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Patients’ Safety, regulatory approval of Biosimilar Drugs in India and WHO Biosimilar guidelines

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Biopharmaceutical drugs are broadly defined as:

”Those medicines produced using a living system or genetically modified organism. These drugs are different from traditional chemical medicines in many ways. Size of the molecule is one of the most obvious distinctions: the molecules of a biopharmaceutical medicine are much larger, have far more complex spatial structures and are much more diverse (“heterogeneous”) than the chemical molecules which make up classical drugs.”

The Biosimilar drugs:

Biosimilar drugs are follow-on versions of original biopharmaceutical medicines. Biosimilar medicines are intended to have the same mechanism of action for the same diseases as the original biopharmaceutical drugs.

The term “bio generic” will be misleading for off patent biopharmaceutical products, as no two biopharmaceutical products could possibly be exactly identical. This is mainly because of the following reason:

“Whereas generics of chemistry based medicines are identical in the molecular structure and therefore copies of the original product, based on a strict definition of “sameness”, a corresponding definition cannot be established for biosimilar medicines because of their nature and the complexity of their manufacturing process. Here post-translational modifications are dependent of the host cell and the process.”

Thus the common terminologies used to describe such products when the original products go off-patent are follow-on biologics and biosimilars.

Manufacturing Conditions of biosimilars ultimately define the final product:

Unlike chemical drugs, the manufacturing conditions and the process followed to produce biopharmaceutical drugs largely define the final product and its quality. Any alteration to the manufacturing process may result in a completely different product. Additionally proteins are relatively unstable. Thus additional measures in their storage, formulation and delivery are very critical.

Key concerns with the existing regulatory approval process for Biosimilar drugs:

• Small changes in the manufacturing process of biosimilar drugs could significantly affect the safety and efficacy of the molecule.

• Due to the very nature of a biologic it is virtually impossible for two different manufacturers to manufacture two identical biopharmaceutical drugs. Identical host expression systems, processes and equivalent technologies need to be demonstrated in extensive comparability trials. Thus, as stated above, a ‘bio generic’ cannot exist.

• As against the situation applicable for generics of chemical molecules which can be replicated, biosimilar drugs cannot be replicated. At the most such biopharmaceuticals can be at the most “similar” but not “identical” to the original reference products. To ensure desired efficacy and safety of biosimilar products, these products should only be approved after charting out a formal and well validated regulatory pathway for the biosimilar drugs in India.

• Currently biosimilar drugs are given marketing approval by the regulator without such guidelines for large molecule biological and following just the bioequivalence model as specified in the Schedule Y of the Drugs and Cosmetics Act (D&CA) of India for small molecule chemical entities only, as the current Drugs and cosmetics Acts of India, very unfortunately, do not differentiate between large and small molecular drugs. This could, in turn, endanger patients’ safety with serious medical consequences.

Although, Central Drugs Standard Control Organization (CDSCO) and the Drugs Controller General of India (DCGI) are responsible for approvals of the new drug applications, health being a state subject, respective state regulatory authorities are responsible for granting manufacturing license to the pharmaceutical manufacturers.

Pharmaceutical manufacturers setting up facilities in the states, where regulatory oversight and incidences of weaker enforcement are common, will be able to market their products, including biosimilars, across the country. It is alleged that there are hardly any regulatory control over the mistakes or offences committed by the State Drug authorities who permit manufacture of drugs even unapproved by the DCGI. The existing issue of mushrooming of various irrational Fixed Dose Combinations (FDC) products in India will vindicate this point.

The Government’s response to this public health concern:

Express Pharma in its June 30, 2009 edition reported Dr M K Bhan, Secretary, Government of India, DBT, saying, “The first question is do we have written guidelines available to people? Currently, we have a large committee of about 30 people in the Review Committee on Genetic Manipulation (RCGM) which frequently discusses the current FDA and EMEA guidelines and makes sure that it is updated as per the guidelines in case by case approvals.”

He acknowledged, to make sure that the product is identical or original is harder for biological than for chemical entities and said, “So the next question is, what is the degree of difficulty you create to be sure that some of the products in the in vitro laboratories and the strength of the biomolecule, are to be characterized in details, and the other side is how expensive should the chemical evaluation be? At this moment, RCGM is seeing the issues and is in touch with both the FDA and the EMEA, and they are taking case by case decisions while trying to standardize the minimum information that is required to show how companies have characterized their products.”

“If we ask a big established company on this issue they will tell us to be strict, whereas a smaller company will suggest otherwise. What we are trying to do is being very scientific and come to a conclusion,” reported Express Pharma quoting Dr. Bhan.

The current practice:

Much water has flown down the bridge since the above interview was published. Nothing much has changed on ground regarding this critical issue, thus far. The industry sources allege that even today regulatory approval of biosimilar drugs (large molecules) are granted based on Phase III clinical trials, as specified in the schedule Y of the Drugs and Cosmetics Acts for the small molecules (chemicals) and that too conducted mostly on just 40 to 45 patients. At times the number of patients studied is even lesser. Immunogenicity study, which is so important for biosimilar drugs is, more often than not, overlooked. This could seriously compromise patients’ safety with such category of drugs.

Conclusion:

It is, indeed, quite surprising that in our country there is still no separate transparent and published guidelines for regulatory approval of Biosimilar drugs even when the World Health Organization (WHO) has come out with the same and India had actively participated in that exercise.
The question, therefore, comes to my mind whether the Biosimilar drugs manufactured in India would conform to international quality and safety standards, like in the U.K or what has been recently announced in the USA? If not, who will address the safety concerns of the patients administering these life saving medicines?

Such a concern gets vindicated by widely reported serious quality problems, detected by the drugs regulatory authorities, at some large and well known Biosimilar drug’s manufacturing units in India, in not too distant past and also from the condition of some vaccine manufacturing units in our country. The recent example of WHO cancelling the pre-qualification of ‘Shan 5’ (Shanta Biotech) vaccines for quality related problems, perhaps may help opening the eyes of our regulators, on the related patients’ safety issues arising out of regulatory laxity.

This issue assumes even greater importance considering the very recent development of the Department of Biotechnology (DBT) unfolding an interesting scheme to encourage development of biosimialr dugs in India by offering financial support to the domestic pharmaceutical and biopharmaceutical industry.

The proposed new regulatory pathway for the marketing approval of Biosimilar drugs in India will immensely help paving the way for the Biopharmaceuticals drugs manufacturers in India to adequately prepare themselves to grab a significant share of the fast emerging Biosimilar drugs markets, particularly, in Europe and the USA, in the years to come.

The Ministry of Health and the Department of Biotechnology of the Government of India should, therefore, urgently and jointly consider amending the Drugs & Cosmetics Acts of India accordingly and establish robust regulatory guidelines for marketing approval of biosimilar drugs in the country, acknowledging the widespread concern for patients’ safety.

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.

 

Absence of appropriate and functional ‘Cold Chain’ infrastructure dedicated to pharmaceutical and bio-pharmaceutical products at the Indian airports and seaports – A serious concern

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Drugs are complex entities and many of these are temperature sensitive in nature. This entails them requiring precise and continuous temperature conditions in transit in order to retain their potency and resultant efficacy. Many lifesaving drugs including biotech products and vaccines fall under such category. Any break in the cold chain process for such drugs can lead to immediate denaturing or deterioration in their quality parameters. It is imperative that a careful consideration is given by all concerned including government agencies at the sea port, airports while providing storage space at their warehouses for such drugs.
Current bottlenecks: Currently in India there are bottlenecks at the Airports that include authorities not being able to assure cold room space despite getting advance notices from the companies about the possible unloading of large consignments of temperature sensitive products. Some of the other gaps include improper training and refresher courses for some of the handling staff who handles such products at the Airport. Storage of Pharmaceutical products along with meat and food products is against the GMP norms.

Lack of special temperature control:

Cold Chain Medicines require special temperature controlled Cold storage. There are two commonly recommended temperatures specified on labels on cold chain products:

1. Products requiring temperature between 2 to 8 degree centigrade
2. Products requiring temperature around -10 to -20 degree centigrade

Cold Chain is an uninterrupted series of storage and distribution activities which maintains required temperature range of 2 to 8 degree centigrade or -10 to -20 degree centigrade as per product requirement.

Ensuring the right product quality:

Proper Cold Chain Management of pharmaceuticals will ensure that the right quality of such products is maintained not only during storage but during transportation also to meet right regulatory specifications. There is a greater focus and stringent regulatory guidelines and standards today in the developed markets around the world on strict adherence to right storage and transportation process for cold chain sensitive pharmaceuticals.

It should be kept in mind always that Cold Chain products are mostly sensitive biological substances that can become less effective or lose potency if not properly stored.
Some examples:

Products requiring 2 to 8 degree storage will not be effective if:

i. They are frozen or stored below 2 degree centigrade
ii. Exposed to temperatures above 8 degree centigrade
iii. Exposed to direct sunlight or fluorescent light

The loss of potency is cumulative and irreversible. If products are exposed to conditions outside the established range, the quality may be adversely affected, reducing their assigned shelf life, diminishing their effectiveness or making them ineffective. The exposed product may look the same – the loss of potency may not be visible.

Quality of storage is critical:

Quality of storage and handling of Cold Chain Pharmaceutical products at Airports and Seaports in the course of Export from or Import into India requires special care and attention. Since multiple products are stored and handled at Seaports/ Airports, personnel may not be able to appreciate the special need for Cold Chain Pharmaceuticals Storage & Handling. Thus, there should be Standard Operating Procedures (SOPs) for storage and handling of pharmaceuticals laid down by the Port Management authorities, so that the personnel handling pharmaceuticals strictly adhere to the pre-set norms.

Rapidly growing demand of cold-Chain facilities:

Pharmaceutical Products for which efficient Cold Chain facilities are required are rapidly growing in numbers. In its movement across the supply chain from the manufacturers to the patient, the medicines are handled and stored by various stakeholders like transporters, Airports, Sea ports, Distributors, Stockists, Retailers etc. Since the storage and handling of Cold Chain Pharmaceutical Products are unique, an uninterrupted Cold Chain is to be maintained in the entire supply chain network without any discontinuity, even for a short while, so that medicinal products of high quality reach the patients, always. Thus it is very important for all concerned stakeholders to ensure maintenance of proper Cold Chain facility.

Currently no ‘Pharma Zones’ in India:

At present there are no ‘Pharma Zones’ in India. However, Mumbai International Airport Private Limited (MIAL) has created 4 new cold rooms for pharmaceuticals and Delhi International Airports Limited (DIAL) has reported to have assured that the new Cargo Terminal, which is expected to be commissioned later in the year, will have around 4000 square metres of additional cold room capacity compared to the current cold room capacity of 400 square metres. Similarly, MIAL has agreed for a dedicated Cold Room facility for Pharmaceutical Products in the proposed new set–up.

The serious Concern continues:

Poor cold room storage facility at the country’s major airports and seaports is indeed an ongoing serious concern.

Unfortunately, even today, pharmaceuticals and bio-pharmaceuticals are, by and large, treated like just any other common product at our ports. It is high time, the authorities should note that due to inadequate storage and handling of these lifesaving drugs at ports, high dwell time and dispersed multiple authorities from whom clearances are required, the quality of these products may get adversely affected exposing the user patients at a great risk. The absence of a temperature monitoring mechanism in such facilities adds to the concern.

Recent Plan of “Pharma Zones” in India:

The DCGI has planned a separate dedicated controlled environment – ‘Pharma Zone’, within the cargo premises at Airports and Sea Ports for proper storage of Pharmaceutical products in line with Good Manufacturing Practices and Good Distribution Practices so as to assure the quality, safety and efficacy of Pharma products, which are to be either imported or exported.

Need for outsourcing Cold Chain services:

In the developed markets of the world there are private cold chain storage and third party logistics providers to offer contract logistics and storage services especially to cater to the growing demands Biopharmaceutical segment, which is the fastest growing manufacturing sector within global pharmaceutical industry.

Thus it is expected that spend of the Biopharmaceutical companies towards outsourcing of cold chain facilities will grow by over 10 – 15% for the next three to five years in the developed markets. India being the second largest producers of Biopharmaceuticals after China, similar opportunities exist in the country.

In India some renowned international courier companies like DHL and World Courier have been reported to have developed an efficient cold-chain management process, especially for the pharmaceutical companies to maintain the cold chain in their logistics network.

Conclusion:

An efficient cold chain infrastructure and its efficient management within the country will help immensely to Indian domestic pharmaceutical companies as they are exploring more and more opportunities to export pharmaceuticals in the global market. To achieve this objective modern cold chain warehouses, their efficient management as per regulatory guidelines will play a key role in ensuring right product quality standard.

Over a period of time cold-chain management practices of global standards will be required to achieve this goal. Currently for both import and export of cold-chain sensitive pharmaceuticals, as indicated, before, this area in particular poses to be one of the key challenges encountered by the industry to maintain high product quality during shipment. Individual pharmaceutical companies like Eli Lilly, India have their own vehicles equipped with cold-chain management systems for transportation of their cold chain sensitive products.

Greater initiative by the DCGI in this area in collaboration with the pharmaceutical industry as a whole, sooner, is absolutely essential, for the patients’ sake.

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.

George Washington University Law School’s “The India Project” – Arguments and Counter Arguments

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Recently we witnessed yet another huge controversy on the ‘IP Summit’ organized by the George Washington University Law School (GWULS), USA. It was alleged that this summit supported by law firms, some pharmaceutical companies and others, was intended to influence the participating sitting judges on the pharmaceutical patent related cases currently being fought in various courts in India.

The Arguments:

However, the GWULS reiterated that this summit is intended to help India to build capacity in the IP law of the country. GWULS states the following in its magazine of winter 2009:

“From New Delhi to Bangalore, GW Law is building bridges of understanding between the United States and Indian legal communities through its fast-growing India Project, a collaborative enterprise fostering broad-based relationships and heightened international dialogue on issues of mutual concern”.

During their recent visit to India, in an announcement to the media GWULS explained the following:

“We have contributed to education by heightening the dialogue and understanding between India and the U.S. on IP law. We have done so in a collaborative way, as we have much to learn from our Indian counterparts. For example, the new Indian patent law, enacted in 2005, involves a range of issues that require clarification, and the project has resulted in a two-way discussion of real importance to the future of IP protection in India and across the world. Is the new law in compliance with Indian constitutional standards? How does it compare with U.S. law in addressing issues that arise during the processing of a patent application? (With regard to this question we recently held educational sessions with patent examiners at various Indian patent offices). Is it consistent with international standards? These are just some of the issues that attract the attention of people associated with GW’s India Project.”

The Counter Arguments:

The other group strongly counter argues highlighting that Indian judiciary and lawmakers have a long history of dealing with the patent laws since 1911. Although in between from 1970 to 2004, the situation slightly changed with the abolition of ‘Pharmaceutical Product Patent’, the re-introduction of the same effective January 1, 2005, does not call for an ‘un-called for’ indirect intervention in the judicial process of the country by law schools located beyond the shores of India.

This group feels that GWULS indirectly casts aspersions on the legal standard of the country and the competence of Indian judiciary, which needs to be protested, unequivocally. Moreover, the group argues, “even if IP awareness had to be taken to the people once again after the 2005 amendment, why did GWULS mount such a major campaign here?”

So far the Patent Law is concerned; this group accepts that our Patent Attorneys and particularly those lawyers who will argue the cases in front of the judges must possess impeccable knowledge in the nuances of patent law with all its nitty- gritty. Thus lawyers rather than judges should regularly update their knowledge on the details of patent related issues.

Laws are by and large country specific, with an exception probably of international law. After hearing the arguments of respective lawyers, this group feels that the judge will interpret the law of the land and give his/her judgment accordingly, as happens in any other comparable sphere of law. Just as for laws related to ‘terrorist’ act, India will not require its judges to be trained by other countries, this group reiterates, the same argument holds good for patent law, as well.

The Times of India (March 29, 2010), a leading daily of the country, reported the following in a news item titled, “’Vested interests behind discussion on patents”:

“Several civil society groups have come together to question the commerce and industry ministry’s alleged complicity in allowing meetings and interactions undermining India’s legal position on intellectual property (IP). These interactions are being organized annually with Indian judges and policy makers by the George Washington University Law School (GW Law), under its India Project, with funding from multinational pharmaceutical companies, industry associations and corporate law firms”.

Conclusion:

Be that as it may, the arguments from either side do not seem to be unbiased without any vested interests and are not convincing enough. In a globalized economy, from such comments it appears that the one group is feeling that Indian legal system is inefficient, if not incompetent, to deal with its patent related cases involving global pharmaceutical companies. On the other side, the local voice seems to be afraid of a ‘foreign hand’ intruding into the judicial space of India, which in my view is stretching the imagination far too much.

Overall, Indian Judiciary has a long tradition of keeping the institution robust enough and free from any external influences, whatsoever, notwithstanding GWULS coming to India almost every year, since around 2005.

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.

To avoid “Heparin” like tragedy in future, a robust “supply chain integrity and security” system is of critical importance

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Globally the pharmaceutical industry is going through a metamorphosis. The types of changes that are taking place today globally, perhaps has no precedence..

The key drivers of these changes are mainly the following:

1. A large number of patent expiration hugely impacting the top-line growth
2. Research pipeline is drying-up
3. The cost of bringing a new molecule from the ‘mind to market’ has now touched around U.S$ 1.75 billion
4. Regulatory requirement to get the marketing approval is getting more and more stringent, basically for patients’ safety, making clinical development more expensive and time consuming
5. Cost containment measures of various governments around the world is putting an immense pressure on product price, adversely affecting the profit margin

Strategic measures of enormous significance:

All these are triggering other sets of consequential events of enormous significance. Among those following key corporate strategic measures indeed stand out:

1. More mergers and acquisitions of various sizes and scales to achieve both revenue and cost synergy, with new products and newer types of resources
2. Transformation in the fundamental operating models, e.g. R&D focused companies like Pfizer, GSK, sanofi aventis are extending their business interest to the pharmaceutical generics space
3. Increasing globalization and greater focus on the emerging markets of the world like, Brazil, Russia, India, China, Turkey, Mexico
4. Growing emphasis on partnering, as we see in India, like for example, between Pfizer and Aurobindo, Claris, GSK with Dr. Reddy’s Lab (DRL)
5. Global outsourcing in the ‘Contract Research and Manufacturing Services (CRAMs)’’space, mainly to rationalize costs and deliver the bottom lines, when the top line is under immense pressure.

Demand on all round effectiveness of the “Supply Chain”:
The changing requirements of all types, in sales and marketing, manufacturing and research and development have created a challenging, if not a rather volatile operating environment. In this situation supply chain will increasingly play a key role to ensure that the right product is available at the right place, at the right time, at a right price and following the right process…always.

Outsourcing initiative is not just about cost:
There is at the same time, a new trend emerging for increased outsourcing initiative, especially from countries like India and China. This initiative, which in turn is in the process of making these two countries the key global outsourcing hubs, is definitely not all due to just cost advantages. It encompasses increased integrated value proposition for the customers. Cost is just one of the key factors, others being quality, speed and suppliers’ reliability. Nothing in this value chain is mutually exclusive. Supply Chain will need to go through a set of complex algorithms to strike a right balance between all these vital parameters.

Robust “supply chain integrity and security’ will assume critical importance:
In the days to come by one of the greatest challenges in supply chain management will be to improve the supply chain integrity and security.
An appropriate definition of integrity for supply chains is:

“the requirement that the system performs its intended function in an unimpaired manner, free from deliberate or inadvertent manipulation.”
A safe and secure supply chain is definitely not a new requirement. However, in the list of priority of importance, it has now come up significantly compared to what it was just a few years back.

Are the pharmaceutical companies aligned on this issue?
Though the issue of improving the supply chain integrity and security has now assumed global importance, unfortunately, any uniformity in national regulatory requirements for this vital parameter is glaringly missing. Such a lack of regulatory uniformity clearly highlights that the pharmaceutical companies, engaged in manufacturing, are still not aligned with each other on what will be the right way to ensure absolute integrity, safety and security in the supply chain operating process to guarantee patients’ safety.

RFID is just one component of supply chain integrity:
Globally many Pharmaceutical Companies are getting engaged in improving supply chain integrity, security and patient safety with the introduction RFID. This, as many may know, is an inventory tracking system for improved product traceability, which in turn extends some protection to its customers with genuine products from the genuine pharmaceutical manufacturers. It is worth noting that RFID is just one component of overall patients’ safety initiative.

Suppliers’ qualification process through stringent ‘supplier audit’ is of critical importance:
Along with high tech measures like RFID, to improve supply chain integrity, I reckon, pharmaceutical companies will need to further enhance their respective supplier qualification process.
The process of supplier audits should include all important and critical areas of manufacturing, testing and quality, related to each individual product. Only a stringent supplier qualification process will be able to guarantee integrity, safety and the quality of products from the suppliers.

Heparin tragedy, where the supply chain integrity was grossly violated:
Before I conclude, I would like reinforce my recommendation with the example of Heparin tragedy where the supply chain integrity was violated and seriously challenged thereafter.

In the beginning of 2008, there were media reports on serious adverse drug events, some even fatal, with Heparin, a highly-sulfated glycosaminoglycan of Baxter International. Heparin is widely used as an injectable anticoagulant. Baxter voluntarily recalled almost all their Heparin products in the U.S. Around 80 people died from contaminated Heparin products in the U.S. The US FDA reported that such contaminated Heparin was detected from at least 12 other countries.

A joint investigation conducted by Baxter and the US FDA ascertained that the Heparin used in batches associated with the serious adverse drug events was contaminated with over sulfated chondroitin sulfate (OSCS). It was reported that his Heparin was supplied to Baxter by Scientific Protein Laboratories, Changzhou, China.

The cost of OSCS is just a fraction of the ingredient used in Heparin. Being driven by the criminal profiteering motive the manufacturers in Changzhou, China had reportedly used OSCS for highly-sulfated glycosaminoglycan as the former could not be detected by the pharmacopeia test in use, until 2008. This is because OSCS mimics Heparin in the pharmacopeia test and thus could not be detected in the case in question.
Post this criminal event, at present, all over the world more specific pharmacopeia test methods have been adopted for Heparin.

Conclusion:
Let us all ensure that such a tragedy does not get repeated in future due to a breach in the supply chain integrity, anywhere in the world…for the patients’ sake.
In today’s deliberations I am sure this issue will be touched upon to ponder over the possible implementable steps to address such future threats effectively.

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.

Bt Bringal…health and food safety…agricultural independence…biodiversity, are all intertwined

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Bacillus Thuringiensis (Bt) Brinjal has now become a subject of intensive debate for various important reasons. Bt Bringal is a genetically modified strain of Brinjal, developed by the premier seed company in India Mahyco in collaboration with the American major Monsanto. The main claim of such seed varieties is improving yield by protecting the crop from the pests.
The key concerns related to products like Bt Brinjals are in the following areas:

1. Health and Food Safety

2. Dependence on overseas companies year after year for agricultural products

3. Compromising ‘biodiversity’

4. Effectiveness of Bt products

Health and Food Safety:

The main focus of the debate revolves round the health and food safety concerns with such biotech food products. Environmentalists point out that the genetically modified foods while fed on rats have already shown fatal kidney and lung disorders.

Gilles-Eric Seralini, a French scientist has opined that the tests conducted by Mahyco for Bt Brinjal are unsustainable and would raise very serious health and food safety concerns.

Adverse safety results with Bt cotton, like respiratory tract related problems, skin allergy, immunological disorders etc., from many countries of the world further aggravate the health and food safety concerns with Bt Brinjal. Many experts have opined, as mentioned above, that such disorders could lead to even death with long term use of these products. It will perhaps be imprudent on the part of the civil society to take such ‘public health’ concerns lightly.

Alleged bias by GEAC:

Besides, health and food safety concerns many activists feel that the initial approval of Bt Bringal by the Genetic Engineering Approval Committee (GEAC) raises a suspicion of bias towards overseas Bt seed manufacturing companies.

Could it lead to Agriculture dependence on overseas companies?

Another important point that needs to be deliberated by all concerned is the impact of such technology producing ‘terminator gene’. Many apprehend that such a move by India could pose a threat to the agriculture of the country over a period of time, with Indian farmers buying these costlier varieties of seeds from the overseas companies year after year and being dependent on them for the same.

Since India does not recognize patents on life-forms, farmers will be required to pay a type of royalty to the manufacturer, usually known as ‘Trait Fee’. Such fees used to be levied for Bt cotton seeds. However, on this type of fees, in response to a petition filed by farmers in Andhra Pradesh against an international manufacturer and supplier, Monopolies and Restrictive Trade Practices Commission (MRTPC) gave its ruling in 2006, which is as follows:

“The trait fee being charged by the respondent not only imposes unjustified costs on the farmers by way of manipulation of prices but is also unreasonable in view of lack of competition.”

Many experts feel that such anti-competitive practices involving food products could lead to a different type of dependence on the overseas suppliers of Bt seeds, even if such products are found safe.

Further, concerns related to the control of such seeds and the lack of investment in the public sector for biotech research in this area should be urgently addressed.

The concern related to ‘Biodiversity’:

There is also another important concern related to ‘Biodiversity’. It has been reported that around 2500 varieties of Brinjal are available in India. Brinjal being a plant resulting from cross pollination, entry of Bt.Bringal could lead to genetic contamination affecting existence of many such locally grown varieties raising the contentious issue of ‘biodiversity’.

In the context of Bt Bringal, Dr. Manmohan Singh, the Prime Minister of India has recently issued a statement, as follows:

“It was agreed that biotechnology is an important option for higher agricultural productivity and ensuring food security. At the same time, we must ensure that it has no adverse effects on human and animal health and bio-diversity.”

“Keeping this in mind, the government will soon be moving forward in setting up a National Biotechnology Regulatory Authority which will inspire confidence and stimulate public and private investment in biotechnology.”

If ‘Food security’ is the issue, why choose Bt Brinjal?

However, if Bt products will help the nation to address the ‘food security’ issue, the question that will logically emerge, “why then Bt Brinjal?”

As far as I know, India is one of the largest producers of Brinjal in the world with so many varieties of it and there is no shortage of Brinjal in the country either. Thus ‘Food Security’ could hardly be an issue, at least in this case.

Effectiveness of Bt products:

We all have read the media reports related to many incidences of mass suicides by Indian farmers due to crop failures with Bt Cotton. The effectiveness claimed by the manufacturers of Bt cotton is now shrouded with doubts. The following report from ‘The Times of India’ dated March 7, 2010 vindicates this point:

“Bt cotton failed to thwart pests in Gujarat”. Monsanto also concedes, “During field monitoring in 2009, the Bt cotton variety used in four Gujarat districts – Amreli, Bhavnagar, Junagadh and Rajkot was found to attract the pink bollworm, a major pest that attacks cotton plantations”.

Such reports further strengthen the argument of the Environment Minister of India, Mr. Jairam Ramesh that Bt seed varieties should be evaluated with utmost care and precision before nationwide operationalization, for the reasons mentioned above.

Conclusion:

Be that as it may, I believe that uncontrolled entry of Bt products should NOT be encouraged in India without:

- Proper knowledge of their serious adverse effects on human and animal health on long term consumption

- Having scientific proof on their long term effectiveness

- Protecting agricultural independence of the country

- Encouraging indigenous biotech research in this field

- Satisfactorily addressing the concern related to ‘biodiversity’ of the nation.

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 ‘Climate Change’ and its impact on ‘Public health’: is there anything in it that we can do ourselves?

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The Lancet in its December 5, 12 and 19, 2009 issues published the following interesting studies:A. Public health benefits of strategies to reduce greenhouse-gas emissions: household energy
B. Public health benefits of strategies to reduce greenhouse-gas emissions: urban land transport
C. Public health benefits of strategies to reduce greenhouse-gas emissions: low-carbon electricity generation
D. Public health benefits of strategies to reduce greenhouse-gas emissions: food and agriculture
E. Public health benefits of strategies to reduce greenhouse-gas emissions: health implications of short-lived greenhouse pollutants
F. Public health benefits of strategies to reduce greenhouse-gas emissions: overview and implications for policy makersThe findings of these studies clearly indicate that climate change is intimately linked to the global public health.

The key highlights:

1. In rural households (particularly in a developing country like India), if low carbon emission cooking stoves are used, the incidence of acute respiratory tract infections, chronic respiratory illnesses and even cardiac disorders can be brought down significantly.

2. For city transportation, increased usage of more fuel efficient or even hybrid vehicle will not be just enough to effectively reduce the greenhouse effect and improve public health. To achieve this some fundamental change in our life style and urban pedestrian infrastructure will be necessary rather than building more and more flyovers. Encouragement of ‘foot- and pedal-powered mobility’ could prove to be more useful for specific public health benefits, which could come in terms of reductions of cardiovascular disease by around 20%, in addition to reduced incidence of depression, dementia and diabetes.

3. The civil society would require putting more efforts to burn less of fossil fuels and increase in production of cleaner energy through solar and wind power to substantially improve the quality of air that we breathe.

4. In areas of agriculture and food production, initiatives like lesser usage of fossil fuel, innovative usage of manure, reduced livestock production and intensive programs of carbon capture could significantly lower the impact of climate change on public health.

“A 30% fall in the adult consumption of saturated fat from animal sources would reduce heart disease in the population by around 15% in the UK and by 16% in the city of São Paulo, Brazil. If the study had used additional health outcomes such as obesity and diet-related cancers, the health gains might have been even more substantial”, the Lancet highlighted.

The studies further indicated, “Recognition that mitigation strategies can have substantial benefits for both health and climate protection offers the possibilities of policy choices that are potentially both more cost effective and socially attractive than are those that address these priorities independently.”

India perspective:

‘Climatico national first assessment report’ of March 8, 2009 makes important observations on the general trends between national policies to understand how climate policy is developing in the major greenhouse gas-emitting countries like, UK, EU, France, Germany, Canada, USA, Mexico, India, China, Indonesia, Japan, Australia.

Key findings of the report are as follows:

1. “A significant funding gap is appearing for adaptation, as developing country lack domestic resources and capacity and also appears unable to rely on international transfer mechanisms to meet their financing needs. It is at present unclear how adaptation will be effectively financed”.

2. “The financial crisis is allowing a mainstreaming of climate change into recovery packages, accelerating otherwise difficult shifts to low carbon growth in developed countries. However, the same crisis is causing a major slow down in projects that do not contribute to financial recovery”.

It has been reported that the above observations have prompted the Government of India to seek global cooperation both in terms of funding and technology to facilitate the capacity building exercise in these areas to effectively address all issues arising out of ‘climate change’.

Conclusion:

It has now been well accepted by the policy makers in India that there is a dire need to effectively address the critical public health issues related to global ‘climate change’. Based on the findings, as published in ‘The Lancet’, the Government of India should take appropriate collaborative measures to neutralize the adverse impact of ‘climate change’ on ‘public health’, sooner the better.

At the same time, let me hasten to add that there are many other measures, as stated earlier, which we all can take ourselves as a civil society in general and a responsible citizen in particular, to prevent this impending crisis.

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.

Amendment of ‘Professional Conduct, Etiquette and Ethics’ Regulations for the Doctors by the MCI could dramatically change the Pharmaceutical Marketing Practices in India, hereafter.

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As reported in the media, the notification of the Medical Council of India (MCI) dated December 10, 2009 amending the “Indian Medical Council (Professional Conduct, Etiquette and Ethics), Regulations 2002″ has been welcomed by the medical profession.
Areas of stricter regulations:

The notification specifies stricter regulations for doctors in the following areas, in their relationship with the ‘pharmaceutical and allied health sector industry’:

1. Gifts
2. Travel facilities
3. Hospitality
4. Cash or Monetary grants
5. Medical Research
6. Maintaining Professional Autonomy
7. Affiliation
8. Endorsement

These guidelines have come into force with effect from December 14, 2009.

Possible implications:

With this new and amended regulation, the MCI has almost imposed a ban on the doctors from receiving gifts of any kind, in addition to hospitality and travel facilities from the pharmaceutical and allied health sector industries in India.

Moreover, for all research projects funded by the pharmaceutical industry and undertaken by the medical profession, prior approval from the appropriate authorities for the same will be essential, in addition to the ethics committee.

Although maintaining a cordial and professional relationship between the pharmaceutical industry and the doctors is very important, such relationship now should no way compromise the professional autonomy of the medical profession and a medical institution, directly or indirectly.

It also appears that the common practices of participating in private, routine and more of brand marketing oriented clinical trials could possibly be jettisoned as a pharmaceutical strategy input.

The new MCI regulations is much stricter:

Since the new amended regulations of the MCI are much stricter than the existing codes of marketing practices of the pharmaceutical industry associations, there could be an emerging disconnect between these two practices till such time a clearer picture emerges after due deliberations by all concerned, in this matter.

It is also interesting to note, how would the pre December 14, 2009 commitments for the post December 14, 2009 period, of both the medical profession and the industry related to such regulated practices, be handled by the MCI, in future.

Conclusion:

Be that as it may, the new ball game of pharmaceutical marketing strategies and practices will no longer be driven by more of a ‘deep pocket’ syndrome and less of ‘cerebral power’, by all concerned.

If this happens, I shall not be surprised to witness a dramatic change in the prescription share of various companies in the next 3 to 5 years thereby impacting the ranking of these companies in the Indian pharmaceutical industry league table.

Thus, the name of the game in the pharmaceutical marketing space, in not too distant future, will be “generation and effective implementation of innovative ideas”.

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.

India as a global pharmaceutical outsourcing hub: Some key advantages and the areas of improvement.

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All over the world, pharmaceutical research and development pipelines are gradually getting dried up. Lesser and lesser blockbuster drugs are now coming up from the ‘mind to the market’. Currently the average annual turnover of over 90% of patented drugs is around US $150 million each. At the same time regulatory requirements to obtain the marketing approval are becoming more and more stringent, spiralling the R&D costs of the innovator companies very significantly.
The name of the game:

In today’s perspective of the global pharmaceutical industry, ‘competitive efficiency’ in speed of implementation of various projects and optimizing costs of operations, can be easily considered as the ‘name of the game’.
Such competitive efficiency is as much essential for a relatively quick turnaround from ‘the mind to market’ of New Chemical Entities (NCEs) or New Molecular Entities (NMEs), to reducing manufacturing costs through various outsourcing opportunities and/or innovative application of technology and spreading geographical marketing operational network.

Towards this direction, ‘Business Process Outsourcing’ in R&D, manufacturing, clinical trials etc. is now gradually emerging as one of the most critical ways to achieve this important objective. It is expected that gradually outsourcing of specialized manufacturing like, biopharmaceutical and sterile manufacturing and specialized processes like, improvements in catalyst activity, will be gaining grounds.

India is emerging as a potential outsourcing hub:

India is fast emerging as a key player in the outsourcing business of the global companies, with its high quality facilities, world class services at a very competitive cost, in various areas of pharmaceutical business operations. India is not only a vibrant democracy, it has now a good Intellectual Property Rights (IPR) system in place and offers very significant cost advantages both in contract research and contract manufacturing space, as compared to many other countries.

Many Indian pharmaceutical companies are scaling up their capacities and investing in establishing more number of world class facilities. Currently India has over 100 pharmaceutical plants approved by the US foods and drugs administration. Incidentally this number is the largest outside the USA.

The key advantages:

India with its total pharmaceutical market size of around US $ 14 billion offers both value and cost arbitrage, which are as follows:

1. Familiarity with the regulatory environment and requirements of the developed markets

2. Extensive global operations in the generics business

3. World class facilities

4. Lower employee wages

5. Large number of young workforce

6. High capacity of skilled labour (350,000 engineers/year)

7. High quality of engineers, process chemists

8. Low communication barriers due to high levels of English

9. Speed of operation

10. Cost effective IT infrastructure, facilitating all key business processes

Contract research investment strategies of the global companies in India:

Most common investment strategy in the collaborative arrangement is risk-sharing outsourcing co-development of a NCE/NME. For example, Johnson & Johnson (J&J) signed an outsourcing agreement with Advenus Therapeutics of India in November 2008 with a contract value of US $ 247 million including milestone and royalty payments in the areas of inflammation and metabolic diseases. In this contract Advinus will be responsible for development upto ‘the proof of concept’ (Phase II a) and then J&J will take over till commercialization of the molecule.

Areas of improvements:

1. Biotech contract research as a whole

2. Economies of scale in manufacturing products like, recombinant proteins, small interfering Ribonucleic Acid (siRNAs), vaccines, antibodies etc.

3. Fully integrated service offerings in contract research and contract manufacturing

4. In genomics and proteomics research

5. Pre-clinical research

In all these important areas our neighbouring country China seems to score over India

Conclusion:

Availability of world class contract research and manufacturing facilities and the ability of the domestic pharmaceutical industry to deliver the agreed deliverables in a cost-efficient manner with desired operational speed, make India a potential contract research and manufacturing hub of the world.

India can expect to compete effectively in these areas with any other countries, including China, provided the improvement areas, as indicated above, are addressed with equal speed of action and with a missionary zeal.

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.