilar drugs fall under high growth segment within Indian pharmaceutical Industry. Recombinant vaccines, erythropoietin, recombinant insulin, monoclonal antibody, interferon alpha, granulocyte cell stimulating factor like products are manufactured by a number of domestic biotech companies like Biocon, Panacea Biotech, Wockhardt, Emcure, Shantha Biotech, Bharat Biotech, Serum Institute of India, Dr. Reddy’s, Ranbaxy, etc. The ultimate objective of all these Indian companies, I am sure, will be to get regulatory approval of such products in the EU and then in the U.S. when the time comes.

It is worth mentioning here that to give a fillip to the Biotech Industry in India, the National Biotechnology Board was set up by the Government of India under the Ministry of Science and Technology in 1982 and the Department of Biotechnology (DBT) came into existence in 1986. The DBT now spends around US$ 200 million annually to develop biotech resources in the country and have been making reasonably good progress. The DBT is reported to have undertaken an initiative to prepare regulatory guidelines for Biosimilar Drugs, which is expected to conform to international quality and patients’ safety requirements.

The points to ponder with the Biosimilar Drugs in India:

It is, indeed, quite surprising that in India there is still no separate transparent and published guidelines for regulatory approval of Biosimilar drugs, although the Drug Controller General of India (DCGI) seems to have a different view in this matter. The Drugs and Cosmetics Acts of India have no separate provisions either, for Biosimilar Drugs. In a situation like this, we find that many Biosimilar Drugs are still getting regulatory approval in India.

Currently India supplies 30% by volume of the global requirements of generic drugs both in regulated and non-regulated markets. In the regulated markets like North America and EU, for small molecule generic products, Indian manufacturers conform to the global safety and efficacy standards by getting these products approved by the most stringent regulators of the world like, U.S. FDA, MHRA (Medicines and Healthcare products Regulatory Agency) etc. The very fact that none of the Biosimilar drugs developed in India could get approval in the EU as yet, may well suggest that the stringent regulatory requirements for both efficacy and patients’ safety followed in the EU for Biosimilar drugs, could not be met by the Indian manufacturers, as yet. The question, therefore, comes to my mind whether the Biosimilar drugs manufactured in India conform to international quality and safety standards? If not, who will address the safety concerns of the patients who are or will be administering these medicines?

Such a concern gets vindicated by widely reported serious quality problems, detected by the drug regulatory authorities, at some large and well known Biosimilar drugs manufacturing units in India and also from the condition of some vaccine manufacturing units in our country.

India needs to manufacture the world class Biosimilar drugs conforming to the highest efficacy and patients’ safety standards, just the way Indian pharmaceutical manufacturers have demonstrated with ‘made in India’ generic drugs, the world over. The Indian drug regulatory authority should now take some important initiative with the publication of world class Biosimilar drugs regulatory approval guidelines, may be following the similar process as what we see in the EU.

Currently, experts from India are participating towards preparation of ‘WHO Guidelines’ for Biosimilar Drugs. The progress made towards this direction is yet to be ascertained. Simultaneously, the DBT is reported to have under taken an independent initiative to prepare similar guidelines, the progress of which is also yet to be known.

Before other developed markets open up for Biosimilar drugs, if India can align itself with its own world class regulatory standards for the same, yet another significant export opportunity could be created for the country, competing with the best performers of the world in this category.

Meanwhile, it will only be good to know that like many other initiatives, India has taken one more important initiative to address this important issue, for the sake of humanity. As the existing process of granting regulatory approval for Biosimilar drugs continues in India, the lurking fear towards patients’ safety with such drugs will remain unabated with a large majority of experts in this field.

By Tapan 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.