GlobalDataSpecial supplement:GESensing & Inspection TechnologiesNEW ! Kaye LabWatch ProNext generation monitoring/alarming system combines state of the art RF Wireless Sensor Technology with enhanced software features to elevate the functionality and robustness of the LabWatch system. This combined with the confidence that over 50 years experience and proven product reliability can bring. Visit us on www.gesensing.com/kayeproducts/ Better Safe than Sorry ! GE imagination at workWhen it comes to the monitoring and alarming of Critical Temperature Units (CTU's) in the industry there is no room for risk. Products stored in Stability Rooms, Warehouses, Cryo Freezers and other CTU's can represent millions of dollars. Undetected process failures can result in:- 0e|oy new drug |ounches / processes- l||||ons o dollars |ost |n reseorch hours ond product |oss- Comprom|se morket pos|t|on From the editorWORLDPHARMACEUTICALFRONTIERS | www.worldpharmaceuticals.net 3World Pharmaceutical Frontiers2010 Vol. 1EDITORIALEditor Andrew TunnicliffeAndrewTunnicliffe@globaltrademedia.com Chief sub-editor Elliott AykroydSub-editor Naomi MackayFeatures editor Phin FosterFeatures writers Elly Earls, Ian DuncanProduction manager Dave StanfordGroup art director Henrik WilliamsDesigner Michelle KimEditor-in-chief John LawrenceCOMMERCIALClient services manager Derek DeschampsClient services executive Ilona MolnarovaSales manager Nathan ParkCirculation executive Daniel TrigueirinhoHead of sales Richard JamiesonPublisher William CrockerWorld Pharmaceutical Frontiers is published by Global Trade Media, a trading division of Cornhill Publications Limited, a member of the Audit Bureau of Circulations.John Carpenter House, John Carpenter Street, London, EC4Y 0AN, UKTel: +44 207 753 4200 Fax: +44 207 724 2089Email: info@globaltrademedia.comWebsites: www.globaltrademedia.comwww.worldpharmaceuticals.net ISSN 1742-3791 2010 Global Trade Media, a trading division of Cornhill Publications Limited. Registered in England No. 01564127.All rights reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic, photocopying or otherwise, without prior permission of the publisher and copyright owner. While every effort has been made to ensure the accuracy of the information in this publication, the publisher accepts no responsibility for errors or omissions.The products and services advertised are those of individual authors and are not necessarily endorsed by or connected with the publisher nor Deloitte. The opinions expressed in the articles within this publication are those of individual authors and not necessarily those of the publisher nor Deloitte.The products and services advertised are those of individual authors and are not necessarily endorsed by or connected with the publisher. The opinions expressed in the articles within this publication are those of individual authors and not necessarily those of the publisher.Copies of World Pharmaceutical Frontiers are available from Global Trade Media at a cost of 5.95, 8.00 or $8.95 per copy.Printed by Williams Press Visit www.worldpharmaceuticals.netGlobalDataWPF017_FINAL COVER.indd 1 17/3/10 11:25:59On the web...Keep up with the latest developments in the pharmaceutical industry by visitingwww.worldpharmaceuticals.netAlso in this issuePage 8: A look at some of the biggest developments to shape the industryPage 12: What do executives feel about their companys future prospects?Page 126: Hans Lindn tells World Pharmaceutical Frontiers about his careerR esearch and development (R&D) is the lifeblood of the pharmaceutical sector. This important role is undertaken by both industry and academia; sometimes as a collaborative partnership and sometimes as independent research projects. Its importance is clear, without it there would be no pharmaceutical pipeline.This years Pharma 40 list shows just how important it is, according to our panel of industry experts, with no less than eight out of the top ten spots occupied by leading scientific figures. That is in stark contrast to the 2009 list where pharmaceutical executives dominated, which is perhaps symptomatic of the climate at that time.Phin Foster looks at an important part of the R&D, animal testing. Speaking with Pfizers Dr David Reynolds he asks what the future holds for this necessary, if not controversial, function on page 89. Reynolds, a senior director of experimental biological sciences, argues that while animal testing has declined over the past couple of decades it remains an essential ingredient and will continue to do so for some time to come.In our special supplement on supply chain and logistics beginning on page 49, Ian Duncan talks with Laurent Boer of UCB on the issue of supply chain disruption and the strategies pharma can employ to try to secure the delivery of their products and other essential materials. The recent earthquakes in Haiti and Chile and ongoing concerns of pirate attacks off the Horn of Africa have served to highlight the difficulties facing companies looking to transport their products around the world. On page 77, Sven Stegemann discusses what he says is an uncomfortable shift for pharma manufacturers moving from the tradition of quality testing to quality by design. Although, he says, it is a difficult transition, the rewards for doing so make it worth the effort.And finally, as the economies of the world tentatively emerge from recession, the focus of the industry turns back to more traditional issues and confidence grows as pharma execs discuss in the latest ICD research on page 12. I hope you find this edition of benefit and look forward to welcoming you to our next one later in the year. In the meantime, if there is anything you have seen that you have thoughts on, then drop me a line. And for those of you that have been eagerly awaiting the Pharma 40, I would welcome your comment. Andrew Tunnicliffe, editor,World Pharmaceutical FrontiersPeople powerAndrew Tunnicliffe, editorWORLDPHARMACEUTICALFRONTIERS | www.worldpharmaceuticals.net 5ContentsHow to prepare and plan for supply chain problems.3 From the Editor Andy Tunnicliffe, editor World Pharmaceutical FrontiersMarket intelligence8 News A round-up of all the latest business and healtcare news.10 Vital stats Key facts from the industry.12 The futures bright Hopes for the short- to mid-term future of pharmaceuticals.14 Special delivery GlobalData takes a close look at worldwide drug delivery. market.Special report18 2010 Pharma 40 The top 40 most influential people in the industry. Business overview22 A spoonful of sugar R&D costs for life sciences have been rising for years, but the pill could be sweetened by EHR data. Regulatory issues24 Non-stop action Continuous manufacturing is the future, but it has its own series of challenges, writes Nic Paton.Regional focus28 A Latin swing GlobalData investigates the steadily growing Latin America market and assesses theinvestment opportunities.30 Experience todays and tomorrows metal-based APIs UmicoreSite selection33 Where culture meets business innovation Varadin Park for Life Sciences and Technology34 Gothenburg a leader in drug development Business Region GoteborgRaw materials36 Upwardly mobile The CPAs Marcello Fumagalli examines the API sectors performance globally.Drug discovery & development42 The rise of the robots As automation and robotics becomes ever more advanced, their importance is on the rise.Data management / IT47 LIMS reducing cost and improving efficiencies Thermo Fisher Scientific 50Cover story1836Our annual round-up of the most important people in Pharma.101ContentsWORLDPHARMACEUTICALFRONTIERS | www.worldpharmaceuticals.net6Risk management50 A clear road to market Laurent Boer of UCB on robust delivery strategies.53 The earlier the better DHL56 Kings of the cool chain EnvirotainerCold chain59 The shipping forecast Ensuring shipping is as efficient and waste-free as possible.64 A degree of control Tinytag (Gemini Data Loggers (UK) Ltd)64 Moving to electronic temperature monitoring SensitechProduct security69 Border control EFPIAs new coding initiative provides a model for an end-to- end verification solution.71 Anti-counterfeiting solutions protection where it is needed Constantia Hueck Folien GmbH & Co.KG72 Serialisation solution for a counterfeit crises Siemens IT Solutions and Services75 The real deal Original1Manufacturing76 Better by design The industry is moving from quality by testing towards quality by design.79 Protect your assets ABB80 Pursuing a policy of automatic containment Mettler Toledo82 Save your energy Arup85 Test the water GE Analytical Instruments86 Awash with ideas Dr John Hutcheson explains the issues surrounding the use of water in manufacturing.Contract services89 Of mice and men Pfizers Dr David Reynolds on the advances that may see animal studies become obsolete.92 The higher you climb, the harder you fall Pharmatest Services94 The best of both worlds Medicilon/MPI Preclinical Research-Shanghai 97 Considering Asian clinical trials? INC Research98 Rescuing clinical trials Harrison Clinical ResearchContract manufacturing101 Who can you trust? Eric Langer offers some practical advice on contracting out any function and an insight into the future of outsourcing.106 Where technology meets versatility Alfa Wassermann SpA108 Business expansion in Brazil Nycomed111 The outsourcing code Rechon Life Science Drug delivery & formulation113 When two become one GlobalData examines the success of drug-device convergence.119 Developing a cure for protein instability Do-Coop Technologies 120 Predictable behaviour of drugs TNO122 Health in Gum Cafosa125 Needle free injection CrossjectPeople126 Teaching a lifestyle Executive director of the EUFEPS, Hans H Lindn, talks to Andy Tunnicliffe about his work.Directory128 Product showcase 137 Index76LogisticsPharma supply chain and logisticsCONTENTS TECHNICAL PAPERSTurn to p49 for our special supply chain and logistics supplement.5989113126www.multipharma.ch | info@multipharma.chCMYCMMYCYCMYKMultipharma_Ad_03082010_Final.pdf 3/8/10 4:05:11 PMAstraZeneca (AZ) has announced a five-year restructuring plan that will see it cut 8,000 positions around the world, according to David Brennan, the companys chief executive. Refusing to speculate on exactly where the cuts would be made until employees had been consulted, Brennan said the companys research and development unit and its sales and marketing arm would see the largest losses. This latest round of cuts comes off the back of an extensive exercise since 2007, which has seen headcount fall by more than 12,000. The news comes at a time when AZs closest British rival, GSK, also announced cost-cutting measures, leaving industry-watchers to ponder the level of possible staff reductions. GSK CEO Andrew Witty told the media of plans to reduce costs by as much as 500 million within two years, resulting in the loss of up to 4,000 of its 99,000 global workforce. We remain very conscious of the impact restructuring has on our employees. Where possible, we will continue to try to preserve jobs. As before, we will not be providing targets for job reductions and we will announce restructuring outcomes once employees, relevant works councils and trade unions have been consulted.Meanwhile, Merck has announced plans to cut 17,500 jobs worldwide as part of a restructuring programme following its acquisition of Schering-Plough. Its plans were revealed at the same time as it announced a leap in fourth-quarter profits. However, the company said an ongoing reevaluation of manufacturing and R&D facilities worldwide has not yet been completed. It said it would continue to hire new employees in strategic growth areas. M&AAbbott deal opens up marketAbbott has completed the purchase of Solvay Pharmaceuticals in a 4.5 billion deal. The sale is seen by many analysts as key to helping Abbott break into emerging markets and secure sustainable growth, as well as providing it with branded generics, a foothold into a market now seen by big pharma as a viable option. The acquisition of the Belgium-based company is expected to add as much as $2.9 billion to Abbotts 2010 sales.The acquisition of Solvay Pharmaceuticals is a key part of Abbotts strategy to bolster our presence in key markets and deliver sustainable, industry-leading growth, said Chairman and CEO, Miles D White. He went on to say the deal would also add to Abbotts R&D investment.The combination of Solvay and Abbotts pharmaceutical businesses will enable Abbott to attain leadership in key emerging markets, where there is significant opportunity for branded generics, said Olivier Bohuon, executive vice president, pharmaceutical products group at Abbott. The addition of Solvay Pharmaceuticals is the catalyst for Abbotts growth and leadership in this area, and will ensure Abbott has the infrastructure, reach and product offerings to continue meeting the needs of patients around the world.Solvays products will add to Abbotts already established involvement in specialist areas such as cardiovascular disease, neuroscience and gastroenterology. They include treatments for mens and womens hormonal health, and exocrine pancreatic insufficiency (the inability to properly digest food), which is also associated with several underlying conditions including cystic fibrosis and chronic pancreatitis.businessAstraZenecas restructure will cut 8,000 jobs worldwide.Jobs to go at british-owned firms in briefIsrael-based generics manufacturer Teva Pharmaceuticals has announced bumper profits for the final quarter of 2009. Sales rose by 34% to be worth $3.8 billion from $2.85 billion during the same period in the previous year. The company said much of its $379 million profit was the result of sales of recently-acquired Barr products. Teva said its yearly profits stood at $2 billion, more than three times the $609 million of 2008.Germans and Italians are the most likely to purchase medicines online, despite knowing that such purchases are unregulated. The findings were part of a recent Pfizer-funded 14,000-strong survey across 14 European countries into the 10.5 billion counterfeit market. Of the prescription-only medicines purchased, the most popular are those for weight loss (45%), flu (35%) and erectile dysfunction (25%).The global recession and a pledge by President Obama to rein in lobbyists failed to quell the spending on Capitol Hill, according to a recent study. The Center for Responsive Politics said lobbying spend for 2009 broke all records, amounting to $347 billion, with the final quarter of 2009 seeing the most activity at a time when the Obama healthcare reform plan gained most attention. Healthcare and pharmaceuticals accounted for $267 million, described by a Center analyst as being the biggest amount ever spent on lobbying efforts by a single industry for one year.GSK has announced plans to open up its work on anti-malaria compounds, as well as pumping funds into what it called an open lab, aimed at independent research teams studying malaria. The news will mean that other pharmaceutical companies and academia will have access to as many as 13,500 already-tested molecules, raising hopes of a collaboration that could yield treatments or even preventative medicines. The announcement, made by CEO Andrew Witty, is the latest in a number of initiatives to gain the trust of society, he said.Market intelligence > NewsWorldPhArMAceuticAlFrontiers | www.worldpharmaceuticals.net 8$2.9bnThe amount the deal will add in sales for Abbott in 2010.Xxxxxxxx > xxxxxxxxxx WorldPharmaceuticalFrontiers | www.worldpharmaceuticals.net 9healthcare British patients at risk of drug shortageExperts in the UK have warned that patients are at risk of serious harm if NHS hospitals do not stop selling drugs abroad. Healthcare providers have been accused of sending drugs intended for patients on the NHS, out for export, in an attempt to raise funds.Of the 40-or-so medicines affected, well-known products such as weight pill Xenical, erectile dysfunction drug Cialis, contraceptive Cerazette, breast cancer drug Arimidex (also known as Anastrozole) and Ailect for Parkinsons relief are known to be in short supply. The Royal Pharmaceutical Society of Great Britain called for the practice to stop, while UK Health Minister Mike OBrien said it was unscrupulous. Rather than selling drugs to NHS patients as they should, they are selling them abroad for greater profit, he added. Manufacturers such as Roche, AstraZeneca and Novartis are also concerned. Neal Patel, a Royal Pharmaceutical Society spokesman, said: Our members are spending long hours chasing down supplies, which are increasingly difficult to obtain. The Society fears that if we do not identify a solution through real understanding of the problem, then patient care will continue to suffer.The UK Government is believed to be holding a summit shortly to discuss the issue and ways it can be resolved. Product saFety middle east ring smashed by authoritiesSyrian authorities believe they may have smashed a counterfeit drugs ring in the country. The series of operations, believed to have recovered millions of dollars worth of medicines, has resulted in the detention of up to 65 individuals.The seizure included drugs for the treatment of cancers and anticoagulant pills that were claimed to be for treating heart attacks and other diseases. Manufacturers such as Novartis, Roche, Pfizer, Bristol-Myers Squibb and Sanofi-Aventis have had their products forged. Sanofi-Aventis, Novartis, Bristol-Myers Squibb and Pfizer confirmed that an operation had taken place and counterfeit drugs had been seized. It is believed the ring was supplying fake medications across a large part of the region including Iraq, Turkey, Lebanon, Iran and Egypt.After breaking the news, one Syrian official said: When we started the investigation, we had no idea of the scale of these counterfeit networks. It is understood that in just one seized shipment during the operation one brand of a leukemia drug with a street value of more than $4 million was uncovered.Syria has approved new measures to tackle the growing problem of counterfeit medicines on its shores. Health Minister Reda Saed said the countrys president had passed a law that would carry heavy penalties. He went on to say Chinese counterfeiters were also involved in the ring, although China refused to comment.research & develoPment elderly miss out on clinical trialsA European-based group of professionals has called on the pharmaceutical industry to start using older patients in itsclinical trials. The EU project, known as PREDICT, warned that trial data taken from a younger pool of recipients cannot always easily be extrapolated, and that older people are being excluded from trials despite the fact that they take the most medication. If treatments are not evaluated for elderly people it is difficult for doctors to balance the risks and benefits, said Dr Gary Mills, director of Medical Economics and Research Centre, Sheffield, one of the project co-ordinators. The group reviewed literature produced on treatments aimed at the older population but found they showed clear evidence that the elderly were underrepresented among the pool of subjects in clinical trials. As part of their research they interviewed health professionals in nine countries as well as more than 50 focus groups with elderly patients and their carers.Dr Mills called on the industry to take practical steps to rebalance the clinical trials pool. Other professionals called on governments to regulate in an effort to encourage the pharmaceutical industry to open up clinical trials to the elderly. Stephen Jackson, Professor of Clinical Gerontology at Kings College, London, said the sector saw it as too much trouble to involve older people.m&a deal catches eye of novartisIn a move seen by many as an attempt to move away from prescription drugs, Swiss giant Novartis has agreed to take full control of Alcon as part of a $40 billion deal. The company spent more than $28 billion raising its stake in the eyecare developer to 77%. It follows the purchase of 25% from Nestl back in 2008.The news has ended the uncertainty over Novartis plans for the company and will be followed by a further acquisition worth $11 billion in coming months, securing outright ownership. Daniel Vasella, chairman and chief executive of Novartis, said: The addition of Alcon will strategically strengthen our healthcare portfolio and our position in eye care, a sector with dynamic growth. It is hoped that the two companies can merge their research and development operations, potentially saving $200 million over three years. research & develoPment milestone reached in tB vaccine searchA group of US-based scientists are hopeful that they have reached a significant milestone in the search for a vaccine that could help reduce the level of TB infection among HIV sufferers in Africa. The group, working out of Dartmouth Medical School, conducted research over seven years involving 2,000 patients in Tanzania. They found the vaccine could potentially cut the number of cases of the disease the leading killer of HIV sufferers on the continent by almost two-fifths (39%). It could herald a new, cheaper way of protecting people from the condition in countries struggling to meet the cost of the HIV epidemic.Lead researcher, Professor Ford von Reyn, said: It is the first time we are going to have a vaccine that is influential in preventing opportunistic infections in HIV patients.The vaccine boosts the immune response of patients that have had the BCG vaccine. Market intelligence > NewsAlcons intraocular lens. Vital statisticsMarket intelligence > Vital statisticsWORLDPHARMACEUTICALFRONTIERS | www.worldpharmaceuticals.net 1026The number of new drugs approved for use in the US by the FDA in 2009. This was just one more than the previous year.R&D30%The amount invested back into R&D by the global pharmaceutical industry annually. Source: ABPI5,281The number of drugs to treat cancers such as leukaemia, colorectal cancer, small cell lung cancer and melanoma currently under development or awaiting FDA approval in the US.Source: MedTRACK10mThe amount spent each day in the UK by pharmaceuticals on R&D. Source: ABPIGENERICS50%The amount of pharmaceutical products dispensed to EU patients that are now generics. Source: European Generic Medicines AssocThe amount that can be saved by individuals requiring drugs daily if they switch to generics. Source: The US FDA (FDA)52%Value of patent expiries 2001-2015 (constant US$ billion)2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 Source: PricewaterhouseCoopers LLP25-20 -15 -10 -5 -0 -Average annual loss US$ 16.4bn$157 billion sales exposed to generic competition by 2011Research on new therapies is critical for scientic advancement, but we also need data that will help doctors use existing therapies appropriately.Dr Michael Hochman, of the Keck School of Medicine at the University of Southern California Many more companies will shift towards a greater externalisation of their drug portfolios, meaning that the returns could be three times as high from investing in less-risky drugs already brought to mid-stage development by biotech companies.Source: Financial Times, LondonTALKING POINTCandida yourpoint of entryto new vaccinemarkets?We believe our new PEV7 vaccine against vulvovaginalcandidiasis (VVC) demonstrates the potential of virosomedelivery to address current vaccine limitations.Clinically and market approved, Pevion-technology-based virosomes deliver High quality antibody responses Excellent safety profiles Uniquely balanced tolerability/immunogenicity Suitability for vulnerable populations Rapid commercial manufacturing scale-upPEV7 is now in Phase I with our RSV and flu candidates due to enterclinical trials in 2011. We are looking now for partners to further exploreopportunities. Whether you have an existing target or are looking atnew markets, get in contact. Find out more at www.pevion.comAdvanced vaccine technology against infectious diseaseswww.pevion.comPevion Biotech Ltd Worblentalstrasse 32 3063 Ittigen/Berne SwitzerlandPhone +41 31 550 4444 Fax +41 31 550 4445 Mail info@pevion.comUp to 75% of women experience an episode ofvulvovaginal candidiasis (VVC) at least once in theirlifetime. About 6% of the infected women suffer fromrecurrent VVC with more than 4 attacks per year, whichstrongly impacts their quality of life. Currently there isno satisfactory treatment or longterm protection.Up to 75% of women experience an episode ofvulvovaginal candidiasis (VVC) at least once in theirlifetime. About 6% of the infected women suffer fromrecurrent VVC with more than 4 attacks per year, whichstrongly impacts their quality of life. Currently there isno satisfactory treatment or longterm protection.candida ad_repro_Layout 1 10/03/2010 13:59 Page 1Overall, across the global pharmaceutical industry, half (50%) of respondents in the What The Global Pharmaceutical Industry Is Planning in 2010-2011: Procurement, Investment & Industry Trends Outlook survey said they were more optimistic about revenue growth for their company in the coming 12 months, relative to the last 12. A further 31% were neutral about revenue growth, compared with 17% who were less optimistic. The expectations regarding revenue growth over the next year are mixed.Industry professionals believe the pharmaceutical industry has been shielded somewhat against recessionary pressures, with many believing the greatest threat to revenues is patent expiry of many blockbuster drugs. The number of executives who were neutral about revenues in Q2 2009 remains similar to today. In Q2 2009, it was 35% compared with today where neutral responses stand at 31%. The pharmaceutical sector portrayed positive signs of economic growth as respondents are far more optimistic compared with Q2 2009 survey. The optimism of manufacturers grew by 10%, CRO and CMO experienced a rise of 13% and industry suppliers saw a surge of 20%. This illustrates that the industry is comparatively positive, no doubt boosted by the fiscal stimuli by governments worldwide. These findings reveal that the number of less-optimistic respondents has declined relatively as they anticipate positive growth in the global economy through increased industrial production, a rebound in global equity market and augmentation in international trade. When compared with buyers, suppliers seem to be more optimistic about the global recovery. Overall in comparison to Q2 2009, respondents are more optimistic about revenue growth. Asia takes its placeAsia Pacific emerged as the market with the largest expectations for growth. Emerging economies constitute about 80% of the worlds population and more than 20% of the global economy. The trade liberalisation and opening up of economies have played a greater role in revenue growth and high level of optimism in the region. The International Monetary Fund (IMF) projects that Chinas GDP will grow at 9% during 2010 and at 6.4% for India during the same period. It also expects that economies will start recovering from 2010.Most of the countries in the Asian region were hit by the financial crisis. The IMF expects that exchange rate flexibility will continue to be important in most countries to allow the region to regain competitiveness and build confidence. Targeted government spending The futures brightAs the world emerges from one of the most difcult economic climates for a generation, pharmaceutical executives tell ICD Research as part of its research for its latest sector survey of their hopes for the short- to mid-term future of the sector, and share their companys future prospects.Market intelligence > Market researchWORLDPHARMACEUTICALFRONTIERS | www.worldpharmaceuticals.net 12Key findings: Overall, pharmaceutical industry respondents are optimistic about the companys revenue growth Respondents from Asia Pacific and the rest of the world are relatively more optimistic about their companies revenue growth in comparison with respondents from North America and European regions due to globalisation of R&D operations and M&A activity Asia is growing into a drug manufacturing powerhouse and has emerged as a leading source of drug discovery and high-end innovation over recent years Brazil, Russia, India and China prominently figure among the most important business development destinations throughout the different stakeholder segments Overall, executives from the pharmaceutical industry expect to see increased levels of consolidation in their industry due to attractive valuations and opportunistic takeovers, cost containment/reduction on R&D and thinning pipelines. Source: ICD Research Industry Survey 2010 Question: Are you more or less optimistic about revenue growth for your company over the next 12 months? (% respondents)Colour guideNeutral More optimistic Less optimistic Dont know-2010.-2009. -50% 31% 17% 2%37% 35% 27% 1%15% -10% -5% -0% --5% --10% --15% -Next difference between 2009 and 2010 revenue expectationsNeutral More optimistic Less optimistic Dont know13%-4%-10%1%will help protect poor and vulnerable groups and continued efforts will be needed to identify financial sector risks and ensure appropriate banking supervision to reduce vulnerabilities.Most companies are facing significant pressure to change, with thinning pipelines, skyrocketing R&D costs, calls for lower prices and a greater regulatory burden, these conditions, and the financial crisis, have made the work of creating new drugs harder than ever. Big pharmaceutical companies are being forced to globalise R&D, especially to emerging markets. Merger and acquisition activities are taking place, giving way to small biotech companies. Asia is growing into a drug manufacturing powerhouse and is emerging as a leading source of drug discovery and high-end innovation. Big pharmaceutical companies now rank China as the best location for R&D in Asia, followed by India, Korea and Taiwan.The optimism level is very high in Asia Pacific and in the rest of the world in comparison to the results showcased in Q2 2009. The IMF believes that financial conditions returning to normal should support a rebound of private investment, sustaining demand even as the fiscal stimulus wanes. The result of the survey reveals that ongoing economic growth in emerging markets will contribute more than half of the global growth. European companies will earn benefits from the recovery in the US as it is their most important export destination.Developing countries are more optimistic about global economic recovery as the effects of they were less affected by the financial crisis. The economic crisis has affected every industry but the drug manufacturing sector may continue to thrive through increasing productivity and cost of goods reduction promoting efficiency.More than half (52%) of respondents from the global pharmaceutical industry with revenue turnover up to US$100 million and those with runovers between US$100 million and US$500 million are more optimistic about revenues this year. More executives from larger pharmaceutical companies are considering where to make future investments and are less optimistic about company revenue growth.The net difference in optimism trends for the pharmaceutical industry was mapped with the individual results of 19 other industries. The pharmaceutical industry is a significant one with a relative optimism trend of 33%. This indicates that the sector is well on the recovery path along with other sectors that are driving the economy. Market intelligence > Market researchWorldPharmaceuticalFrontiers | www.worldpharmaceuticals.net 13 Source: ICD Research Industry Survey 2010 Question: are you more or less optimistic about revenue growth for your company over the next 12 months? (% respondents by type)colour guideNeutral More optimistic Less optimistic Dont know----------2010.------2009.----------47% 35% 18% 2%37% 35% 27% 1%Pharmaceutical manufacturer----------2010.------2009.----------55% 31% 10% 3%42% 27% 29% 2%Contract research organisation (CRO) / Contract manufacturing organisation (CMO)----------2010.------2009.----------56% 26% 17% 1%38% 37% 27%Drug manufacturing industry supplier Source: ICD Research Industry Survey 2010 Question: are you more or less optimistic about revenue growth for your company over the next 12 months? (% respondents by region)colour guideNeutral More optimistic Less optimistic Dont know----------2010.------2009.----------49% 30% 19% 2%34% 36% 29% 1%North America----------2010.------2009.----------40% 36% 22% 2%33% 35% 32% Europe----------2010.------2009.----------73% 23% 4%40% 35% 23%Asia Pacifc----------2010.------2009.----------68% 20% 8% 4%45% 31% 22%Rest of the world1%2%the report is available for purchasePlease visit www.industryreview.com or email icdreports@progressivedigitalmedia.comReport Name: What The Global Pharmaceutical Industry Is Planning in 2010-2011: Procurement, Investment & Industry Trends OutlookReport Reference Code: ICDR1049 Price: US$2,000 www.industryreview.comWORLDPHARMACEUTICALFRONTIERS | www.worldpharmaceuticals.net 14As the pharmaceuticals industry continues to explore and innovate in order to maintain growth and profitability, the use of new and innovative drug delivery technologies is being explored for many disease areas. The introduction of new technologies and new routes of delivery combined with increasing research and development (R&D) spending, an ever-expanding competitive landscape and a larger marketplace, have resulted in the creation of new market opportunities for drug-delivery devices. Market to more than triple in sizeThe global drug delivery devices market, comprising infusion systems, inhalation systems and needle-free injections segments, was valued at $26 billion in 2009. The market is expected to grow at an average annual rate of about 18% to exceed $80 billion in 2016. Infusion systems and inhalation systems remain the key segments, accounting for more than 96% of the overall drug delivery devices market in 2009. However, with an expected average annual growth rate of more than 65%, the needle-free injections market is forecast to be the largest segment within the drug delivery devices market by 2016.The inhalation systems market, comprising of dry powder inhalers (DPIs) and metered dose inhalers (MDIs), was valued at Special deliveryThe global drug delivery market is changing like never before. Driven by the introduction of new and innovative technologies with improved product features, the drug delivery market is forecast to attain signicantly high growth in the future. GlobalData takes a close look at this market, asks who the key players are, and provides the lowdown on market dynamics.Market intelligence > Industry in guresJyoti Ranjan Padhi Jyoti Ranjan Padhi is a senior analyst with leading business information and analysis company GlobalData. Jyoti has authored several research reports on topics related to medical equipment, pharmaceuticals and biotechnology industries. He has also led and managed many research engagements on functional areas such as market opportunity analysis and competitive intelligence.$21.8 billion in 2009, contributing 84% to the overall drug delivery devices market value in 2009. The key factors driving growth in the inhalation systems market are the increasing incidence of pulmonary diseases and an increasing awareness of the inherent benefits offered by the pulmonary route for systemic drug delivery. This global inhalation systems market is forecast to grow by an average annual growth rate of 7% during 2009-2016 to reach $35 billion in 2016. As the MDIs segment attains a flat growth pattern, the DPIs segment is forecast to grow by an average annual growth rate of about 11% during 2009-2016 to reach $22 billion in 2016. However, the MDIs market segment will continue to be a value segment within the overall inhalation systems market. MDIs remain the most widely used inhalers, particularly for treating asthma and chronic obstructive pulmonary disease (COPD). MDIs are small, relatively inexpensive and user-friendly, and are suitable for a variety of drugs. On the other hand, DPIs are relatively expensive and rely on inhalation strength and duration for efficient and effective drug delivery. However, the fact that DPIs are well-suited for systemic drug delivery and are perceived as more environmentally-friendly than MDIs are some of the factors driving demand for these devices.Overall, while the inhalation systems market will continue to be a significant revenue contributor in spite of its moderate growth expectations, the infusion systems market is expected to grow faster to reach $7 billion in 2016. The global infusion systems market, comprising of infusion pumps, syringe pumps and infusion disposable sets, was valued at $3 billion in 2009. While the market has suffered over the past two to three years due to negative publicity following product recalls initiated by the FDA and also by leading companies such as Baxter, Cardinal Health and Hospira, the underlying demand drivers seem to be in place. Infusion systems can administer an amount as small as 0.1mL per injection, every minute. Infusion systems deliver medication and fluids into a patients circulatory system in way that, if performed manually by a healthcare professional, would not only be very expensive, but impractical and unpredictable in a good number of cases. This makes a strong case for infusion systems as one of the most ideal and cost-effective devices intended for use in home healthcare settings. Most importantly, the speed with which infusion systems have undergone technological evolution is another factor driving demand. Infusion systems have been continuously evolving from simple microprocessor driven devices to software-controlled sophisticated drug libraries. Improvements have also been made in standardising concentrations and delivery limits. One of the most recent and advanced features available with infusion systems is the integration with hospital information systems. The end result is improved efficiency and a reduction in medication dosage errors, realised through the timely transmission of patient information.Needle-free injectorsThe global needle-free injections market, valued at $1.2 billion in 2009, is forecast to be worth $39 billion in 2016. Factors such as precise dosing, reduced risks of cross-contamination, and pain-free drug delivery have helped to propel market growth. Valued at only $2.3 million in 2000, the market has grown at an average annual rate of more than 99% in the past nine years. While the initial adoption of these systems was slow due to the high start-up and maintenance costs, needle-free injections are now being widely used for the intradermal administration of drugs, vaccines, hormones and anaesthetics. They are also being used in preparing hazardous injections such as cytotoxic chemotherapy injections, thereby reducing the risks of accidental operator injury and environmental hazards. Market intelligence > Industry in guresWORLDPHARMACEUTICALFRONTIERS | www.worldpharmaceuticals.net 15 Figure 1: Global drug delivery devices market, revenues ($bn), 2009 2016 2009 2010F 2011F 2012F 2013F 2014F 2015F 2016F 90 -80 -70 -60 -50 -40 -30 -20 -10 -0 - Source: GlobalDataRevenue ($bn)2629333947576781 Source: GlobalData Figure 2: Global inhalation systems market, revenues ($bn), 2009 2016 2009 2010F 2011F 2012F 2013F 2014F 2015F 2016F 40 -35 -30 -25 -20 -15 -10 -5 -0 -Revenue ($bn)2830333522232526Colour guideDry powder inhaler devices Metered dose inhaler devicesValued at only $2.3 million in 2000, the global needle-free injections market has grown at an average annual rate of 99%.Market intelligence > Industry in guresWORLDPHARMACEUTICALFRONTIERS | www.worldpharmaceuticals.net 16Another factor contributing to the acceptance and market penetration of these products is the fact that needle-free injections have been successful in addressing a range of challenges posed by traditional devices. While these systems are easy to use and eliminate the risk of infection, from a patients standpoint these devices result in the painless delivery of drugs and have been successful in overcoming patients aversion towards needles. From a technology standpoint, new formulations are being designed to gradually release the injected drug, thereby reducing the frequency of injections.More than anything else, the fact that the needle-free injection technique is also being used for insulin delivery is motivating the leading companies to continue to pump in funds for advancing research and strategic collaboration efforts. It is important to note that the insulin delivery devices market is one of the highest growth areas within the medical devices industry. The global insulin delivery devices market, valued at $4.1 billion in 2009, is forecast to grow at an average annual growth rate of about 8% to reach $7 billion in 2016. Strong pipeline and emerging technologiesWith about 235 products in different stages of development, the global drug delivery devices market landscape could undergo significant changes in the coming years. Transdermal Drug Delivery is clearly emerging as the technology of the future. Transdermal drug delivery systems can be based on both passive and active transport mechanisms. Passive transdermal patches are meant for delivery of drugs that are stable and which have a small molecular weight. The drug is preloaded into the adhesive on the patch and these systems do not require customised delivery. The active transdermal patches, on the other hand, are meant for the delivery of drugs with a large molecular weight and require various modalities such as heat, microporation and iontophoresis to deliver the drug. While being a pain-free alternative to injections, transdermal drug delivery systems are also convenient and have minimum systemic side effects. Also, the fact that these devices have led to increased patient compliance resulting in subsequent increase in demand is one of the key driving factors behind the continued research and innovation efforts in this area.While a host of transdermal drug delivery systems are already in the market, many are being developed that are not just innovative but which are also expected to address previously unmet need. More than 40 transdermal drug delivery systems by both small and large companies were in different stages of development in 2009. GSK, for instance, is working on developing and commercialising innovative needle-free patch-based vaccines, in collaboration with the Austria-based Intercell AG. Early in December, 2009, the companies announced an agreement to form a strategic alliance to accelerate the development and commercialisation of needle-free, patch-based vaccines. The agreement includes Intercells candidate vaccine for travellers diarrhoea (TD) and an investigational single-application pandemic influenza vaccine, as well as the use of the patch technology for other vaccines in GSKs portfolio.Interestingly, Intercell is not the only company working on needle-free patch-based vaccines. The Denmark-based Nordic Vaccine A/S and the Australia-based Apollo Life Sciences are also pursuing R&D efforts in this area. Once approved and launched, the needle-free patch-based vaccine delivery technology is expected to revolutionise the way vaccines are delivered by offering benefits such as simplified administration, faster delivery and increased compliance. This technology is also expected to enhance the effect of injected vaccines and result in the development of new vaccines, which require transcutaneous administration in cases where the antigen can not be delivered safely through other routes.Increasing realisation of the market opportunity that the transdermal drug-delivery technology can address has also resulted in heightened deal activity in the recent past. The Figure 3: Global infusion systems market, revenues ($bn), 2009 2016 2009 2010F 2011F 2012F 2013F 2014F 2015F 2016F 8 -7 -6 -5 -4 -3 -2 -1 -0 -Revenue ($bn)4.85.46.16.83.03.43.84.3Colour guideInfusion pumps Infusion disposable sets Syringe pumps Source: GlobalData Figure 4: Global drug deliverydevices market, revenues ($bn), 2009 2016 2009 2010F 2011F 2012F 2013F 2014F 2015F 2016F 45 -40 -35 -30 -25 -20 -15 -10 -5 -0 - Source: GlobalDataRevenue ($bn)1 25814232939Needle-free injections have been successful in addressing a range of challenges posed by traditional devices.WORLDPHARMACEUTICALFRONTIERS | www.worldpharmaceuticals.net 17Market intelligence > Industry in guresUS-based Altea Therapeutics Corporation (Altea) seems to be at the forefront in making strategic partnership agreements. In January 2010, the company announced that it had entered into a partnership with KAI Pharmaceuticals, for the preclinical and clinical development of some of the KAI proprietary peptides, using Alteas PassPort Transdermal Delivery System. In April 2009, Altea announced an agreement with Eli Lilly and Amylin Pharmaceuticals for the development and commercialisation of a novel daily transdermal patch delivering sustained levels of exenatide, also using Alteas PassPort Transdermal Delivery System. In July 2008, Altea announced a partnership with Hospira, for the development and commercialisation of an undisclosed product using the same delivery system.Apart from the acquisition of Iomai Corp by Intercell AG in May 2008, the other notable deal announced in this area in the past two years includes the licensing and development agreement between Eli Lilly and TransPharma Medical. In June 2008, the two companies entered into a licensing and development agreement related to TransPharmas ViaDerm-hPTH (1-34) product, which is administered transdermally using TransPharmas proprietary technology. The product is being developed for the treatment of osteoporosis.Fragmented competitive landscapeWhile market opportunities remain immense, the global drug delivery devices competitive landscape continues to be fragmented, with the top five players not even accounting for one-third of the market. GlaxoSmithKline (GSK) was the global leader in the market with a 13% market share, followed by AstraZeneca with a little less than 9% in 2008. GSK and AstraZenecas leadership position in this market is attributed to their strong presence in the inhalation systems market. Interestingly, the inhalation systems and infusion systems segments remain the only ones with clear market leadership visibility. On the other hand, the needle-free injections segment remains the most fragmented, with many small and medium-sized companies such as Glide Pharma, Bioject, Antares Pharma, Zogenix, BioValve Technologies, Crossject Medical Technology and PenJet Corporation.Considering the fact that the needle-free injections segment is projected to achieve significantly high growth in future, the global drug delivery devices competitive landscape is heading towards obvious dynamism in the market positions of the leading manufacturers. The inhalation systems and infusion systems segments remain the only ones with clear market leadership visibility.It could be argued that now is the time to sit back and take stock after what has been a financially turbulent year. If you were looking for the defining issue of the past 12 months you would not fail to notice the return of the so-called mega-merger. Pfizers $68 billion acquisition of Wyeth, the $47 billion merger between Roche and Genetech, and Mercks $41 billion deal with Schering-Plough may have grabbed the headlines but other deals went through too.With all the change since our last Pharma 40, it was perhaps inevitable that there would be some dramatic movements in the list. But most notable is that of President Barack Obama down from the top spot into 31st place. While it was recognised he has a key role to play within the pharmaceutical sector and wider healthcare reform, our panellists felt he still had more to do. He needs to achieve much more in order to move up the list, commented one.The fact that this year the top ten is dominated by scientists and innovators tells the story of the industry at the moment. There is a need for pharma to refocus on its R&D in the face of the demise of patents and the challenge of the generics market. The product pipeline is key to any future success and now that the worst of the financial crisis is over it is time to get back to the real business.This year we have highlighted four areas that our panellists feel will be key over the coming year. Legislators and regulators feature heavily this year perhaps because of the Healthcare Reform Bill currently going through Congress in the US. And charitable concerns also get fair representation. Then there are the usual contenders from business and science. Do you agree with our panels conclusions? What are your thoughts on this years list? Email me at: andrewtunnicliffe@progressivedigitalmedia.com and let me know.World Pharmaceutical Frontiers presents 2010s top 40 most inuential people in the industry, as judged by our panel of industry experts. Editor Andrew Tunnicliffe takes stock of the ups and downs in what has been a turbulent year for everyone. WORLDPHARMACEUTICALFRONTIERS | www.worldpharmaceuticals.net 181 N Ada Yonath, director of the Helen and Milton A Kimmelman Center for Biomolecular Structure and Assembly 2 N Sir Martin J Evans, Cardiff University, UK3 39 Jeffrey Kindler, CEO, Pzer4 6 Bill and Melinda Gates, co-chairs of the Gates Foundation5 N Craig Venter, president of the J Craig Venter Institute6 23 James Alexander Thomson, director of regenerative biology, Morgridge Institute for Research 7 N Professor Rolf Krebs chairman of the supervisory board of Epigenomics AG8 N Geoffrey Ginsburg, founding director of the Center for Genomic Medicine in the Duke Institute for Genome Sciences & Policy9 N Gregory J Hannon PhD The Hannon Laboratory, Cold Spring Harbour 10 10 Professor Robert Langer, Langer Labs11 N Eric Green, MD, PhD, director of the National Human Genome Research Institute12 N Professor Shinya Yamanaka Institute for Frontier Medical Sciences, Kyoto University13 13 Dr Margaret Chan, World Health Organization (WHO) director general14 35 Ronald D Luff director of anatomic clinical trials, Quest Diagnostics15 27 President Bill Clinton, founder of the William J Clinton Foundation16 N Professor Marvin Caruthers University of Colorado17 4 Dr Janet Woodcock, director of the Center for Drug Evaluation and Research, FDA18 10 Arthur Levinson, former chairman and CEO, Genentech19 N Dietmar Hopp, German billionaire20 N Margaret Hamburg, commissioner of the US Food & Drug Administration21 26 Chris Viehbacher, CEO, Sano Aventis22 5 Shlomo Yanai, president and CEO, Teva Pharmaceuticals23 N Marijn Dekkers, CEO at Thermo Fisher Scientic24 N DW Laske and Ed Oldeld National Institutes of Health and University of Virginia School of Medicine 25 N Lonnel Coats, COO of Eisai Inc and head of Human Health Care26 25 James M Cornelius, chairman and CEO, Bristol Myers Squibb27 N Haruo Naito, president of IfPMA 28 2 Sir Michael Rawlins, chairman of the National Institute of Health & Clinical Excellence (NICE)29 31 Frances M Visco, president of the National Breast Cancer Coalition30 N Michael J Fox, founder of Michael J Fox Foundation31 1 President Barack Obama, President of the United States 32 9 Daniel Vasella, chairman and CEO, Novartis 33 N Dr Thomas Tuschl, group leader at Tuschl Lab34 8 Dr Surinder Singh, Drugs Controller General of India35 N Dr John Sampalis, founder and president of JSS Medical Research36 N Katherine Sebelius, US secretary of health and human services 37 N Ranjit Shahani, president, of the OPPI (Organisation of Pharmaceutical Producers of India)38 29 Billy Tauzin, PhRMA president and CEO39 14 Sir Mark Walport, director of the Wellcome Trust40 N Bono, spearheaded The Red CampaignThe final listPosition in 2009 New entrantKEYNScience & Innovation Business Philanthropists & Legislation & Charitable causes regulation39Special report > Pharma 40WORLDPHARMACEUTICALFRONTIERS | www.worldpharmaceuticals.net19SCIENCE & INNOVATIONInnovation in this field is the bedrock of the sector. That is perhaps why this years list can boast so many renowned individuals; the likes of Ada Yonath, Craig Venter and Dr Thomas Tuschl. In the 2009 list there was not a single scientist within the top 10. Then, it was business leaders that were seen to be the people influencing the sector whereas now it seems normal service has resumed. Our panellists celebrated our winner, Ada Yoneth, on her enduring leadership and mentoring in research as well as for being one of very few women to win the Nobel Prize for Science.Big pharma need to innovate to stay ahead of their competition. Apart from the usual commercial rivals, there is a growing threat from generics further squeezing competition. Add to that the ongoing advances in technology that mean even the unimaginable just a few years ago is now a distinct possibility. The next 12 months could be big for science and innovation.Top 51 Ada Yonath2 Sir Martin J Evans3 Craig Venter4 James Alexander Thomson5 Professor Rolf KrebsBUSINESSAlthough the pharmaceutical sector fared better than many others, it has seen its share of difficulties. While innovation will continue to be key, the work of C-level executives to steady their ships has been obvious. However, this year they have slipped down the list. In 2009 there were six C-level executives in the top 20 whereas this year there are just two, including Arthur Levinson, former chairman and CEO of Genentech. Perhaps the reason for this is the improving economic climate, which has thrown the focus back on science. Of Jeffrey Kindler our panel had mixed views. Agreeing he is a big player and that despite its difficulties Pfizer continues to move forward and innovate under his leadership, one panellist wanted to see more from him. One of the biggest surprises is the omission of Andrew Witty, CEO at GSK and president of the European Federation of Pharmaceutical Industries and Associations (EFPIA). Despite not making it beyond the shortlist, the panel branded him forward thinking in his efforts to raise the issue of access to healthcare. PHILANTHROPISTS & CHARITABLE CAUSESMany would see the donation of money as he main gift of a philanthropist but it could also be said that the personality of the donor can offer something more: a high profile and access to the decision-makers that otherwise might not have been available. President Bill Clinton, is one of those personalities. He was in particular applauded by our panel for his work on trying to bring HIV/AIDS treatments to the worlds most impoverished nations. One panellist remarked that he was getting the job done and said it was an impressive second act. Proof of the importance of charitable work is that Bill and Melinda Gates are still in the top 10. The foundation is respected around the world for its work in a number of fields. They continue to set an example in charitable work through innovation, said our judges.Top 51 Jeffrey Kindler2 Arthur Levinson3 Chris Viehbacher4 Shlomo Yanai5 Marijn DekkersTop 51 Bill and Melinda Gates2 President Bill Clinton3 Dietmar Hopp4 Frances M Visco 5 Michael J FoxLEGISLATION & REGULATION2010 is a big year for regulators, particularly in the US. With President Obamas Healthcare Reform Bill still going through, US lawmakers will play a pivotal role in shaping the industry. The major story of this years top 40 is that President Obama, last years winner, finds himself in 31st place. There has been criticism of his tactics in trying to get the Reform Bill passed. Our judges felt the President needed to achieve more but one felt he would succeed in his effort while another said he was a future prospect.India has also slipped down the list with Dr Surinder Singh, drugs controller general of India, at 34th place. New to the list in 2009 Singh, then in eighth place, was only just beaten by his Chinese counterpart Shao Mingli. But perhaps even more telling is the failure of Mingli to make it onto the list at all this year. Our panel felt he had not risen to the challenges the Chinese industry is facing. Top 51 Dr Margaret Chan2 Dr Janet Woodcock3 Margaret Hamburg4 Haruo Naito 5 Sir Michael RawlinsDr Margaret Chan. Bill and Melinda Gates.Jeffrey Kindler. Ada Yonath.Special report > Pharma 40WorldPharmaceuticalFrontiers | www.worldpharmaceuticals.net 202. sir martin J. evans One of the 2007 winners of the Nobel Prize for Medicine, Sir Evans continues to conduct research and gain the respect of his peers. He was awarded the Gold Medal from the Royal Society for Medicine, the Copley Medal from the Royal Society, and appointed to the Advisory Board of the Faraday Institute in 2009. A Cambridge University graduate, Evans continued to research genetics including his work on the knockout mouse throughout his career. He went on to prove new genes could be introduced into cultured embryonic stem cells and used to produce chimeric embryos. 3. Jeffrey Kindler Appointed CEO of one of the biggest pharma companies in the world back in 2006, Kindler has presided over the company during a year when it was fined $1.8 billion by the US government for misleading sales advice, and swallowed up one of its rivals, Wyeth, in a $68 billion deal. In recent months Kindler has become more vocal on a number of issues including stepping up support for US healthcare reform, which he hopes will help address the inequalities in the US healthcare system, and bringing in new laws that will help regulate generics whilst fostering a culture of innovation. 4. Bill and melinda Gates While their Foundation continues to support work in public health both inside the US and around the world there has been a little more emphasis put on other social projects in teaching, housing, technology and an array of other areas. The foundation recently committed itself to working with the Obama Administration on its six-year, $63 billion Global Health Initiative which, among other things, aims to combat AIDS, TB and malaria, as well as increasing access to care for women and children. In one of its latest commitments, Bill and Melinda told the Davos summit the foundation was pledging $10 billion over the coming decade to help fund R&D into vaccines.5. craig Venter Founder of the J Craig Venter Institute, Venter continues to make a substantial contribution to the genetics arena. In 2009 he was awarded the National Medal of Science by President Obama. Dr Venter is being recognised for his dedication to the advancement of the science of genomics, his contributions to the understanding of its implications for society, and his commitment to the clear communication of information to the scientific community, the public, and policymakers, stated the notice of the award. 6. James alexander thomson Renowned for his pioneering work in the isolation and culture of non-human primate and human embryonic stem cells and named as one of the 100 most influential people in the world Thomson continues to work in this increasingly important field. He currently holds the post of director of regenerative biology at the Morgridge Institute for Research and professor in the Molecular, Cellular, and Developmental Biology at the University of California.7. Professor rolf Krebs In a career spanning more than 35 years, Krebs has been responsible for the development of a large number of pharmaceutical products, served on many advisory boards and committees, and contributed to more than 30 books. He has held a number of distinguished positions culminating in his role as chairman of the supervisory board of Epigenomics AG. Stating that he has had an incredible career our judges said he has made an important contribution to research and the wider pharmaceutical community. 8. Geoffrey Ginsburg Having won a number of awards for his research accomplishments including the Innovator in Medicine Award from Millennium in 2004 and the Basic Research Achievement Award in Cardiovascular Medicine from Duke in 2005, Ginsburg was recently appointed to the FDAs Clinical Pharmacology Advisory Council. Our panel applauded his achievements this year. What will the next herald? 9. Gregory J hannon, Ph.d Hannon was singled out for his work in an important new area of cancer. His ongoing research into molecular imaging and exploring the mechanisms and regulation of RNA interference, as well as its applications to cancer research stands out and has won him numerous awards. A key figure in cancer research and treatments, he hopes to apply the RNAi pathway as a tool to unravel oncogene and tumour suppressor pathways and to identify new anticancer targets. Research into this field is at an exciting stage will the next 12 months provide the breakthrough we have been waiting for?10. Professor robert langer Robert Langer has spent much of his life working in medicine, holding esteemed positions such as chairman of the United States Food and Drug Administrations Science Board. One of his latest projects could, one day, provide an effective treatment for diseased arteries. 11. eric Green, md, Phd Greens research looks at the application of large-scale DNA sequencing and problems in human genomics, genetics and biology. Human genomics will be a big part of the future of pharmaceuticals as research continues with the possibility of medication being targeted for individuals with specific genetic make-ups. Our panel said they had big hopes for things to come.12. Professor shinya Yamanaka Known for his work on induced pluripotent stem cells, and having received the Robert Koch Prize and Shaw Prize, Professor Yamanka is a leading figure in the pharmaceutical world.13. dr margaret chan Chan was appointed to her position in 2006 and since then has faced a number of issues. None have been as big as this past year; the first pandemic of the 21st century. The WHO coordinated the global response, collated statistics and managed the public, commercial and NGO response. 14. ronald d luff Luff found himself in the top 40 because of his contributions in cytology and cytopathology, most notably for his work as the former Chairman of the Editorial Committee for The Bethesda System. 15. President Bill clinton Said to be impressive by our judging panel, the Clinton Foundation continues to support 01 ada YonathYonaths most notable success came in 2009 when she was awarded the Nobel Prize in Chemistry along with Venkatraman Ramakrishnan and Thomas A. Steitz for discovering the structure of ribosomes, a potential target for drug discovery and metabolism. The Israeli-born crystallographer became the first woman in 45 years to win the prize for sciences and the first-ever female Israeli to be awarded a Nobel Prize. Having endured a difficult childhood and the untimely loss of her father, Yonath returned to Jerusalem, where she was born, to study, achieving a bachelors degree in chemistry in 1962. She received a masters degree in biochemistry n in 1964 and PhD in x-ray crystallography in 1968. Her professional career includes a number of distinguished positions and remarkable achievements including setting up the very first protein crystallography lab in Israel in 1970. She went on to work in Europe and the US but remains at the Weizmann Institute where she leads the Helen and Milton A Kimmelman Center for Biomolecular Structure and Assembly. Her pioneering research into ribosomal crystallography the study of the mechanisms underlying protein biosynthesis will, it is hoped, lead to the discovery of new medicines such as antibiotics. Announcing her award, the Nobel Committee said: These models are now used by scientists in order to develop new antibiotics, directly assisting the saving of lives and decreasing humanitys suffering.Special report > Pharma 40WORLDPHARMACEUTICALFRONTIERS | www.worldpharmaceuticals.net 21JUDGING PANELWe would like to thank the panel, without whom we would not be able to bring you what is the definitive list of the 40 most influential people in the pharmaceutical sector. ANDREW JACK is the pharmaceutical correspondent with the Financial Times in London. Andrew is a distinguished writer with a wealth of industry knowledge.AGNES S KLEIN MD, DPH is director of the Centre for the Evaluation of Radiopharmaceuticals and Biotherapeutic Products in the Biologics and Genetic Therapies Directorate. JOHN RHODES is global managing partner in life sciences industry practice at Deloitte. He is also the Founder & Chair of the Annual Pharmaceutical Accounting & Reporting Congress.MICHAEL SANTORO serves as an Associate Professor with tenure at Rutgers Business School in New Jersey.He is a world renowned expert on intellectual property, ethics, human rights, and trade.ED SILVERMAN is a prize-winning journalist who has covered the pharmaceutical industry for well over a decade.ANDREW TUNNICLIFFE is editor of World Pharmaceutical Frontiers.work being undertaken to promote healthier lifestyles in the US and around the world. 16. Professor Marvin CaruthersScoring highly with our judges, Caruthers was singled out for his work, which led to the automation of DNA synthesis. 17. Dr Janet WoodcockWith a long and distinguished background in pharmaceuticals and regulation, Dr Woodcock has been involved with the FDA for the past 24 years. Her most-recent initiatives have included the Safety First and Safe Use programmes designed to improve drug safety management within and outside FDA, respectively.18. Arthur LevinsonHaving worked in the industry for many years, Levinsons experience is undeniable. He oversaw the merger with Swiss rivals Roche in 2009 and remains an influential player within the company. He is also expected to be nominated to the Roche board at their 2010 general meeting. 19. Dietmar HoppAs a major shareholder in an array of biotech companies having invested hundreds of millions Hopp has gone rather quiet over recent months. But as he has proved before, acquisitions are second nature to him and can sometimes come out of the blue.20. Margaret Hamburg, MDDr Hamburg follows von Eschenbach as the 21st Commissioner of the US FDA. Having been appointed by a unanimous Senate vote in May 2009, she became the second woman to take the role. The judges praised her new and innovative leadership.21. Chris ViehbacherBoasting a 20-year career in the industry, Viehbacher has been at the top of the French drug maker for more than a year. He believes in the model of big pharma and says there will be far more of an academic focus in coming years. 22. Shlomo YanaiAs CEO of one of the largest generics company, this could be the year this individual makes waves. The judges felt Teva was developing into a strong player.23. Marijn DekkersDekkers will replace current CEO of Bayer Healthcare, Arthur Higgins, when he steps down from the role later in 2010. He joins at a time of change as a number of senior level executives are moving on to pastures new. How will he steer the ship through what will surely be a complex and potentially destabilising transition? 24. DW Laske and Ed OldfieldAs inventors of convection-enhanced drug delivery these two will always be in the back of the mind of the pharmaceutical industry watchers. They are both continuing what the judges called their innovative research, and could well present another huge breakthrough at any time. 25. Lonnel CoatsHuman Health Care has, in the past, said: Human Health Care is giving first thoughts to the patients and their families and contributes to increasing their benefits. Thanks to Coatss consistent lead on that mission, the company tends to pass on very profitable projects if they are not benefiting patients. 26. James M CorneliusLauded for his drive to promote ethical behaviour within the industry, Cornelius remained in his post during a year that saw the company ride out the financial crisis.27. Haruo NaitoIt may be somewhat tough to have a major impact as his position as president of IfPMA only lasts until November 2010. 28. Sir Michael RawlinsNow in his 11th year in the post, Sir Michael is on the list again for the continued role of excellence and example set by NICE. 29. Frances M ViscoRemaining at the top of one of Americas most powerful pressure groups, the National Breast Cancer Coalition, she has used her influence to push the issue of breast cancer up the political agenda.30. Michael J FoxFox found himself on the list for his continuing efforts to raise awareness and millions of dollars for research into Parkinsons disease. 31. President Barack ObamaIn his first year, President Obama has taken great steps to reforming the US healthcare system, although there is work still to be done. 32. Daniel VasellaHaving been chairman and CEO of Novartis since1996, Vasella has a wealth of experience. 33. Dr Thomas TuschlHe is continuing his research into regulatory mechanisms of RNA interference, RNA-mediated translational control, and nuclear pre-mRNA splicing. 34. Dr Surinder SinghAs Drugs Controller General of India, our panel felt he was doing a good job in a difficult setting. 35. Dr John SampalisRemaining one of Canadas leading epidemiologists; involved in academic and pharmaceutical research. 36. Katherine SebeliusIf and when the US Healthcare Reform Bill passes into law this leading politician will be responsible for its implementation, 37. Ranjit ShahaniIndia is on the threshold of becoming a major player in pharmaceuticals but as director of the OPPI, Shahini still faces some big challenges. 38. Billy TauzinIn his time as PhRMA president and CEO, Tauzin has been renowned for his efforts to drive down the cost of healthcare. 39. Sir Mark WalportResponsible for the day-to-day running and strategic management of the Wellcome Trust, he received solid and consistent marks from our judges. 40. BonoThe Red Campaign aims to help fight HIV/AIDS in Africa. Under Bonos leadership it has raised as much as $140 million. Most life sciences (LS) research & development (R&D) functions are under increasing pressure to improve innovation, reduce development inefficiencies and improve product safety. Patient-level data, collected through electronic health record (EHR) systems, offers one promising avenue for redefining R&D and revolutionising the LS value chain. Globallyaggregated, patient-level data could support identification of disease mechanisms and new discovery areas, quick termination of unsuccessful compounds, rapid recruitment of patients for trials, and continuous drug safety surveillance. Although it has potential for the entire enterprise, this article focuses specifically on how EHR data can improve research, development and post-marketing surveillance. R&D costs have increased sevenfold in the past 25 years without a corresponding increase in new chemical entities (NCEs). A widely accepted estimate for R&D cost per new compound was $802 million, however this estimate has been re-assessed at $1.7 billion with the expectation that it will only continue to increase in the future. As they seek to lower costs, industry leaders must find ways to support innovation and collaborate more effectively as the industry moves toward personalised medicine. At the same time, regulators and payors are demanding better safety and surveillance mechanisms. Lengthy trials and delays raise costs Skyrocketing development costs are partly attributable to the slow pace of discovery and validation. Efforts to find better biomarkers and terminate ineffective compounds more quickly are hampered by the complex analysis required. Most LS researchers do not have access to the large, comprehensive patient data sets necessary to readily compare disease behaviour to associated genetic alterations.The increasing rigour of clinical trials also drives up R&D costs: average durations of the clinical phase have increased from 3.1 years in the 1960s to 8.6 years in the 2000s. Inefficient patient recruitment and subsequent delays are another source of R&D cost increases. In 1998 only 40,000 of the 778,000 physicians in the US participated in clinical trials. Trials miss patient enrolment deadlines almost 80% of the time because of the large number of participants required and the inability to track patients that meet prescreening criteria. The average delay from missing enrolment deadlines is about 90 days; each day of delay costs an estimated $1.3 million in lost sales.Current methods dont support the demand for safety and surveillanceIncreased media attention has piqued public concern over drug safety at the same time as federal regulations have become more stringent, mandating risk mitigation plans and improved visibility into clinical trials. Since 1998, more than 70% of New Molecular Entities (NMEs) were approved with post-marketing commitments. Despite the increased focus on safety, most LS companies currently measure safety and efficacy through the limited information reported by physicians. Not only is this reactive surveillance unsatisfactory for improving safety, it provides limited insight into a drugs overall risk/benefit profile. To compound the problem, payors increasingly want medical evidence on the safety and effectiveness of a drug as a prerequisite for reimbursement decisions and are challenging the cost of drugs that lack this evidence. The EHR effectAccess to secondary EHR data could provide scientists with a large database of patient information for quantitative polymerase chain reaction (PCR) results in relation to a variety of treatments. Instead of performing lengthy and expensive pre-clinical experiments to uncover toxic compounds, within minutes they would be able to draw correlations between gene expression, disease progression, and treatment efficacy for similar classes of drugs. Also, access to any disease demographic, locating the largest target patient populations, and recruiting those patients during routine clinic visits will cut not only reliance on investigators to recruit patients but will also dramatically reduce the cycletime for clinical trials.Automated adverse event reporting through the EHR system would also allow tracking of the safety and efficacy of a treatment and could stop a potentially damaging treatment or trial before exposing any more patients.A long-term enabler for LS companiesEHR-derived data has the potential to transform the industrys approach to research, development, and post-market surveillance (Figure 1). Some of the capabilities are already within reach while others require further development. Early adopters can improve efficiency, reduce costs and gain a competitive advantage in post-marketing surveillance and clinical trial cycle time.Research: As EHR integration becomes more sophisticated, companies will be able to use patient-level data within the discovery process. This data should facilitate biomarker discovery and validation, earlier termination of unsuccessful or toxic compounds, and advances toward personalised medicine.A spoonful of sugarR&D costs for life sciences have been on the increase for many years, but at last the pill may be sweetened by EHR data, which can cut the time and cost of clinical trials and pretrials, as Deloitte Life Sciences Divisions Terri Cooper and Glenn Carroll explain.Market intelligence > Business overviewWoRLdPHARMACEuTiCALFRonTiERS | www.worldpharmaceuticals.net 22Development: Access to longitudinal patient records should help reduce clinical trial cycle times by enabling search capabilities that track specific disease demographics, and by identifying investigators and trial-ready sites. By using EHR data, patient populations that meet the inclusion/exclusion criteria can be quickly identified, which could help reduce patient recruitment times. Going one step further, slightly altering the inclusion/exclusion criteria could dramatically increase the patient population and in turn help further reduce recruitment cycle times. In addition, prior clinical and diagnostic data could help improve clinical trial design as a result of better understanding disease progression and care pathways. Post-marketing surveillance: There is an immediate opportunity to use EHR data within post-marketing surveillance to measure drug safety. In the near future, large, anonymised longitudinal patient data sets will be available to help identify emerging health problems and populations at high-risk for disease, support outcome studies on the effectiveness of treatment(s) and evaluate the usefulness of diagnostic tests. As EHR data becomes more widely available and accessible, pharmaceutical companies are at risk from other healthcare organisations who will compete to master EHR information to measure drug effectiveness and outcome statistics. It is imperative that LS companies adopt an EHR strategy early to overcome the growing pains of leveraging a new technology and develop a means to elucidate sophisticated, comprehensive data sets from EHR systems. The limitations of a nascent fieldAlthough there are many benefits from an EHR strategy, LS organisations will face several challenges. Conceptually, using this data effectively depends upon integrating multiple EHR systems in a way that maximises query and search capabilities. The lack of a common language for patient information may prevent effective interoperability between EHRs and the IT systems used by LS companies. Other hurdles include confidentiality issues, intellectual property concerns, ownership/governance regarding EHR data, and other legal and ethical considerations related to using patient data. These issues will require the collaboration of relevant stakeholders to establish standards and develop innovative solutions.An EHR strategy requires proactive communication and relationship building In an environment focused on short-term success, communicating the value of a long-term EHR strategy may be difficult. Executives must first create believers and enable the industry collaborations that will demystify the value of applying EHR data. Theyll need to:gain internal buy-in: resolve varied and conflicting perspectives on the relevance of patient-level data and alleviate skepticism regarding how use of that data will impact research innovation and decision-makingestablish cross-functional lLinkages : Promote effective internal and external collaboration; because EHR data resides in hospitals and health systems, gaining access to patient-level information hinges on the LS companys ability to develop relationships with provider institutions. Building a foundation for long-term EHR successEarly adopters of an EHR strategy will focus on developing the processes that will be positioned to accelerate their ability to use patient-level data to drive cost reduction and operational efficiencies. The first step is to develop a comprehensive approach that is aligned with Corporate Strategy and drives measurable business value.Industry leaders are paving the way to an EHR strategyCompanies such as Pfizer have already recognised the significant potential for integrating patient-level data across multiple areas of drug discovery, development and commercialisation. Life Sciences companies have dedicated resources to health informatics and is in the process of evaluating applications for EHR data use. A variety of other healthcare companies are currently assessing opportunities to apply external EHR data using methodologies and governance models for future-state, EHR-based operations. Market intelligence > Business overviewWoRldPHARmAcEuTIcAlFRonTIERs | www.worldpharmaceuticals.net 23Figure 1: Potential benefts of integrating EHR data within drug development. Trial design(refning inclusion/exclusion criteria)Patient and investigator recruitment (patient recruitment)Execution and analysis(patient compliance tracking) EHR alerts increased enrolment rates from 2.4% to 22% of recruited patients (prior knowledge of health status could drive further improvement) Total cost savings for screening 40,000 patients with a 5% hit rate is approximately $3.2 millionStudies show EHF data can drive: a 28% increase in eligible patient identifcation a doubling of monthly patient enrollment rate a near ten-fold increase in the enrolled to referred ratio. Journaling compliance increased from 11% with paper-based methods to 94% electronically EHR-based monitoring enables intervention before patient must be excluded from dataset Use of EHR data and patient alerts reduces attrition rate by 50%, reducing overall trial sizeSavings: $3.2 million Additional revenue: $125 million Savings: $1.8 millionAssumption for calculating savings and additional revenue Phase III clinical trial 40,000 patients screened givent 5% hit rate 2,000 patients enrolled in anticipation of 25% attrition rate Recruitment expected to last 250 days Per patient screening cost: $100 Cost per enrolled patient: $6,000 Anticipated product revenue: $1m/daySource: DeloitteThe pharmaceutical industry inevitably relies on scientific and technological advances and breakthroughs to maintain its dynamism, relevance and lets not be shy about it its profitability. But technological change and advances can, in turn, create new challenges and headaches. So it is with the rise of continuous manufacturing and the industrys gradual move away from batch manufacturing, which in turn poses challenges to national regulators and the industry alike when it comes to the regulation and validation of pharmaceutical product.Continuous manufacturing or processing allows a pharmaceutical manufacturer to run, as its name suggests, a continuous end-to-end manufacturing process. Although relatively common in process manufacturing industries such as food or chemicals, it is something still very much in its infancy in the pharmaceutical world. Up to now, batch manufacturing where there might be a constant flow of product in and out (as with continuous manufacturing) but where production is run for a limited or defined period of time or for a fixed amount or batch of product has very much been the prevailing mode of production. Other manufacturing operations, such as blending, drying and tablet coating have also traditionally been operated in batch mode.While the intricacies of pharmaceutical regulation are notoriously complex, in the US, the Food & Drug Administration has relied on a three-batch quality validation process. Quality Non-stopactionContinuous manufacturing is the future for the pharmaceutical industry, but it brings with it its own series of challenges, as Novartis-MIT Centers Professor Bernhardt Trout explains to Nic Paton.Insight > Regulatory issuesWORLDPHARMACEUTICALFRONTIERS | www.worldpharmaceuticals.net 24is assured by each batch within each unit of operation being tested in quality control laboratories, with the processing cycle being stopped until product quality is assured and pre-set quality parameters are met. If, of course, the standards are not met, the entire batch is rejected or sent back to be reprocessed.But as Professor Bernhardt Trout, director of the Novartis-MIT Center for Continuous Manufacturing, points out, continuous manufacturing has the potential to change this approach forever. The centre is a ten-year research collaboration aimed at developing new technologies to replace the batch-based system with a continuous manufacturing process, with Novartis investing $65 million to get the centre up and running.The biggest leap in manufacturing terms when it comes to regulation is the move to continuous manufacturing. So rather than stop-and-start manufacturing, where you have a number of batches, you have a continuous flow. This in turn creates challenges for the traditional three-batch validation approach because, of course, you do not have batches, so how do you do validation? asks Trout.Of course, not every pharmaceutical manufacturing process can, or even should, run continuously: mixing and crystallisation are key areas where progress is only just starting to be made. But the other side of the coin is that, with batch manufacturing, manufacturers will often experience higher labour costs and greater inventory costs. A drugs active ingredients, for example, have to be synthesised in a chemical manufacturing plant and then shipped to a separate facility, where they are converted into large batches of pills, liquids, or creams. With multiple interruptions, including transport to separate locations, this can mean the production of just one batch of drugs can take weeks. Whats more, the manufacturing design and scale-up required to produce a new drug can be financially unsustainable and exceedingly time-consuming, argues Trout. Continuous manufacturing, conversely, can be more efficient, producing less waste and higher quality, as well as offering better control and flexibility over the process. While there is clearly a challenge around validation and regulation, once you have it right and can show you are adhering consistently to tight specifications built into the process, you should not have to throw out any batches, thus reducing costs significantly.What also has to be stressed is that the FDA has made it very clear that continuous manufacturing will not necessarily have to mean a complete overhaul of its regulatory frameworks. In 2004, for example, it issued Process Analytical Technology (PAT) guidance around innovative pharmaceutical development, manufacturing and quality assurance www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070305.pdf.This argued that flexibility, coordination, and communication with manufacturers were going to be critical going forward. Manufacturers are encouraged to use the PAT framework to develop and discuss approaches for establishing mechanistic-based regulatory specifications for their products, the FDA recommended.What this all means for pharmaceutical manufacturers is that validation will need to be embedded within the continuous manufacturing process rather than being something laid on top of that process, suggests Trout. The FDA has consistently stated that certain regulatory frameworks are suitable for continuous manufacturing, so the framework may not itself need to change very much, but some of the processes will probably have to evolve, he explains.It will probably be more a case of tweaking or creating new procedures within the existing framework rather than having to create a whole new framework, he adds.What also needs to be recognised is that current regulations do not distinguish between batch and continuous Continuous manufacturing can be more efficient, producing less waste and higher quality, as well as offering better control and flexibility.Insight > Regulatory issuesWORLDPHARMACEUTICALFRONTIERS | www.worldpharmaceuticals.net 25Benefits of continuous manufacturingContinuous manufacturing can benefit patients, healthcare providers, and the pharmaceutical industry, by: accelerating the introduction of new drugs through efficient production processes allowing the use of smaller production facilities with lower building and capital costs minimising waste, energy consumption, and raw material use monitoring drug quality on a continuous basis rather than through post-production, batch-based testing enhancing process reliability and flexibility to respond to market needs. Source: Novartis-MIT Center for Continuous ManufacturingProfessor Bernhardt Trout, Novartis-MIT CenterProfessor Bernhardt Trout is director of the Novartis-MIT Center for Continuous Manufacturing and co-chair of the Singapore-MIT Alliance Program on Chemical and Pharmaceutical Engineering. He received his SB and SM degrees from MIT and his PhD from the University of California at Berkeley. In addition, he performed postdoctoral research at the Max Planck Institute. He has published more than 80 papers and currently has four patent applications submitted.Insight > Regulatory issuesWORLDPHARMACEUTICALFRONTIERS | www.worldpharmaceuticals.net 26manufacturing, so in this context the definition of batch means the quantity of pharmaceutical product, rather than the mode of manufacture.The validation has to be done in time rather than in batches. So, for example, if you previously had a certain amount of pharmaceutical product, now you have to look at it in terms of its uniformity over a certain amount of time, explains Trout.The other big challenge when it comes to regulation for the industry is globalisation, with pharmaceutical companies working on an ever-more global basis and with ever-greater standardisation, with continuous manufacturing a key element within this shift. Yet the regulatory environment,