Notes

Don’t miss the internal net benefit to the India CP

Lots of pharma defense in the Abelkop / Fitzmier Deep Sea Exploration neg, including (1) a good “tropical rainforest solves bioprospecting” card and (2) lots of disease impact defense.

Disease Reps K from BRAG lab?

Status Quo Solves

Ocean Bioprospecting Now

There is massive ocean bioprospecting nowNobel 2009 (Justin, writer for Audobon Magazine, "Up for Grabs," archive.audubonmagazine.org/webexclusives/bioprospecting-webExclusives.html, ADL)Biotech companies don’t necessarily have to rely on biologists and oceanographers to gather material that will benefit commercial enterprises. For example, ZyGEM, a New Zealand-based biotech corporation,

and Unilever, a European corporation that markets health and hygiene products, have begun sending their own bioprospectors to the bottom of the globe. Indeed, there are more than 250 bioprospecting projects currently under way in Antarctica, according to data collected by United Nations University —and those don’t include voyages like Barnes’s, which are aimed at pure research but whose finds could later end up in the hands of bioprospectors. (Great Britain isn’t the only country trawling. Last year the Japanese surveyed the Cosmonaut Sea, and the Germans probed the Weddell Sea. A team of Italians and New Zealanders investigated the Ross Sea.) Many bioprospecting projects in Antarctica are global efforts that jibe with the communal spirit of the ATS, says Alan Hemmings, a senior fellow in Antarctica governance and environmental policy at the University of Canterbury, New Zealand. This is illustrated in the case of Deschampsia antarctica, one of two species of flowering plants in Antarctica and the only type of grass found on the continent. The genus occurs around the world, but several nations have shown interest in the Antarctic variety, which grows despite extreme cold and prolonged darkness. Genes from this species could help enhance the productivity of grasses that grow in other extreme environments, such as high in the Andes or Rocky Mountains, thereby providing food for cattle pastured in those areas. This past April

bioprospecting received significant attention at the annual ATS meeting, in Baltimore. The topic was the subject of the most research paper submissions—even more than tourism, says Rogan-Finnemore. The ATS member nations agreed that bioprospecting was an important issue that demanded more discussion, and they will hold meetings throughout the year on the topic in order to move the dialogue along before the next ATS meeting. “The critical thing is there was agreement that Antarctic Treaty parties should continue to discuss bioprospecting,” says Rogan-Finnemore.

Solvency

Bioprospecting Fails

Bio-prospecting is useless and fails – structural hurdles, economics, and lack of knowledgeFirn 02 – Richard D. Firn, Department of Biology, University of York, York Y01 5DD, UK, published in Kluwer Academic Publishers (21 January 2002, “Bioprospecting – why is it so unrewarding?,” Biodiversity and Conservation 12: 207–216, 2003, ADL)Abstract. Some economic analyses have placed high values on the chemical diversity residing in threatened habitats [Balick and Mendelsohn (1992), Conservation Biology 6: 128–130; Principe (1996), In Biodiversity and its Importance to Human Health, Columbia University Press, New York; Rausser and Small (2000), Journal of Political Economy 108: 173–206]. Consequently, bioprospecting (searching for new biologically active chemicals in organisms) is considered by some to be a way of funding the preservation of biodiversity, especially in the less developed

countries. However, the large multinational pharmaceutical and agrochemical companies spend very little of their research effort on bioprospecting [Cordell (2000), Phytochemistry 55: 463–480].Why is this? The answer lies in the fact that any chemical (whether a synthetic or a natural product) has a very low probability of possessing useful biological activity. The common belief that every natural product has been selected by its producer such that only biologically active natural products are made is not correct. Given that random collections of synthetic or natural products have a similar chance of containing a chemical with specific activity against any one target, and given that synthetic chemicals are nearly always much easier to synthesise on an industrial scale, it is predictable that major agrochemical and pharmaceutical companies will devote only a limited amount of their R & D budget to bioprospecting. Although Rausser and Small (2000) argued that scientific advances will make bioprospecting more cost-

effective in future, an alternative scenario is presented where current biotechnological developments will further erode the value of bioprospecting. It is concluded that there should be no reliance on large-income streams being available from bioprospecting agreements to help fund the preservation of biodiversity. Bioprospecting – the hope Pharmaceutical drugs currently have annual sales exceeding $200 billion. It has been estimated that over 25% of the drugs sold in the developed world and 75% in the less developed countries (LDCs) are based on chemicals made by organisms (Pearce and Puroshothamon 1995). These two facts have been given considerable emphasis by those seeking to put the case for conserving biodiversity. Noting that only a small fraction of the chemicals made by plants or microbes has been fully assessed for useful biological activity, it was argued that there was a real commercial value in retaining this unexplored biodiversity in order to preserve the valuable chemical diversity (Eisner 1989; Balick and Mendelsohn 1992; Principe 1996; Rausser and Small 2000). For example, Balick and Mendelsohn (1992), studying the harvesting of medicinal plants from a rain forest, estimated that annual revenues of $16–61 per ha could be achieved by exploiting the pharmaceutical value of such plants. The general public readily picked up these ideas in a simpler form from the 208 popular press, which emphasised the possible miracle cancer cures that awaited discovery in rain forests, in coral reefs or in the deep ocean. It was argued that the preservation of these habitats, and the organisms they contain, was a matter of self-interest for the health-conscious wealthy nations. Pearce and Puroshothamon (1995) estimated that OECD countries might suffer an annual loss of £25 billion if 60000 threatened species were actually lost as a medicinal resource. The widely publicised agreement by Merck and Co. to enter into a bioprospecting agreement with the National Institute for Biodiversity (INBio) in Costa Rica in 1991 and a significant investment by Eli Lilly in Shaman Pharmaceuticals seemed to offer verification of the logic of bioprospecting. During the 1990s there was evidence of renewed interest in screening natural products (Reid et al. 1993; Garrity and Hunter-Cevera 1999; ten Kate and Laird 1999). The pharmaceutical companies were not alone in renewing their interest in screening chemicals from the natural world. The US National Cancer Institute (NCI) had screened 200000 extracts of organisms for anticancer activity in the period 1955–1980, with such limited success that they had turned their attention instead to ‘rational drug design’ (Aylward 1995). However, the introduction of improved screening methods (much higher throughputs, lower costs and targeting more specific biological targets) encouraged the NCI to begin screening biological samples again in 1986. By 1995 the NCI had produced 40000 extracts for screening and of the 18000 screened for anticancer activity about 1% showed some positive activity. This renewed interest in plant products as a source of pharmaceutical leads led optimists in the development community to identify an opportunity to build a revenue stream between the rich and the poor countries. The health-conscious, rich countries might be willing to pay the less developed countries for access to their biodiversity (Swanson 1995). Discussions about bioprospecting moved on to consider issues of equity. How could the poor, developing nations negotiate a good deal with the powerful drug multinationals? How could any income stream that was negotiated be targeted at the most appropriate groups within the developing country? Much has been written about these equity issues (ten Kate and Laird 1999; Svarstad and Dhillion 2000), but less about the scientific principles that underpin the basic premise. Are rain forests, coral reefs or pristine oceans a wonderful source of chemical diversity? More importantly, is this chemical diversity likely to contain the next

generation of blockbuster drugs? Bioprospecting – the reality Drug development is more than drug discovery Scientific drug discovery is essentially a reductionist extension of herbalism but with one crucial difference. Humans can make chemicals to supplement those that occur naturally. Drug discovery at its initial phase is thus composed of two parts: • obtaining chemical

samples, • testing the samples for a useful biological effect (often called ‘screening’). 209 However, the discovery of a potentially useful biological activity by screening is only the first step of a lengthy, expensive process. Each of the following questions must be addressed: • Will the drug be safe to use? (e.g. are there adverse side effects due to the chemical having more than one effect?) • Is the drug clinically useful? (e.g. does the effect found in the test tube translate into a positive outcome for the patient?) • Can the chemical be extracted, synthesised or produced by fermentation on an industrial scale economically? •

Can the drug and its derivatives be adequately protected by patents? • Is the market big enough to repay the typical .$500 million development costs for the drug? Bioprospecting must thus be seen not as an independent process but as a contributor to a larger activity. The fact that so many large, successful pharmaceutical and agrochemical companies spend much more on making and screening synthetic chemicals than they do on isolating and testing natural products suggests that bioprospecting must bring with it disadvantages as well as advantages. The extent of this neglect of bioprospecting is brought into sharp focus when it is appreciated that the much publicised $1 million bioprospecting investment by Merck and Co. in INBio in 1991 was less than 0.1% of that company’s R & D budget for that year. Although

evidence has been presented (ten Kate and Laird 1999) as to the extent and value of natural product screening programmes to some pharmaceutical companies, it is sometimes overlooked that the total expenditure on such projects remains at best a very small fraction of the R & D budget of the major companies. Indeed, several major pharmaceutical companies have totally eliminated or scaled down their natural product screening programmes (Cordell 2000). A recent survey of companies involved in bioprospecting concluded that no major

pharmaceutical company had found investment in bioprospecting especially rewarding (Macilwain 1998). However, a recent sophisticated economic analysis (Rausser and Small 2000) has suggested that technological advances could increase the success of bioprospecting. Unfortunately, that analysis ignored some fundamental scientific considerations and it is only by appreciating these factors that a realistic evaluation of the potential for bioprospecting can be achieved.

Economics makes bio-prospecting failFirn 02 – Richard D. Firn, Department of Biology, University of York, York Y01 5DD, UK, published in Kluwer Academic Publishers (21 January 2002, “Bioprospecting – why is it so unrewarding?,” Biodiversity and Conservation 12: 207–216, 2003, ADL)Enzymes versus chemical reagents – the crucial difference If one compares the structures of a collection of chemicals made by organisms with structures of chemicals that have been made by humans, the most striking difference is that of structural complexity. Humans, late starters in the art of chemical synthesis, have tended to make huge numbers of chemicals that are relatively simple in structure. Most of the chemical diversity that has been made by humans (80000 different chemicals have been synthesised industrially) comes from making small alterations or additions to fairly simple chemical structures. Humans have only a limited number of chemical tricks (reacting chemical X with chemical Y). The ingenuity of the successful chemist is to combine the right tricks, in the right order, to generate the desired chemical from an available simple starting material. However, as the molecule built by the chemist becomes more complex, it becomes harder to find reagents that are sufficiently selective to bring about only the desired change. Consequently, a very large incentive is needed to embark on a programme of synthesising structurally very complex molecules. Very complex structures are rarely elaborated by humans just on the off chance that they might be biologically active. Indeed, such an ambitious synthetic programme usually only begins after a need has already been established (for example, when it was desired to make more light-stable analogues of the natural insecticide pythrethrin). In contrast to the chemists, organisms use enzymes instead of chemical reagents to bring about chemical transformations. The crucial advantage of using enzymes in biosynthetic sequences is that enzymes can bring about specific structural changes to very specific sites in a complex molecule. This facility of microbes and plants to make structurally complex molecules with relative ease means that humans inevitably find it hard to manufacture natural products. This difference in the chemical complexity between synthetic chemicals and natural products, stemming from a fundamental difference in the methods used to make the chemicals, is crucial to understanding one of the major disadvantages of

bioprospecting. When the rare potent, biologically derived chemical is found, it is often so chemically complex that it is hard or 212 1 impossible to synthesise economically . In contrast, if a synthetic chemical is found to be potentially useful, the chances are good that an economically viable manufacturing process for that chemical, or another biologically active analogue, can be devised. Evidence in support of this logic can be found in the case of the most important naturally derived biologically active compounds that humans utilise – the polyketide antibiotics, including penicillin, streptomycin, etc. These chemically complex molecules are made economically viable because the micro-organisms that make them can be cultured easily under factory conditions and the organisms can be highly selected to increase the yield of desired product. The enzymes produced by the microbes can carry out a synthesis which would be impossible or very expensive using chemical reagents. Thus, bioprospecting in plants or microbes tends to give lead chemicals that have been made using methodologies that are not easily duplicated by humans. The failure to recognise and

to account for this severe limitation to bioprospecting undermines the recent economic analysis of bioprospecting (Rausser and Small 2000). In Rausser and Small’s analysis the cost of obtaining a chemical to screen was considered to be independent

of subsequent development costs, yet it is clear that natural products often bring with them higher manufacturing costs. A summary of the key fundamental scientific principles underpinning bioprospecting The majority of natural products found in plants and microbes are

unlikely to possess potent biological activity. Such organisms are even less likely to contain specific, potent biological activity that could be usefully exploited for

pharmaceutical use. Furthermore, even when a naturally derived chemical is found to give a good lead, the chemical complexity so characteristic of natural products may make commercial production expensive or impossible. A lead compound produced by a microbe offers the best opportunity for the economic production of

a natural product 1 Taxol is an excellent example of a natural product that has great value as a drug, yet is so chemically complex that factory synthesis is not yet economically feasible. Taxol was discovered over 30 years ago in the bark of Pacific Yew trees (Taxus brevifolia) where it occurs at only 0.02%.When Taxol was found to be a useful treatment of certain forms of cancer, initially the only source was the bark and removal of the bark, for extraction, killed the tree. The bark from

3000 trees produces only 1 kg of Taxol. To treat ovarian cancer with Taxol in the USA alone would require the destruction of 75000 trees per year. Conservationists rightly worried about harvesting trees on such a scale – the Spotted Owl was considered to be at risk if such harvesting continued. The exploration of other Taxus species identified the needles of the ornamental shrub T. baccata as a source of a related chemical that could act as a precursor for a close relative of Taxol, hence pressure on the Pacific Yew has decreased. Although synthetic routes to Taxol have been reported, none have been successfully brought into commercial production despite considerable effort. Likewise attempts to grow Taxus cells in culture have not yielded an alternative commercial source of the chemical. It is clear that a natural source of a very important drug is not always good news for conservation (Dhillion and Amundsen 2000). Taxol also holds another interesting lesson for us. It is unlikely that Taxol was evolved because of its anticancer properties. The cancers found in animals are not common causes of death or disease in plants. Thus ethnobotanical knowledge could not be a reliable indicator of where to seek such compounds. 213 because the fermentation industry has extensive experience of optimising the production of fermentation products. Despite considerable effort, plant tissue or cell

cultures have yet to prove a commercially viable way of making natural products. Hence, the commercial exploitation of complex plant-derived compounds may be severely limited by high extraction or production costs. Bioprospecting – is there a future? Will ecological and ethnobotanical knowledge come to the rescue? Rausser and Small (2000) propose that the success of bioprospecting will increase as ecological and ethnobotanical knowledge directs the screening effort. Such optimism may be unjustified. Firstly, the chemical interactions between organisms are usually very specific and while a generalised model of such interactions may be constructed, such a model can make no predictions as to which chemicals may be utilised or in which way. The very specificity that has evolved makes generalised exploitation of the knowledge very hard. Secondly, the links between some aspect of ecological knowledge and human health will often be very limited. For example, knowing that plant A is not eaten by insect B hardly helps the making of a judgement as to whether plant A might contain a chemical that could help treat HIV. Even ethnobotanical knowledge can only be of limited help, because the diseases that are common in one society will be uncommon in another – communities with a rich ethnobotanical

knowledge might be expected to have a very different age structure, diet and gene pool from the rich, older patients in the developed world. The major pharmaceutical companies seek products that can be sold to the rich; hence ethnobotanical knowledge, of great relevance to the poor, is not always a useful guide when seeking

commercially valuable products. Although it has been shown that ethnobotanical knowledge can be used to enhance the success rate of screening natural products in some specific cases (Sheldon and Balick 1995), the mismatch between the health needs of rich and poor countries may leave much

ethnobotanical knowledge under-exploited. Combinatorial chemistry vs. bioprospecting The low probability of finding a biologically active molecule in any screening trial has prompted two major developments in the pharmaceutical and agrochemical industries. Firstly, chemists have developed quicker and cheaper ways of making diverse collections of chemicals. Combinatorial chemistry recognises that the old goal of a chemist, to devise a synthetic route that led to the maximum yield of one pure product, was not strictly rational if one was seeking to discover any new biologically active chemical. In the initial phases of a screening programme, instead of devising an elegant way of producing a single pure chemical (which has a very low probability of possessing useful biological activity), the combinatorial chemist devises ways of generating as much chemical diversity as possible in the hope that 214 one of the many compounds generated might be biologically active. The analogy could be the use of the shotgun rather than the rifle in unskilled hands to hit a partly hidden target.

Complexity of human biology dooms bio-prospecting to failureFirn 02 – Richard D. Firn, Department of Biology, University of York, York Y01 5DD, UK, published in Kluwer Academic Publishers (21 January 2002, “Bioprospecting – why is it so unrewarding?,” Biodiversity and Conservation 12: 207–216, 2003, ADL)Enzymes versus chemical reagents – the crucial difference If one compares the structures of a collection of chemicals made by organisms with structures of chemicals that have been made by humans, the most striking difference is that of structural complexity. Humans, late starters in the art of chemical synthesis, have

tended to make huge numbers of chemicals that are relatively simple in structure. Most of the chemical diversity that has been made by humans (80000 different chemicals have been synthesised industrially) comes from making small alterations or additions to fairly simple chemical structures. Humans have only a limited number of chemical tricks (reacting chemical X with chemical Y). The ingenuity of the successful chemist is to combine the right tricks, in the right order, to generate the desired chemical from an available simple

starting material. However, as the molecule built by the chemist becomes more complex, it becomes harder to find reagents that are sufficiently selective to bring about only the desired change. Consequently, a very large incentive is needed to embark on a programme of synthesising structurally very complex molecules. Very complex structures are rarely elaborated by humans just on the off chance that they might be biologically active. Indeed, such an ambitious synthetic programme usually only begins after a

need has already been established (for example, when it was desired to make more light-stable analogues of the natural insecticide pythrethrin). In contrast to the chemists, organisms use enzymes instead of chemical reagents to bring about chemical transformations. The crucial advantage of using enzymes in biosynthetic sequences is that enzymes can bring about specific structural

changes to very specific sites in a complex molecule. This facility of microbes and plants to make structurally complex molecules with relative ease means that humans inevitably find it hard to manufacture natural products. This difference in the chemical complexity between synthetic chemicals and natural products, stemming

from a fundamental difference in the methods used to make the chemicals, is crucial to understanding one of the major disadvantages of bioprospecting. When the rare potent, biologically derived chemical is found, it is often so chemically complex that it is hard or 212 1 impossible to synthesise economically . In contrast, if a synthetic chemical is found to be potentially useful, the chances are good that an economically viable manufacturing process for that chemical, or another biologically active analogue, can be devised. Evidence in support of this logic can be found in the case of the most important naturally derived biologically active compounds that humans utilise – the polyketide antibiotics, including penicillin, streptomycin, etc. These chemically complex molecules are made economically viable because the micro-organisms that make them can be cultured easily under factory conditions and the organisms can be highly selected to increase the yield of desired product. The enzymes produced by the microbes can carry out a synthesis which would be impossible or very expensive using chemical reagents.

Thus, bioprospecting in plants or microbes tends to give lead chemicals that have been made using methodologies that are not easily duplicated by humans. The failure to recognise and to account for this severe limitation to bioprospecting undermines the recent economic analysis of bioprospecting (Rausser and Small 2000). In Rausser and Small’s analysis the cost of obtaining a chemical to screen was considered to be independent of subsequent development costs, yet it is clear that natural products often bring with them higher manufacturing costs. A summary of

the key fundamental scientific principles underpinning bioprospecting The majority of natural products found in plants and microbes are unlikely to possess potent biological activity. Such organisms are even less likely to contain specific, potent biological activity that could be usefully exploited for pharmaceutical use. Furthermore, even when a naturally derived chemical is found to give a good lead, the chemical complexity so characteristic of natural products may make commercial production expensive or impossible. A lead compound produced by a microbe offers the best opportunity for the economic production of a natural product 1 Taxol is an excellent example of a natural product that has great value as a drug, yet is so chemically complex that factory synthesis is not yet economically feasible. Taxol was discovered over 30 years ago in the bark of Pacific Yew trees (Taxus brevifolia) where it occurs at only 0.02%.When Taxol was found to be a useful treatment of certain forms of cancer, initially the only source was the bark and removal of the bark, for extraction, killed the tree. The bark from 3000 trees produces only 1 kg of Taxol. To treat ovarian cancer with Taxol in the USA alone would require the destruction of 75000 trees per year. Conservationists rightly worried about harvesting trees on such a scale – the Spotted Owl was considered to be at risk if such harvesting continued. The exploration of other Taxus species identified the needles of the ornamental shrub T. baccata as a source of a related chemical that could act as a precursor for a close relative of Taxol, hence pressure on the Pacific Yew has decreased. Although synthetic routes to Taxol have been reported, none have been successfully brought into commercial production despite considerable effort. Likewise attempts to grow Taxus cells in culture have not yielded an alternative commercial source of the chemical. It is clear that a natural source of a very important drug is not always good news for conservation (Dhillion and Amundsen 2000). Taxol also holds another interesting lesson for us. It is unlikely that Taxol was evolved because of its anticancer properties. The cancers found in animals are not common causes of death or disease in plants. Thus ethnobotanical knowledge could not be a reliable indicator of where to seek such compounds. 213 because the fermentation industry has extensive experience of optimising the production of fermentation products. Despite considerable effort, plant tissue or cell cultures have yet to prove a commercially viable way of making natural products. Hence, the commercial exploitation of complex plant-derived compounds may be severely limited by high

extraction or production costs. Bioprospecting – is there a future? Will ecological and ethnobotanical knowledge come to the rescue?

Rausser and Small (2000) propose that the success of bioprospecting will increase as ecological and ethnobotanical knowledge directs the screening effort. Such optimism may be unjustified. Firstly, the chemical interactions between organisms are usually

very specific and while a generalised model of such interactions may be constructed, such a model can make no predictions as to which chemicals may be utilised or in which way. The very specificity that has evolved makes generalised exploitation of

the knowledge very hard. Secondly, the links between some aspect of ecological knowledge and human health will often be very limited. For example, knowing that plant A is not eaten by insect B hardly helps the making of a judgement as to whether plant A might contain a chemical that could help treat HIV. Even ethnobotanical knowledge can only be of limited help, because the diseases that are common in one society will be uncommon in another – communities with a rich ethnobotanical knowledge might be expected to have a very different age structure, diet and gene pool from the rich, older patients in the developed world. The major pharmaceutical companies seek products that can be sold to the rich; hence ethnobotanical knowledge, of great relevance to the poor, is not always a useful guide when seeking commercially valuable products. Although it has been shown that ethnobotanical knowledge can be used to enhance the success rate of screening natural products in some specific cases (Sheldon and Balick 1995), the mismatch between the health needs of rich and poor countries may leave much ethnobotanical knowledge under-exploited. Combinatorial chemistry vs. bioprospecting The low probability of finding a biologically active molecule in any screening trial has prompted two major developments in the pharmaceutical and agrochemical industries. Firstly, chemists have developed quicker and cheaper ways of making diverse collections of chemicals. Combinatorial chemistry recognises that the old goal of a chemist, to devise a synthetic route that led to the maximum yield of one pure product, was not strictly rational if one was seeking to discover any new biologically active chemical. In the initial phases of a screening programme, instead of devising an elegant way of producing a single pure chemical (which has a very low probability of possessing useful biological activity), the combinatorial chemist devises ways of generating as much chemical diversity as possible in the hope that 214 one of the many compounds generated might be biologically active. The analogy could be the use of the shotgun rather than the rifle in unskilled hands to hit a partly hidden target.

No FDA Approval

No solvency – FDA won’t approveForbes 11 (Steve Forbes—the creator of Forbes magazine, “How the FDA May Kill Millions of Us”, http://www.forbes.com/forbes/2011/0214/opinions-steve-forbes-fact-comment-fda-may-kill-millions.html)

The FDA, for instance, will capriciously change its rules in the middle of an expensive clinical trial, suddenly telling a company that it must add thousands of new patients to the tests. Even when trials are

successfully completed the FDA is reluctant to give a new drug the green light .¶ Normally if big companies can’t respond to an opportunity or a need in health care–or anywhere else–entrepreneurial startups will leap in. But small companies are even more disadvantaged by the FDA’s increasingly horrific bureaucratic roadblocks. ¶ Thus today we are faced with potential catastrophe. Lethal bacteria now threaten to colonize U.S. hospitals. Fearsome germs that are resistant to our current antibiotic arsenal include MRSA (methicillin-resistant Staphylococcus aureus), which currently kills

nearly 20,000 Americans a year. An even more dangerous genetic mutation is NDM-1 (New Delhi

metallo-betalactamase 1). If nothing is done, we will be facing a bacterial apocalypse. The horrors that we thought were banished 70 years ago are coming back.

FDA approval takes on average 9 years Glasgow 1 (Lara J, “Stretching the Limtis of Intellectual Property Rights: Has the Pharmaceutical Industry Gone Too Far”, http://www.heinonline.org.turing.library.northwestern.edu /HOL/Page?handle=hein.journals/idea41&id=239&collection=journals&index=journals/idea#244)

The profit power of brand name prescription drugs relies heavily on a drug company's patent rights. With a valid patent and regulatory approval by the Food and Drug Administration ("FDA"), a drug

company can lawfully exercise its monopoly rights and reign as the sole producer of a particular drug until the

patent expires and generic manufacturers enter the market. Securing a patent for a brand name prescription drug carries with it enormous costs. For instance, it is estimated that the cost of bringing a single brand name

prescription drug to market is somewhere between $250- 500 million.,u This figure includes the costs of research and development of the drug, extensive testing for FDA approval and production of the drug.11 Because the FDA approval process generally occurs once the drug has been approved for a patent, the drug's time in waiting at the FDA severely cuts down on the effective patent life, the term used to describe how long a patented drug has left on its patent once it enters the market. The average length of time it takes to secure marketing approval from the FDA for a new brand name drug is nine years."

No Impact

AT: Pandemics / Zoonotics

Upcoming zoonotic diseases won’t escalate – they either dead-end, burn-out, or have low mortalityWang and Crameri 13 - Linfa Wang and Gary Crameri of the Commonwealth Scientific and Industrial Research Organisation (March 22 2013, "First Hendra, now bat lyssavirus, so what are zoonotic diseases? Read more: http://www.brisbanetimes.com.au/queensland/first-hendra-now-bat-lyssavirus-so-what-are-zoonotic-diseases-20130321-2gisj.html#ixzz37mUXiSPU,"www.brisbanetimes.com.au/queensland/first-hendra-now-bat-lyssavirus-so-what-are-zoonotic-diseases-20130321-2gisj.html, ADL)Zoonotic diseases in humans can take several different courses. For some, like rabies and West Nile virus, humans are “dead-end” hosts. That is, they transmit (spill over) from their animal reservoir (host) into humans but as there’s no subsequent human-to-human transmission, the disease is restricted from spreading. Others, such as SARS and avian influenza, spill over to humans, cause disease and are able to transmit from person to person before being eradicated or “burning out” from the human population, leaving no residual infection except in its animal host. The third are diseases such as HIV AIDS, which spilled out of primates decades ago and has persisted in the human population ever since. And measles and mumps, which probably entered the human population thousands of years ago and are somewhat controlled but still circulating. It’s impossible to completely safeguard against zoonotic diseases but steps can and are being taken to limit the opportunity for spill-over events through monitoring and rapid response when and where they do occur. Controlling zoonotic diseases and protecting our animals, people and environment from increasing biosecurity threats will not only take a global effort but a multidisciplinary one. It cannot be addressed adequately with traditional human medical strategies where disease is fought in the human population only.

Pandemics won’t cause extinction – empirics proveBrooks 12 - Brooks holds a PhD in Quantum Physics from the University of Sussex. He was previously an editor for New Scientist magazine, and currently works as a consultant for that magazine (Michael, 2012, "100,000 AD: Living in the Deep Future," cosmictoquantum.tumblr.com/post/18837836239/100-000-ad-living-in-the-deep-future, ADL)We are also unlikely to be extinguished by a killer virus pandemic. The worst pandemics occur

when a new strain of flu virus spreads across the globe. In this scenario people have no immunity, leaving large populations exposed. Four such events have occurred in the last 100 years - the worst, the 1918 flu pandemic, killed less than 6 per cent of the world’s population. More will

come, but disease-led extinctions of an entire species only occur when the population is confined to a small area, such as an island. A severe outbreak will kill many millions but there is no compelling reason to think any future virus mutations will trigger our total demise.

Drug breakthroughs solve antibiotic resistance nowKnapton 6/21 Sarah Knapton (Citing reports from the science journal Nature) is a reporter for The Telegraph, “Scientists Find The 'Achilles Heel' Of Antibiotic Resistant Bacteria”, 6/21/14, Businessinsider.com, http://www.businessinsider.com/key-to-antibiotic-resistant-bacteria-2014-6#ixzz35MfR7juH//OFThe global threat of antibiotic resistance could finally be tackled after British scientists discovered a chink in the armour of deadly bacteria. Health experts have warned that within 20 years even routine operations like hip

replacements and organ transplants could be deadly because of the risk of infection. But now scientists at the University of East Anglia have discovered how the bug responsible for E-coli and salmonella builds an impenetrable wall to keep out antibiotics . They believe that within a few years they could develop a drug which switches off the wall-building mechanism, making the bacteria vulnerable. “It is a very significant breakthrough,” said Professor Changjiang Dong, from

the University of East Anglia's (UAE) Norwich Medical School. “This is really important because drug-resistant bacteria is a global health problem. Many current antibiotics are becoming useless, causing hundreds of thousands of deaths each

year. “Many bacteria build up an outer defence which is important for their survival and drug resistance. We have found a way to stop that happening. "The number of superbugs are

increasing at an unexpected rate. This research provides the platform for urgently-needed new generation drugs." The discovery, reported in Nature journal, could pave the way to a new generation of antibiotic drugs that work by bringing down the defensive wall. Bugs such as MRSA (methicillin resistant Staphylococcus aureus) are becoming increasingly immune to "last resort" antibiotics. If the trend continues the world may see a return to the pre-antibiotic era when even a trivial scratch could prove fatal. At the heart of the breakthrough is the way "gram negative" bacterial cells transport the barrier's molecular "bricks" to the surface of the cell and form a wall. "Gram-negative" bacteria, which include Escherichia coli (E. coli) and the bugs that cause gonorrhea, cholera and Legionnaire's disease, are especially resistant to antibiotics. They can evolve a number of mechanisms to make them immune to drugs, including reducing the permeability of their outer membrane. But if the membrane barrier falls, the bacteria die - whatever other defensive ploys they may have developed. Haohao Dong, another member of the UAE team, said: "The really exciting

thing about this research is that new drugs will specifically target the protective barrier around the bacteria, rather than the bacteria itself. "Because new drugs will not need to enter the bacteria itself, we hope that the bacteria will not be able to develop drug resistance in future." The science community and the government said the research was a ‘welcome piece of news’ “We are facing

a difficult era in terms of antibiotic resistance; the need for new efficacious drugs to treat infectious disease is clearly an important issue,” said Mark Fielder, Professor of Medical Microbiology at Kingston University and Hon Gen Sec of the Society for Applied Microbiology. “The publication of data from the two groups is a

welcome piece of news. Their findings give science an insight into some of the structures that are important in the development of a bacterial membrane. “This could be of great importance as if we fully understand the workings and construction of structures that help bacteria function as effective entities we can hopefully then exploit weaknesses therein and kill the organism.” Prof Brendan Wren, Professor of Microbial Pathogenesis, London School of Hygiene & Tropical Medicine, added: “The studies open new avenues to the design a novel class of antibiotics to disarm and kill pathogenic bacteria." Deputy Chief Medical Officer John Watson said: “Antimicrobial resistance is a hugely important issue facing the world today. “We welcome all efforts in this area and we will follow any further developments with interest.”

FAO, OIE, and WHO protocols and systems solveFAO, OIE, and WHO 6 - Food and Agriculture Organization of the UN, World Organisation for Animal Health, World Health Organization (February 2006, "Global Early Warning and Response System for Major Animal Diseases, including Zoonoses (GLEWS)," www.oie.int/doc/ged/D11304.PDF, ADL)2.2 Existing Early Warning Systems OIE has set up an animal health information search and verification system for non-official information from various sources on the existence of outbreaks of diseases or exceptional epidemiological events that have not yet been officially notified to the OIE. It then relies

on the capacity of its Member Countries and on their capabilities to verify the outbreak information. OIE operates an early warning system to warn the International Community of exceptional epidemiological events in its

Member Countries. This alert system is aimed at the decisionmakers, enabling them to take any necessary protective measures as quickly as possible. FAO, through its special EMPRES priority programme

established in 1994, developed an early warning and response system. The system benefits from the official information furnished by the OIE and combines other sources of information such as those generated by technical projects, consultancy missions or personal contacts and provides an analysis of the situation through bulletins,

electronic messages and reports for better disease containment and control. In addition, FAO has also developed

information search and verification systems of information from various sources (so-called ì data miningî ). WHO systematically gathers official reports and rumors of suspected outbreaks from a wide range of formal and informal sources. Reports of suspected outbreaks are received from ministries of health, national institutes of public health, WHO Regional and Country offices, WHO collaborating centres, civilian and military laboratories, academic institutes, and nongovernmental organizations (NGOs). With the advent of modern communication technologies, many initial outbreak reports now

originate in the electronic media and electronic discussion groups. 2.3 Existing Response systems The Global Framework for Transboundary Animal Diseases (GF-TADs) launched by FAO and OIE initiates and supports strategic regional and national cooperation for the control of TADs. The Framework is designed to empower countries and regional alliances in the fight Final version adopted by the three organisations ñ tripartite 2006 ñ 01/02/2006 ñ 6:00 PM ñ VF 10 against TADs, to provide capacity building and to assist in the establishment of programmes for the targeted control of certain

TADs based on their regional priorities. It contributes to the strengthening of national disease reporting structures and mechanisms to fulfill international animal health monitoring functions effectively. The GLEWS initiative is a major contributor to this Framework. The Technical Cooperation Programme (TCP) is an instrument that enables FAO to respond rapidly to urgent needs for technical and emergency assistance in member countries and to contribute to their capacity building. The programme

does not operate in isolation, but is closely associated with other normative and field activities of the organization. In addition, FAO has launched the Emergency Centre for Transboundary Animal Diseases Operations (ECTAD) within its EMPRES programme in November 2004, to operate as the corporate centre for the design and delivery of FAOís services as the Chief Veterinary Officer of the organization. ECTADís primary aim is to implement a clear, simple chain of command between AGAH/EMPRES and the field to deal efficiently with the emergency at hand and to ensure an integrated approach of the relevant groups and services involved in the response. WHO offers assistance to affected countries in the form of technical advice, supplies and by

mounting coordinated international investigations The Global Outbreak Alert and Response Network (GOARN) is

building on new and existing partnerships of national and international institutions and networks, to deal with the global threats of epidemic-prone and emerging diseases in humans and to prepare for rapid deployment and coordination of international resources in response to an outbreak of international importance. GOARN aims at ensuring appropriate technical support to affected human populations quickly, assessing risks of rapidly emerging epidemic disease threats and sustaining containment and control of outbreaks by contributing to national outbreak preparedness. OIE has emergency funds that can be rapidly mobilized for sending experts from OIE Reference Laboratories to

assess the epidemiological situation in a country and define the actions required. 2.4 Existing systems for dissemination OIE disseminates official information about animal diseases including zoonoses in the three OIE official languages. The dissemination of emergency messages and follow-up reports (as per the OIE Early Warning System) is done using different tools: faxes, electronic distribution lists and the OIE website. Also, Animal Health Information, from the OIE six-monthly and annual monitoring system is disseminated using the OIE website and in hardcopy (World Animal Health publication). FAO disseminates bulletins, reports, descriptive and analytical early warning and emergency messages. The tools used to disseminate information are: FAO/AGAH/EMPRES web site and electronic distribution lists. The EMPRES bulletin is also distributed in hardcopy. Concerning HPAI, a specific bulletin FAO AIDENews is issued every month or when appropriate. WHO disseminates information through a restricted e-mail list, the WHO web site and information bulletins. The Weekly Epidemiology Record is available in hard copy and electronically. Final version adopted by the three organisations ñ tripartite 2006 ñ 01/02/2006 ñ 6:00 PM ñ VF 11 INFOSAN has been developed by WHO in cooperation with FAO to promote the exchange of information on food safety and to improve collaboration among food safety authorities at

national and international levels.3 GLEWS: A joint FAO/OIE/WHO initiative to enhance Early Warning and Response at international level 3.1 Project background and rationale The GLEWS initiative started with the voluntary participation of representatives of FAO, OIE and WHO, who share the common objective to enhance the Early Warning and Response capacity for the benefit of the international community. Mutual benefit through collaboration has been identified throughout the

Early Warning and Response process. Early Warning The three organizations use complementary and partly overlapping sources of information to identify infectious disease events. Through sharing of information on disease alerts, the capacity for early warning of the three organizations could be enhanced while avoiding unjustified duplication of efforts. In some instances the geographical coverage of disease alerts could be improved, e.g. through the use of FAO/AGAH

animal health information for non OIE countries. For zoonotic events, alerts of animal outbreaks provide direct early warning so that human surveillance could be enhanced and preventive action taken. Similarly, there may be cases where human surveillance is more sensitive and alerts of human cases precede known animal occurrence of disease. There is also added value in combining and coordinating the verification processes. One source of information is often not sufficient to verify or deny the presence of a disease in a country that did not spontaneously report it. A rumour might be denied by an official institution, although the epidemiological context tends to demonstrate the contrary. Each disease event tracked has therefore to be verified in light of the current and most updated epidemiological knowledge. Socioeconomics and demographic data on livestock also

represent a valuable source of information in this exercise. Joint dissemination of risk assessment would also benefit

from the different information sources providing a comprehensive analysis of the event and its possible consequences in its specific context. Response Sharing assessments of ongoing outbreak undertaken by either of the organizations, e.g. based on reports from local representation or field missions, would be of value to all three organizations. Furthermore,

the organizations would, in accordance with their different mandates, bring together different pieces of information from different sources that would enable a joint assessment of the outbreak. Immediate notifications to the OIE would provide initial details of the outbreak and any immediate control measures taken. FAO would bring the integration of other data and information, e.g. on animal production systems, factors affecting movements of livestock etc, crucial for the assessment of the risk of

further spread. Joint analysis and assessment by the three organizations would also benefit from the different specific competencies and resources of the three different organizations and may form the basis for a joint infection control strategy. Joint dissemination would enable harmonized communications by the three organizations regarding disease control strategies. Final version

adopted by the three organisations ñ tripartite 2006 ñ 01/02/2006 ñ 6:00 PM ñ VF 13 The existing response systems of FAO and OIE enable the provision of assistance to countries facing national or regional animal disease threats. WHO and the Global Outbreak Alert Response Network (GOARN) on the other hand ensures quick and appropriate technical support to populations affected by

human disease epidemics on a national, regional or even international level. For the control of animal disease epidemics with a complex epidemiological appearance, the potential for regional or international spread and/or a public health dimension, no global response network has yet been established. There is a clear need to fill this gap by building a response network ideally complementary to GOARN when relevant, so both can share their expertise in responding to disease emergencies A system for joint response to disease emergencies would improve international preparedness for epidemics and provide timely and coordinated assistance to countries experiencing them. Jointly, the three organizations would be able to cover a wider range of outbreaks or exceptional epidemiological events with the provision of a wider range of expertise.

AT: Antibiotic Resistance

Drug breakthroughs solve antibiotic resistance nowKnapton 6/21 Sarah Knapton (Citing reports from the science journal Nature) is a reporter for The Telegraph, “Scientists Find The 'Achilles Heel' Of Antibiotic Resistant Bacteria”, 6/21/14, Businessinsider.com, http://www.businessinsider.com/key-to-antibiotic-resistant-bacteria-2014-6#ixzz35MfR7juH//OFThe global threat of antibiotic resistance could finally be tackled after British scientists discovered a chink in the armour of deadly bacteria. Health experts have warned that within 20 years even routine operations like hip

replacements and organ transplants could be deadly because of the risk of infection. But now scientists at the University of East Anglia have discovered how the bug responsible for E-coli and salmonella builds an impenetrable wall to keep out antibiotics . They believe that within a few years they could develop a drug which switches off the wall-building mechanism, making the bacteria vulnerable. “It is a very significant breakthrough,” said Professor Changjiang Dong, from the University of East Anglia's (UAE) Norwich Medical School. “This is really important because drug-resistant bacteria is a global health problem. Many current antibiotics are becoming useless, causing hundreds of thousands of deaths each

year. “Many bacteria build up an outer defence which is important for their survival and drug resistance. We have found a way to stop that happening. "The number of superbugs are

increasing at an unexpected rate. This research provides the platform for urgently-needed new generation drugs." The discovery, reported in Nature journal, could pave the way to a new generation of antibiotic drugs that work by bringing down the defensive wall. Bugs such as MRSA (methicillin resistant Staphylococcus aureus) are becoming increasingly immune to "last resort" antibiotics. If the trend continues the world may see a return to the pre-antibiotic era when even a trivial scratch could prove fatal. At the heart of the breakthrough is the way "gram negative" bacterial cells transport the barrier's molecular "bricks" to the surface of the cell and form a wall. "Gram-negative" bacteria, which include Escherichia coli (E. coli) and the bugs that cause gonorrhea, cholera and Legionnaire's disease, are especially resistant to antibiotics. They can evolve a number of mechanisms to make them immune to drugs, including reducing the permeability of their outer membrane. But if the membrane barrier falls, the bacteria die - whatever other defensive ploys they may have developed. Haohao Dong, another member of the UAE team, said: "The really exciting

thing about this research is that new drugs will specifically target the protective barrier around the bacteria, rather than the bacteria itself. "Because new drugs will not need to enter the bacteria itself, we hope that the bacteria will not be able to develop drug resistance in future." The science community and the government said the research was a ‘welcome piece of news’ “We are facing

a difficult era in terms of antibiotic resistance; the need for new efficacious drugs to treat infectious disease is clearly an important issue,” said Mark Fielder, Professor of Medical Microbiology at Kingston University and Hon Gen Sec of the Society for Applied Microbiology. “The publication of data from the two groups is a

welcome piece of news. Their findings give science an insight into some of the structures that are important in the development of a bacterial membrane. “This could be of great importance as if we fully understand the workings and construction of structures that help bacteria function as effective entities we can hopefully then exploit weaknesses therein and kill the organism.” Prof Brendan Wren, Professor of Microbial Pathogenesis, London School of Hygiene & Tropical Medicine, added: “The studies open new avenues to the design a novel class of antibiotics to disarm and kill pathogenic bacteria." Deputy Chief Medical Officer John Watson said: “Antimicrobial resistance is a hugely important issue facing the world today. “We welcome all efforts in this area and we will follow any further developments with interest.”

Nanotech solves drug resistant diseaseContera and Trigueros 09 - Dr. Sonia Contera and Dr. Sonia Trigueros of the Institute of Nanoscience for Medicine of Oxford University (17 Nov 2009, "A novel ApproAch to Antibiotic resistAnce," www.oxfordmartin.ox.ac.uk/downloads/briefings/nano-antibiotics-breifing.pdf, ADL)James Martin Fellow Dr Sonia Trigueros and Co-Director Dr Sonia Contera, senior researchers in the Institute of Nanoscience for Medicine, are currently developing a targeted drug delivery system (using nanostructures to deposit drugs within specific cells) which they believe could be put to use as an antibacterial treatment. This approach relies on the fact that, while bacteria are very well adapted to meeting the challenges faced by current antibiotics,

the larger, metallic nanostructures would be an alien concept which bacteria could not recognise as a threat. These nanostructures should therefore be capable of depositing drugs within individual bacteria cells – thus bypassing the problem of resistance. A nanoscale approach could offer further advantages over traditional antibiotics, as nanostructures could be programmed to act more precisely. One exciting possibility is the idea of designing treatments capable of distinguishing between ‘good’ and ‘bad’ bacteria.

And PPMOs solveNetDoctor 13 (16 Oct, "PPMOs could solve antibiotic resistance issue," www.netdoctor.co.uk/interactive/news/ppmos-could-solve-antibiotic-resistance-issue-id801649973-t116.html, ADL)A new type of antibacterial agent could hold the key to killing bugs without the need for traditional antibiotics, researchers believe. The team at Oregon State University tested PPMOs (peptide-

conjugated phosphorodiamidate morpholino oligomers), which are synthetic analogs of DNA or RNA that are able to silence the expression of specific genes. In an animal study, one particular form showed significant control of two strains of Acinetobacter, a group of bacteria that are currently of global concern to microbiologists. Even better, PPMOs were more powerful than many conventional antibiotics but specifically targeted the genes of a bacterium, so were less damaging to the rest of the cells nearby, plus

they could solve the issue of antibiotic resistance. Lead author Professor Bruce Geller said in the

Journal of Infectious Diseases that the findings are revolutionary and more research will now be carried out to

see if PPMOs are suitable for human use. 'They can be synthesised to target almost any gene,' he added. In Britain, antibiotic resistance is viewed as such a serious problem that the Chief Medical Officer and Public Health England recently launched a surveillance and strategy programme to deal with it.

India CP

Solvency

India’s pharmaceutical sector and coastal biodiversity solve microbial bioprospectingDemunshi and Chugh 9 (Ypsita, Archana, “Role of traditional knowledge in marine bioprospecting”, http://download.springer.com.turing.library.northwestern.edu/static/pdf/608/art%253A10.1007%252Fs10531-010-9879-9.pdf?auth66=1405870147_f547ffa10a184ab9b78cdbb37eb6122e&ext=.pdf)

Indian companies and research organizations are gradually realizing the potential of the Indian marine organisms in pharmaceutical, nutraceutical, cosmeceutical, and bioenergy sector. Marine biotechnology can be an effective and a potential tool for marine bioprospecting as it can suitably

combine traditional knowledge with advanced scientific techniques for scaling up the production of a marine bioresource derived drug to commercialization level. The industrial base in India in marine biotechnology, although still lags behind US and European countries, some of the known Indian companies are Cellgen Biologicals, Samudra Biopharma, GeoMarine Biotechnologies, Nurture Aqua Technology and ABL Biotechnologies. Most of these are situated either in Chennai or Vishakhapatnam. ABL Biotechnologies, a marine biotechnology company in Chennai, has been working on identification and commercial extraction of bio-chemicals, predominantly

from marine microbes, that have far reaching applications as nutritional, cosmetic, pharmaceutical and industrial intermediates. The company has also collaborations with Samudra Biopharma and CellGen Biologicals. GeoMarine Biotechnologies on the other hand is involved in production of veterinary and aquaculture products. The veterinary products such as Spiromac, is obtained from the unicellular alga Spirulina, several beneficial bacteria and a special strain of yeast. Except in the field of marine biotechnology, India has made considerable progress in aquaculture.

Hence, the Department of Biotechnology of the Government of India has initiated promoting marine biotechnology in India for the last one and half decades. Many R&D programs on marine biotechnology sponsored at different Indian Universities and Institutions in collaborative mode are leading towards products and process development that will culminate into viable technology for commercial

production systems. National Institute of Oceanography (NIO), Goa, is among the pioneering institutes that promotes biodiversity based marine biotechnology. It is also extensively associated with the maintenance,

management, research and mapping of the flora and fauna in the Indian seas. The institute has collaborative projects with other countries and has filed marine biodiversity based patents worldwide (Fig. 1). The geographical trend of the patents filed by NIO shows that the maximum patents were filed in the United States of America followed by India. The Indian government encourages research activities and initiatives in marine biotechnology and related areas under various other programs especially in the coastal states. The Indian states with coastal areas such as Kerala, Tamil Nadu, Andhra Pradesh, Gujarat, Karnataka, Maharashtra, Orissa, and West Bengal have also shown keen interest in promoting marine biotechnology. They have introduced various marine bioresource based policies and programmes. Maharashtra’s biotechnology policy includes efforts to exploit the marine organisms along its coastline; Karnataka biotechnology policy plans to set up a marine biotechnology park at Karwar to promote marine biotechnology.

India’s innovative pharmaceutical market allows for quicker growth and medicine development Kumar 3 (Nagesh, Economics and Politics Weekly, “Intellectual Property Rights, Technology and Economic Development: Experiences of Asian Countries”, http://www.jstor.org.turing.library. northwestern.edu/ stable/4413100)

The increasing technological capability is reflected in terms of rising exports of drugs and pharmaceuticals. With their cost effective process innovations, Indian companies have emerged as competitive suppliers in the world of a large number of generic drugs that are now outside the patent protection. That

has resulted in a steady growth of India's exports of drugs and pharmaceuticals. Thus the industry has evolved from being one being highly import dependent to one that generates increasing export surplus for the country. The faster growth of pharmaceutical ex- ports has resulted in their share in India's exports rising from 0.55 per cent in 1970-71 to over 4 per cent by the 1999-2000 (Table 3). Emerging revealed comparative advantage of India in pharmaceuticals is apparent from Table 4 which shows that India's share in world exports of pharmaceuticals

has risen by 2.5 times while her share in all merchandise exports has stagnated at1998 period. India ranks second after China among developing countries in export of pharmaceuticals and is ahead of such technologically advanced countries as Mexico, South Korea*, Brazil, Israel (Table 5). Indian exports of pharmaceuticals received a boost in the late 1980s when a number of drugs went off the patents and Indian companies manufacturing them with cost-effective processes entered the international markets after obtaining FDA approval. Therefore, in the late 1980s, as much as 61 per cent of India's pharmaceutical exports comprised bulk drugs. However, subsequently some of the larger and more dynamic Indian enterprises such as Ranbaxy Laboratories, Dr Reddy' s Labs. Cipla and Cadila, have started marketing their own formulations in different countries with the help of a growing network of overseas offices and subsidiaries set up in key international markets. As a result of India includes generic drugs like Ibuprufen, Sulphamethoxazolc, Metron- idazole. Amoxycillins Ampicilline. Mebendazole, Beta lonone, Erythromy- cin, Pappain. Potassium iodide. Brucine Salts. Cephalexin, Ethambuiol Hydro- chloride. Trimethoprim, etc. A study comparing the performance of MNE affiliates and domestic enterprises in Indian pharmaceutical industry over the 1990s based on a balanced sample of 76 firms (60 domestic and 16 MNE subsidiaries) found the domestic enterprises are more dynamic in terms of growth of investment and output, export-orientation, R&D technology purchases from abroad and in terms of labour productivity (defined as ihc net value-added per rupee spent on labor), as shown in Figures 2-5 (Kumar and Pradhan 2002]. However, MNE affiliates enjoyed considerably higher profit margins because of (heir greater focus on more value adding formulations and their well-established brand names (Figure 7). The development of process innovation capability of Indian enterprises has en- abled them to introduce newer medicines within a short time lag. Table 7 shows that most of the drugs could be introduced within 4-5 years of their introduction in the world market. Table 7 also shows that the prices of these drugs in India have been much cheaper compared to rest of the world. For instance. Ranitidine. Famotidine. Astcmizolc, Ondansetron sell in the US market at about 50 times the Indian prices! The cheaper prices of drugs have made them affordable to the masses of poor in the country and thus have served an important social cause of providing access of modern medicine lo poorer people.

AT: U.S. Better

India’s Pharmaceutical is rapidly expanding outpacing U.S. Investment Green 7 (William, U.S. International Trade Commission, “The Emergence of India’s Pharmaceutical Industry and Implications for the U.S. Generic Drug Market”, http://www.usitc.gov/publications/332/ working_papers/EC200705A.pdf)

There are approximately 34 foreign drug companies engaged in the Indian pharmaceutical market and among them are 15 of the world’s 20 largest pharmaceutical companies. According to

FICCI, although MNCs have not launched new products they have invested in new production facilities and R&D centers and many are engaged in contract manufacturing, clinical trials, and other forms of outsourcing.25 In 2005-06, MNCs invested more than $172 million in India’s pharmaceutical industry and FDI has grown by a compound annual growth rate (CAGR ) of 62 percent during 2002-06.26 However, many industry experts believe that the return of the world’s leading pharmaceutical companies will gradually erode India’s cost advantages. According to the Organization of Pharmaceutical Producers of India, multinational drug companies currently command 24 percent of the domestic Indian market, through their share could rise to 40 percent by 2010.27GSK-India, a 51 percent subsidiary of GSK Plc (UK), is the largest foreign company in India’s pharmaceutical market, its fourth largest pharmaceutical company, and leading prescription drug supplier. GSK-India operates two Indian manufacturing plants and controls approximately 5.9 percent of the domestic Indian market. GSK-India is among India’s leading suppliers of anti-infective, anti inflammatory, analgesic, gastroenterological,

anti-allergic, and dermatological drugs. GSK-India announced plans to extend its product line by launching several antibiotic, cancer, and cardiovascular products in India in the near term. Likewise, MNCs dominate India’s OTC (over the counter) drug market, with Pfizer accounting for 5.1 percent of the market, Sanofi-Aventis for 5.0 percent, and Johnson & Johnson for 4.8 percent. These companies offer analgesics, cough and cold preparations, indigestion medicines, skin care products, and vitamins and minerals. Other foreign multinationals active in India’s pharmaceutical market include: Bristol-Myers Squibb, Eli Lilly, Boehringer, Bayer, Chiton Corp, Abbott, AstraZeneca, Janssen, and Roche. Recently, Teva Pharma (Israel), the world’s leading generic drug manufacturing company, acquired a bulk drug manufacturing and intermediate facility in the State of Uttar Pradesh, announced plans to add two more units, and more than triple the value of its exports from India by the end of 2007. Teva also opened an R&D facility in India and announced plans to register between 10 and 15 bulk drugs per year in the United States from its Indian facilities. Mergers, acquisitions, and other alliances: The last 3 years have seen a significant rise in the number of consolidations, mergers & acquisitions, and other types of alliances and tie-ins in the Indian pharmaceutical industry. Most of the acquisitions involve Indian companies searching for ways to penetrate overseas markets and widen their global footprint, diversify and enhance their product portfolios, offer their customers a ‘nearshore-offshore’ option, improve their custom manufacturing, packing, and R&D capabilities, acquire existing brands, and gain access to the highly regulated markets of Western Europe and the United States. Indian companies without significant R&D capabilities for drug discovery are also purchasing Western drug discovery companies. In 2005-06, 18 Indian companies spent approximately $1.6 billion to acquire generic drug manufacturing firms in Europe, North America, and Mexico.29 These companies included Ranbaxy, Dr. Reddy’s Labs, Nicholas Piramal, Sun Pharmaceutical, and Jubilant Organosys (table 5).30 Although eleven of these transactions were for medium-and-small sized companies valued between $5 million and $30 million, several have been significant acquisitions valued in excess of $500 million. To date, Dr. Reddy’s purchase of Betapharm Arzneimittel of Germany for $572 million is the industry’s largest overseas acquisition. Other significant deals include Ranbaxy’s purchase of Terapia (Romania) and RPG Aventis (France) and Matrix’s acquisition of API of Belgium. With these acquisition; Dr. Reddy’s became Germany’s fourth largest generic drug company and Ranbaxy became Romania’s third largest generic drug company and one of Belgium’s top 10 generic providers.31 India’s pharmaceutical industry should witness a significant decline in the number of smaller companies that either leave the market or are acquired by larger Indian or foreign companies. Since 2000, a number of smaller Indian pharmaceutical companies have been acquired by larger companies including Wockhardt’s acquisition of Merind and Tata Pharma; Ranbaxy’s purchase of Crosland; Nicholas Piramal’s acquisition of Roche, Boehringer, and Sumitra Pharma, and Glaxo-Wellcome’s merger with Ciba-Sandoz. Matrix, one of India’s and the world’s leading producers of APIs, was acquired by Mylan (US) in January 2007 for $546 million. Mylan, one of the largest generic drug producers in the United States, acquired Matrix to expand its manufacturing capabilities, gain a foothold in key markets, and gain access to Matrix’s technical and scientific expertise.

India’s Industry is more than sufficient to solve- R&D improvements and were already outsourcing all research to IndiaGreen 7 (William, U.S. International Trade Commission, “The Emergence of India’s Pharmaceutical Industry and Implications for the U.S. Generic Drug Market”, http://www.usitc.gov/publications/332/ working_papers/EC200705A.pdf)

Contract outsourcing: Western pharmaceutical companies are now outsourcing a wide range of activities including: the manufacture of APIs, chemical intermediates, and formulations; clinical research and clinical testing; and packaging and labeling. The Indian market for contract outsourcing has been driven by the need of leading MNC pharmaceutical companies to reduce production costs and increase revenues. These companies have shifted portions of the production, research & development, clinical trials, packaging and labeling, stability testing, and other types of drug development and discovery activities to India. In 2004, India’s drug outsourcing sector was valued at $470 million and was expected to grow by 30 percent per year to $800 million in 2005. Leading drug firms like Pfizer, AstraZeneca, Novartis, and Eli Lilly have already begun shifting a portion of these activities to India. According to India’s Chemical Pharmaceutical Generic Association, the domestic contract research market is growing between 20 percent and 25 percent per year and was valued at $120 million in 2005 and is projected to grow to $200 million by the end of 2007. The Chemical Pharmaceutical Generic Associations also predicted that this segment will reach $1 billion by 2010.44 The Association indicated that India dwarfs its nearest rivals, Italy ($60-$70 million) and Spain ($25 million to $33 million), and projected that contract research in India will grow at an annual rate of between 20 percent to 25 percent. Clinical trials represent 65 percent of this market and new drug discovery makes up the remaining 35 percent.45 Companies active in India’s contract research market include: a limited number of

multinational corporations, subsidiaries of large international contract research firms (Quintiles, Covance), joint ventures and tie-ins between Indian and foreign companies, and stand-alone and offshoots of Indian companies. Several multinationals active in the Indian market have designated India as a hub for their production of active pharmaceutical ingredients and finished formulations. Divi Labs, Shasun Chemicals & Drugs, and Dishman Pharmaceuticals are among India’s leading contract research firms. Research and development (R&D): With the reintroduction of product patents, leading Indian pharmaceutical majors are altering their business strategies by placing greater focus on R&D and the discovery of new chemical entities. Traditionally, the vast majority of India’s pharmaceutical R&D spending was concentrated

on reverse engineering and the adaptation of patented foreign drugs to the Indian market. Most of the industry’s funding went to research rather than to new drug discovery and development. Low levels of industry productivity and the relatively small size of India’s pharmaceutical companies limited funding for R&D as they dedicated only less than 2 percent of their annual turnover to R&D compared with between 15 percent and 20 percent allocated by Western innovator companies. After 2005, India’s leading drug companies recognized that they could not survive as global players without significant R&D capabilities. Since 1995, total industry R&D spending has

grown from nearly $30 million to more than $495.3 million in 2005-06 (table 8).46 The vast majority of the industry’s R&D spending is conducted by 15 companies whose R&D spending rose to $192.3 million in 2005 from $131 million in FY2004, representing an increase of 47 percent. R&D expenditures are expected to gradually rise to between 9 percent and 10 percent of total industry spending by the end of 2007.47 Likewise, the vast majority of the industry’s R&D expenditures on new drug discovery and development is conducted by a limited number of companies, with Dr. Reddy’s and Ranbaxy at the forefront. In 2005, Dr. Reddy’s committed 14 percent of its annual sales to R&D, whereas, Ranbaxy

India is the global leader and source of worldwide pharmaceutical research Mani 6 (Sunil, “The sectoral system of innovation of Indian pharamaceutical industry”, http://opendocs.ids.ac.uk/opendocs/bitstream/handle/123456789/3108/wp382.pdf?sequence=1)

India, at the moment, is the most preferred destination for clinical research because of its heterogeneous huge but treatment naïve patient population; English-speaking western educated investigators (physicians) and track record of sincerity in meeting regulatory and recruitment timelines, and most importantly well accepted good quality auditable data. While the global pharmaceutical companies are

increasing their clinical trial investments in India, many small and big regional pharma companies are considering India in their drug development initiatives. There is a perceptible change in the old mindset of

people - from skepticism to acceptance - of the capability, skill-sets and quality of data in Indian trials. Cost-effectiveness, competition and the increased confidence on capabilities and skill sets have propelled many global pharmaceutical players (Pfizer, Novartis, Astra Zeneca, Eli Lilly, GSK, Aventis, Novo

Nordisk to name but a few) to expand their own clinical research investment and infrastructure in India. Evaluating the business progression and futuristic projections of top notch services firm likeErnst & Young, McKinsey, Strategic Associates etc, while global pharmaceutical companies and Contract Research Organisations (CRO) are opening up their branches / offices, the small biotech, pharmaceutical and Research and Development (R&D) companies are looking for preferred partners to conduct their research activities in India. The report captures the striking regulatory change i.e. the amendment of Schedule Y (2005), which is a step towards harmonizing the Indian regulatory framework with international Good Clinical Practice (GCP) for all the stakeholders in clinical research including the sponsors, CROs, Site Management Organisations (SMOs), Institutional Ethics Committees (IECs), Investigators and the subjects participating in clinical trials in India The country can accommodate these business expansions because of the availability of huge talent pool of Investigators and clinical research professionals. India's growth in pharmaceutical and biotech manufacturing, and contract research supported by IT skills has led to promising outsourcing

business in various other segments including Clinical trial data management, statistical analysis. The clinical research industry in the country is currently valued at $100 million (• 83 million) and is almost doubling each year, reflecting the shifting focus of the pharmaceutical outsourcing industry to Asia. The findings are published in a recent report analyzing the clinical research industry and 33 leading contract research organizations (CROs) in India, put together by US pharmaceutical consulting firm, Proximare12

AT: FDA Approval

FDA approval is bad – turns their U.S. key warrants:

Stifling bureacracyForbes 11 (Steve Forbes—the creator of Forbes magazine, “How the FDA May Kill Millions of Us”, http://www.forbes.com/forbes/2011/0214/opinions-steve-forbes-fact-comment-fda-may-kill-millions.html)

Governments are notorious for lacking innovation, for being wedded to caution and routine. After all, if you take a risk and it doesn’t pan out, you could be raked over the political coals. A

prime example of this stifling bureaucratic approach is the Food & Drug Administration, whose notoriety for making the approval of new drugs ever more expensive–with nothing to

show in efficacy and safety–has been increasing over the years. The FDA’s behavior is no surprise to the organization’s watchers: Approve a medication that has an unintended side effect and congressional headline-seekers will be giving officials the third degree. Better to let people die by depriving them of new medicines than to be excoriated by the likes of McCarthyite demagogues such as Representative Henry Waxman (D-Calif.).

Approves the wrong drugs – turns antibiotic resistanceForbes 11 (Steve Forbes—the creator of Forbes magazine, “How the FDA May Kill Millions of Us”, http://www.forbes.com/forbes/2011/0214/opinions-steve-forbes-fact-comment-fda-may-kill-millions.html)

But this play-it-safe attitude–even at the expense of human lives–is creating a devastating and potentially far more deadly impact: The pipeline for new antibiotics is drying up. Since

the 1940s the miracle of penicillin and its relatives has saved tens of millions of lives. Antibiotics easily conquered such illnesses as pneumonia and tuberculosis, which routinely killed countless numbers of people each year. Bacteria, of course, can become drug-resistant, but for decades

pharmaceutical companies, especially in the U.S., routinely came up with new antibiotics to fell new killer germs. Now, however, the flow of new stuff has dried to a trickle.¶ Authorities are taking note of all

this, as is the U.S. Congress. Henry Waxman has declared that the pharmaceutical industry’s failure to develop a reliable new class of antibiotics is an example of “market failure.” No it isn’t, Henry; it’s a failure of government regulation. The FDA has made clinical trials cost-prohibitive.¶ Many reasons are being bandied about for the dearth of new drugs: Research is becoming more expensive, thus pharmaceutical companies are finding the cost/benefit risks too high; we are overusing antibiotics, thereby reducing their potency too quickly. But the chief villain is the FDA.¶ In Antibiotics: The Perfect Storm (Springer, 2010) David M. Shlaes lays it out. “Regulatory agencies like the FDA are contributing to the problem with a constant barrage of clinical trial requirements that make it harder, slower and more costly to develop antibiotics.” Another bad guy: “The National Institutes of Health was for many years [biased] against funding antibiotic research.”

Blocks innovationForbes 11 (Steve Forbes—the creator of Forbes magazine, “How the FDA May Kill Millions of Us”, http://www.forbes.com/forbes/2011/0214/opinions-steve-forbes-fact-comment-fda-may-kill-millions.html)

A more fruitful approach would be to overhaul the FDA and remove its capricious hurdles.

Entrepreneurs would then rush in to fill the void. The opportunities would be vast.¶ Even

though the Earth’s soil is not as rich in readily findable antibiotic building blocks as it once was, the Earth’s oceans, scientists are discovering, are a treasure trove for new antibiotics and other medicines to fight diseases such as cancer. Scouring the oceans, experts believe,

could quickly expand the number of drugs tenfold or more. There may even be totally new approaches (see “Antibiotic Artisan”).¶ The new Congress should hold hearings on the FDA’s increasingly deadly and bizarre behavior. One recent atrocity: In December the FDA withdrew its approval for Avastin, an advanced drug used for late-stage breast cancer, even though Avastin has had success here and also has the green light in western European countries. Why has it been withdrawn? Because it’s enormously expensive–$88,000 a year. This is the dismal prospect of ObamaCare: Save money, lose lives.

Bad dataPeart 14 (Karen N. Peart is a writer at Yale News, Yale News, “All FDA drug approvals not created equal”, http://news.yale.edu/2014/01/21/all-fda-drug-approvals-not-created-equal)

Downing and the team evaluated the strength of clinical trial evidence supporting FDA approval decisions for new drugs by characterizing key features of efficacy trials, such as trial size, design

duration, and end points. They used publicly available FDA documents to identify 188 novel therapeutic agents for seven years. These medical review documents summarized in great detail the rationale behind FDA approvals.¶ “Based on our analysis, some drugs are approved on the basis of large, high-quality clinical trials, while others are approved based on results of smaller trials,” said Ross, assistant professor of internal medicine at Yale School of Medicine. “There was a lack of uniformity in the level of evidence the FDA used.”¶ He added: “We also found that only 40% of drug approvals involved a clinical trial that compared a new drug to existing treatment offerings. This is an important step for determining whether the new drug is a better option than existing, older drugs.”¶ Downing said survey data shows that patients expect drugs approved by the FDA to be both safe and effective. “Based on our study of the data, we can't be certain that this expectation is necessarily justified, given the quantity and quality of the variability we saw in the drug approval process,” he said. ¶

CorruptionFassa 13 (Paul Fassa is a writer for Natural Society and The Waking Times, Waking Times, “Medical Authority’s System Kills: FDA-Approved Drugs Kill over 100,000 People Annually”, 7/24/13, http://www.wakingtimes.com/2013/07/24/medical-authoritys-system-kills-fda-approved-drugs-kill-over-100000-people-annually/)Greed, fraud, and corruption within Big Pharma and the FDA are the constructs of deception, with the mantle of authority leading to over 100,000 American deaths each year from correctly prescribed FDA approved pharmaceutical drugs. ¶ That’s an earlier conservative figure based on Dr. Barbara Starfield’s study published in the Journal of the American Medical Association July 26, 2000, “Is US health really the best in the world?”¶ And that doesn’t include those who are sickened, needing more medications from side effects, hospitalization, or years of rehab for crippling adverse “side effects.” Nor does it include the effects from over-the-counter (OTC) drugs that lead to an almost equivalent number of casualties as their prescribed counterparts.¶ How the Medical Mafia Maintains its Monopoly¶ The FDA-Big Pharma partnership scheme calls for long trials involving cruel animal testing and testing on humans with their placebo control groups. The real problem is that the pharmaceutical companies pay for all this and conduct the trials themselves. This expense keeps effective, safe natural medicines from private individuals and small providers out of the FDA approval loop. ¶ The

big boys make their own reports for FDA approval, often paying ghost writers to create favorable medical journal reports that medical professionals sign off for a significant fee. Then Big Pharma pays the FDA a fee for approval. And to top it all off, many FDA “consultants” are Big Pharma insiders with financial ties whose careers depend on that big corporate/government revolving door. All of these situations are corrupt signals.¶

No benefitsFassa 13 (Paul Fassa is a writer for Natural Society and The Waking Times, Waking Times, “Medical Authority’s System Kills: FDA-Approved Drugs Kill over 100,000 People Annually”, 7/24/13, http://www.wakingtimes.com/2013/07/24/medical-authoritys-system-kills-fda-approved-drugs-kill-over-100000-people-annually/)Other Pharmaceutical Testing Flaws¶ An FDA approved substance is a deception that leads most everyone to think the drug they’re taking is safe. But even if taken according to instructions, that’s

probably not true. ”Evidence based medicine” is the arrogant assertion while accusing alternative healers of fraud or lacking science. But what do they consider scientific? ¶ Large scale studies reduce people to improbable statistics. Here’s an example: A shoe company in NYC surveys the foot sizes of 10,000 men, women, and children. Then they take the average size, make all their shoes that size and market them throughout the country. One size does not fit all. ¶ Also, the magnitude and expense of these large studies preclude repeating any tests. But scientific methodology requires the ability to repeat an experiment with the same results.¶ Another aspect of Big Pharma’s reportage includes good editing. Adverse effects, non-efficacy situations, can and are often left out. Long term studies on humans are shunned.¶ The FDA doesn’t bother investigating until well

after marketing and large real-life casualties and lawsuits pile up. By then, the pharmaceutical companies have made their money.¶ Actor-comedian George Burns once said, “The secret of acting is sincerity. If you can fake that, you’ve got it made.” Faked sincerity from pompous authoritative positions is what the Medical Mafia uses to promote their lies to a naive public or attack alternative systems of healing.

Generics Net Benefit – Link

U.S. drug development locks out Indian genericsCarter, senior political economy writer for Huffington Post, 2013(Zach, Obama Administration, Congress Intensify Opposition To Global Generic Drug Industry http://www.huffingtonpost.com/2013/06/28/obama-generic-drugs_n_3513011.html)The Obama administration and members of Congress are pressing India to curb its generic medication industry. The move comes at the behest of U.S. pharmaceutical companies, which have drowned out warnings from public health experts that inexpensive drugs from India are essential to providing life-saving treatments around the world.Low-cost generics from India have dramatically lowered medical costs in developing countries and proved critical to global AIDS relief programs; about 98 percent of the drugs purchased by President George W. Bush's landmark PEPFAR AIDS relief program are generics from India. Before Indian companies rolled out generic versions priced at $1 a day, AIDS medication cost about $10,000 per person per year.But India's generic industry has also cut into profits for Pfizer and other U.S. and European drug companies. In response, these companies have sought to impose aggressive patenting and intellectual property standards in India, measures that would grant the firms monopoly pricing power over new drugs and lock out generics producers.

India is committed to generic drugs – American companies will repeatedly patent any new drugsKumar, writer for Pakistani newspaper The Dawn, 2/17/2014(Anand, “US concerns about Indian generic drugs,” http://www.dawn.com/news/1087496)THOUGH India is one of the largest exporters of generic drugs to the US, ties between the two nations are often tetchy over issues relating to protection of patents and intellectual property rights and the quality of drugs that are manufactured in India.A major crisis is currently brewing between the two countries over the issue, with the bipartisan US International Trade Commission (USITC) launching an investigation – backed by both the US Senate finance committee and the House of Representatives’ ways and means committee – on ‘Trade, investment and industrial policies in India: effects on the US economy.’And later this month, the US Trade Representative (USTR) will also start hearings as a prelude to its ‘Special 301 report,’ reviewing IPR rules and practices by America’s trade partners. Trade bodies, activists and other organisations both from the US and India have begun lobbying for or against the Indian pharmaceutical industry.The US Chamber of Commerce, for instance, has demanded that the USTR classify India as a ‘Priority Foreign Country,’ which is a label generally given to the worst intellectual property offenders and which could result in trade sanctions.“We highlight India as a country with particular challenges with respect to intellectual property protections,” the global intellectual property center of the chamber told the bipartisan commission. “Because India has not shown a record of engagement on these issues and the environment has deteriorated significantly since last year, we are now recommending that India be designated a Priority Foreign Country.”Last year, India annoyed the international pharmaceutical industry and several western governments when it denied patents to cancer drugs Glivec (by Novartis) and Nexavar (Bayer) and allowed domestic producers to churn out generic versions of these expensive drugs. Even the Indian Supreme Court dismissed the plea by Novartis for patent protection of its blood cancer drug. The Indian Patent Office also gave a compulsory licence allowing a domestic firm to make Nexavar, Bayer’s advanced kidney cancer drug by paying a revised royalty of seven per cent.

Organisations that are testifying against India include the Alliance for Fair Trade with India, the National Association of Manufacturers, the International Intellectual Property Alliance, Pharmaceutical Research and Manufacturers of America and the Biotechnology Industry Organisation.But non-profits including Public Citizen and Doctors without Borders, besides a few academics are backing India. “Recently, some pharmaceutical industry groups have criticised India’s patent rules and practices,” Peter Mayburdak of Public Citizen, told the commission. “But India’s practice complies with the WTO’s agreement on trade-related intellectual property rights.”Representatives from the Confederation of Indian Industry, the Indian Pharmaceutical Alliance (IPA), the US-India Business Council and others are defending India’s IPR and patent regime at the hearings.According to the submission by the IPA, after India implemented the TRIPS agreement in 2005, over 1,500 patents have been granted to nine leading international pharma firms, for products and compositions and for manufacturing processes. “When the innovator pharmaceutical industry talks of ‘denial’ of patents, it is not talking of patents for medicinal products in general, but actually of second or third patents for the same product,” it said.

Generics Net Benefit – Case Turns

Generics are the only way to solve for pandemics – IPR creates barriers in less developed countries that allows for diseases to spread Orsi et al 3 (6/25, Fabienne, Lia Hasenclever, Beatriz Fialho, Paulo Tigre, Benjamin Coriat, “Anti-AIDS Policy and Generic Drugs. Lessons from the Brazilian Public Health Program”, http://www.lepublieur. com/anrs/ecoaids8.pdf)

The evidence, after some 20 years of fight against the AIDS pandemic, has led to outcomes that seem totally different from the ones predicted by the proponents of strong protection. This is because

the multinational companies, sitting on their monopolies and protected by international law, have not at all delocalized their activities to the South. On the contrary, after the clauses that used to be beneficial to the locally

established firms were suspended, certain multinational companies began to abandon some of their facilities in the South, regrouping their world- wide manufacturing units in an attempt to achieve economies of scale

[7]. [17]. Furthermore, even before generics began to be produced and distributed locally, multinational drugs manufacturers did anything but lower their prices. In other words, they preempted a situation in which access to treatment remained totally out of reach for patients in the South. Lastly, local firms, the vast majority of whom lack sufficient R&D capabilities, have tended to regress rather than progress. As for the fine chemicals firms that used to produce active principles. Brazil witnessed a mass destruction of its stock of manufacturing once the free-trade agreements that were signed in 1994 came into effect (remember that TRIPS are only one aspect of the general agreements signed under the WTO framework). In addition, it was only once the Brazilian authorities made a commitment to local production that the multinational firms, for once under considerable pressure, began to lower prices visibly. In other words, aside from its remarkable effects in terms of Public Health, one of the main achievements of the Brazilian program is that it provided unambiguous elements for dealing with key issues in the country's political economy. 4. For all of these reasons, the ensuing phase (the 2001 Doha Declaration) has been crucial, with WTO members now openly admitting that it is essential that countries facing epidemic threats be able to use compulsory licenses of patented drugs . Depending on whether this statement of intent is followed by tangible after-effects and enacted in law. the circumstances surrounding the continuation of the battle against tliis epidemic could vary greatly14. The United States' recent opposition (the U.S. is the only country to refuse a compromise text accepted by the 143 other countries represented in Geneva) was a disastrous signal for the wealthy nations to send to the countries of the South. In any event, and even if "South-South" exports of ARVs and other active principles are finally authorized (something that was refused in Geneva in 2002). the Brazilian experience clearly shows that the use of a "compulsory licensing" clause (or the credible threat to use it) constitutes a key strategic tool for achieving the significantly lower prices of drugs that are needed to fight the epidemic.

IPR kills Data Sharing which is key to stopping disease outbreaks Correa 4 (Carlos M, Case Western Reserve Journal Of International Law, “Bilateralism in Intellectual Property: Defeating the WTO System For Access to Medicines”, http://web.b.ebscohost.com.turing.library.northwestern.edu/ehost/pdfviewer/pdfviewer?sid=07000908-d12f-4020-8f78-07157ab24ebe%40sessionmgr114&vid=2&hid=124)

CAFTA significantly departs from the TRIPS Agreement in many areas, particularly in those of interest to the pharmaceutical industry. Thus, it obliges to extend the term of patent protection to compensate for

delays in patent examination and in the marketing approval of pharmaceutical products. It also establishes a sui generis regime of "data exclusivity" for the protection of test data submitted for registration of pharmaceuticals. According to Article 15.10.1 (a) of CAFTA: If a Party requires, as a condition of approving the market Pharma new pharmaceutical or agricultural chemical produ I previous If submission of undisclosed data concerning safety or efficacy, the Party shall not permit third persons, without the consent of the person who provided such information, to market a product on the basis of (1) the information, or (2) the approval granted to the person who submitted the information for at least five years for pharmaceutical products and ten

years for agricultural chemical products from the date of approval in the Party. Thus, if the original medicine is approved in a Central American country, no approval to a generic company can be given during the following five years from the date of approval of the original medicine in that country, whether using the data submitted by the originator company or relying on such approval. Despite the fact that, applications for registration can languish for years,27 and that the company that originated the data has no obligation to file for marketing approval within a limited deadline, the five years period will be counted from the date of approval in the country

Empirics prove IPR doesn’t spur investment and hurts domestic growth of pharmaceuticals Scherer 2k (F.M., “Taking Stock: The Law and Economics of Intellectual Property Rights: The Pharmaceutical Industry and World Intellectual Property Standards”, http://www.lexisnexis.com.turing.library.northwestern.edu/hottopics/lnacademic/?verb=sr&csi=7362&sr=AUTHOR(Scherer)%2BAND%2BTITLE(TAKING+STOCK%3A+THE+LAW+AND+ECONOMICS+OF+INTELLECTUAL+PROPERTY+RIGHTS%3A+The+Pharmaceutical+Industry+and+World+Intellectual+Property+Standards)%2BAND%2BDATE%2BIS%2B2000)

Evidence on the first of these possibilities is provided by the experience of Italy. During the 1950s and 1960s, Italy did not grant drug product patents. A thriving "knock-off" drug industry emerged, selling drugs at bargain prices in the home market and becoming the world's leading exporter of new drugs to other nations that also denied patent protection to drug products. n10 During the 1970s, however, multinational enterprises challenged the Italian law, and in 1978, the Italian Supreme Court ruled that the law denying drug product patents was unconstitutional. It ordered that the law be amended and that the Italian authorities begin accepting drug patent applications immediately. Analyses of events during the decade that followed yield three principal conclusions: (1) no significant increase in Italian drug R&D expenditures relative to world trends; (2) no significant increase in the number of new drug entities introduced by Italian firms; and (3) a sharp deterioration of the Italian trade balance in drugs into the negative realm as export sales faltered and multinational firms imported many of their products into Italy from

elsewhere in Europe. In addition, numerous Italian drug manufacturers were acquired by multinational firms seeking to strengthen their foothold in the Italian market. It is unclear why Italy failed to make the transition from drug imitator to drug innovator. It may be that a decade is too short a time to do so, or price controls may have impaired domestic market incentives for the development of pioneering drugs. Also, Italy lacked the university research infrastructure and cooperative university-industry relationships needed to nourish drug innovation. What is clear is that leadership in the production and export of knock-off drugs to nations lacking product patent protection shifted to India. There is little evidence on the second possibility--an increase in the targeting of drug development efforts toward low-income nations' health problems by multinational drug companies. An early investigation of this possibility and also the hypothesis that the anticipation of domestic future product patent protection [*2251] stimulated Indian manufacturers' new drug discovery efforts up to 1997 yielded equivocal findings. n11 What some multinational drug companies have done is to donate already developed drugs such as Zithromax (effective against trachoma blindness), Ivermectin (effective against river blindness), and Albendazole (effective against lymphatic filariasis parasites) to especially poor nations with a high incidence of such diseases. n12 Four pharmaceutical companies led the list of U.S. corporations, ranked by the total amount of money devoted to philanthropic giving in 1998.

IPR kill Pharmaceutical Industry InnovationGlasgow 1 (Lara J, “Stretching the Limtis of Intellectual Property Rights: Has the Pharmaceutical Industry Gone Too Far”, http://www.heinonline.org.turing.library.northwestern.edu /HOL/Page?handle=hein.journals/idea41&id=239&collection=journals&index=journals/idea#244)

One of the primary justifications advanced by intellectual property law proponents for asset protection is the incentive such protection provides inventors to invest in risky or otherwise costly endeavors necessary to create innovative works that may contribute to the public good. An examination of the findings

presented in this article, however, suggests that this justification is not being met when dealing with the pharmaceutical industry. The risk inherent in bringing brand name drugs to market cannot be used to validate the strong intellectual property protection that has been described in the present article. "The top 10 drug companies are reported to spend on average about 20 percent of their revenues on research and development.*"" These companies have "so many drugs in the pipeline at any given time that they can count on being able to bring a certain number of drugs to market regularly."'*' To illustrate just how financially sound the drug business actually is,

consider the research and development costs of the large drug companies relative to their profits. The top ten drug companies report profits averaging 30% of their revenues—a substantial margin.1** "[l]n 1999, the pharmaceutical industry realized on average an 18.6 percent return on revenues," which exceeds that of commercial banking (15.8%)."* These profits are over and above the considerable governmental assistance available from the National Institutes of Health (NIH) that subsidize much of the early pre-clinical research, as well as favorable tax treatment that enables a rate of 16.2%."' It is difficult, therefore, to characterize an industry that is consistently the most profitable industry in the United States as risky.Despite low risks, the American drug industry fails to achieve true innovation. While the

benefits enjoyed by consumers for the hundreds of recently launched drugs cannot be underestimated, it is difficult to reconcile the observation that many other new drugs add little to the therapeutic arsenal except expense and confusion for consumers. Recall the layering of patents that are secured on several elements of a blockbuster drug so as to preserve its monopoly power and profit potential; or the cleaning up of old drugs in order to secure a new patent on what is essentially a minimal variation on the old version. The surplus of "me-too" drugs additionally exemplifies the dearth of innovation in the drug industry. For instance, there are currently several effective drugs to treat high cholesterol, yet each one varies modestly in terms of therapeutic benefit. To make a profitable cholesterol drug, a company need only synthesize a chemical derivative of a preexisting blockbuster drug that is sufficiently capable of meeting the requirements of patentability. With some extensive marketing, the new drug can then return revenues to the maker with minimal research and development costs. Thus, instead of expending funds on research and development for drugs that treat ailments not yet treatable, many drug companies attempt to focus on developing patentable5 distinct derivatives of preexisting drugs. The American drug industry cannot be cited as the world leader in pharmaceutical innovation. "The United States accounts for 36 percent of global pharmaceutical research and development.""1 "Europe accounts for 37 percent and Japan for 19 percent."'" Many other countries contribute significantly to the research and development of new drugs, many operating under government regulations that provide far less protection for individual intellectual property rights. The evidence suggests that the extension of patent rights over the past decade, due to exploitation of various legislative loopholes and clever patent

applications, does little to stimulate the research and development of new therapies.

Generics are good alleviates unfair medicinal distribution and doesn’t harm the pharmaceutical industry Harrelson 1 (John, “TRIPS, Pharmaceutical Patents, and the HIV/AIDS Crisis: Finding the Proper Balance between Intellectual Property Rights and Compassion”, http://heinonline.org/HOL/LandingPage?handle=hein.journals/wlsj7&div=12&id=&page=)

One reason cited for the high cost of HTV treatment is that the cost of bringing a drug from idea, through development, testing and approval to market is about $500 million.'" Shannon S.S. Herzteld, senior vice president of international affairs at Pharmaceutical Research and Manufacturers of America (PhRMA) states " '[f]or every 15,000 compounds that you look at, three become medicines. Of those three, one makes a profit. . .The International Federation of Pharmaceutical Manufacturers Association (IFPMA), representing research-based pharmaceutical companies in over fifty countries, argues that compulsory licensing only benefits the company receiving the license.1" IFPMA further argues that granting an adequate period of exclusive rights is the only way to promote innovation.1SS Without innovation, patients will suffer from lack of new treatments in the future.'56 A second argument against compulsory licensing, is that it leads to drugs of lower quality.'5 This argument, however, is not persuasive because drug quality does not directly correlate with compulsory licensing.15* Industry standards in the country granting the

compulsory license would be responsible for the manufacturing quality.159 Despite the opposition of the

pharmaceutical industry to compulsory licensing, many developing countries have traditionally avoided the high costs of drugs by developing generic equivalents.'60 Compulsory licensing can decrease the cost of pharmaceutical drugs by seventy-five percent or more.'61 For example, in India, one can obtain a two dollar generic form of Pfizer's patented fluconazole, an AIDS related meningitis drug, that originally cost seventeen dollars.162 An argument in favor of allowing compulsory licensing is that compulsory licensing will promote increased sales that will offset lower prices.'" As a result of the increased sales, if a reasonable

license fee is granted, pharmaceutical companies will not be significantly harmed Furthermore, developing countries account for only ten percent of pharmaceutical profits internationally, with

Africa accounting for only 1.6%.163 Therefore, compulsory Licensing in these countries will not impact the ability of pharmaceutical companies to make sufficient profits to support research and development.166 The United States has been accused of being hypocritical in its opposition to compulsory licensing.'67 The United States has required compulsory licensing to the military on satellite technology and night-vision glasses for public interest reasons.163 Several United States statutes provide for compulsory licensing. For example, the United States government

can issue a compulsory license for air pollution control patents,'69 for nuclear power paten ts,,7n for public health related patents,171 and for items needed for government use.'72

India proves generics are a huge success and key to spurring tech development in LCD’s Lanoszka 3 (Ana, International Political Science Review, “The Global Politics of Intellectual Property Rights and Pharmaceutical Drug Policies in Developing Countries”, http://www.jstor.org.turing.library. northwestern.edu/stable/1601639)

India has argued within the WTO that compulsory licensing is perfectly justified with respect to

pharmaceutical inventions because the public interest should prevail when it comes to assuring the supply of life-saving medicines. Compulsory licensing can create a strong domestic generic drug industry and is generally associated with greater competition and lower consumer prices. It can also lead to a necessary transfer of technology to less developed countries. Prior to the global consolidation

of the pharmaceutical industry in the past decade, compulsory licenses had been routinely used in North America and Europe to facilitate the distribution of new (generic or not) medications. The use of generic

medicines, in turn, has resulted in important economies for the public healthcare system, thereby

contributing to its viability and the protection of public health. The World Health Organization (WHO) has endorsed the legitimacy of measures to promote the use of generic drugs as a means of protecting public health. In its resolution of the Revised Drug Strategy, the WHO (1999) encourages its members "to explore and review their options under relevant international agreements, including trade agreements, to safeguard access to essential drugs."

Current Pharmaceutical Prices prohibit developing countries from accessing medicine that guts disease solvency. Only Indian Generic Drug Production reduces prices and increases drug accessPecoul et al 99 (Benard, Pierre Chirac, Patrice Trouiller, Jacques Pinel, “Access to Essential Drugs in Poor Countries A Lost Battle?”

Increasingly Prohibitive Prices? A study sponsored by US pharmaceutical companies shows that granting drug patents does not tend to increase the price of drugs on the market.30 This study,

however, does not examine the prices of new innovative drugs and declares that, logically, the price of these new drugs should be higher. Naturally, when the manufacturing company is assured that its product cannot be copied, it holds a stronger position to negotiate prices with public health authorities. Moreover, the liberalization of international pharmaceutical trade entails the development of parallel imports between countries where the same drug is sold at different prices. Pharmaceutical companies, which are consequently less inclined to grant significantly lower prices to less developed countries, may instead set unique world- wide prices or delay marketing their drugs in developing countries.28 In either case, access to drugs is jeopardized.

WHO's Revised Drug Strategy and the essential drugs concept are still key strategies to help improve access to essential drugs and worldwide health. The essential drugs concept is evidence based, is simple, promotes equity, and is rooted in firm public health principles. WHO's assistance to countries and advocacy work to promote the essential drugs concept and support countries in the formulation and implementation of national drug policies has resulted in change for the better. This strategy is a proven success but it needs to be continued and strengthened, and new ways of implementation have to be explored, given the changing context. In this spirit, the following recommendations are made with respect to the 4 main issues that have been developed in this article. Procurement of Quality Drugs To improve the quality of existing drugs and their procurement, it is important to develop a permanent "Observatory of Drug Quality," established by WHO in collaboration with organizations involved in the provision of essential drugs (eg, UNICEF, World Bank, the European Union, and nongovernmental organizations), that would oversee the implementation of adequate and effective control procedures. The practical knowledge acquired by international organizations to ensure the quality of generic drugs must be shared with health authorities in developing countries. Invitations to bid, required by big sponsors such as the World Bank, European Union, and the US Agency for International Development, must combine quality criteria and lower costs. Furthermore, procurement of drugs should be centralized at a national level to rein- force the responsibility of governments to make procurement, quality control, stock management, and distribution of essential drugs a priority.

Patents will lead to 242 percent increase in prices Watal 2 (Jayashree, “Pharaceutical Patents, Prices and Welfare Losses: Policy Options for India Under the WTO TRIPS Agreement”, http://onlinelibrary.wiley.com.turing.library.northwestern.edu/doi /10.1111/1467-9701.00299/pdf) Using the luethodplogy given in the Appendix, Table 2 shows that overall maximum weighted price increase for

the entire patentable pharmaceutical segment would be a mean of 26 per cent with linear demand and 242 per cent with constant elasticity of demand. Additional welfare losses in moving from the current largely

oligopolistic markets to patent monopoly would be $50 million with linear demand and $141 million with constant-elasticity-type demand function. These sums amount to about three and eight per cent of the total pharmaceutical market respectively.12 Consumers would lose, in terms of consumers' surplus,

anything between $11 and $67 million at the maximum- depending on the type of demand function assumed.13 Calculations available with the author show that price increases are the highest for the product where price elasticity is the least, i.e. for the pharmaceutical, aciclovir, an anti-herpes medicine that has almost no substitutes. Further, there is no change in price (or welfare losses) where a pre-patent monopoly already exists, irrespective of elasticity, as is the case in two of the 22 patentable pharmaceutical markets and there are minimal changes in a third market where pre-patent H= 0.9 (see Table 1). However, there are significant differences in the results based on the type of demand function assumed. This is because under linear demand the monopolist moves to a more elastic point on the demand curve, unlike in the constant elasticity case where, by definition, both pre- and post- monopoly elasticity is the same.

Other

Massive Exploration Project

Bioprospecting requires tons of exploration and resource collectionBruckner, coral reef ecologist in the National Marine Fisheries Service’s Office of Protected Resources, Spring 2002(Andrew, “Life-Saving Products from Coral Reefs,” Issues in Science & Technology, posted online 11-27-2013, http://issues.org/18-3/p_bruckner/)Expanded efforts by the United States and other developed countries to evaluate the medical potential of coral reef species are urgently needed in particular because of the need for a new generation of specialized tools and processes for collection, identification, evaluation, and development of new bioproducts. The high cost and technical difficulties of identifying and obtaining marine samples, the need for novel screening technologies and techniques to maximize recovery of bioactive compounds, and difficulties in identifying a sustainable source or an organism for clinical development and commercial production are among the primary factors limiting marine bioprospecting activities.The identification and extraction of natural products require major search and collection efforts. In the past, invertebrates were taken largely at random from reefs, often in huge quantities, but bioprospectors rarely provided an indication of the amount of organisms they were seeking, making it difficult to assess the impact associated with collection. Chemists homogenized hundreds of kilograms of an individual species in hopes of identifying a useful compound. This technique often yielded a suite of compounds, but each occurred in trace amounts that were insufficient for performing a wide range of targeted assays necessary to identify a compound of interest. For example, in one report a U.S. bioprospecting group collected 1,600 kg of a sea hare to isolate 10 mg of a compound used to fight melanoma. Another group collected 2,400 kg of an Indo-Pacific sponge to produce 1 mg of an anticancer compound. Yet, as much as 1 kg of a bioactive metabolite may ultimately be required for drug development.

States / Private Sector Solvency

States or private sector can bioprospect without licensing or permitsU.S. Commission on Ocean Policy 04 (2004, "An Ocean Blueprint for the 21st Century: Final Report," govinfo.library.unt.edu/oceancommission/documents/full_color_rpt/000_ocean_full_report.pdf, ADL)Individual states regulate the collection of marine organisms quite differently, sometimes requiring an array of research permits to collect organisms and licenses to gain access to particular areas. Regulations that ban the

removal of specific organisms, such as corals and other sensitive species, often exist in both state and federal protected areas. In protected federal waters, such as national marine sanctuaries, research permits are required for all collections.

However, bioprospecting outside state waters and federal protected areas is unrestricted, except for

certain species subject to regulation under existing legislation, such as the Endangered Species Act. Both U.S. and foreign researchers, academic and commercial, are free to collect a wide range of living marine organisms without purchasing a permit and without sharing any profits from resulting products.

Weird EU Pseudo Impact Turn

Antibiotic resistance strengthens the EUWahlberg, Swedish Civil Contingencies Agency, et al, 2012(Maria, “Five challenging future scenarios for societal security,” https://www.msb.se/RibData/Filer/pdf/26562.pdf)The world in 2032 In 2032, the EU is a stronger player than ever before with far-reaching political, economic and cultural affinity. The member states have transferred more and more decision-making powers to the common institutions and the “pan-European political parties” are engaging more people. Among other things, the emergence of common threats such as antibiotic-resistant bacteria and tough competition in global trade has driven this development.