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www.ngpharma.com • Q1 2009

ONE IN A MILLION

DREAM ON

How Shire ensures its products stand out from the crowd

Where Andreas Barner’s researchers get their inspiration

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A NEW IMAGE

GOING GLOBAL

Aperio’s digital pathology solutions help advance preclinical research

International clinical trials bring good results for Wyeth

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BAD REMEDY Why pouring money into mergers won’t cure the pharmaceutical industry’s ills Page 32

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FROM THE EDITOR

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Bigger isn’t always better Why massive mergers can’t take the place of innovative research.

S

“This growth through M&As cannot form a sustainable business model for long.

This is a stop-gap arrangement, to satisfy investors” Shabeer Hussain, Pharmaceuticals Program Leader, Frost & Sullivan (Page 32)

“That differentiating factor – focusing on symptomatic conditions – helps us. We don’t have a lot of big products in primary care categories that are high on the radar screen” Mike Cola, President of Specialty Pharmaceuticals, Shire (Page 38)

“It became almost an irrational fear of new clinical trials, and we had to get beyond that using really strong science to convince people that our trials are safe” Brian Kotzin, Vice President, Medical Sciences, Amgen (Page 44)

o Pfizer is buying Wyeth. The deal will create one of the biggest pharmaceutical companies the world has ever seen, a company with more than 15 products with $1 billion each in annual revenue.

Pfizer isn’t the only one looking to grow by acquisition. The Roche/ Genentech deal has been in the works for some time, and analysts believe other companies will follow, spurred on by the twin threats of the recession and patent expiries nipping at their heels.

An understandable reaction to current circumstances, perhaps, but not necessarily the right one. When mergers happen, layoffs usually follow. Pfizer has already announced that some of the planned ‘synergies’ to arise from its takeover of Wyeth will involve 20,000 people losing their jobs. Not all of these will be in R&D of course, but some are bound to be.

This should be a time for ramping up research rather than cutting back.

In difficult times, with a steady stream of blockbusters no longer there for the taking, the way forward is to make your research more innovative, to focus on new targets, to diversify your pipeline from within instead of just swallowing up someone else’s.

But a pharmaceutical company is a business first, and despite the most humanitarian intentions of its researchers – intent on curing disease and saving lives – the people at the top have to be interested in profit. As long as mega mergers provide a short-term quick fix to prop up the bottom line, they will remain an attractive option for companies with the cash reserves to pursue them.

There are other ways to thrive in difficult economic times. In this issue, Mike Cola and Sylvie Grégoire explain how Shire stays ahead of the game by focusing on the niche area of orphan diseases, those with between 2000 and 3000 sufferers worldwide. The market is still willing to pay for drugs aimed at these conditions, because their impact on patients’ lives is so huge.

Other interesting areas of research covered in these pages are the work

by Abbott’s Yu Shen to target tumor cells using siRNA, and Brian Kotzin’s biomarker research at Amgen.

Good research is still happening, and it will continue to as long as there are researchers out there who are passionate about their work – nothing will stop that, no matter what the big bosses are up to. It’s what drives the industry forward, and produces the important treatments that can change our lives – we shouldn’t lose sight of that.

Marie Shields Editor

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CONTENTS NGPUS15:jan09

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CONTENTS FEATURES

Money, money Why short-term gain means long-term pain for the pharmaceutical industry

76 The freedom to dream How Andreas Barner lets his researchers follow their inspiration

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Standing out from the crowd

38

Shire carves a recession-defying niche in R&D

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CONTENTS NGPUS15:jan09

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CONTENTS DRUG DISCOVERY, CLINICAL RESEARCH & MARKETING

INDUSTRY INSIGHT

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60 Tina Rogers, MPI Research 86 Paul-André de Lame, Anabase International Corp.

90 Kevin JD Smith, Eurofins Medinet 105 Richard Vanderveer, GfK Healthcare

ASK THE EXPERT 64 Steven Potts, Aperio 70 Ron Ranauro, GenomeQuest, Inc. 100 David Stievater, PDI, Inc.

THE NEXT BIG THING 116 Dean Hart, NanoGuardian

72 Leaping the hurdles Lundbeck works to stay at the front of the R&D race

44 Making the leap Amgen’s Brian Kotzin translates science into medicine

80 Building relationships around the globe Joan Shen extols the benefits of international patient recruitment

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50 High standards How CDISC is pushing for international standardization of clinical trials

88 The world on trial Janet Flisak examines geographical diversity in clinical trials

56 The genetic advantage Allen Roses on using pharmacogenetics to make clinical trials more efficient

92 Patient power

PROJECT FOCUS 128 Mike Rodd, Bürkert Fluid Control Systems

Isabelle Mercier explores the influence of patients over pharmaceutical marketing

62 Going digital Shealynn Harris on the benefits of digital pathology

94 Astroturfing and big pharma

68 It’s all in the genes

103 Down but not out

Abbott’s Yu Shen looks at siRNA and gene expression

Frost & Sullivan’s latest survey shows marketers are not giving up the fight

By Natalie Brandweiner

TROUBLESHOOTER 54 Richard Lake, Restek Corporation 95 Daryl Gaugler, Innovex

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CONTENTS IT & MANUFACTURING

EXECUTIVE INTERVIEW

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37 John Benbrook, MMG 66 Joseph Fischer, Lifeblood Medical 96 Christopher Giuliani, TARP Worldwide 106 John Moran, IMS Health 108 John Miller, Velocity LLC 110 Paul Hilditch, Watermeadow Medical

IN THE BACK 134 Comment 138 Travel 140 Events 142 In review 144 Final word: Gail Adinamis suggests taking protocol visits to the patient

112 Keeping the corporate heart beating Why information is the lifeblood of a pharmaceutical company

118 Staying on track Nina Schwenk tackles reform in the nation’s healthcare IT infrastructure

124 Only as strong as the weakest link Robert Arendal looks at the issues in the pharmaceutical cool chain

131 Worlds apart Genzyme’s Raun Kupiec on the regulatory challenges of a global market

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S I LV E R S P O N S O R

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CREDITS NGP US15:feb09 18/02/2009 16:16 Page 12

28-30 October 2009 The Ritz Carlton Amelia Island, Florida

Chairman/Publisher SPENCER GREEN CEO JAMES CRAVEN Director of Projects ADAM BURNS Editorial Director HARLAN DAVIS

Editor MARIE SHIELDS Managing Editor BEN THOMPSON Associate Editor NATALIE BRANDWEINER Deputy Editors MATTHEW BUTTELL, REBECCA GOOZEE, DIANA MILNE, JULIAN ROGERS, HUW THOMAS

Creative Director ANDREW HOBSON Design Directors ZÖE BRAZIL, SARAH WILMOTT Associate Design Directors MICHAEL HALL, CRYSTAL MATHER, CLIFF NEWMAN

The Next Generation Pharmaceutical Summit is a three-day critical information gathering of C-level R&D executives from the pharmaceutical industry.

A Controlled, Professional & Focused Environment NGP ’09 is an opportunity to debate, benchmark and learn from other leaders. NGP ’09 is a C-level event reserved for 75 participants that includes expert workshops, facilitated roundtables, peer-to-peer networking and coordinated technology meetings.

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A Proven Format This inspired and professional format has been used by over 100 R&D executives as a rewarding platform for discussion and learning.

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Subscription Enquiries +44 117 9214000. www.ngpharma.com General Enquiries info@gdsinternational.com (Please put the magazine name in the subject line)

“A well organized and productive meeting with good topics and open discussion – worth the effort!”

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Letters to the Editor letters@gdspublishing.com

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FRONTLINE

TRAFFIC POLLUTION INCREASES SEVERITY OF ASTHMA IN CHILDREN

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AIR POLLUTION CAUSED BY TRAFFIC near the home affects asthma severity in children, resulting in repeated hospital encounters according to recent study published in Annals of Allergy, Asthma & Immunology.

Ralph Delfino from the University of California, Irvine, and colleagues studied records for 2768 children from two hospitals in northern Orange County. Beginning with the first hospital encounter, investigators analyzed children’s estimated exposures at their home addresses to the

traffic-related air pollutants nitrogen oxides (NOx) and carbon monoxide (CO).

The researchers estimated the risk of recurrent hospital encounters from exposure to air pollution using recurrent proportional hazards analysis. Results were adjusted for sex, age, health insurance, census-derived poverty, race/ethnicity, residence distance to hospital and season.

Previous studies have demonstrated that high traffic density is associated with prevalence of asthma, but the impact of exposure to traffic on repeated episodes of

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FRONTLINE

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NUMBER CRUNCHING

7.3% of American adults currently have asthma

9.4% of American children currently have asthma

Number of asthma-related physician visits

10.5 million Number of asthma-related hospital visits

6.3 million Number of asthmarelated deaths per year asthma was unclear. The study found that traffic-related NOx and CO were associated with repeated hospital encounters for asthma in children, suggesting that local trafficgenerated air pollution near the home affects asthma symptom severity.

Approximately half of the repeated encounters in this study population occurred in children aged between one and three years.

Based on their significant findings in infants with a primary diagnosis of asthma at their first hospital encounter, the authors suggest that early-life exposures to traffic pollutants

may affect asthma severity and development.

Investigators did not find that children of lower socioeconomic status were at increased risk from air pollution exposures; however, they did find evidence that this unexpected result was due to follow-up data that was less accurate in this group.

Environmental data are sparse for highrisk asthma populations. The researchers concluded that additional work with improved assessments of air pollutant exposures and asthma outcomes in high-risk populations is needed.

3884 Asthma deaths per 100,000 per year

1.3 www.ngpharma.com

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FRONTLINE

TAKING IT FOR GRANTED ON WORLD CANCER DAY, February 4th, Pfizer and the Pfizer Foundation announced that they have awarded $7 million to help 13 non-governmental organizations (NGOs) focus on improving both treatment and prevention for cancer patients, through its Global Health Partnerships (GHP) grants program. Their report showed that, since 2007, 29 GHP grants have been awarded to NGOs working in more than 46 countries around the world.

According to Pfizer, these new grants support the global commitment of the Pfizer Foundation and Pfizer's Oncology Business Unit to promote access to quality health care and education and to advance science and innovation in the development of breakthrough medicines that will cure or control cancer.

Currently, cancer accounts for one in eight deaths globally – that’s more than AIDS, tuberculosis and malaria combined. One in three people will get cancer in their lifetime and more than 11 million new cases of cancer are diagnosed annually. “These grants represent an important step in enabling us to partner with key scientists and organizations to encourage the advancement of cancer education and research globally,” said Mace Rothenberg, M.D., vice president of Clinical Development and Medical Affairs for Pfizer's Oncology Business Unit.

The Bloomberg School of Public Health at Johns Hopkins University is tasked with evaluating the GHP grants to build sustainable evaluation capacity among grantees.

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www.ngpharma.com

NEW SOFTWARE INSPIRES SEARCH FOR NEW IDEAS MUSE, A NEW SOFTWARE workflow designed to accelerate the identification and optimization of lead candidates, is now available. CADD scientists and medicinal chemists can use Muse to identify novel structures scaffolds or side-chains that meet specific design objectives.

Use Muse to invent novel structures, scaffolds, or side-chains that meet specific design objectives. Lead hopping, scaffold hopping and inventing new R-Groups around a fixed scaffold are all possible with Muse.

Muse helps advance discovery projects by eliminating traditional barriers to identifying and optimizing lead candidates. Using Muse, you can: • Generate new ideas that meet many different design objectives • Rescue your project when you’ve searched your existing compounds and you’ve run out of ideas, or when filtering virtual screening results leaves you with nothing that meets your design objectives

Molecular design with Muse allows you to address all of organic chemistry to get more ideas. As delivered, Muse can help you generate ideas that optimize shape and pharmacophoric similarity to a set of lead structures.

Successful drug design candidates are reviewed in the context of a significant number of parameters and variables, like potency at the target, selectivity, good ADME properties, toxicity and many more. Muse empowers you to integrate additional computed properties and use them to optimize design ideas. You can get these properties from any in-house or third-party scoring function you have available – like blood brain barrier, ADME, toxicity, docking, etc., to allow you to generate ideas that meet multiple design criteria.

Use Muse to lead hop to clear patent space, scaffold hop to new chemistry, or invent new Rgroups around a fixed scaffold to optimize physicochemical properties. Muse currently operates on Windows XP and Vista (32 bit), and is powered by Tripos’ highly flexible Pantheon platform.

A free evaluation of Muse is available from Tripos International at www.tripos.com/muse

GREEN PHARMA WITH OBAMA’S ENERGY FOR AMERICA PLAN highlighting the need for an increase in

green policies and greater use of renewables, all industries are finding themselves in the spotlight to comply to such demands and reduce their environmental impact. Pharma is no different.

With the manufacturing of drugs seeing a huge amount of packaging used, Rexam Prescription Products claim to

be the first packaging company to develop and market a form of packaging to meet the environmental demand.

The package is an oval, liquid prescription, made with 100 percent post-consumer recycled PET resin which can be recycled again and again, reducing resource consumption.

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FRONTLINE

LARGEST PROVIDER OF CLINICAL/SCIENTIFIC STAFFING SERVICES AEROTEK, A GLOBAL STAFFING PROVIDER, and its parent company Allegis Group, were recently recognized as the largest clinical/scientific staffing provider based on 2007 revenue, according to a report by Staffing Industry Analysts, Inc. (SIA).

According to the SIA report, Aerotek alone generated approximately $200 million in clinical/scientific revenue in 2007 – more than 13 percent of the entire clinical/scientific Aerotek alone generated segment, esapproximately timated by SIA to be $1.5 billion.

Aerotek operates nine divisions that specialize in niche industries. The Aerotek Scientific, LLC division provides clinical/scientific staffing placements for industries such as, pharmaceuticals, biotechnology, healthcare, food and beverage, clinical research, and chemical and plastics.

In April 2008, Aerotek Scientific acquired the scientific division of Kforce, a professional staffing firm providing flexible and permanent staffing solutions.

The scientific division of Kforce generated approximately $27 million in flex revenue in 2007.

Aerotek currently operates more than 150 non-franchised offices throughout the United States, Canada and Europe.

$200 million

Aerotek, headquartered in Hanover, Md., is a leading provider of technical, professional and industrial staffing and program services.

Established in 1983, Aerotek is an operating company of the Allegis Group, the largest provider of staffing services in the United States. Aerotek operates a network of more than 150 non-franchised offices throughout the United States, Canada and Europe. For more information, visit www.aerotek.com.

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ELEVATING THE ROLE OF LABORATORY INFORMATICS AT THERMO FISHER SCIENTIFIC, we believe that Built on the Microsoft.NET framework, the challenges facing life science companies can Thermo Scientific Darwin LIMS can easily be be ideally addressed using a portfolio of purextended to include dashboard-ready tools pose-built solutions that provide as much applithat provide immediate information on recation-specific functionality as possible to meet source and instrument utilization so laborathe particular needs of the various laboratories tory managers can maximize productivity by that service the pharma value chain. For examoptimizing resources. The company’s new inple, our Thermo Scientific Darwin LIMS is a fully tegration initiative, Thermo Scientific validated Laboratory Information Connects, draws on the collective capabilManagement System (LIMS) that is ities of the company’s industrybeing successfully implemented leading laboratory worldwide in pharmaceutical instruments, Laboratory Global deployments of LIMS manufacturing R&D and Information Management QA/QC environments. Darwin Systems (LIMS) and LIMS is specifically designed Chromatography Data have become more to address, out-of-the-box, the Systems (CDS), technoloconsistent and unique needs these laboratogies and services, and capimore rapid ries face to help them meet US talizes on its ongoing Food and Drug Administration (FDA) partnerships with industry leadregulations, resulting in significant time ers including Microsoft, SAP and savings in validation efforts and cost savings in Oracle, as well as members of the Informatics personnel and production time. Among Darwin’s Thermo Scientific Global Partner Alliance. industry-specific functionality, the system hanThermo Scientific Connects is the latest dles dissolution (single-point and multi-point), strategic innovation from Thermo Fisher environmental monitoring, stability manageScientific that continues to leverage the ment, product management, batch management power of the company’s product and services and system interfacing. offerings to bring key business knowledge Today, global deployments of LIMS solutions originating in the laboratory to management have become more consistent and more rapid, alat all levels of the enterprise. lowing for simplified system upgrades, minimized For more information about Thermo Scientific Informatics project risks, and enhanced compliance. solutions, please call + 1 866 463 6522 e-mail marketing.informatics@thermofisher.com or visit Enterprise-level LIMS, like Thermo Scientific www.thermo.com/informatics Darwin LIMS, present pharmaceutical companies with unique integration opportunities. Integrating LIMS with instrumentation and enterprise systems facilitates the harmonization of business processes, automation of operations and consolidation of data management in one system.

This type of enterprise integration allows for near-instant decisionmaking, while helping to streamline processes and reduce costs.

solutions

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FRONTLINE COMMON COLD CURE US RESEARCHERS HAVE DECODED the genome for 99 strains of the common cold, and as a result, may have come one step closer to finally finding the long awaited cure. Stephen Liggett of the University of Maryland created findings from a process of cataloguing the vulnerabilities of the virus; he advised the benefits to be a breakthrough for asthma sufferers and those with chronic obstructive pulmonary disease.

However, the cost for devel-

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FROM THE VAULT opment of such drugs is no easy feat. Anti-viral drug experts predict the typical cost of developing a new drug to be around $700 million, along with an extremely long process of regulations to go through first.

With the effects of the common cold being only very minor, combined with an expensive process in which to manufacture and market the drug, it seems highly unlikely that the common cold cure is to dramatically take off.

SUPPLEMENT FAILINGS

AN OVER-THE-COUNTER dietary supplement taken by arthritis patients has been found to be not as affective as once thought.

Glucosamine, a substance that is naturally produced in the body, has failed to emerge from its trials as a suitable supplement for sufferers.

Anomalies in the wideranging results of the trials of glucosamine sulphate mean the results of the study to be inconclusive, and therefore the sub-

stance is too unstable to be used as a supplement.

Another study was conducted as a follow up to the glucosamine trial; the second study also tested chondroitin sulphate, a carbohydrate that helps cartilage retain water, which is often to be found taken in combination with glucosamine. The results of this study deemed the substance to be just as unreliable as straight glucosamine, and therefore no treatment could be suggested.

RECRUITMENT IN PHARMA ON THE INCREASE AS TRADITIONAL SECTORS, such as banking and finance, are placing employment opportunities on the backburner, it has emerged that industries, such as pharma and healthcare, are now taking centre stage as the major recruiters.

Pharma companies especially are finding it easier to recruit from Bschool placements for jobs in marketing, human resources and finance.

With pharma companies suffering less of an effect from the economic recession than most other sectors, they have the funding available to recruit from those industries.

In the Q1 2008 issue, JOHN LECHLEITER, CEO of Eli Lilly, divulges his plans for the company’s direction following his recent appointment as CEO, and why a renovation of image is essential to the pharmaceutical industry.

Go to www.nextgenpe.com to browse ‘Past issues’ and view the cover story of the Q1 2008 issue, and read of Lechleiter’s innovative leadership as he steps into the Chief Executive Officer position.

EXECUTIVE CHANGES FEBRUARY 2009 SAW THE RESIGNATION of former CEO, Richard Donnelly of biotech company, AspenBio Pharma Inc. Taking his place, as interim CEO, is the company executive chairman, Daryl Faulkner. Donnelly has made known his plans to pursue other business opportunities, but has agreed to provide transition services for a period of time.

Robert Caspari will also be taking on a new role as the company’s COO and CMO.

www.ngpharma.com

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FRONTLINE IN MY VIEW William Weldon CEO of Johnson & Johnson The challenge for me is to make sure I have the right people in place to run the businesses and to be able to look across the whole breadth of healthcare. On the one hand, healthcare is so dynamic and rapidly changing, and on the other we face many of the same challenges we have for years. Fortunately, our business model is decentralized, so we have extraordinary people who are real experts in each area they operate in.

Innovation in healthcare is truly the lifeblood of the industry. You have to continue to innovate in order to stay on top of everything that is going on. It’s critical to making sure we are addressing medical needs and bringing value to patients and people who use our products all around the world.

The easiest thing to do is to focus on the short-term.

You have to be very careful that you don’t take investments away from your strategic prospects. When the economic situation reverses itself, you are likely to find yourself in a difficult position.

The real role of leadership is to understand that you work for other people. You need to enjoy seeing their accomplishments and seeing the people you’ve touched in a small way be very successful.

Decentralization allows us to develop wonderful people and great leaders; it allows us to be close to the customer and understand the customer’s needs wherever they are, and in any area of healthcare.

A business leader has to stand up and have the courage to make tough decisions, yet has to have the compassion to understand the impact this has and to deal with it in the appropriate ways.

Everything is based upon the strength of the individuals in the company. You see it time and time again – if you have great people you have a great organization, even if you don’t have the right structure or the right products. When you have less than great people inside the best structure and the best products, they probably don’t excel the same way the other group would.

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FRONTLINE NATIONAL EVENTS

June 11-12 Philadelphia Pennsylvania

A round-up of pharmaceutical and life sciences conferences and conventions taking place across the country

Pricing and reimbursement conference www.bharatbook.com/general/PharmaceuticalConferences.asp

April 14-16 Columbia South Carolina

July 28 Aspen Colorado

South Carolina Science, Technology and Health Conference research.musc.edu/new_inklings/0209/SCSTH.html

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Aspen Allergy Conference www.aspenallergy.org/program.html

April 23-24 Bethesda Maryland

September 21-23 New York City

Auditing your pharmaceutical and biopharmaceutical operations www.pharmaconference.com/index_pharm.htm

Pharmaceutical strategic alliances www.windhover.com/windhover/content/conferences /psa.aspx

May 18-21 Atlanta Georgia

October 28-30 Amelia Island Florida

BIO International convention www.bio2009.org/

Next Generation Pharmaceutical summit www.ngpsummit.com/

www.ngpharma.com

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INTERNATIONAL NEWS

SUN PHARMA ON THE LOOKOUT

A SLIGHT AVERSION

THERE ARE INDUSTRY RUMORS that Mumbai based drug company, Sun Pharmaceutical is doggedly looking for an acquisition to strengthen its position.

Sun Pharma Chairman and MD, Dilip Shanghvi advises, “This is the time we have kept our money

FIRST DATABANK HAS RESPONDED to the publication of a study

by PLos One looking into the frequency of Adverse Drug Reactions. David Flavell, President at First DataBank International, has praised the study, which identifies electronic prescribing as a possible intervention strategy for the reduction of adverse drug reactions. He commented that the real tragedy is that injury and death caused by adverse drug reactions doesn’t have to happen. “There are electronic prescribing systems (with integrated clinical decision support) available which are able to prevent medication errors. Such systems are demonstrating real

for. We are waiting for the valuations to correct further through.”

With Taro acquisition predicted to be completed within several months, Shanghvi has said he is looking to acquire many smaller firms, both within India and abroad.

GSK TO DRAMATICALLY RESTRUCTURE Witty did not reveal to the FT UK PHARMACEUTICALS GIANT how many jobs would be lost – GlaxoSmithKline is to spend and claimed many would US$5.1 billion on rebe reallocated. The structuring its ornews followed the ganization, the Glaxoannouncement by group’s CEO SmithKline is to spend GSK that it has Andrew Witty sustained a fall in told the full-year pre-tax Financial on restructuring its organization profits from Times. The move US$10.7 billion to could see the comUS$9.5 billion on sales, pany cut thousands of which were up by seven percent jobs in a bid to achieve annual from US$32.3 billion to pre-tax savings of £1.4 billion US$34.7 billion. within the next three years.

US$5.1billion

EXPANSION INTO ASIA GERMAN DRUG FIRM BAYER SCHERING has reported it will be investing $129 million to open a new global research and development centre in Beijing over the next five years.

As the third largest market for Bayer, China will become the third country beside Germany and the US to accommodate such a center for the Bayer Schering group.

benefits in the hospitals where they have already been introduced,” said his report. “Paper-based systems are no longer an acceptable means of recording and cross checking patient records against potential interactions. We strongly urge more hospitals to consider transferring from paper-based systems, which can be subject to error.”

The PLos One study, entitled Adverse Drug Reactions in Hospital In-Patients: A Prospective Analysis of 3695 Patient-Episodes was picked up recently by the BBC, highlighting that ‘one in seven hospital patients experience adverse drug reactions, half of which are completely avoidable’.

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INTERNATIONAL NEWS COMBATING COUNTERFEITS

PROBLEM MERGERS

here. But we cannot say that the IN FEBRUARY 2009, a forum held in Middle East region is free of fake Sharjah, UAE saw the attendance of medicines.” representatives from the Ministry of WithDubaibeingthecenterof Health and the private sector to disthebusinessnexusoftransit,goods cuss the increasing amount of fromAfricaandAsiaare counterfeit pharmaceutipassedthroughthe cals emerging worldThe Ministry of UAEonroutetothe wide. The Middle Health will be making restoftheworld.

East has been TheMinistryof specifically targetHealthrequiresall ed, as despite rerequirements of companiesthatare cent initiatives to limit drug trading importingprescription, the amount of trade in alongwithnon-prescription fake, and potentially dangermedicinestoobtainapermittomove ous, medicines, due to the freedom of movement and trade. Steve Allen, theproducts.Withimportationoffaux Europe and MENA Senior Director of medicinesontherise,theMinistryof HealthwillbemakingstricterthereGlobal Security for Pfizer advised quirementsofdrugtradingandplacthat, “There are lots of initiatives ingabanonnon-registereddrugs. being taken against counterfeiting

TEVA PHARMACEUTICALS INDUSTRIES LTD, the world’s largest generic drug maker, reported a Q4 loss following its acquisition of rival Barr Pharmaceuticals. The Israeli based company advised of a net loss of $688 million, which resulted in a loss of 88 cents per share, compared with a net profit of $570 million and a share price of 69 cents from the previous year. The international com-

stricter

ROCHE IN PURSUIT ROCHE’S DETERMINED ATTEMPTS to acquire Genentech Inc led to a regulatory filing on February 9th in which Genentech are demanding takeover to be bought at a price no less than $112 per share, for the remainder of the company. Despite Roche already owning 55.8 percent of the company, the South San Francisco-based company has advised that in order for the acquisition to be complete, Swiss company Roche Holding AH must pay the remaining $52 billion.

Genentech’s demands can be certain to come from Roche’s very conservative funding offered so far, when only six days before, on the third February, Roche cut its share offer from the original $89, that Genentech’s board has previously rejected as too low, to $86.50. For Roche, the current economic recession poses enough reason for them to reduce their proposed share price.

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pany acquired New Jersey based Barr for $7.46 billion in late December 2008, and was forecasted to post a new profit of $2.9 billion from the merger.

In a statement given at the time, Shlomo Yanai, Teva’s President and CEO advised, “With the integration process (of Barr) well underway, we believe we will realise even greater synergies from the combination than we initially anticipated.”

HEPATITIS B SUCCESS STUDIES AT THE MAJOR ASIAPACIFIC liver disease meeting (APASL) have shown that for the first time, hepatitis B patients, treated with Pegasys(R) (peginterferon alfa-2a) can now receive predictions from doctors as to which patients can achieve a positive treatment outcome. The APASL studies focused on provid-

ing insight into the success of the treatment by measuring the decline in levels of a viral protein called surface or ‘s’antigen. Pegasys. S-antigen clearance, which is considered to be a clinical cure, is associated with greatly reduced liver cancer, cirrhosis and an improved life expectancy.

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P&G OUT OF THE GAME PROCTOR & GAMBLE ISTAKING itself out of the pharmaceutical branding industry in an attempt to focus more heavily on its high growth business arms.The company is working with Goldman Sachs to identify potential buyers for its consumer products, following record low share prices of $52.21 in February.The company’s healthcare division, which includes its pharmaceutical business, recorded $14.6 billion in sales in 2008, with a net earning of $2.5 billion.With the company’s focus moving away from investment into new drug development, P&G has now taken the direction of shedding some of its key pharmaceutical brands.

The company saw record low share prices of

$52.21 in February Pharmaceutical business recorded

$14.6 billion in sales in 2008 With a net earning of

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HOT OFF THE PRESS GEM GRAVURE, leader in providing fluids and marking equipment for the wire and cable industry and KBA-Metronic, specialists in design and production of continuous ink jet, laser, hot foil coding and thermal transfer equipment, have joined forces to provide the highest quality coding solutions for product identification.

The new venture, OnCode, Inc. sells and services coding equipment and supplies across North America. OnCode, Inc. is the exclusive supplier of KBA-Metronic printers for the USA and Canada.

The superior engineering of KBA-Metronic coding systems combined with cutting edge fluids formulations from GEM give OnCode, Inc. unbeatable solutions to customer requirements.

David Gemelli, President of GEM Gravure, stated, “We are excited to start this new chapter in GEM history. GEM’s participation in this joint venture provides our current customers with the best in ink jet printers. In addition, it allows us to offer unique, high tech coding solutions to new markets.”

Helge Hansen, CEO of KBA-Metronic AG, added, “The US industrial marking and coding world will experience a merger of German reliability and the American spirit of customer orientation by this venture.”

OnCode, Inc. is based in Hanover, Massachusetts, with sales and service representatives across North America. The main products featured include alphaJET ink jet printers and the full range of GEM Gravure fluids. Also available are laser, thermal transfer and hot foil coders.

GEM Gravure Co., Inc. is a leader in product identification featuring specialty inks, continuous ink jet and contact coding. GEM has been family-owned and operated since 1952.

KBA-Metronic AG is a technology company that specializes in the engineering, design, production, marketing and service of printing and coding systems. The company is also a leader in patented innovations.

KBA-Metronic AG belongs to the Koenig & Bauer group of companies, founded 190 years ago in Germany.

BIOPHARMA PARTNERSHIP WITH GSK apoptosis (programmed cell death) in cancer SYNTA PHARMACEUTICALS CORP and cells; it is not yet approved for any indication GlaxoSmithKline have entered into an in the market. agreement for the development and The partnership makes Synta elcommercialization of the igible for a total of $585 million drug, Elesclomol. The colThe partnership in pre-commercial milestone laboration was secured makes Synta eligible payments, of which $50 upon a $10 million payfor a total of million have been paid ment from GSK to the to date, $100 million biopharma company are related to addithat focuses solely upon tional progress in the treatment of severe melanoma, and the remedical conditions. mainder is related to progress Elesclomol is an investigational, in other cancer indications. oxidative stress inducer that triggers

$585 billion

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FRONTLINE

WEB-BASED LABELING SYSTEM THE FIRST PURPOSE DESIGNED web-based labeling system for FDA 21 CFR Part 11 -compliance is to be revealed to the life sciences industry. A special event launching the new web based version of PRISYM Medica, the world’s only purpose designed labeling management software for FDA regulated environments was held in Philadelphia on February 20th 2009.

PRISYM ID today announced the official launch event for a web based version of PRISYM Medica, a market leading GMP based labeling management software for FDA 21 CFR Part 11 regulated environments. Medical device, pharmaceutical manufacturers, clinical trials companies

and industry press have been invited to see the product demonstrated live.

PRISYM Medica Web is the first web based labeling solution to include web accessed label design and approval routing as well as printing. The web version delivers significant benefits in terms of efficiency, accuracy and compliance in the design and approval of labels. PRISYM Medica offers a collaborative labeling environment with automated processes and prompts for those involved in label design, approval and production whereever they might be located.

Manufacturers using PRISYM Medica Web are also able to give trusted suppliers, distributors and

GOUT’S RE-EMERGENCE AFTER 40 YEARS THE FDA HAS ORDERED APPROVAL for the marketing of a new drug that provides treatment to those suffering from the common condition, claiming the current treatment, introduced almost 40 years ago, has let many patients untreated.

Gout, a painful form of arthritis, causing swollen and stiff joints is brought on by a build up of uric acid in the blood, due to the body producing too much or its inability to get rid of it. The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NAMS), advise that there could be as many as 6 million Americans, as young as 20,

who will have the symptoms of gout during at least one point in their lives.

The new drug, ULORIC (whose generic name is febuxostat), is being solely developed and marketed in the US

by Takeda Pharmaceuticals North America. In a statement, Takeda advise febuxostat to be a new, highly portent nonpurine selective inhibitor of xanthine oxidase, and has a completely different structure from the current treatment.

The drug works by lowering the concentration of uric acid in the blood, and will be available as 40mg or 80mg tablets to be taken once a day.

partners secure, print only access to approved labels in an environment that monitors and records every activity along with electronic signatures in a time and date stamped audit log maintaining a high level of security and FDA compliance.

This can deliver major operational and production advantages as product can more easily be switched from one production site or distribution centre to another. This enables manufacturers to capitalize on the labor, tax, shipping or production efficiencies of using a particular site for certain types of products or shipment destinations.

More information on PRISYM Medica Web and registration for the launch event is available on PRISYM ID’s website www.prisymls.com

ISSUE IN NUM8ERS The World Health Organization estimates that

86

180 million

3

adults around the world are currently living with diabetes (p76)

orphan disease is one that hits anywhere between 2000 and 250,000 people in the United States (p38) An

106,000 deaths and 2.2 million serious events are caused by adverse drug reactions in the US each year (p56)

Between

2007 and 2012, the top

50 pharmaceutical companies are facing patent expiries on

$115 billion worth of

drugs (p32) 28

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DRUG ADS NEED MORE FACTS PEOPLE COULD MAKE BETTER decisions The FDA requires pharmaceutical compaabout which drug to choose if all ads carnies to list the risks associated with a drug ried a facts box clearly stating the medbut not its benefits. But in order to make any ication’s pros and cons, a new study sense of side effects, you have to know suggests. what the benefits are, and if it is “People don’t have acworth exposing yourself to They say cess to information about any potential risks. this drug reduces your how well drugs work,” Woloshin’s team conrisk of stroke by says Dr. Steven Woloshin, ducted two trials to see an associate professor at what choices consumers but they won’t tell you Dartmouth Medical would make when shown 30 percent of what School and co-author of the drug ads that did and did study. “The ads don’t tell not include a facts box. them the most fundamental inforParticipants looked at ads for two mation they need.” He suggests adding a prescription heartburn medications and facts box to provide that information. two cardiovascular drugs.

According to Woloshin, current drug The addition of facts boxes to prescripadvertising can be deceptive. “For example, tion drug ads resulted in consumers making they say this drug reduces your risk of better choices of drugs for their symptoms stroke by 30 percent, but they won’t tell and being better informed about the benefits you 30 percent of what,” he says. of drugs used for prevention.

30 percent

THE RISE OF RADIOPHARMACEUTICALS A NEW REPORT by Global Industry Analysts has advised that the therapeutic radiopharmaceuticals market in the US will soon be displaying a significant growth, due to rising efforts of companies in the development of their drug research. As interest heightens in therapeutic efficiency and utilization of nuclear medicine equipment, the functionality of radiopharmaceuticals is being extended to other disease applications, such as infection imaging, neurology applications and nephrology.

COMPANY INDEX Q1 2009 Companies in this issue are indexed to the first page of the article in which each is mentioned.

Abbott Laboratories Adlib Software Aerotek

68 114 8, 18, 34

Alpharma

13

SICPA

Johnson & Johnson

88

Siemens

Cool Chain Association

124

King Pharmaceuticals

72

Takeda Pharmaceuctical

137 72

Visitors Bureau

Laureate Pharma

Dr. Reddy’s

Lifeblood Medical, Inc.

126

Mayo Clinic

118

56

Millennium

92

Duke University

Anabase International Corp.

75, 86

Eurofins Medinet

82, 90

Aperio

64, 65

Frost & Sullivan

32, 103

Aragen Bioscience

59

GEM Gravure

Aspen Groups Resort

141

Genentech

AstraZeneca

112

General Dynamics

BBS Systems

128

GenomeQuest

BioProcessing Inc. Blue Spoon Consulting Group

MeettheBoss MMG MPI Research

60, 61

NanoGuardian

11, 116, 117

120 70, 71

New Orleans Convention & Visitors Bureau Novo Nordisk

21

Genostar

49

Genzyme

131

PDI, Inc.

Germanischer Lloyd

124

Pfizer

GfK Healthcare

105

PRISYM

Cabernet Pharmaceuticals Inc.

56

Hartness International

133

Quintiles Laboratories

CDISC

50

IBM

112

Restek Corporation

85

IMS Health

Charles River Clinical Services Clinical Resource Network

www.ngpharma.com

144, IBC

Innovex

2, 37

32

134 76

136

26, 27

Bürkert Fluid Control Systems 128, 129

Boehringer Ingelheim

31 66, 67

135

44, 131

Amgen

30

Convention & Visitors Bureau Dallas Convention and

Albuquerque Convention & Visitors Bureau

Ionics 143

Columbia Metropolitan

106, 107 4, 95, OBC

Company Limited TARP Worldwide

72 100, 101 32 28, 29 62 54, 55

Roche

32

Shire Pharmaceuticals

38

72 96, 98, IFC

Thermo Fisher Scientific

18, 46

Tripos International

16, 17

TVG Velocity LLC Verix Watermeadow Medical Wyeth

23

122 6, 130

102 108, 109 43 110, 111 32, 80

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COVER STORY

Y

ou’d have to have been living on another planet not to have heard about Pfizer’s planned takeover of Wyeth. As far as news goes in pharmaceutical circles, this is about as big as it gets – equaled only by the ongoing saga of Roche’s bid to buy the remaining shares in Genentech.

Pfizer’s $68 billion dollar bid for Wyeth will give it access to its rival’s vaccines, consumer health and animal products. The move was widely seen as an attempt to boost Pfizer’s pipeline in advance of Lipitor – the cholesterol drug that earned the company nearly $12 billion last year – losing patent protection in the US in 2011. In all, 38 percent of Pfizer’s current sales will face competition from generics by 2013.

The merger will create a massive player in the industry, with more than 15 products with $1 billion each in annual revenue, allowing the

company to move away from its dependence on a single blockbuster.

The Roche/Genentech affair is a little more complicated. The two companies have been linked since the 1980s, when Genentech licensed one of its first drugs to Roche. In 1990, Roche and Genentech merged, with Roche acquiring 60 percent of its smaller rival’s shares. At the time, it purchased an option to buy the remaining shares at a pre-set price – an option it exercised nine years later. Roche then brought Genentech back into the market twice in the next year, keeping a 58 percent stake in the company.

In July, Roche offered to buy back the remaining shares not under its control. But the deal stalled when Genentech shareholders rejected Roche’s offer as too low. The matter remained unresolved as NGP went to press.

MONEY FOR NOTHING Where is this new round of mergers and acquisitions coming from? Is the pharmaceutical industry in danger of consuming itself in its endless quest for profit? By Marie Shields

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Old news Mergers and acquisitions in the pharmaceutical industry are not new.

Pfizer itself has been down this route before, buying out Warner-Lambert in 2000 and Pharmacia in 2003. In both cases, sweeping job cuts followed, and this time round seems to be no exception. Despite Pfizer CEO Jeffrey Kindler’s assertion that the new deal is not about “a single product or costcutting, but about creating a broad, diversified portfolio,” the company has announced that $4 billion in cost savings will result from the merger, including the shedding of 20,000 jobs.

What if this is only the beginning? Most major drug companies are facing similar challenges from patent expiries, and the magic money fountains of blockbusters are running dry. Between 2007 to 2012, the top 50 pharmaceutical companies are facing patent expiries on $115 billion worth of drugs.

In the opinion of Shabeer Hussain, Program Leader in Pharmaceuticals for Frost & Sullivan, “Though plagued with R&D challenges, patent expiries, generic competition and high drug attrition rates, pharmaceutical companies have resorted to various crisis management strategies to stay afloat during trying times. One of these strategies is M&A activities. With Pfizer taking a strong and bold step in this direction, there may be other companies to follow.”

Companies with patents set to run out on major drugs between 2007 and 2012 include Ratiopharm, Sandoz, Merck KgaA, Actavis, Apotex, Barr, GSK and Watson. Wyeth, so eagerly snapped up by Pfizer, faces a tricky situation of its own. Its two biggest selling drugs, Effexor for depression and Protonix for heartburn, will lose patent protection in 2010 and 2011.

The latest report from PricewaterhouseCoopers, Pharma 2020: Virtual R&D, Which path will you take?, points out that: “Pharma’s traditional strategy of placing big bets on a few molecules, promoting them heavily and turning them into blockbusters worked well for shareholders for many years.

“However, its productivity in the lab is now plummeting, as it switches its attention from diseases that are relatively common and easy to treat to those that are much more complex or unusual. In 2007, the FDA approved only 19 new molecular entities and biologics – a smaller number than at any time since 1983.”

The report quotes estimates that generic erosion will knock between two percent and 40 percent off the revenues of the top 10 companies between now and 2015.

Generic erosion will knock between two and 40 percent off the revenues of the top 10 companies between now and 2015 One strategy for coping with this massive loss of income is that exemplified by the Pfizer/Wyeth deal: swallow up your rivals, slim them down by radically cutting staff, and take over their pipelines in the hope that, even if they don’t produce the next blockbuster, you will at least add some diversity to your portfolio and gain enough to prop up your bottom line in the short term.

Quick fix The crucial phrase is ‘bottom line’. Such mergers are often nothing more than a quick fix, aimed at making companies look good for shareholders and investors. But how well does this work? When news of the merger broke, many analysts and industry leaders were skeptical. Michael Rainey of Accenture commented that nine out of 10 of such big deals created no value or negative value. Bain’s Charles Farkas called the deal a halfstep forward: “Wyeth’s assets will buy Pfizer some time but will not be enough to replenish its research pipeline or replace Lipitor.”

Jeremy Batstone-Carr, head of research at Charles Stanley, was quoted as saying: “By deciding that big is best, Pfizer is only delaying current

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POSSIBLE FUTURE MERGERS AND ACQUISITIONS

sanofi-aventis/Crucell: sanofi could make a bid for Crucell to strengthen its position in vaccines. sanofi-aventis/Bristol Myers Squibb: If sanofi and BMS merged, the new company would be number two behind Pfizer/Wyeth.

Eli Lilly/Takeda: The two companies have an existing collaboration in the diabetes arena.

problems and buying a portfolio of products that are approaching the end of their patent lives.” And David Brennan, CEO of UK-based AstraZeneca, weighed in with the view that if big improvements in efficiency were really possible, good managers would make them anyway without having to rely on mega-mergers.

As Shabeer Hussain points out: “As blockbusters fall off patent, organic growth has witnessed major hits. Pharma companies have resorted to inorganic growth through M&A. However, this growth cannot form a sustainable business model for long. This is a stop-gap arrangement, to satisfy investors.

“Though Wyeth’s Prevnar and Enbrel are expected to benefit Pfizer by softening the loss incurred due to the Lipitor patent expiry, the deal may not add the expected value as imagined by Pfizer. This expensive acquisition is unlikely to bring in great dividends. In fact, expanding the business will make it even more difficult for Pfizer to handle its enormous empire.

Growing a huge business of that size is a tall order.”

Get creative This brings us to the question of what such corporate cannibalism will do to the engine that has driven the industry for decades – innovation in research. Despite the layoffs, bigger companies usually have more layers of management, something that tends to stifle research, rather than encourage it.

Shabeer Hussain: “Innovation is not the primary focus for these companies and these activities are just crisis management measures. Such short-term arrangements enhance their stock prices and are purely business-oriented, not innovation-oriented.”

Johnson & Johnson/Vertex: J&J has a history of deals with Vertex and may want to acquire its pipeline of candidates for cystic fibrosis and rheumatoid arthritis.

Bristol Myers Squibb/Amgen: Amgen’s biotech pipeline would boost BMS’s position in the industry.

Source: Frost & Sullivan

According to the PwC report, This ‘innovation deficit’ has enormous strategic implications for the industry as a whole: “Pharmaceutical companies need to decide what they want to concentrate on doing and identify the core competencies they will require, a process which may involve exiting from some parts of research and development.

“But even those that regard research and development as a core element of their business will have to make fundamental alterations in the way they work. They may, for example, have to focus more heavily on specialty therapies, since most of the diseases for which there are currently no effective medications or cures are not amenable to mass-market treatments, as well as reducing the time and costs involved in researching and developing such medicines to ensure that society can afford them.”

To add to the industry’s woes, President Obama’s plan for healthcare aims to lower drug costs by allowing the importation of safe medicines from other developed countries, increasing the use of generic drugs in public programs and taking on drug companies that block cheaper generic medicines from the market. Obama has also hinted that he will allow Medicare to negotiate directly with drug groups, as opposed to the current arrangement of companies dealing with smaller organizations. Obama’s team claims this could drive down prices by up to 40 percent.

While such pronouncements may make consumer groups happy, they do nothing to remedy the situation pharmaceutical companies are facing – in fact, they make it worse. Championing the rights of patients to have access to cheaper medicine may seem like common sense, but pharmaceutical companies, like any commercial enterprise, are driven by profit, and patents ensure there is one to be made. Shrinking profits from fewer blockbusters and the loss of patents mean less money going into research,

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COMPANIES WITH THE BIGGEST CASH RESERVES which dries up pipelines even further, and the whole thing becomes a vicious circle.

Is it really necessary to give generics the upper hand? Shabeer Hussain doesn’t think so: “The main agenda is to reduce healthcare costs. People are paying more on healthcare than on mortgage loans.

Bringing generic drugs in to the market will lower the value of the original drugs; however, the government should also bring in legislation to reduce the price of branded drugs and make them affordable.”

High need The truth is, no matter how much the public loves to hate big pharma – much as we love to hate any powerful industry with a major impact on our lives – the world needs the pharmaceutical industry.

Without the innovative research and development it funds and carries out, many serious diseases would remain untreated.

So what’s the answer? It could be what some observers were expecting Jeffrey Kindler to do when he took over the top job at Pfizer in 2006: instead of gorging yourself on your rivals, then going on a ruthless job-cutting purge, try slimming down from within, focusing on your core areas, finding yourself a niche. Accept that the days of big blockbusters are over. Build yourself a portfolio of mid-performers – then if you lose one drug to generic competition, it won’t smash a meteor-sized hole in your profits.

Smart companies, the lucky ones with strong enough cash flows to ride out the recession, will target emerging markets or focus on core competencies or rare conditions with high unmet need.

None of this can happen in a vacuum. It will require the support of regulators and vendors in making the strategic changes necessary to carry the industry forward. As the PwC report puts it, “If pharma is to remain at the forefront of medical research and continue helping patients to live longer,

Most major drug companies are facing challenges from patent expiries, and the magic money fountains of blockbusters are running dry 36

www.ngpharma.com

Novartis $15 billion Roche $13.5 billion Johnson & Johnson $13 billion Merck & Co. $10 billion GlaxoSmithKline $9.5 billion healthier lives, it must become much more innovative, as well as reducing the time and money it spends developing new therapies.

“Incremental improvements are no longer enough; the industry will need to make a seismic shift to facilitate further progress in the treatment of disease. It will have to learn much more about how the human body functions at the molecular level and the pathophysiological changes disease causes.

“Only then will it be able to develop a better understanding of how to modify or reverse these changes. This is a huge undertaking – and one that pharma cannot complete alone. It will require the support of academia, governments, technology vendors, healthcare providers and the regulators.”

Easier said than done, perhaps. But in these ruthless times, there may be no other choice. n

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EXECUTIVE INTERVIEW

Patient recruitment planning and retention What’s your patient recruitment philosophy? One sponsor’s words of wisdom.

By John Benbrook, CEO, MMG

E

very day I talk with sponsors facing decisions about investing in patient recruitment support. I thought it might be helpful to hear what a fellow sponsor with many years of experience has to say about it. Sue Blaustein has focused on patient recruitment needs for the past 12 years of her 20-year GSK career. In 1997, she established an internal patient recruitment team. Since 2004, Sue has led the outsourcing of patient recruitment services for all of GSK’s therapeutic teams.

“Our focus is on transparent collaboration and the best use of everyone’s resources to get the study done” John Benbrook. What’s your philosophy on working with a dedicated patient recruitment group versus relying solely on the study team or CRO? Sue Blaustein. My company’s perspective has evolved as the industry’s capabilities have grown. Full service patient recruitment groups are no longer PR companies. Now they have added strategic services, increased operational abilities, deeper therapeutic expertise and sophisticated metrics tools. We have come to recognize that patient recruitment is a crucial communications function and appreciate the value of working with a dedicated patient recruitment group.

JB. Do you find yourself trying to convince colleagues that an early investment in recruitment will save money later?

SB. Not anymore – planning patient recruitment and retention is now a standard part of our study launch process. Of course, timelines and budget

come into play, but the cost effectiveness of outsourcing patient recruitment has improved.

Additionally, the project management capabilities of full service groups have become more sophisticated. They are using IT and database tools to identify and analyze issues more creatively. We have found that their capabilities help catch things we would miss if we were looking at the program in pieces or only at a segment of the sites.

JB. We are sometimes asked about potential overlap of our site support services with the study team and/or CRO. What has your experience been with site support and patient recruitment groups?

Sue Blaustein is Senior Contract Manager of Patient Recruitment Programs for GlaxoSmithKline. Sue has attended to GSK’s patient recruitment needs for over 20 years.

In 1997, she established their internal patient recruitment team. Since 2004, Sue has led the outsourcing of patient recruitment services across all of GSK’s therapeutic teams.

SB. Monitors and study managers are stretched to the limit with their core responsibilities. They don’t have time to perform their GCP functions and oversee a well-targeted patient recruitment plan for each of their sites. It’s a challenge to staff and time based resources to efficiently interface with a collection of niche providers. My colleagues don’t really need to be convinced of this reality. If you want the program to come together, you need to seriously consider having the support of a dedicated patient recruitment group.

Additionally, we’ve developed an appreciation for the value of having the patient recruitment group support sites directly.

Experience has taught us three important lessons in this area: 1. Set up the program so that sites expect contact from the patient recruitment group, 2. Limit the number of people from the patient recruitment group who contact the site, and 3. Acknowledge the patient recruitment group as a partner. Our focus is on transparent collaboration and the best use of everyone’s resources to get the study done.

JB. What’s your advice to someone who is trying to introduce the use of a dedicated patient recruitment group to their study teams or management?

SB. Look at it as a business case. Do you have the resources to do it right? Is your company an expert in developing pharmaceutical products or in communications? Years ago, outsourcing patient recruitment wasn’t as viable an option as it is today. It takes time and mutual commitment to develop high quality relationships with patient recruitment groups (particularly from the project management and business operations perspectives). There are more moving parts than you might think; it is a lot to manage effectively. I believe this reality makes a strong case for developing partnerships with a few full service groups that have breadth and depth of experience, as well as strategic partnerships with niche providers. n

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THE BIG INTERVIEW

Standing out from the crowd Mike Cola and Sylvie GrĂŠgoire of Shire Pharmaceuticals explain why being different is increasingly important in the dark days of economic recession.

BY NATALIE BRANDWEINER

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W

ith the state of the pharmaceutical industry beginning to reflect that of the financial markets, we are starting to see big drug companies buying out those unable to maintain a respectable share price. In a multi-billion dollar industry, differentiation from competitors is key to keeping one’s head above water, and Shire’s entire corporate structure is based upon this principle.

In a bid to stay competitive in the trend of large pharma company buyouts, Shire have adopted a strategy that sets them apart, irrespective of their annual revenue intake or the number of employees. “We’re a highly specialized business in that we focus on diseases that are very rare and have a very high unmet meet,” explains Sylvie Grégoire, President of Human Genetic Therapies. Shire’s focus on genetic diseases sets them apart from other larger pharmaceutical companies, who produce a vast array of drugs for a cross section of patients. “Our populations qualify as orphan, which confers a certain protection in terms of intellectual property from the governments in the US, Japan and Europe.”

An orphan disease is one that hits anywhere between 2000 and 250,000 people in the United States. “Our portfolio of products in the Human Genetic Therapies business focuses on the very rare end of the orphan diseases: the target populations we treat are between 2000 and 3000. What that means is that the development programs in order to be able to bring products to the market have to be global in nature because when I say 2000, I mean 2000 worldwide patients,” explains Grégoire.

By focusing on a niche area of patient care, Shire must trawl the world to find patients to complete its clinical studies, and as a result must operate in over 43 countries to create a viable business model. Commercialization of product is then very important to completing the model; the success of such a strategy can be seen in two of the company’s currently marketed products, Elaprase and Replagal, which are used in over 43 countries as enzyme replacement therapies.

This business strategy has not necessarily been a safe one, but the choice to develop and bring products to the market in such a way has ultimately generated sufficient profits, despite the higher price of such products and the rarity of patients available for treatment. “Governments and the populations we are serving are willing to pay for such products because the impact they have on patients’ lives is significant,” says Grégoire. “If they don’t have replacement therapies or the drugs that we develop, their quality of life results in very high morbidity as well as often early mortality.”

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New products

Mike Cola is President of Specialty Pharmaceuticals

Shire’s aim is to introduce eight new products to such rare disease populations by 2015, which they hope will bring in $1.5 billion dollars in revenue. The company’s expansion is due to the strategic reinvestment of this revenue into new drug development. As a big fish in a relatively small pond, Grégoire believes focusing on a niche market will benefit the company, in comparison to the approach of larger, more generic pharma companies.

Key for Shire are those life-changing products within a highly specialized area. “Those are the revenue generators, but they also provide hope for those with rare and dire diseases, and that really motivates our team, who come to work every day with the hope of helping and transforming families’ lives as well as the patients’ lives.”

However, producing drugs with such high-profile capabilities brings with it both challenges and responsibilities. “It’s a highly specialized area but within our human genetic therapies business we’ve developed the internal capabilities to counter this. When you can leverage those capabilities in terms of both the clinical development of the products and the commercial infrastructure you have, once you’ve done it with success with one product, you can leverage the know-how as well as the capabilities to add products to that particular model, as opposed to being in multiple therapeutic areas.

“It doesn’t matter whether the specific therapeutic areas are cardiovascular or GI. Generally, these patients with rare genetic diseases have multiorgan system problems, so it’s a general way of developing multi-organ disease expertise, and we can leverage that know-how internally. Clearly, a very good understanding of the regulatory approval process, as well of as pricing and reimbursement, in all of these countries is key,” explains Grégoire.

“This year we anticipate doing a little over $2 billion in revenue out of our Specialty Pharma business” Mike Cola

Wider range

Sylvie Grégoire is President of Human Genetic Therapies

Product focus is obviously an essential component of Shire’s success.

As Mike Cola, President of Specialty Pharmaceuticals explains, the company’s Specialty Pharmaceuticals business model is far more wide ranging, with a vast array of drug programs. “We have everything from an orphan drug in Xagrid in Europe all the way to something that’s more of a mass marketed product in the US for ADHD, Vyvanse, and in the past, Adderall XR. So it really spans the gamut.

“We have three business units now in our Specialty Pharma business, ADHD, GI and EPU, our emerging products business unit. Within each one of those business units we have sales forces fairly well aligned. These units try to run as semi-autonomous companies within a company focused very much on the needs of the specialist physician, which is very similar to the model in our Human Genetic Therapies business that Sylvie oversees.

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Within the ADHD area, our lead product is Vyvanse, which we launched Medicaid now needing states to pay their bills, the Shire model certainly about 18 months ago and it is growing nicely. We think it’ll be the market guarantees a much better strategy for coping financially and makes them leader over time.” far more recession proof than other primary care products.

EPU is the side of the business that allows the company to become more Despite the upcoming loss of patent protection on Adderall , Shire has commercial. “We haven’t talked a lot about it, but we have a number of a portfolio of products wide and big enough for it to cover the gap. Cola reCarrierwave initiatives under way. Carrierwave is a technology that was aclates the company’s growth story, and explains that with six new prodquired in our 2007 acquisition of New River Pharmaceuticals. It came along uct launches in the last three years, that will continue to drive the with Vyvanse and we’re discovering ways to apply that technology. We hope company’s success. “We know we need to work through the end of the to be able to share more about it by the middle of 2009. life for Adderall XR. We understand the dynamic of losing the exclusiv“Overall the consistency between the two businesses is there. We leverity in April, but in fact we have a citizens’ petition in place. We don’t age the same model, the same principles, just a little bit different as far as size know the impact of the citizens’ petition. There may not be multi-source and scale. This year we anticipate doing a little over $2 billion in revenue out generics but we’re not counting on that happening, so it’s really a growth of our Specialty Pharma business and we’ll drop somewhere in the neighborstory with the new products,” he says. hood of $1 billion to our overall bottom line. So our Specialty Pharma unit is a growing business,” says Cola.

A TIMELINE OF SHIRE Shire’s achievements as a specialty pharma company has allowed it to propel itself into the commercial side of the industry and has brought financial success, even in difficult economic times. As Grégoire explains: “We’ve had success 2006 from a business perspective, achieving $300 million in revShire prepares for the launch of enues in 2007, and in 2008 we anticipate being somewhere five products (DAYTRANA, FOSRENOL, DYNEPO, ELAPRASE, around $450 million, so our human genetic therapies busiSPD476) ness is growing very rapidly. Through geographic expanJULY 2005 sion, we’re making these products available worldwide.”

Shire merges with TKT

Survival

As a specialized pharma company with a much smaller sales force and very few patented products, it’s certainly going to be easier for Shire than for the larger and more generic pharma companies to survive the current challenges, given the financial markets.

“Beyond Adderall XR, we do not have a lot of patent exposure. If you look at the IP of our current products it goes out very long into the 2023-2024 range,” explains Cola.

“If you look at all our diseases they’re highly symptomatic. We create tremendous value for the patient. If these patients don’t have their medication they will feel the difference quickly, as opposed to an asymptomatic drug lowering your cholesterol or even your blood pressure, where you may not notice it for a long period of time.

“That differentiating factor – focusing on symptomatic conditions – helps us. We don’t have a lot of big products in primary care categories that are high on the radar screen. Most of our products are number one or two in a niche category. They’re not typically the things that managed care or Medicaid can go after first. We provide a lot of value for a smaller patient population and that value we don’t think will be taken away from these folks through reduced access to healthcare.”

The minimal amount of exposure of Shire to Medicare and Medicaid, around 15 percent, only heightens its strong position. With both Medicare and

2004 Global registration of FOSRENOL, a Shire first 2001 ADDERALL XR launch MARCH 1997 Shire aquires Pharmavene

MARCH 2003 Matthew Emmens succeeds Rolf Stahel as CEO AUGUST 1997 Shire acquires Richwood Pharmaceutical Company

FEBRUARY 1996 Shire goes public in the UK MARCH 1994 Rolf Stahel becomes chief executive JANUARY 1987 Nycomend agreement yield’s Shire’s first product, CALCICHEW FEBRUARY 1986 Harry Stratford and Dr James Murray discuss launching a new pharmaceutical company

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Grégoire attributes a large portion of the company’s growth to its recently launched products. “They still have a lot of growth in them, whether it’s from our Specialty Pharma business or our Human Genetic Therapies business. From the growth perspective of our currently marketed medicines, and then the pipeline products that we have, we feel it’s a nice story for the overall growth beyond the Adderall XR story, which had been a significant part of Shire’s history. In our Human Genetic Therapies business, we’ve added 300 people in 2007 and 2008 to our team, and in 2009 we have plans to add more than 275 people.”

Emmens took over as CEO in 2003, it really was not in a good place and each year we’ve added a fair amount of new products and new structure, building new opportunities for Shire,” says Cola.

Grégoire explains the company’s approach for the future, highlighting recruitment of people to Shire’s already expanding operations as central to strategy.

“We plan on hiring to support our growing business; specifically, we’re launching a medicine in Europe, Firazyr and we are now hiring people to work on that project. We’re projecting to hire in 2009 in a prudent way, based on the fact that we have the uncertainties that come with XR. It’s completely justified by the growth of the business and achieving the goals of the business,” she explains.

“We have a courageous way of approaching business opportunities and want to manage the company in a non-big pharma way” Sylvie Grégoire New jobs Shire’s development as a company is largely due to the substantial growth it has undergone in the last two to three years. It currently employs about 3500 people globally, with a sales force of approximately 1400 to 1500 without having thousands of salespeople relying on what’s going to be next in the pipeline, the model becomes much more efficient.

“Out of that 3500 people we’ve hired at Shire, we’ve hired close to 2500 of them in the last three and a half years; so I’ve seen tremendous changes. We’re trying to consolidate all of those recent hires and make things more efficient. If you think of the state of the company when Matt

Strategy

Her experience in both the traditional and the entrepreneurial aspects of the pharmaceutical industry have contributed to her tenure at Shire and her influence on the company’s strategy. As she explains: “These kinds of experiences in terms of business, thinking about how to run a company in a nimble and entrepreneurial fashion and with a global view is very important, and is something that helps me in mapping out the potential for our HGT business to grow.

“In just that year and a quarter that I’ve been here we’ve added a significant amount of projects to the pipeline through business development, and our HGT business has a research component. So we look at what’s in our research portfolio and we’re always working on different potential new drugs that will enter the pipeline, both internally and externally. The economic difficulties that small companies are facing today in terms of raising capital – whether they’re private or public – provide an opportunity for Shire to aggressively consider acquisitions of products that fit our strategy, making sure that we focus on that specialist strategy. We have a courageous way of approaching business opportunities that come from the external world, and want to manage the company in a nonbig pharma way.”

That “non-big pharma way” certainly seems to be an approach that has boosted the company’s revenue and allowed them to further their development of new discoveries.

However, with the credit crunch expecting to last at least well into 2010, only time will tell if such a strategy will pay off.

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TRANSLATIONAL MEDICINE

MAKING THE LEAP Brian Kotzin, Vice President of Medical Sciences at Amgen, tells NGP how biomarkers help translate basic science into medicine.

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B

rian Kotzin is the first to admit that his background is a little unusual compared to that of his senior colleagues at Amgen. “I was at the University of Colorado, at The National Jewish Center for Immunology, now called the National Jewish Medical and Research Center,” he explains. “I was a physician scientist and did the usual things they do in academic medicine. I’m a clinician, a rheumatologist, so I saw patients within the internal medicine and rheumatology setting. I also ran a laboratory, and I did a lot of teaching.”

Kotzin’s appointments were in medicine, immunology and genetics.

Over 25 years, he headed clinical immunology and rheumatology groups, as well as a center of excellence devoted to autoimmune diseases. As this research developed, he realized the next step would be to develop it into a therapeutic, which can be hard to do in an academic setting.

“At some point in your career, you want to do something that’s a little bit more broad-based and has more applicability to more people, and this seemed like a great opportunity,” he says. “When I came to Amgen, I headed up the development group for inflammation therapeutics. The main therapeutic that Amgen had at that time was Enbrel, a TNF inhibitor, which had dramatic effects for certain diseases like rheumatoid arthritis. After a short time, I became Vice President of Medical Sciences, which was a much larger group focused on the early development of Amgen’s pipeline in all therapeutic areas and the science needed to put molecules into humans. My background seemed to be suited for this job – it seemed a natural position for me because it is right at the interface between research and clinical development.”

Biomarkers Much of the work that Kotzin and his team carry out in medical sciences is related to biomarkers. “Our group is composed of combined groups from research and clinical development,” he points out. “For example, we have a molecular sciences group that’s devoted to molecular biomarkers, we have an imaging sciences group that’s devoted to advanced imaging biomarkers, we have a clinical immunology group that includes a group focused on cellular biomarkers, and we have the development group. It’s a very biomarker-oriented function here in medical sciences.”

The goal of Kotzin’s studies is to maximize the information he gets from early clinical trials. Because the therapeutics are being introduced into a small number of people, it’s important to get as much information as possible, which is accomplished by dividing biomarkers up into different categories. “One of our biomarker-directed questions is, when we introduce a therapeutic into people, did we hit the target? Did we do what we really thought we did?” says Kotzin. “Then we ask, did we cover the biochemical pathway? Were the intracellular signaling pathways inhibited to the full extent that we thought they were?

“Then we have biomarkers that are a measure of clinical activity. We can’t do large clinical studies where we use a clinical endpoint, like survival – we don’t do that in these early clinical trials. Instead, we try to incorporate biomarkers that will give us a clue as to whether we have a clinical effect. For example, if it’s a cancer therapeutic, did we shrink the tumor, or were the tumor cells killed within the tumor?

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“The last group of biomarkers that we try to get insight into are those terface, moving it all forward. And it’s all the science that goes along with that might predict who’s going to respond to a therapeutic. We call them that transition. stratification biomarkers or predictive biomarkers.”

“It’s this interface of translating the discoveries you have – either in cell One other important category of biomarker is that related to safety. culture or in animals – into human disease. It’s a very difficult thing because Most therapeutics at this early stage do not work out: they fail for one reathe animal models are frequently not predictive of the human disease. son or another, and the importance of being able to make a strong con“We’re measuring pathways in animals, and we have to measure the clusion regarding that failed molecule is critical. The team needs to same pathways in humans. All of the science we do here is centered around know, if it has a failure, is it because the target that they chose was not how do we take what we’ve learned in the animal studies, or in the preclinthe right target, or is it because the therapeutic they developed wasn’t ical studies, and move that into humans, so that we can truly understand the right therapeutic? things. And it’s much more difficult. In an animal study, you can look at the “By knowing whether you hit the target and whole animal to see whether your drug has had an efwhether you covered the pathway, this gives you esfect. But in human studies, you may be limited to samsential information on whether the approach is going pling blood. You have to be very ingenious, very to be useful. If there was no effect on the disease, innovative in how you get the information. This whole we don’t want to develop another molecule to hit process is translational medicine.” that particular target. And you only discover that by having those biomarkers that tell you whether you did hit the target.

“We may have a molecule, for example, where we have a safety concern. The question is, did we use it at a dose that was much higher than we need, or was Brian Kotzin joined Amgen in it the right dose, or was it not enough? By having the 2004, as Vice President and Head, information that says yes, we did hit the target, or we Global Inflammation Development, didn’t even reach the dose that we needed to hit the before transitioning to his current target, this will tell us what the next step is in terms of position as Vice President, Medical trying to develop something for the same pathway.”

Sciences. He leads this integrated function comprised of Early Clinical Predictions Development, Molecular Sciences, Kotzin and his colleagues have had successes in Approval Imaging Sciences, Clinical which they have used biomarkers that predict the clinHow difficult is it to get approval to carry out these Immunology, and Computational ical effect. For example, instead of going to a several early clinical trials? Kotzin explains that there are exBiology. Medical Sciences is hundred-patient study that measures hemoglobin A1c tensive regulations that govern this process. This is to responsible for the planning and for a diabetes drug, he has been able to measure the ensure the safety of the participants when investigatexecution of early-phase clinical effect in a study with only 20 to 30 subjects, using bioing a therapeutic that has never been put into people development as well as the markers. “We were able to come to the conclusion before. Patient safety is paramount. Because of this, discovery and implementation of that the drug really didn’t work, and it wasn’t going to there are many regulations regarding what doses you pharmacodynamic biomarkers in work even if we studied many more subjects. That’s a can start at and what types of animal preclinical studclinical studies at Amgen. great help. It’s much faster, and we expose fewer peoies you need in order to know that the therapeutic is

“There are many regulations regarding what doses you can start at and what types of animal preclinical studies you need in order to know that the therapeutic is likely to be safe”

ple to the therapeutic.

“We get to make our conclusion earlier and faster, and we get to move on to other molecules within the portfolio. Within our cancer therapeutics, we’ve been able to see tumor shrinkage. We’ve been able to measure the death of cancer cells within the tumor. And that’s really important early information that says, ‘Yes, this potentially important cancer therapeutic should be moved forward, so that we do larger studies and measure clinical effects like progression-free survival and overall survival.’”

Kotzin’s definition of translational medicine is very closely tied to medical sciences. He defines it as the interface between research and clinical development. “When I think of the term ‘translational medicine’, I think of discovery research: animal studies, basic research at the bench. And then you move that science into clinical trials, trying to understand whether there’s going to be a benefit in patients. Translational medicine is that in-

likely to be safe.

These regulations have become much more stringent in the last few years, because of the tragic outcome of TeGenero’s TGN1412 study. TGN1412 was a therapeutic that was designed to target T-cells, but instead of inducing the lymphocytes to not respond, it triggered them to release massive amounts of cytokines. One of the study’s major flaws was in the decision to inject all of the participants at the same time, and all who received the active drug became seriously ill.

“That catastrophe understandably colored early development around the world,” says Kotzin. “Although at Amgen we’re very stringent and we like to believe we would not have done anything like that, everyone became afraid of approving new therapeutics, especially biologics. Now nearly every time we apply to put a new biologic into people, the specter of the TeGenero catastrophe comes up. This has resulted in new regulations being put into place around the globe that delay the process.

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“There has been an explosion in basic science, which has had a big impact in translational medicine, because there are so many new ideas and new discoveries that can now be translated to humans” “I remember traveling to the MHRA and presenting a molecule that was an immunologic molecule, and we arrived shortly after the TeGenero tragedy. The regulatory group in the UK just didn’t know what to do. They were faced with the results of this tragedy and how to prevent something like that from ever happening again.

“It became almost an irrational fear of new clinical trials, and we had to get beyond that using really strong science to convince people that our trials are safe. We’ve been trying to convince regulatory groups – for example, when we come forward with a new therapeutic – that the science predicts that this will be safe. We’ve been successful, but sometimes there has been an inordinate delay related to the fact that people are still afraid.”

Certainly one way to improve safety is not to inject all study participants at the same time at the beginning of the study. Instead, one individual is exposed to a very low dose, and if that causes no ill effects, researchers can feel more comfortable about exposing several people to that therapeutic. The dose can be gradually increased after the first subjects have been safely dosed.

Animal studies are often carried out to provide enough information to ensure that the compound will not cause problems in people. But as Kotzin explains, sometimes a negative result in animals will not necessarily translate into humans.

“This is challenging because we’re sometimes faced with situations where we have an animal toxicity which we don’t believe will translate into humans. When this happens, we have to figure out how to get beyond the problem and convince ourselves, investigators and regulators that this shouldn’t prevent us from going into people, especially when the illness is grievous, such as a cancer therapeutic.

“Another example of regulations that have been challenging is related to biologics. Amgen is a leader in the development of biologic therapies, and these types of molecules are a major portion of our portfolio.

Sometimes, regulatory groups apply principles used for small molecules,

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the usual types of drugs taken orally, to biologics. Sometimes, these regulations are just not applicable. It’s a teaching process. You have to explain to them why the same rules that they use for small molecules don’t apply to these large protein molecules.”

Developments There has been an explosion in basic science, which has had a big impact in translational medicine, because there are so many new ideas and new discoveries that can now be translated to humans. As Kotzin says, “The whole understanding of disease has been an important development for translational medicine. That’s very dependent on new research technologies, which give us the ability to develop new molecular techniques.

“There have been tremendous advances in proteomics, and in how to measure intracellular pathways by measuring proteins that get phosphorylated. And there’s been a tremendous explosion in genetics in terms of the tools you can use. Now, you can screen the whole genome for polymorphisms that might affect whether your therapeutic will work in certain people and not others.

“There are also new sequencing machines that sequence at an unbelievable rate, something that nobody even a few years ago could believe that we could do. And that’s added to the information we can add in our early clinical trials. We can sample tumors, for example, and do unbelievable amounts of sequencing of all the different genes that have changed in those tumor cells.”

“We’ve also become more innovative in our clinical trials. We’re no longer fixed into the same type of experiments. We’re doing clinical trials where we learn as we go, right in the same clinical trial. We’ve combined different, single dose and multiple doses in the same trial. Again, ensuring safety at the same time we go, but increasing the information that we get, as well as the speed that we can move in terms of getting the information that we need.”

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STANDARDS

High standards

Standardization across the whole spectrum of clinical trials is vitally important.

NGP talks to CDISC’s Dave Iberson-Hurst and Tim Jaeger about the challenges of achieving this goal.

T

he Clinical Data Interchange Standards Consortium (CDISC) is a global, open, multidisciplinary, nonprofit organization whose aim is to establish standards to support the acquisition, exchange, submission and archiving of clinical research data and metadata.

Originally formed in 1997, CDISC was incorporated as a nonprofit in the US in 2001, and has now grown in to a global organization with over 240 members around the world.

David Iberson-Hurst, CDISC’s VP of Technical Strategy, explains that as an officially accredited standards development organization (SDO), CDISC enjoys a formal liaison status with the International Standards Organization (ISO), which enables it to establish standards within the clinical trials arena.

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And as Tim Jaeger, Chairman of the European CDISC Coordinating Committee, and Head of Divisional Medical and Scientific Affairs at F. Hoffmann-La Roche Ltd., points out, the fact that CDISC is vendor neutral and technology neutral, and works on a consensus-based approach, helps it to develop standards that are usable by and attractive for the majority of stakeholders in the organization.

“These stakeholders encompass not just the pharma industry, but also clinical research organizations, the device and diagnostics industry, electronic health record vendors and the big academic institutions. Then there are regulatory bodies like EMEA and the FDA. We cover the full range and breadth of organizations working in the standards arena, and we try to ensure through our processes and through our organization that all these partners are heard, and

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that standards that are robust and relevant to all of these groups are developed and adopted.”

By joining CDISC, companies have the opportunity to drive the direction of the development of standards, as well as seeing a financial benefit in terms of discounts on training. More importantly, Jaeger fully expects that one day bodies like the FDA will expect companies to submit and capture all their data in CDISC standards. “It’s critical and relevant for all of our partner organizations to have their say, and to be able to help shape standards, and it’s a true advantage if you’re sitting at the table when new standards are developed or existing standards are advanced, to be aware of the ongoing discussions with EMEA and the FDA and other important institutions. Things that are being considered and talked about at these levels today will come out as draft guidance in two to three years.

“In today’s world, no matter what area you’re working in, be it pharmaceuticals, medical devices or diagnostics, designing a trial or protocol and gathering and working with the data, then submitting and archiving it, is a long process. During this process you will have to liaise with literally dozens of other groups, organizations and contractors. Only if you’re able to seamlessly exchange your data across time and across this multitude of partners can you ensure that in the end you have good robust data, something that EMEA or the FDA will accept.”

Mission control

do it in a standardized way. They can’t monitor 4000 drug companies without standards, so that oversight function is driving standards.”

Global reach CDISC is working to develop global standards that will work equally in countries around the world, though as Iberson-Hurst explains, different areas have different requirements. “For every drug submission, companies in the US must submit all of the data, whereas in Europe they need only submit the reports produced from the data. There is an increased need in the US for an additional data standard, but even if you’re not sending in that final block of data, your processing around how you get to that point should be the same. It’s much easier for companies operating internationally to have a common process that fulfills the needs of all regulatory authorities.

“We are developing a continuum of standards, which are designed to support the process as a whole. These include a protocol standard, which is there to support the writing of clinical trial protocols and have them in a format such that they can be consumed not only by humans in document form but also by a machine. We will have the high level model of that available soon, with an XML implementation probably early this year.

“There is also the Clinical Data Aquisition Standards Harmonisation (CDASH) standard. This is a standard that lays out the minimum set of content that pharmaceutical companies and biotechs should be collecting when they collect data. This makes it easier to combine data when we bring trials together within a pharmaceutical company or within a regulatory authority, and also to start reusing data collection forms. This will make setting up trials quicker, has had a lot of support from the FDA, and is also applicable across the globe.”

Another standard CDISC is working on is the study data tabulation model (SDTM). These are the data tabulations that pharmaceutical companies submit primarily to the FDA, but which are also embedded in the way a pharma company works. These tabulations are the cleaned raw data that are collected from trials, organized in a standardized way so that the regulatory authorities can understand what has been collected. The analysis data model (ADaM) is the standard for presenting analyses based on the raw data found in SDTM: how you took the raw, cleaned data and through your analysis show the efficacy and safety of the product that you’re submitting for approval.

There is also an operational data model (ODM) used as the basis to pass standards from machine to machine, and a laboratory model (LAB) dedicated to the passing of laboratory data from the central laboratories through to pharmaceutical companies.

“Only if you’re able to seamlessly exchange your data across time and across this multitude of partners can you ensure that in the end you have good robust data” Dave Iberson-Hurst

CDISC’s official mission is to develop and support global, platform-independent data standards that enable information system interoperability to improve medical research and related areas of healthcare.

“We need the platform-independent, vendor-neutral, global data standards that help us to streamline data flow from a protocol design to submission and archival of the data,” says Jaeger. “We need this level of interoperability and compatibility not only within the clinical research environment, but also on the edges where clinical research borders with healthcare. There are synergies with the healthcare arena, where many patients are treated within clinical trials, following certain trial protocols.

“There is always the challenge when you’re identifying potential candidates for trials of whether you need to re-collect and re-document all the data points that already exist within the electronic health records, or are there ways to bridge the worlds of clinical research and healthcare? At CDISC, we believe it’s of vital importance to build that bridge.”

Iberson-Hurst adds that the growing public pressure for drugs to be developed with fewer side effects and adverse events has in turn put increased pressure on regulatory bodies to provide better safety monitoring. “They need data to perform that oversight function, and given the multitude of companies that produce drugs, they need to

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Keeping in touch One of CDISC’s mandates is to act as a kind of intermediary between companies and regulatory bodies like the FDA and EMEA. “We have a very good working relationship with both EMEA and the FDA,” says Iberson-Hurst. “We work to find the best solutions that meet the needs of both groups: the pharmaceutical companies, biotechs and academic institutions, and the regulatory bodies.

“We work with them through Health Level 7 (HL7) and ISO to move standards forward internationally. We do tend to be more heavily involved with the FDA because of its requirement to submit the underlying data. However, we are also working with regulatory bodies across the globe on projects such as standardizing the data required for clinical trial registries.”

Working in different geographic areas and within a variety of regulatory authorities can present challenges, as Jaeger explains, “CDISC was originally very much a US-centric organization, because a lot of

Dave Iberson-Hurst is founder of Assero Limited, with 25 years experience of computer system development within a number of industry sectors. Iberson-Hurst is active within CDISC and was appointed as VP for Technical Strategy in September 2007 to oversee all technical work within CDISC. He is Vice Chair of the European CDISC Coordinating Committee (E3C), co-leads the CDISC Technical Advisory Committee (TAC) and is co-lead of the CDISC electronic Source Data Interchange (eSDI) group that is working with the FDA to examine the difficult topic of electronic source documents and data.

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the critical pharmaceutical activity was taking place in the US, and the FDA tends to have the ‘highest’ authority, in that it influences much of the work in Europe. However, we increasingly see that trial activities are shifting. If you look back 10 or 15 years, a lot of trial activity went from the US to Western Europe, then Eastern Europe, and now it’s going into the India, China and other places.

“There are good reasons for that: the availability of patients, the possibility of running large trials, and of course the fact that these are emerging markets and companies want to have a presence there.

CDISC supplies global standards for global organizations, to allow them to work seamlessly across these borders.

“One important area of this is electronic data capture, which allows you to work fairly independently, because all you need is a laptop with an internet connection and you can start accessing data regardless of where you are. This is something that we want to promote and enable with the establishment of global standards that help companies use a lean front end and that allow them to collect data in a robust and compliant fashion all the way through the process. We want to eliminate the situation toward the end of the process where historically people would pull up in trucks in front of the FDA and deliver via forklift literally tons of paper.”

“The FDA always wants to be able to check source data, and if you do this via 10, 15, 20 different applications, via a number of organizations, institutions, contractors or parties, and if you do this across 10 years, how can you provide access to all that original data without having to provide mountains of paper? Doing this electronically and providing standards that allow you to reach into the data is obviously very valuable and helpful.”

“One of the big challenges is getting the paper out of the process,” says Iberson-Hurst. “The other challenge is that when you have a clinical program over 10 years, technology moves on and process improves, so some of the data you’re working on toward the end is quite old.”

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Implementation What, then, can companies do to implement CDISC standards?

According to Jaeger, there are a number of possibilities. “CDISC offers a wide range of informational and educational activities from very broad introductory courses to extremely specialized and detailed tutorials that potentially take you into the most finely granular level of any specific standards. CDISC has very appropriate, attractive and up-to-date educational events and courses for both novices and experts, that people can use to build their understanding of this area.

“There’s also the opportunity to attend the meetings that CDISC organizes, including the international interchange – a two-day meeting plus three days of courses, tutorials, and other educational events held every autumn in the US – and the similar European CDISC interchange in April. We’ve also recently started interchanges in China and other countries.”

Jaeger explains that companies with a presence in Europe can also get involved with user groups organized by language, along with a large number of groups that are independent of CDISC but whose members are heavily involved with establishing standards in their organizations and using them as part of their daily work.

The main way, of course, to benefit from CDISC’s activities is to become a member. Members have privileged access to all materials and events at attractive rates, and CDISC will even design programs especially for you, come to your company and educate your people and set up specific courses to meet your needs.

Looking ahead

Tim Jaeger is Chairman of CDISC’s European Coordination Committee, a member of the CDISC Board of Directors and a member of its global strategy committee. He joined the Diagnostics Division of F. Hoffmann-La Roche Ltd in November 2005, and is currently Head of Divisional Medical and Scientific Affairs and develops and coordinates divisional medical strategies. Jaeger establishes and maintains relationships with key thought leaders, investigators and institutions strategic to Roche Diagnostics. He also is the business owner for the global Diagnostics Clinical Information Management System, where currently more than 500 trials are registered and conducted electronically.

data needs to be visible to the right people and supported by the standards we’re developing.”

Jaeger names three key themes for CDISC: simplification, globalization and a broader approach. “First, we need to simplify a very complex process, with all the different parties involved, all the different data types over a long period of time with different applications. We aim to simplify that through the use of commonly accepted and globally adopted standards.

“We’re also working on simplifying our own standards. We started with a range of standards that became a continuum, and those now are being integrated into something that is increasingly simple.

“The second theme is globalization.

CDISC was originally US-centric, but we have made strong, bold moves over the past few years to venture out into other parts of the world, beginning with Europe, where there’s a lot of activity and a strong foundation for CDISC. Some of our European activities are now at the same level as the US ones, and we’re moving into India, China and other areas.

“The third theme is to carefully broaden some of the activities CDISC carries out. We’re working to better define the convergence between healthcare and clinical research and to provide to this area the standards, the insights, the expertise and the experience that CDISC undoubtedly has. We also want to move from the traditional pharmaceutical research model into models for the diagnostics of the medical device world, and other areas where there is a different type of research going on compared to the traditional big pharma model of running trials in multi-national environments. These are the three themes that CDISC will be driven by over the next few years.” n

“We want to eliminate the situation where people would pull up in trucks and deliver via forklift literally tons of paper”

CDISC’s future plan is to move toward ensuring the continuum of standards is well-implemented, works together and is easily adopted by pharmaceutical companies and everyone else within the industry. This will make it easier for companies to work with their partners to, for example, exchange protocols and the collected data, because the data will be exchanged in a form that everyone can use and understand.

“It’s all about making the move into the data much more smooth within companies and across company boundaries,” Iberson-Hurst explains. “This is one of the reasons we work with bodies like the National Cancer Institute, because they have a lot of academic institutions who all want to share and pool data so they can see things that maybe they’re not seeing in their own data.

“Our aim is to ensure that they can use the data quickly without having to worry about how do I get the data and how do I merge it with my data and how do I combine it, and can I even combine it?

Our task over the next 10 years or so is to look at how people can get the data they need to make better safety decisions. The right

Tim Jaeger

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TROUBLESHOOTER

Increasing your return on instrument investment

By Richard Lake, Pharmaceutical Market Development Manager, Restek Corporation.

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mproving data quality and streamlining operations, while decreasing costs and drug development time, are ongoing goals for pharmaceutical labs. Significant investments have been made in UHPLC platforms and mass spectrometry technology to improve productivity. However, these assets cannot perform optimally if chromatographic separations are not adequate, as is often the case when attempting to separate drug compounds on C18 columns.

Phenyl columns offer some aromatic selectivity, but little hydrophobic retention. Restek’s unique Biphenyl phase incorporates a novel end-to-end bonding that is a significant advance in phenyl columns, providing both high hydrophobic retention and aromatic selectivity in a single column. These attributes maximize versatility and can be used to increase utilization and return on investment for UHPLC and LC/MS systems.

Proper column choice UHPLC in the pharmaceutical laboratory is commonly used to accelerate development of methods, which are then scaled to a conventional HPLC-based platform for routine analysis.

This common application of UHPLC makes the need for selective column phases just as great in UHPLC as in HPLC. While UHPLC does produce significant gains in efficiency and speed, the gain is not so extreme that the stationary phase is inconsequential; selectivity is still the driving force behind separations, as it affects resolution to the greatest mathematical degree.

Higher quality separations, not just faster separations, are needed by pharmaceutical laboratories. To fully realize the potential of UHPLC, labs need to consider both speed and selectivity. Biphenyl columns offer both C18like and phenyl-like selectivity (easily controlled with mobile phase choice), and, when used in conjunction with UHPLC, they can provide much faster and more effective resolution for drug substances and impurities.

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Richard Lake is the Pharmaceutical Market Development Manager at Restek Corporation. He is responsible for overseeing the development and application of chromatographic products for the pharmaceutical industry. He has over 13 years’ experience, including positions as lead chemist, LC and GC method developer, stability manager and study director for pharmaceutical studies.

LC/MS asset Novel Biphenyl column chemistry can also increase return on investment for mass spectrometers. Here, the benefit is not so much selectivity (the mass spectrometer can provide deconvolution) as it is increased retention.

Since Biphenyl columns strongly retain analytes, highly organic mobile phases are used to elute the compounds into the mass spectrometer. This leads to higher sensitivities in electrospray ionization as desolvation of the mobile phase becomes more efficient, ultimately giving better ionization.

“Significant investments have been made in UHPLC platforms and mass spectrometry technology to improve productivity” Another advantage of using highly retentive stationary phases, like Biphenyl, for mass spectrometry is eliminating unwanted adduct formation or charge competition from matrix interferences that are less retained by the column.

Commonly used C18 columns are excellent for retaining hydrophobic solutes, but fail when retain-

ing hydrophilic solutes. In contrast, Biphenyl columns are capable of retaining both hydrophilic and hydrophobic aromatics better than conventional C18 and phenyl phases, resulting in a wider range of applications and better mass spectrometer asset utilization.

Alternative and easily controlled selectivities give Biphenyl columns a unique versatility, leading to a higher return on investment and better utilization of instrument resources. Since Biphenyl columns offer both aromatic selectivity and hydrophobic retention, orthoganol separations can be achieved with simple mobile phase changes. This ‘tunable’ selectivity gives markedly better separations for molecules differing in a degree of unsaturation, double bond position, or electron withdrawing groups.

Improved MS sensitivity is also possible, due to the use of more organic mobile phases.

Biphenyl columns are available on a variety of silicas, including a fully scalable line accommodating UHPLC-HPLC method transfer. Versatile Biphenyl columns can improve utilization of UHPLC and LC/MS resources and are an ideal tool for method development.

For more information, visit www.restek.com/biphenyl.

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PHARMACOGENETICS

THE GENETIC ADVANTAGE Allen Roses tells NGP how pharmacogenetics can help cut the size and cost of clinical trials.

NGP. What have been the most important moments of your career, and how did they lead to your current position at Duke University?

Allen Roses. During my first period at Duke University, I spent 27 years as a professor and chair of neurology, and started the Duke Genetics Research Clinic here. I was then recruited to GlaxoSmithKline – Glaxo-Wellcome at that point – where I held the position of Senior Vice President for Genetics Research, a worldwide position on the R&D executive board. I retired in October 2007, but decided to return to Duke, where I resumed my endowed professorship, the Jefferson Pilot Professor of Neurobiology and Genetics, and where I am a special scholar in the Fuqua School of Business. I’m also working on setting up virtual relationships, which would be synergistic between the university and industry.

NGP. Why is it hard to predict a patient’s response during the development of a new drug?

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AR. One never knows how one is going to respond to an external chemical given to the body. What is made harder is if you don’t study it when it occurs. Most people have not done so because it was prohibitive and there was no way of really doing so in the past, but now you can apply pharmacogenetic technology during the development period. As a result of this, when an adverse event occurs, there are now ways of finding the genetic markers that are associated with those people who will respond or those people who will may get an adverse effect.

NGP. What effects will multi-gene studies have on the discovery and the drug development?

AR. When we’re working on a drug that’s in a particular therapeutic area, we can use candidate gene lists that have to do with either the disease and what we think we know about the disease, or the mechanism of the molecule that we are providing, which we would know about. These could be

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helpful in terms of focus on efficacy effects that we would see in using the drug. The drug is used in a trial that contains a certain percentage of people that have the clinical endpoints. The initial candidate gene lists that we would use – which actually are polymorphisms, or variances, within the candidate genes or around the candidate genes – those would be the first things we would study. About 80 percent of the time, we achieve reasonable data.

NGP. Why is pharmacogenetics expanding in the industry?

AR. There are a couple of reasons. The industry is contracting because it has been operating on the overall ‘one size fits all’ concept. We’re going to make a drug, everybody’s going to take it at the dose at which we put it out there. With all the failures of proof of concept – the inability to show efficacy with many, many molecules – and with the safety problems that are associated with many molecules, drugs have come under both public and newspaper/journalistic attack for being unsafe and for not working. But the real driving reason for all this is always the finances, and it isn’t as important that you get your drug registered, although that certainly is important, what’s critically important is to get it reimbursed.

Pharmacogenetics can identify the people in advance who will respond to the drug once it’s on the market because of studies that were done during development – companion diagnostics. The insurer or the national health service, or whoever’s making these decisions, can estimate what the cost of the drug will be if given to those people with predicted responses, and not given to those people who don’t have a predicted response.

There is a very different approach in Europe than here in the US. In the US, the government or a government agency doesn’t make the decisions; they’re made by panoply of large healthcare providers. Pharmacogenetics can provide value to the drug at a reasonable cost by identifying people who will respond to that drug, protecting the drug against adverse events by developing prognostic or diagnostic markers and identifying people who might have adverse events.

Pharmacogenetics is expanding less so across the industry, instead we are seeing its expansion in smaller drug firms. There are companies now who are taking the fruits of that development and applying it to their pipelines. We have one signed contract in which we’re working with Eli Lilly, and two more will be announced before the summer.

Allen Roses is Jefferson Pilot Professor of Neurobiology at Duke University and CEO of Cabernet Pharmaceuticals, Inc. He has established an international reputation for his work in pharmacogenetics, exploratory drug discovery and clinical neuroscience.

He also serves in several capacities at Duke University: as Jefferson-Pilot Professor of Neurobiology and Genetics, as Professor of Medicine (Neurology) as Director of the Deane Drug Discovery Institute, and as Senior Scholar at the Fuqua School of Business. He recently returned to Duke after a decade-long career as a Senior Vice President at GlaxoSmithKline .

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NGP. What is the importance of an efficient collaboration between industry and academia in regards to collection of pharmacogenetic data?

AR. There are two ways of looking at this: a pharmacogenetic study, in a single study, can be done in a general university. Usually this isn’t done until after the drug is on the market, before they can have access to it, and is usually looking at adverse events, which are all a negative influence as far as drug companies are concerned.

106,000 deaths and 2.2 million serious events are caused by adverse drug reactions in the US each year We’ve established a series of external companies, small, which are called the Blue Wine Group, after the Duke Blue Devils mascot. The Duke Wine Group has three companies: one of them is Cabernet, and Cabernet Pharmaceuticals has a strictly laser focus on pharmacogenetic consultation and project management for large pharma. This is how I spend 20 percent of my consultation time at Duke. We’re not getting anything out of it except keeping these studies going and allowing them to achieve a better chance of getting proof of concept, and a better chance of keeping their drugs on the market and providing new drugs, all of which they totally own.

However, because we’re creating companion diagnostics for them and their drugs, we also have the opportunity to commercialize those companion diagnostics. Therefore, a second company, called Shiraz Pharmaceuticals, is in charge of making the arrangements and taking care of all the things the drug company doesn’t want to, or doesn’t have the expertise in-house to do, to commercialize those companion diagnostics.

In the case of Shiraz Pharmaceuticals, it’s part of Dean Drug Discovery: it has a relationship with the Dean Drug Discovery research institute that we have, which is called the Dean Drug Discovery Institute. Any milestone

PHARMACOGENETICS: FAST FACTS Pharmacogenetics is the study or clinical testing of genetic variation that gives rise to differing responses to drugs.

The wider use of pharmacogenetic testing could improve prescribing safety and efficacy, cutting the number of adverse reactions to drugs.

Adverse drug reactions are responsible for five to seven percent of hospital admissions in the US and Europe.

ADRs lead to the withdrawal of four percent of new medicines and cost society an amount equal to the costs of drug treatment.

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in royalties that are collected by Shiraz, 80 percent will be paid to Duke University. So it becomes a source of income for Duke, and it also becomes an automatic thought process about, if we have some IP that’s developed inside the university, maybe we should go to Shiraz to see about commercialization.

We get commercializable IP from private individuals, from Duke and other universities, and as time goes on from the companies with whom we have contracts for the development of companion diagnostics. That then allows people within the university to understand how the market for drugs actually works, and it also shows them ways that we can share in technology, not as a one-off but with defined expertise. That defined expertise is being developed transferred in educational programs, both to the Fuqua School of Business and to the Duke Medical School.

The third company that’s been started is a company called Zinfandel Pharmaceuticals, so they’re all red wines. Zinfandel Pharmaceuticals is preparing to do a prevention clinical trial study with Alzheimer’s disease.

It’s taking IP that was developed for diagnostic purposes to predict who will develop Alzheimer’s disease at what particular age, so we can take an epidemiological population between ages 62 and 87 and predict a highrisk group versus a low-risk group.

Then we would design and register our study with the regulators using pharmacogenetics to identify the high risks during the course of the study of the people who would go from normal to the development of Alzheimer’s disease. Instead of needing hundreds of thousands of people to do that

“Pharmacogenetics can identify the people in advance who will respond to the drug once it’s on the market” kind of study, you can do it with much lower numbers, if it works.

We will partner with major pharmaceutical companies who have a molecule that we are interested in. We’re designing the preliminary studies with several epidemiological populations across the world to see how fast we could recruit people who are virtually or seemingly normal between the ages of 62 and 87. At the time the study would be ready to start, probably in late 2010 or early 2011, we would already have names of people who have said they would be interested in participating and get a very, very fast start to the study.

This partnership will be spun out of the Blue Wine Group because it needs a partnership with others in order to perform such an expensive trial.

Duke will also own a piece of that. We’re doing everything the pharmaceutical industry wants to do, but we’re doing it in a much more efficient, costeffective way, using pharmacogenetics as a primary tool in order to cut the cost of studies, to provide better proof of concept studies, and to provide, if successful, a major income to the university. n

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INDUSTRY INSIGHT

Making discoveries MPI Research’s Tina Rogers discusses the specialized services needed to address pharmaceutical companies’ preclinical development needs.

NGP. What exactly is a discovery center and how is it related to a preclinical research contract research organization?

Tina Rogers. A discovery center typically centralizes specialized services to address the early preclinical development needs of pharmaceutical and biotech companies. The MPI Research discovery center is unique in that it is completely customer-driven, and was created to meet the specific discovery needs of our sponsors in these industries. In addition to DMPK capabilities, the discovery center offers expertise in a variety of in vivo models, including surgical, cardiovascular, neurobehavioral, anti-microbial, inflammatory models and others. To support the in vivo studies, we can provide a variety of endpoints, including molecular imaging (micro-PET and micro-CT), gene expression profiling, quantitative PCR, cytokine multiplexing (MSD), flow cytometry and other cell-based analyses.

“The discovery center will extend our commitment of responsiveness and quality to the area of discovery services” NGP. Why did MPI Research think it was necessary to have a discovery center as a separate entity at this time?

TR. The demand for preclinical discovery work continues to increase, as our sponsors are faced with critical decisions about which drug candidates to advance. Even as large pharmaceutical companies continue to downsize and biotechs

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restructure, the need for discovery resources doesn’t go away. The market for outsourced drug discovery services was more than $5 billion in 2007 with expected annual growth of about 16 percent through 2013. MPI Research has the experienced staff, technology, and resources that are needed to establish a dedicated organization that is totally committed to the discovery needs of our sponsors. Toward this end, we recently acquired two research buildings from Pfizer, located in downtown Kalamazoo, just 13 miles from MPI Research headquarters. This will be the site of the discovery center, as the location allows substantial opportunity for future expansion of these services.

NGP. What specific benefits will the discovery center of MPI Research offer to your sponsors?

TR. MPI Research has been one of the fastestgrowing preclinical CROs over the past decade because we are focused on the needs of our sponsors. The discovery center will extend our commitment of responsiveness and quality to the area of discovery services. Following their discovery research, sponsors will be able to seamlessly and cost-effectively transition their drug candidates from the discovery center to other preclinical service areas within MPI Research.

NGP. What distinguishes the discovery center at MPI Research from other discovery service providers in the industry?

TR. MPI Research recognized that discovery services require a different business model and approach than regulatory-driven services such as toxicology. The best way to provide the flexibility and dedicated, individualized attention for our sponsors is to establish a separate organization specifically for that purpose. We

Tina Rogers, PhD, MBA, DABT, joined MPI Research as the Associate Director of Research in August 2007. Rogers brings a unique combination of scientific and business experience to MPI Research. During her first 18 months at MPI Research, she has led initiatives to enhance the Discovery Research offerings of the company and has advanced specialized services in other key service delivery areas. Currently, Rogers is charged with leading the effort to establish MPI Research’s discovery center, which will consolidate drug discovery related services into a distinct business unit within MPI Research.

are convinced that this unique approach will better serve our clients.

NGP. How do you see the discovery center of MPI Research developing over the next five to 10 years?

TR. We will expand and enhance our capabilities in discovery services, based on the needs of our sponsors. Currently, we are exploring partnerships that will provide access to proprietary technologies related to predictive models of safety and efficacy. We will continue to establish collaborations to enhance our scientific perspective, allowing us to gain access to expertise and to participate in comprehensive drug development initiatives that will distinguish MPI Research as a center of excellence for discovery research.

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DIGITAL PATHOLOGY

Going digital Shealynn Harris tells NGP about the benefits of using digital pathology in international clinical trials.

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he process of moving drug candidates through discovery and into clinical trials is hugely dependent upon the development and availability of technology. With digital radiology innovation currently dominating the medical IT industry, a blueprint has been set for digital pathology to take centre stage in innovation.

Shealynn Harris, Medical Director, North America for Quintiles Laboratories, describes the technology currently used for image analysis. “Digital pathology involves taking tissue, processing that tissue as you would through standard histopathology techniques, and applying that tissue to a glass slide.

That tissue is then stained, whether with primary stains or with biomarker stains, and then the slide is sent through a scanner which then takes that section and creates a digital image of that tissue.

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“Traditionally, pathology has involved an anatomic pathologist reviewing a glass slide through a microscope. Whereas, in the case of digital pathology, the image is created to allow the pathologist to view that image on their computer screen, and also be able to view that image remotely. So the image can be scanned at one site and reviewed by a pathologist at another site.

“When we’re looking at global clinical trials, there’s the obvious advantage of improving the turnaround time and logistics by providing the pathologist with a remote solution for analyzing that slide, and then reviewing and analyzing that slide. So instead of shipping the slides across sites or across the globe, the pathologist has access to the image in real-time.”

“The digital transportation of the slide, as opposed to international shipping, is the key advantage for global or multi-site trials”

Benefits The digital transportation of the slide, as opposed to international shipping, is the key advantage for global or multi-site trials.

As a global organization, Quintiles has laboratory facilities in the US,

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Europe, South Africa and Asia, and so access to images the world over is imperative. “The obvious advantages are more real-time availability of the tissue image and reduced logistical cost, because it costs money to ship slides around the world. You also reduce the risk of breakage or loss during transit, and there is the advantage of maintenance of the integrity of the information. We know that stains can fade; with the digital image, the data is maintained, so there’s no degradation.

“The result is a digitized image that can be stored and archived.

The information that goes along with the image, such as a pathologist’s notes, can be annotated on the image, allowing access to it at another site. You can store the glass slide, as well as storing the image, so you have some redundancy as well. Data is critical to clinical trials, and this provides another solution to improved data storage. Another advantage of increased storage is the ability to retrieve data more easily, and certainly so in the case of data mining applications,” says Harris.

As a large laboratory with worldwide operations, Quintiles is able to fully maximize the capacities of digital imaging in its global trials and further its use within the markets into which it is looking to expand.

“We also have expertise in emerging markets, developing markets, and those markets that traditionally have had some limitations in terms of access to patients, such as in China and India. We have logistical and regulatory expertise in China and India, but one of the challenges we face is the ability to ship tissue out to a centralized pathologist, which can lead to limitations in coordinating data for a study.”

Global markets Harris points out that the global advantage of digital pathology is the opportunity it offers to combine the company’s global breadth and its logistical and regulatory expertise in China and India with a new technology that allows it to access tissues that it would not be able to ship out of the country. “We can put a scanner inside China and scan those slides without shipping them out of the country, providing remote access to the images so a pathologist can read them. Again, this improves efficiency and reduces logistical cost, and also provides access in countries in which there are restrictions on exporting shipping tissues.”

The use of digital data collection allows for a much more standardized analysis, avoiding the challenges when opinions differ between pathologists. “Standard pathology reviews and analysis are more subjective: you have a pathologist who is reviewing the slide and writing a report. With digital pathology, software automates that analysis, and this provides unification and harmonization in the data analysis across global sites, providing a more objective reading of the data and reducing the inter-observer variability and intra-observer variability,” explains Harris.

Consistent data is ranked highly among the agenda of Quintiles customers, and digital pathology is one form of technology with which they are able to accommodate that. With the variability between analytical methods abolished, customers feel a lot safer with the results that are delivered, and are assured it is a concrete set of results.

With digital pathology developing at an increasing rate, there are certainly exciting times ahead for Quantiles Laboratories as it continues to develop imaging technologies and further its discoveries in clinical trials. n

What is digital pathology?

Digital pathology is an image-based information environment enabled by computer technology that allows for the management of information generated from a digital slide. It is enabled in part by virtual microscopy, which is the practice of converting glass slides into digital slides that can be viewed, managed and analyzed.

The digital pathology environment is split up into six sections: Scan – digital slides are created from glass slides using a scanning device.

View – digital slides are accessible for viewing via a computer monitor and viewing software.

Manage – digital slides are maintained in an information management system that allows for archival and intelligent retrieval.

Analyze – image analysis tools are used to derive objective quantification measures from digital slides.

Integrate – digital pathology workflow is integrated into the institution’s overall operational environment.

Sharing – digital pathology also allows internet information sharing for education, diagnostics, publication and research.

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ASK THE EXPERT

Improving clinical trial efficiency and accuracy

By Dr. Steven Potts, PhD, MBA, Worldwide Director, Biotech/Pharmaceutical, Aperio

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ncology clinical trials are expanding internationally while laboratory tests become increasingly complex. Pathology is a key diagnostic component of clinical trials used to measure efficacy signals that are decipherable by expert, credentialed pathologists. As more trial sites are added and fewer patients are enrolled at each site, global pathology test standardization is critical. Digital pathology facilitates international clinical trials by allowing the pathologist instant access to histopathology data globally, as well as quantitative image analysis tools to standardize test results. Pathologists working remotely can support international enrollment and the expansion in test complexity, making their test results more quantitative and reproducible.

Digital pathology utilizes whole slide images from a computer monitor rather than glass slides from a microscope. The entire tissue section on a glass slide is scanned and becomes a single, large image viewable from anywhere via the internet. Software enables multiple pathologists to view and discuss the same tissue result concurrently in a digital slide conference, or to simultaneously view and align a series of histology slides stained with different biomarkers. Because digital slides are simply large image files, image analysis programs can help make quantitative, computer-generated measurements of tumor response across entire tissue sections.

Eleven of the 13 largest pharmaceutical companies use Aperio’s digital pathology solution in biomarker discovery and preclinical research. In outsourced toxicity studies, nearly all of the major preclinical CROs offering pathology services have adopted Aperio’s digital pathology solutions. Slides are scanned at the histology lab location, and then viewed by one or more veterinary pathologists from any location.

Pathology working groups, informal peer reviews, archiving and other essential collaborative activities can be conducted remotely with a full electronic record. Because the entire tissue section is scanned as one large image, comput-

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slide to case report. Aperio’s recently lauched Genie histology pattern recognition technology can be used to measure protein expression specifically in the cancerous cells of interest, automatically ignoring adjacent stromal tissue.

Even with patients from hundreds of locations and dozens of international sites, the pathology assessment is centralized and standardized across all study participants.

Instant access

Steven Potts is Worldwide Director for Biopharma at Aperio, rapidly expanding digital pathology in GLP and non-GLP studies. He previously was Head of Bioinformatics at Quest Diagnostics Nichols Institute.

He earned a bioengineering doctorate and MBA from UC Davis, and a B.S. in Physics from Wheaton College, Illinois.

er analysis can be run to quantitate toxicology lesion size or measure protein expression.

New product In response to the clinical needs in drug development, Aperio has recently launched a new product, Digital IHC (immunohistochemistry) for oncology clinical trials. Digital IHC is being offered by select industry-leading contract research organizations, as it leverages their existing large immunohistochemistry test menus. Slides are scanned at remote clinical sites, and then uploaded to a secure HIPAA and 21 CFR 11 compliant database.

Pathologists can conduct confirmatory diagnosis during enrollment, discuss results with distant colleagues or study directors, or complete full electronic pathology workflow from

Instant global secure access to pathology data will revolutionize oncology clinical trials and study design. Digital pathology provides today what the pharmaceutical industry took for granted several decades ago – access to pathologists. Logistics will improve, with the ability for an anatomic pathologist at a pharmaceutical company to do confirmatory reading during patient enrollment at a remote international location without the costs of time and travel.

Communication improves between the pathologists at the CRO and the study directors and oncologists at the pharmaceutical sponsor.

Searchable whole-slide pathology databases post-study will become a standard tool in the near future, similar to how virtual compound databases are used in computational chemistry today. Quantitative results are derived from the entire tissue section, not small ‘representative’ areas photographed using a microscope. For example, Targeted Molecular Diagnostics, a CRO recently acquired by Quintiles, uses Aperio’s Digital IHC to multiplex downstream phosphomarker measurements as efficacy readouts in kinase inhibitor clinical trials.

Digital pathology addresses the dual challenges of international patient enrollment and test complexity in oncology clinical trials. The adoption in early stage tissue-based research and preclinical safety studies has been remarkable. Clinical oncology project teams at leading pharmaceutical companies will expect the same advantages from their CRO clinical pathology service providers.

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Lifeblood Exec Int:12june

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EXECUTIVE INTERVIEW

Tissue preservation Transporting organs without the use of animal tissue.

NGP. Why is it important to continue developing technologies of tissue preservation?

Joseph Fischer. Science is rapidly expanding in the 21st century, and tissue preservation in the broadest context encompasses so many different fields, such as organ preservation, cancer therapies, stem cell, regenerative medicine, fertility, composite tissue allograft and allograft transplantation. The reason tissue preservation affects so many fields is that, in its simplest form, tissue preservation is a process in which an aggregate of cells is kept alive. The ability to preserve tissue outside or away from the body in a state that mimics the body for extended periods of time is a technology that does not receive much thought and attention. If the preservation of tissues (and cells) can be enhanced, then we can produce better science more quickly.

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will remove all of these issues and allow for unlimited sourcing and thus increased production of healthcare related products. It is hard to believe, but many vaccines are still created through the use of chicken embryo. Many large vaccine companies have invested millions of dollars to find an alternate source to produce vaccines with limited or no success.

Joseph Fischer

NGP. How can LIFOR support the recovery, transportation and reimplantation of kidneys, livers and hearts?

JF. Lifor is an animal component free, nutrientrich nanoparticle solution capable of supplying oxygen to cells and tissues. The advantages of Lifor over presently approved solutions used in the organ preservation and transplantation field is that Lifor preserves organs at room or elevated temperatures, thus mimicking in-vivo functionality. This allows for extended preservation time while the organ functions at a low metabolic rate. All the current solutions work at hy-

pothermic levels, which promote cell death. We have performed successful studies using Lifor on heart, liver and kidney in both small and large animal models. Not only can we support the transplant industry by allowing more organs to be procured and transplanted due to extending the preservation time but we can increase the number of viable organs through the regenerative properties of Lifor, so no organ donated goes unused.We have studies that prove Lifor can regenerate an ischemic human kidney in approximately sixteen hours, making it suitable for transplantation while repairing cellular integrity.

Joseph Fischer, President and CEO of Lifeblood Medical, Inc., has 35 years of pharmaceutical and biotech manufacturing and product development experience. In pursuing a solution to extending organ preservation, he founded Lifeblood Medical in 2001 and codeveloped the patented technology, which has a myriad of applications beyond organ preservation.

NGP. What are the benefits of not using animal protein as a carrier?

JF.The use of animal proteins in biotech have gone on for generations, due to its ability to culture cells and promote them to survive, grow and divide. However, there are inherent issues, such as the laborious process that is undertaken to produce, limited sourcing, unpredictability of functionality from lot-to-lot, allergic reaction and contamination. FDA is tightening their oversight in the biotech field, and one area of concern is animal protein in the manufacturing process. Animal Component Free products

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NGP. In 2008, you won the Frost & Sullivan Innovation Award. What affect will this have on your expansion in the industry?

JF. Having the Frost & Sullivan name connected with Lifeblood and our technology gives us instant credibility, as well as a validation on our technology. Prior to receiving this award, many experts in the industry have difficulty understanding and believing in our technology, since it has so many applications in diverse fields, such as cell culturing, cryopreservation without toxic

“The reason tissue preservation affects so many fields is that, in its simplest form, tissue preservation is a process in which an aggregate of cells is kept alive�

DMSO, organ preservation, limb preservation, oxygen therapeutics and room temperature storage of cells and tissues. The Frost & Sullivan award also gives us notoriety within the biotech industry.

One of our goals is to license the technology in such areas as vaccine manufacturing, stem cell, regenerative medicine, oncology and allograft processing, while we focus on organ and limb preservation and oxygen therapeutics. The award grabs the attention of a potential licensor that our technology is worth looking into and since receiving the award we have had companies contacting us inquiring, on our technology and possible collaborations and/or partnerships.

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RESEARCH

It’s all in the

Genes T

he technology used in siRNA is relatively new. It came from the discovery that won the Nobel Prize for Medicine, which showed that we can regulate gene expression in multiple organisms, including lower organisms and mammalian cells in mammals. This spurs a lot of interest in the industry and also academia. We started the research on siRNA technology when I joined Abbott; it was one of the first things I did.

We use this technology in Abbott on several fronts. We use it for drug target identification and the validation: we obtain a so-called siRNA library, which is a library of siRNA against almost the entire human drug books. Then we screen the library in various assays and try to find suitable druggable targets for a small molecule or antibody drug discovery.

We also initiated our efforts to direct the using of siRNA as a therapeutic drug. This effort was primarily focused in the oncology area, so we tried

An update on the latest research into using siRNA to target tumors. By Yu Shen, Abbott Laboratories to develop an siRNA-based cancer therapeutic.

We pick the siRNA’s that we assign against disease-relevant genes.

We would then need to deliver the siRNA into the site that we want; in our case it’s the tumor site, which allows it to get into tumor cells, silence the gene and inhibit the tumor growth, resulting in a therapeutic benefit.

The major difficulty we face with this is the delivery. If you look through the field, there are several lines of work is going on. One strategy used by several companies, and also some academic labs, is picking the so-called low hanging fruit: trying to find the areas where local delivery works. An example of this is the macular degeneration. If you inject naked siRNA into the eye, it can be taken up by the cells in the eye and can silence the gene there, allowing for therapeutic benefit. There are several other areas that are also relatively easy to deliver in: one being the lung, which can be achieved via nasal delivery, and so this is what is being tested for the treatment of respiratory disease.

Another place is the liver, which is actually one of the major focuses in the field. There are many metabolic disease targets in the liver, allowing to use siRNA to inhibit these targets and regulate blood sugar or cholesterol levels.

Tumor focus At Abbott, our primary focus is on delivering SIRNA into tumors. This is much more challenging than the lung and the liver delivery. One of the reasons for this is the structure of the tumor, which is a relatively compact, solid ball. The siRNA is much more difficult to get into a tumor than tissues with sufficient blood supply, such as the liver.

The major focus for our therapeutic effort now is to come up with a suitable delivery system that we can use to deliver siRNA into tumors efficiently, and also with relatively low toxicity so we can proceed with this form of delivery system, and achieve a therapeutic benefit for cancers. This is what we are currently working on.

In addition to this, we’re also working on siRNA library screening to identify cancer targets. We are one of the very few big pharmaceutical companies that started the siRNA library screen in 2002. Although we put a lot of effort in doing the screen-

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Yu Shen is Senior Group Leader in siRNA therapeutics at Abbott Laboratories.

Shortly after joining Abbott in 2001, he pioneered the company’s siRNA program and led the team in successfully developing various RNAi-based methods for cancer target identification and validation.

ing and characterizing the results of the screening, otherwise known as the ‘screen hit’, the outcome was actually not very good. We spent two to three years doing several initial screens but eventually most hits we received turned out to results from the siRNA-mediated off-target effect.

The off-target effect means that we design the siRNA against a particular target, but the effect did not result from the inhibition of the target that the siRNA was designed for, which is the biggest challenge for siRNA library screen work and effort across the industry. After a few years of studying siRNA off-target mechanism, the source of the off-target gene silencing was found, and as a result of this, chemical modifications have been introduced which can specifically inhibit the seed base of target effect.

New target Another version of the library was born, called On-target Plus. The working of that library is much more effective, and as a result we see much less off-target effect in the screen. Also, following the condition that we use for the screen, the new version of the siRNA library has a similar degree of target knockdown compared to the previous version of siRNA library, providing us with similar efficiency but without so much off-target effect. We are currently expanding our screen effort using the new library, allowing us to conduct a higher amount of screens in the cancer area, along with beginning the process for the screening of other disease targets too.

The future looks exceptionally promising. siRNA can therefore begin to be used as a research tool for target identification and validation for scientific investigation regarding the biological process. This is a relatively mature area with many tools readily available. Just as these tools are used, so can be the libraries. That is what we are currently focusing on, and we will continue developing this, along with the therapeutic effort.

The big challenge is to deliver siRNA in vivo.

There are lots of activities going on at Abbott and also across the industry. Recently, we have seen lots of big deals between pharmaceutical companies and biotechs, and this is certainly primary on the delivery side. We ourselves recently announced a deal with a company called Liquidia, which provides us with a delivery platform. Such deals will likely continue to happen as people realize that delivery is the major hurdle for siRNA surface.

PRIZE-WINNING DISCOVERY

The 2006 Nobel Prize in Physiology or Medicine was shared

by Professor Andrew Z. Fire at Stanford University, and Professor Craig Mello at the University of Massachusetts Medical School. They received the prize for their discovery that double-stranded RNA triggers suppression of gene activity in a homology-dependent manner, a process named RNA interference (RNAi).

Their discovery revealed a new mechanism for gene regulation, and the biochemical machinery involved plays a key role in many essential cellular processes. Double-stranded RNA synthesized within the cell can reduce or abolish gene activity by RNAi-like mechanisms.

This control system for gene expression has proven to be important for both the development of an organism and the physiological functions of cells and tissues. RNAi protects against RNA virus infections, especially in plants and invertebrate animals, and secures genome stability by keeping mobile elements silent.

Double-stranded RNA is used as a powerful tool to experimentally elucidate the function of essentially any gene in a cell. The discovery of RNAi has already had an immense impact on biomedical research and will most likely lead to novel medical applications in the future

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ASK THE EXPERT

The dream of personalized medicine Next-generation sequencing takes us closer, but only if we have a sequence data management solution.

T

he field of personalized medicine holds immense potential for human health.Too many drugs fail because they only treat a portion as opposed to the entire human population. The variation in human genetic make-up causes differential responses to drugs.With the advent of nextgeneration sequencing, a clear path is visible toward the enumeration of the variation in the human population with the ultimate goal of using those individual genetic variations to provide medicines tailored for each person’s genome. However, the dream of personalized medicine will only be achieved by an earlier focus on personalized genomics as a means to build the underlying knowledge-base as a foundation for research in personalized medicine.

Ron Ranauro is the Chief Executive Officer of GenomeQuest, Inc., where he oversees the company’s day-to-day operations. Prior to joining GenomeQuest, he founded and led Blackstone Technology Group, a gridcomputing provider to the life science IT field. Ranauro earned a BS degree in management and an MS in computer science from Worcester Polytechnic Institute.

Overcoming past hindrances The limitations of many past genomic approaches have to do with the use of a single genome sequence as representative of an entire species. This approach has provided tremendous insight into the relationship between genetic sequence and biological function at a coarse level, but not at the level of detail associated with personal genetic variation.

The developments made by next-gen sequencing techniques have revolutionized sequencing activities, rapidly bringing forth the era of personalized genomics. In addition, the next-gen advances are expected to supplant a substantial portion of microarray studies with digital gene expression thereby converting today’s analog view of gene expression – to a higher resolution, richer digital view.

The data glut The cost of generating sequence data has dropped ten thousand-fold since 2005, making possible new applications in personalized medicine. By mid-2010, a university laboratory with a next-generation sequencing machine running at 50 percent capacity will produce more sequence data than has been archived in all of GenBank from its inception in 1982 through 2008. As a result, the

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amount of available genomic data is increasing exponentially, and there is no single point of access to multiple sources of disparate in-house, public and private data.

The information systems to manage all of this sequence data do not exist inside of pharmaceutical and biotech companies.The client-server architectural approaches of these companies are based on relational databases that are too expensive to develop, deploy and maintain, causing these companies to increasingly seek commercial solutions to avoid unforeseen scaling risks and hidden costs.

How will commercial enterprises and academic institutions deal with all of this data?

The GenomeQuest solution GenomeQuest provides a software-as-aservice (SaaS) web portal providing centralized sequence data management resources and applications for biological research, patent research, and for computing and working with all types of sequence data and associated text.

GenomeQuest employs commodity computing components at the core of its compute cloud that powers the GenomeQuest product. A centrally managed cloud of commodity computers, scal-

able by design, guarantees the delivery of a lowcost informatics solution that can stay ahead of the growth of our customers’informatics needs.

We are the only complete solution for dealing with the next-generation data deluge and the management of all sequences across an enterprise. GenomeQuest enables scientists to very accurately extract the maximum information from their next-gen sequence data. The GenomeQuest solution provides this information in an intuitive, web-based interface that enables the rapid analysis of the data with the follow-on benefit that those analysis results are in a consumable, sharable and reportable form.

Return on investment It also provides an ROI to the commercial enterprise by increasing end-user productivity by providing a single, centralized access point for all sequence data from any source (public, corporate, personal, or commercial), across your entire enterprise.

In addition, GenomeQuest improves knowledge transfer and collaboration by enabling endusers to upload and share their sequence data, all within the existing informatics resources, inside your enterprise.

Overall, GenomeQuest’s easy-to-use web interface, open system with published APIs, and continuously updated reference data will enable you to reduce your ITcosts, minimize your risks and enable you to more effectively redeploy your talented informatics staff to higher value activities.

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RESEARCH

Leaping the

hurdles As patents expire and pipelines are pressured, NGP finds out how Lundbeck’s Peter Høngaard Andersen is working to stay at the front of the R&D race.

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P

eter Høngaard Andersen has been in the pharmaceutical business for nearly 25 years and has witnessed some major changes in the industry. Perhaps one of the most visible of these has been the shrinking number of independent pharmaceutical companies. “When I started my career there were small pharma companies everywhere,” he says.

“The most striking difference is the consolidation that has taken place. I think that’s going to continue.”

There is a new division in the focus areas of many companies, with some concentrating on research and innovation, while others pursue possibilities in generics. This can be due to the fact that these two areas require different skill sets, but it can also come down to survival, as Anderson points out. “If you want to survive as a small pharmaceutical company you have to be very specialized. The only way you can exist in the long run is if you can innovate and deliver specialized products into your focus area, because the competition and demands these days are so harsh.”

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Andersen started his career in the pharmaceutical industry with Novo Nordisk, where he worked for 13 years in different positions, latterly as a project manager in the metabolic disease area. In 1997 he joined Acadia Pharmaceuticals as Vice President of Drug Discovery, a position he held until he joined Lundbeck. He explains that this diversity of roles has helped prepare him for his current position.

“It’s striking how different the approaches to the issues we’re dealing with can be and the methodologies you have to use. It’s been quite a learning experience to work in a different therapeutic area.

Working as a project manager also requires a different set of people skills than in my current role. When you’re a line manager you have the power of hiring and firing people whereas as a project manager you can only make them walk in the same direction by building passion in them.

“That was also a very big learning experience, and an experience that I use a lot in my present job. As innovation is one of our key challenges it’s so important to make an environment where people are engaged and passionate. The engagement of our scientists is key to our success here.

“What we’ve done is make a project system where the empowerment and responsibility is pushed very far out in the organization.

We make a deal with everyone at least once a year around what they will deliver if they are allocated defined resources and budgets. When this deal has been agreed, we don’t interfere with what they’re doing, although they can come back to management to use us as coaches and/or discuss relevant issues. ”

Lundbeck: the edited highlights 1915 – Lundbeck founded as a trading company 1924 – Begins selling medicines and cosmetics 1937 – Lundbeck moves from trading into becoming an organic chemical manufacturer. Introduces Epicutan, the company’s first original medicine 1950 – Begins to focus research on substances that affect the central nervous system 1965 – Fluanxol is introduced for treatment of mild depression, schizophrenia and psychoses 1972 – Citalopram is invented, forming the basis for Lundbeck’s future success and expansion 1996 – Serdolect is launched in 17 European countries 2002 – Cipralex/Lexapro is introduced on the market for treatment of depression 2005 – A zilect is launched for the treatment of Parkinson’s disease

Major changes

Peter Høngaard Andersen is Executive Vice President of Lundbeck’s research organization. He is responsible for the company’s research and for delivering new development candidates for clinical development.

Andersen joined Lundbeck in 1999 as Director of Biological Research. In November 2003 he was appointed Vice President of Research and Chairman of the Board of Directors of Synaptic Pharmaceuticals (now Lundbeck Research USA, Inc.). He started his career in the pharmaceutical industry with Novo Nordisk A/S.

Andersen’s time at the company has coincided with some big developments. Staff numbers have grown from around 2500 to over 5000 and a series of new product lines have been introduced. Andersen breaks the changes in research down into three distinct phases. “The first phase was very much focused on building up the R&D organization to ensure the output we needed for the future,” he continues. “The second phase centred on delivering projects to secure our pipeline for the patent expiries in 2012-2015. The third phase, which we’re in right now, is to turn the organization around to meet the challenges of the future. We have called this third phase the 2020 challenge.”

And make no mistake, it is quite a challenge. The company has suffered some major setbacks in its pipeline, with a number of big projects running into trouble. “We have seen the termination of our sleep medication gaboxadol, we have seen the failure of desmoteplase in phase three, and then there was bifeprunox, which we decided not to file in Europe,” Andersen explains. “Obviously these three products if they had succeeded would have fuelled a very aggressive growth period for Lundbeck, but that’s not going to take place. We have had to adjust our expectations for the future quite considerably and aggressively look for additional licensing opportunities.”

Such a disappointment has obviously had a substantial impact on the company’s research organization. A lot of effort was put into exploring licensing opportunities, so it is reassuring to hear that there is still an opportunity to salvage some of this work. Both the desmoteplase and

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bifeprunox projects are continuing with adjustments to their development programs, and even gaboxadol is still being evaluated.

Regardless of these hurdles, Lundbeck remains committed to pursuing innovation. By the end of 2008, the company had spent around 20 percent of its revenue on R&D. “We’re a strong believer that innovative products are the future for us and for any serious pharmaceutical company,” Andersen explains. “It’s also very clear that the requirements to get on the market today both from a safety and efficacy point of view are steadily increasing. In order to meet these challenges we’re seeing a heavy investment in R&D as a prerequisite for being a high growth company.”

Main focus The central nervous system has long been Lundbeck’s main area of interest, with the company developing drugs to counteract depression and schizophrenia as far back as the 1960s. More recently, efforts have been stepped up to tackle what Andersen sees as a lack of significant breakthroughs, “Elias Zerhouni, the former director of the US National Institutes for Health, has been quoted saying that the biggest reason we aren’t making progress is because psychiatrists and neurologists do not have a sufficient, solid background in biology,” he says, pointing out that the reason Dr. Zerhouni led a major reform of the translational and clinical research system in the US was because there has not always been enough interaction between people working in the clinical and molecular areas.

To remedy this situation, Lundbeck has been moving in fresh directions and is seeking out new sources of knowledge. A key element of this strategy has involved partnering with top academic institutions that have experience in cutting-edge biology and a solid link to the clinic. The ultimate aim is to identify novel targets that could both prove profitable for the company and provide help for patients whose diseases are not currently very well treated.

On one of the biggest partnerships, with the Mayo Clinic in Florida, Andersen comments, “The collaboration is focused on the basic biology in neurodegenerative diseases, and the hope we have with this collaboration is to get insight into the diseases and thereby information about new targets we could input into our pipeline.”

So what’s next for Lundbeck and the industry? The looming difficulty for everybody in the pharma space is that of patent expiry. “We have our in-house challenge coming up between 2012 and 2014, which is the expiring exclusivity for Cipralex/Lexapro and Ebixa,” notes Andersen. “It’s critically important for us that we progress our late-stage pipeline and reach the market in due time before this happens.” Despite this tough task, Andersen displays a commendable level of optimism.

“With what I’ve seen of data from the pipeline, I’m confident that we’ll make this, and I’m also confident that the profile will be well accepted in the market,” he continues.

The future still holds much possibility. For Andersen, one of the most exciting areas of research is at the genetic level. “Biology around the human genome is now starting to flourish,” he says. “If you follow the academic literature there are a lot of new opportunities coming up, where we can jump in and turn these advances into good drugs. It has taken a few more years than everybody expected, but it is a really big opportunity for the industry.” n

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Strength in numbers Peter Høngaard Andersen explains Lundbeck’s alliance with Takeda.

I had previously been involved in a collaboration with Takeda in my old Novo Nordisk days and had very positive experiences. We’re now working with them to develop and commercialize a portfolio of novel compounds for the treatment of mood and anxiety disorders. As I expected, the collaboration has panned out very positively. They’re extremely efficient, very aggressive, and the projects are moving forward at a very high speed.

The reason why we decided to go into this collaboration was that we could see that our mood disorder disease area would also have a major part of their market share via GPs. Takeda was very strong in the US and had a GP sales force, and that’s been the key driver behind finding a partner for these compounds. Details on the commercial part of the agreement have been published earlier but basically the arrangement is that Takeda will have the GP part of the sales in the US and Japan and we’ll have the specialty sales in these areas.

Making your mark Peter Høngaard Andersen outlines the work Lundbeck has been doing in the field of biomarkers.

Using biomarkers is utilizing biological tools to either diagnose the patient and/or see if the patient is going to respond to your treatment. It’s an area that is pretty advanced in certain cancer areas, but in the central nervous system we’re still in the Dark Ages.

Lundbeck started work in this area a few years ago.

We decided initially to focus on mood disorders and we have established collaborations with a number of major academic institutions in the world involved in this area.

When we started, my expectations were that it would take 10 or more years before this would ever have an impact on what we were doing and the way we saw the patients.

However, the first data are starting to come out now and we are starting to see a picture appear, which makes me believe that within the next five to 10 years we may begin to be able to diagnose certain types of mood disorders from a biological perspective. If we can do that it will be much easier to give them a rational treatment resulting in a better response for the individual.

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FEATURE

The

freedom to

dream Boehringer Ingelheim’s Andreas Barner believes in allowing his researchers the space to follow their inspiration. The result has been three promising new compounds in the last two years for the German company. By Marie Shields

A

ndreas Barner is clearly tired. It’s been a long day at Boehringer Ingelheim’s R&D facility in Biberach, Germany.

The company has just announced its entry into the type 2 diabetes arena, and Barner and a panel of scientists have been busy explaining the new compounds to a room packed with journalists from all over the world.

I am his last interview of the day, and have been forewarned that he has a train to catch, which makes me apprehensive about the kind of welcome I might get as I walk into the light-filled meeting room. Yet Barner, immaculate in a dark suit and crisp white shirt, is unfailingly charming and polite. He offers me water from the bottles arrayed on a silver tray on the table and makes small talk about the brand of digital recorder I am using.

This calm exterior belies a hectic professional schedule. Barner is a member and past Chairman of the German Association of Research-based Pharmaceutical Companies, has served as Deputy Chair Person of the National Genome Research Network Steering Committee, and has been a member of the Advisory Board to the University of Mainz, as well as the Board of Trustees of the German Chemical Industry Fund.

Armed with a doctoral degree in medicine and a PhD in mathematics, Barner began his professional career at Ciba-Geigy, before joining Boehringer in 1992 and working his way up to his current position as Vice Chairman of the Board of Managing Directors and Head of the Corporate Board Division for Pharma Research, Development and Medicine.

New frontiers

“We prefer not to raise hopes and then a year later have to say that unfortunately it didn’t work out”

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It is in this position that he has led the unveiling of Boehringer’s new pipeline of antidiabetic compounds. In his quiet yet authoritative voice, Barner explains the company’s decision to enter the diabetes arena: “When we enter a new area, we always look first to see if there is a true medical need, or a problem that needs to be solved. Secondly, we ask ourselves: do we believe that we can find a research approach to meet this need? The problem must be medically relevant. It’s then up to the researchers to decide if there is a possibility

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that we can deal with this problem. Is there a target? Do we have a mechanism we can use to change the course of the disease?

“In the case of diabetes, it was very obvious that there was a medical problem; it was very obvious that we had approaches that were possible, and the new compounds show that this has worked out well.”

Treatments for type 2 diabetes clearly represent a growing market in the pharmaceutical industry.TheWorld Health Organization estimates that 180 million adults around the world are currently living with diabetes, with this number expected to rise to more than 360 million by 2030.

Type 2 diabetes accounts for 90 percent of all diabetes cases. According to the International Diabetes Federation, the highest rate of diabetes prevalence per capita is in North America at 9.2 percent of the population, but Europe follows closely behind at 8. 4 percent.

Here at the BI’s Biberach location, the company’s research teams have been focusing on the discovery and development of novel oral antidiabetic treatments targeting two new principles, the inhibition of DPP-4 (dipeptidylpeptidase inhibitors) and the inhibition of SGLT-2 (sodium-dependent glucosetransporter-2 inhibitors).

While there have been a number of advances in the treatment of type 2 diabetes in recent years, traditional therapies have failed to meet the demands of the huge number of people currently living with the condition. When Boehringer’s compounds, currently in phase II and III clinical trials, eventually reach the marketplace, they could prove to be a goldmine for the company.

(Top and bottom) Journalists tour BI’s Biberach research facility

A medical necessity?

As with treatments for many chronic conditions, you can’t help but wonder where the true interest lies – in making money or in helping sufferers?

In the case of type 2 diabetes, it can be argued that more money should be put into preventing the onset of the condition as well as treating it. Even the information pack handed out at Boehringer’s press conference points out that up to 80 percent of type 2 diabetes could be prevented by encouraging people to adopt a healthy diet and increase their physical activity.

I suggest to Barner that it would be better to encourage people to live healthier lives rather than waiting until they develop the disease and then treating them with a drug, but he is having none of it. He leans forward in his chair and clasps his hands against the pristine white tablecloth. “I would be fully supportive of making sure that prevention is a cornerstone of any healthcare system,” he says. “Prevention means educating people, especially children, to eat healthy food and to eat less of it, and to be more physically active so they do not become obese and diabetes does not have the chance to develop. That’s the first step.

“However, there will be people for whom this does not work. And then there are those who already have the disease as an existing condition. We have to make sure there are optimal treatments available for them. This is where I see the role of the diabetes medications we are developing.”

In development Boehringer’s frontrunner compound for diabetes is BI 1356, currently in phase III clinical development. BI 1356 (Ondero) is a DPP-4 inhibitor – a new class of oral hypoglacaemics that inhibit DPP-4 and enhance the body’s ability to control blood glucose by increasing active levels of incretin hormones. They control elevated blood glucose by triggering pancreatic insulin secretion, suppressing pancreatic glucagon (a hormone involved in carbo-

Dr Manfred Haehl explains the company’s clinical research focus

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hydrate metabolism) secretion and notifying the liver to decrease production of glucose.

According to Barner, phase IIb trials confirmed the unique properties that may positively differentiate BI 1356 from others in the same class. He says BI 1356’s safety profile was very favorable, and that a large phase III clinical programme currently under way aims to further confirm its efficacy and tolerability for long-term use.

The company also has two other antidiabetic compounds, BI 44847 and BI 10773, in phase II trials. They are both SGLT-2 inhibitors that express their therapeutic effect mainly be eliminating excess blood glucose via the urine. Due to their unique mechanism of action, SGLT-2 inhibitors have a different safety profile to that of other agents traditionally used to combat type 2 diabetes.

Diabetes is not the only area in which Boehringer Ingelheim is forging ahead: the company is also broadening its oncology pipeline. Out of the four leading compounds developed as a result of BI’s entry into oncolocy in November 2006, the agent BIBW 2992 (Tovok) has recently entered phase III clinical trials. BIBW 2992 targets non-small cell lung cancer (NSCLC), the most common form of lung cancer.

The phase II trial, called the LUX-Lung 1 study, will determine the efficacy of BIBW 2992 in lung cancer patients in whom the most commonly used treatments of the same class (gefitinib or erlotinib) have failed. Barner says that phase II data showed that advanced NSCLC patients treated with BIBW 2992 experienced a high rate of disease control (87 percent) and a promsing overall response rate (50 percent).

Another oncology compound, BIBF 1120 (Vargatef), will enter phase III development in the near future. BIBF 1120 is a novel triple angiokinase inhibitor that simultaneously inhibits three growth factors and receptors that play an important role in angiogenesis: VEGFR, PDGFR and FGFR. BI is also active in developing treatments for premenopausal women suffering from hypoactive sexual desire disorder. Its compound Fibanserin is currently being investigated in the ongoing Bouquet phase III trial programme, which involves 5000 women. Results are expected next year.

I have to add that there were some bemused looks among the journalists when this last disorder was mentioned at the press conference, although it is classified as a disorder in DSM-IV and some estimates put its incidence at about 45 percent of premenopausal women. Whether this is the type of condition best treated through medication is open to debate.

Family business The press conference in Biberach was the second of its kind for Boehringer since 2006, which in itself is interesting, since BI is still majority owned by the Boehringer family and so is not required to disclose the progress of its pipeline or research. Why then go to all this trouble?

“We think that a certain amount of transparency is necessary,” Barner explains. “We do have some luxury there, in that we do not report on compounds earlier than phase II, because we prefer not to raise hopes and then a year later have to say that unfortunately it didn’t work out. We might still have to do that, because if a compound fails in later trials, then it fails. But we prefer to go public with compounds only once we have a solid base for doing so. This saves time for everybody, and it’s luxury we can afford.

“We feel obliged to transparency – we publish all trials and we inform the public about all activities in research and development after phase II.”

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BOEHRINGER INGELHEIM The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 135 affiliates in 47 countries and 39,800 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing therapeutic products for human and veterinary medicine.

In 2007, Boehringer Ingelheim posted net sales of €10.9 billion while spending one fifth of net sales in its largest business segment, prescription medicines, on research and development.

The luxury of choosing when and what to disclose is not the only advantage conferred on a non-publicly quoted pharmaceutical company. The industry is having a bit of a rough ride at the moment, with the crisis in the financial markets adding to the existing woes of looming patent expiries and a lack of new blockbusters.

Being family-owned means not having to worry about the ups and downs of the stock market, as Barner points out: “It allows us to be more stable. We are less affected by the stock market, very obviously, and continue to follow our long-term vision, and we do that very successfully.”

The proof of this is that in 2007 BI invested $2.18 billion in research and development, and added 400 new employees, to bring its global headcount in R&D to 6400 people. This stands in sharp contrast to many of its rivals. In October, Merck & Co. announced that it will cut 7200 jobs, more than 12 percent of its workforce, as it faces generic competition to its top-selling drugs and falling sales of its cholesterol medicine and its cervical cancer vaccine, Gardasil.

Schering-Plough will cut 10 percent of its workforce, or about 5000 jobs, to reduce spending by $1.45 billion. Pfizer, the world’s biggest drugmaker, has cut more than 14,000 employees since 2007 and may have to further reduce its workforce.

In Europe, the UK’s GlaxoSmithKline has said that it will cut 850 jobs from its R&D operation, Switzerland’s Novartis will fire 550 people, and France’s Sanofi-Aventis will eliminate 927 positions.

Rising to the top Aside from relative job security, another plus for Boehringer’s staff is that in each of the past four years, the company has been named among the top four scientific employers by Science magazine. This year it was number four, last year number one. I ask Barner whether this has an impact on the calibre of staff the company can attract, but he shakes his head. “It’s good to know. It’s a good group of companies to be in the company of. As always, it’s a challenge to maintain these ratings, and we do hope that we can continue to do so.

“But I’m not sure whether it has had a major impact on attracting employees. I would be concerned if we were in 100th place, but you do have to take

it with a grain of salt. It’s a positive signal, but we should not overestimate it, nor, on the other hand, should we be overly concerned about it.”

Perhaps more important to BI’s staff retention rates is the way it treats its employees once they have been hired. One important tenet of this, mentioned byBarnerduringthepressbriefing,istogiveresearchers‘thefreedomandspace to be curious’. When I ask him exactly what this means, he smiles.

“It means that we ask the research teams to come up with ideas about what they want to do and then they go about it in an interdisciplinary fashion – though of course there is always the question of what is medically relevant. We listen to the researchers, we don’t have it filtered or decided upon based on arbitrary criteria – we encourage the teams to take a creative approach.”

And the future is also looking bright. As Barner puts it, “We have a good pipeline. We believe we have the right strategic approaches to look at the right diseases, and we want to continue in this way. We like what we see – we have our oncology compound, we have the new diabetes compounds, we have new products in the full pipeline; that’s a good situation to be in. We want to keep it like that, which is always a challenge in our industry.”

With that, the interview is over. Barner shakes my hand, collects his briefcase and overcoat, and is off to catch his train. I walk back through the modern wood and glass building to the atrium, where earlier we were served an unusual lunch of hors d’oeurves on a pharmaceutical theme – strange-colored drinks in test tubes, skewered prawns on what looked like sample slides, a mushroom concoction in a glass vial – accented by beakers billowing dry ice. It was all delicious, and yet Barner was whisked away before it began, and I suddenly wonder whether he even had time to eat.

I gaze down through the huge windows separating the atrium from the employees’ restaurant on the ground floor, where a few remaining staff members are lingering over the last of their lunches or placing their trays on the futuristic conveyor belt system. From what I’ve heard and seen today, Boehringer seems like a forward-thinking employer, using its status as a family-owned company to further its research goals and allowing its employees the freedomto follow their inspiration. I’m almost sorry to leave.

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CLINICAL TRIALS

Building

relationships around

globe

the

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Wyeth’s Joan Shen examines the benefits of choosing international locations for clinical trials.

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s Medical Director for Neuroscience at Wyeth, Joan Shen is used to working with people from around the world.

She is currently focused on conducting global trials for phase II and phase III, for indications including schizophrenia, bipolar disorder and depression. “My day-today job is to work with clinical scientists to generate protocols and select the countries, and then conduct trials and analyze the data to get the results,” she explains. “We coordinate with the other project management functions and propose to upper management what we think the best strategy is to move forward with a certain compound.”

Clinical trials are becoming ever more complex, with larger patient groups and are often conducted internationally, meaning it can be challenging to conduct trials in a timely and cost-effective manner. Shen points out that the main factors to keep in mind are speed and quality. “Wyeth has been back and forth in terms of what are the best methods, and in the last two years we have generated a group called country visibility. We call it the site management group, as distinct from the study team.

Joan Huaqiong Shen is Medical Director for Neuroscience at Wyeth. She began her career as a surgeon, then obtained a PhD and training in psychiatry.

Shen, who is board-certified in psychiatry and eligible in clinical pharmacology, worked for Eli Lilly before moving to Wyeth in 2005. She leads clinical trials to China, India, Japan, South Africa and Eastern Europe.

“This group helps us to facilitate the selection of countries and the visibility of studies company-wide. Once we get approval to move forward with a study and get a budget in place, we have a study mobilization meeting with all the functions, including the management group. That needs to be planned six to nine months ahead of time.

“We generate a synopsis of the study and a questionnaire about the site country’s visibility, and the special site management group takes them and sends them all over the world, wherever Wyeth has attachments. They collect the feedback on what is required, such as the number of patients or disease areas or placebos needed. They then give feedback to us and based on that information we select which site we want to go to. That helps us get collective information and from that we can generate a database based on site performance in the past, and the regulatory environment changes.”

Shen points out that the downside of this is that the quality of the site may not get as much consideration as it should. She believes a joint effort works best, between country visibility groups and the study team to look into the specific capacity and the quality of the sites.

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WYETH FAST FACTS International benefits

• Founded in 1926 under the name American Home Products Corporation • Headquartered in Madison, NJ • Operating in more than 100 countries • 47,500 employees worldwide

longer time for regulatory approval.

Shen leads trials in various sites around the “Some countries are quite fast, while othglobe, including China, India, Japan, South Africa ers are very slow. For example, in China in and Eastern Europe. While big pharma compamy experience once you hit the ‘yes, go’, nies have been criticized for choosing these locathey are able to really move very, very tions based on cost, and have been accused of quickly. In one of the trials I remember in ‘taking advantage’ of unsophisticated local popChina, they had already finished their enMAJOR DIVISIONS ulations, Shen explains that there are legitimate rollment but some other countries were reasons to site trials abroad. so behind that we asked China, ‘Can you • Wyeth Pharmaceuticals “We need a diversified patient population, increase the number of patients to finish • Wyeth Consumer Healthcare which is very important for development if you up all the studies?’ And they did.”

• Fort Dodge Animal Health are marketing all over the world; and secondly While Shen is happy to run trials in the trend toward placebo results and so-called the US, apart from the issues with paFINANCIAL failed trials is increasing in the US.That means we tient quality, she prefers to go where • 2007 net revenue – $22.4 billion are getting ‘fake’ patients or treatment resistant there is a bigger potential patient popu• 2007 net income – $4.8 billion patients, or patients who have been recycled lation. “It’s also the market that we’re • 2007 diluted earnings per share – from other studies. We can’t see the true treatlooking for. The regulatory requirements $3.52 ment facts if we repeatedly use the same popufor most of those regions ask for the parlation and the commercial treatment sites who try ticular patient population from their retheir best to get patients don’t necessarily progion. If early on you know you’re vide the best quality. targeting those populations, it makes life “We can lower the placebo rates because we know going to countries like easier when you submit to the FDA to get market approval. That’s one China, India and South Africa you see many more patients who have not been of the incentives we are moving towards with these global studies.” exposed to clinical trials and to second generations of certain drugs; for exDifferent regulations ample, psychotics. It then becomes much easier to see the true effect.

Regulations also vary between countries. Shen has found that India “I remember one of the studies I was involved with in the US in which we has an excellent regulatory environment. She anticipates a three to four had no effect on the treatment between the two populations, but we were able month approval period there, because the board of health is relatively easy to identify the drug effects with Russian subjects. Overall, it was statistically to work with. “As long as the ethic group committee agrees with your prosignificant, but if you put aside the Russian patients you didn’t see it. We were posal, you have no problem. This is not always the case in other countries. able to discuss this with the FDA and they agreed with our data. The quality of “In Japan, the PMDA is really strict on what they do. Usually they ask the data spoke for itself.” for phase I data before you can move forward. The other problem is slow Of course there are disadvantages to international clinical trials. One enrollment, but I think the PMDA is now much more open-minded. They like of these, as Shen points out, is that some countries require a much

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“We need a diversified patient population, which is very important for development if you are marketing all over the world”

JOAN SHEN open dialogue, so the study team has to put a lot of effort in to support this.

We send our experts over there to talk to them so they have a whole picture of the safety data, and then they feel comfortable.

“Right now we anticipate novel chemicals getting approval in eight or nine months, but again this is a regulatory bottleneck. There’s a huge potential for markets so we usually don’t give up; we’ll keep trying.”

According to Shen, South Africa also has an excellent regulatory environment, with an approximate three to five month approval period.

The downside is that it’s on the other side of the world, and to travel there is difficult. “It also depends on disease areas. Some of the diseases are much easier to conduct studies in; some are not; it depends on the availability of the treatment.

“Ethics committees in other countries sometimes also ask a lot of questions about placebo: why you want it and can you do without it.

Eastern European countries are stricter now about placebos as well.

Originally countries like Poland were pretty open to clinical trials but now the psychiatric committee there has issues.

“As long as there’s available treatment they do not suggest that we use placebo in the studies, so we had to withdraw our applications. We don’t know the trend but it looks like as a company we are moving towards more Asian and South American locations instead of Eastern European countries, although Russia currently has a pretty good regulatory environment.”

Patient quality Patient recruitment methods also differ depending on the country in which the trial is being carried out. Shen says she is strongly opposed to the notion that patient recruitment should be conducted based on speed alone.

“I want to recruit patients quickly, but I also want to emphasize the quality of the patient. We also face challenges with patient trust in some regions.

“For example, in China and Taiwan the method of recruiting patients largely depends on the relationship with the site. In those countries patients need therapeutic alignment with the physicians, so if they trust the physician they come to the studies and stay with the treatment, but if they

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don’t it’s hard retain them or get them to come to clinical trials because it’s still a relatively new concept in those regions.

“You have to have a very good relationship with the site. I cannot emphasize that enough because that’s one of the things our company is doing. I’ve currently initiated this in China, to try to build long-term relationships with the key opinion leaders there, as well as the PIs. To better understand their needs we help to train them.We help them to obtain the disease knowledge to get the best quality from the clinical trials.

“Those regions are looking for collaboration. They don’t want to be treated just as a site: give us patients and we’re done. They want to be treated with mutual respect and also have long-term collaborations. They also like to have a co-author on the publication.”

In Shen’s view, it’s about building a long-term relationship. “Many big pharma companies have been operating in countries like China for a long time, so they already have good reputations there. This can mean that when they have four or five trials they prioritize ours, which can be a significant factor in enrollment rates. As a big company, what you need to do is build up a relationship with local government. If you get their support, things are much easier.

“Those are the differences in terms of Asia and the US, because in the US you don’t need to deal with these things as long as you have incentives for the PIs. We also have good relationships with India and many other countries, and this does make a huge difference. We as a study team go to visit the sites. We exchange scientific information and then make ourselves available if they have problems or questions. Once you start the trial, you can’t just throw that out and leave them on their own.

“In those regions they are still learning to ensure study quality. For this reason, I would strongly suggest providing a refresher or other visits to rejuvenate the study’s energy and to refresh the memory of what’s needed, otherwise quality could deteriorate throughout the study, especially if it’s long. That’s how I feel about the energies we need to put in to help get recruitment as we need it.”

Another important aspect of building relationships with international sites is education. As Shen explains, training at sites is very important, as well as training the company site managers. It’s not a matter of setting up the trial and leaving them to get on with it. “You can’t just give it to the region and wait for results. That never works very well.

“We need to educate people, to help them understand that if they want to have those medications available for the local population, they need to make sure patients understand that joining studies helps them and will help others in the future to get medicines early on. That’s also the selling point for the government when they say, ‘You’re trying to test our population.’ Then we’ll say, ‘This is the only way we can get this on the market early so everybody can have this available.’ Those are the things we want to see not just for clinical trials, but also for long-term patient benefit.”

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INDUSTRY INSIGHT

from lawsuits, because such information will thus become available to the medical community, whose insights and interest will help the manufacturer assess and mitigate the issue.

Achieving transparency should not require much additional work, for properly built systems can now allow for results to be shared on an ongoing yet controlled manner with all relevant parties. The public disclosure of protocols and results is only one limited example. What about regulatory reviews?

A view to the future New product development requires the close collaboration of virtually all functions inside a company. The existence of an effective cross-functional team, with clearly defined objectives, is thus critical to the successful development of any new medical product.

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n recent years, new industry trends have evolved. Future industry leaders will be those who embrace these trends fully, as early adopters will have a critical competitive edge. Top performance of cross-functional development teams is critical to ensuring prompt regulatory submissions, immediate market adoption, and favorable reimbursement of new products or new indications.

A good clinical development plan requires contributions from all potentially interested parties, including potential users, payers and beneficiaries of the new product or indication. These entities will each assess the relevance of the new product in terms of risk to benefit ratio and cost effectiveness. Users in particular are critical to the rapid adoption of new medical products. Their position, normally based on published clinical experience, is crucial, especially at launch time. Opinions and anecdotal experience usually don’t convince anyone but maverick adopters.

This defines the basic reality that development teams face in product development, from interactions with the scientific community to working with regulatory agencies. It dictates that teams must integrate transparent, collaborative processes, built on sound

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science, while executing clinical development plans.

Transparency For years, regulatory agencies, manufacturers, physicians, key opinion leaders, patients and payers have increasingly insisted that all pertinent information be shared.

The recent requirement that virtually all trials be fully disclosed on clinicaltrials.gov illustrates that trend; the industry has little choice but to disclose all study information.

Although one can comply minimally to avoid full disclosure, embracing the trend fully will help business in the long run.

For example, let’s assume that the results of a recently concluded trial demonstrate beyond doubt that a product is safe and effective. Clinical study registries could conceivably allow for the immediate dissemination of these results, enabling the quick, low cost sharing of this new knowledge across the world.

On the negative side, let’s assume that a recently concluded trial, related to an already marketed product, suggests potential safety concerns that were not known at the time of approval. The rapid dissemination of the results may actually protect the manufacturer

Integration Data standards and the evolution of electronic filing (i.e. the eCTD) open new perspectives into regulatory review of submissions.

Current requirements are that the conclusion of preclinical and clinical studies be filed, that related data and statistical analysis programs be made available, and that the data be complete and accurate.

Current systems do not allow for the complete integration and seamless distribution of this information. Yet systems can be built that could reduce regulatory submission to simply providing the assigned regulatory reviewers with appropriate privileges.

Such privileges would include access to the documents defined in the eCTD, as well as drill-down capabilities to allow reviewing the data down, possibly, to the record level.

Interim reports and key pre-approval submissions could be accessed similarly, creating an efficient, collaborative environment. Such transparent collaboration will result in faster, easier regulatory review, better workflows both for manufacturers and regulators, and the faster release of better characterized, safer products.

Collaboration For years now, the FDA and other regulatory agencies have openly offered to collaborate more closely with the industry. This makes good sense, assuming that all parties genuinely share the same goal: to make safe and effective products available, save lives and restore or protect human health.

Still, many companies have not taken full advantage of this offering. Close collaboration with regulators helps identify issues and expectations early on in a program. Such col-

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laborations are usually successful, and allow for more focused development plans, tighter time lines and faster, easier reviews.

Pushing the concept further, one could imagine the complete integration of the regulatory review process within shared information systems, allowing for near continuous dialogue around results, data and issues.

Convergence Today, this concept seems utopian. Not only do regulators around the world have varying requirements, but regulations and standards vary across products types, generating more inconsistencies and confusion. The issue goes beyond geographical borders.

current issuance and ongoing adoption of device-specific guidelines does demonstrate consensus. It may not however, if there is further divergence between the standards that apply to drugs and devices.

The critical accomplishments of the ICH cannot be overvalued. This effort demonstrates that cross-border collaboration is possible, improves the consistency of submissions, and saves time and effort. Yet while ICH is a well-established force today, emerging countries add their own standards.

Important cross-cultural issues and regional peculiarities must be taken into account. Yet, why do we need significant differences in the body of an eCTD for submission in the US,

“Convergence in standards would allow for submissions to be prepared consistently for submissions across the world, allowing for the rapid distribution of new treatments globally�

Until very recently there were no devicespecific GCP Guidelines. Manufacturers had to figure out how to comply, using as a reference the GCP Guidelines that were designed for drug studies. This is now changing under the auspices of the ICH, thus illustrating both the issue and the trend.

It seems straightforward that the requirements particular to devices can be integrated into GCP, and that generally, GCP applies to any study involving human subjects. The

Europe, Japan, or ASEAN countries? Differences in filing standards add confusion with seemingly little purpose.

Convergence in standards would allow for submissions to be prepared consistently for submissions across the world, allowing for the rapid distribution of new treatments globally. One may consider this effort aimed at serving big business. However, cynics should consider that delaying the availability of new, useful treatments results in human suffering.

Paul-AndrĂŠ de Lame, MD is President and CEO of Anabase International Corp.

He has more than 20 years of industry experience and a broad knowledge of product development, clinical research and related regulatory issues. He has made a critical contribution to a number of new product launches while organizing multiple research projects at the domestic and international levels.

Divergent standards delay the global availability of treatments that help patients, which should be the practical goal of all involved.

Although accepting data from diverse sources is increasingly possible, global product development remains a daunting challenge. There are reasons for this beyond the absence of collective global regulatory standards.

Few manufacturers have the in-house expertise to design globally symbiotic development programs; most companies address one region at a time. This has an immediate impact on clinical trial design, beyond delays in obtaining multi-region approval. Single trials that are consistent with both EMEA and FDA submissions must be conceived at the onset of development. Companies will realize better and more efficient results by thinking globally in the planning stages.

Scientific and medical relevance The success of any product, drug or device depends on the data supporting it.

The paramount importance of leading scientific endeavors and top quality studies is made evident by the success of statins, angiotensin converting enzyme inhibitors or bi-ventricular pacemakers. Although virtually all leading products attain their status on the basis of solid clinical research, proportionally few companies actually endorse or promote extensive research programs that help knowledge progress. As transparency increases, as collaboration among and between key players improves, and as the technical tools that facilitate such approaches become available, it will make clear business sense for all companies to join the trailblazers who support genuine scientific endeavors while marketing their products.

Conclusion We have observed a few key trends emerge in clinical development: increased transparency, integration, collaboration and convergence of key processes, while enhancing focus on medical relevance. These trends will continue to propagate, building on this recent evolution. The leading companies of tomorrow will be those who actively embrace such trends. n

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CLINICAL TRIALS

The world

on trial Johnson & Johnson’s Janet Flisak talks to NGP’s Matt Buttell about completing clinical trials in an international landscape, and discusses the difficulties associated with patient recruitment.

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ohnson & Johnson (J&J) is no strangers to the challenges of the pharmaceutical industry. It is also no stranger to the pages of this magazine. Having been founded more than 120 years ago, the company is today dedicated to advancing the health and wellbeing of people around the world, and has presence in approximately 50 different countries worldwide.

Like many of today’s global industries – manufacturing, retail, financial – pharmaceuticals has found that it too is not wholly immune to the affects of the economic crisis and has had to learn to operate in an everchanging and faster-paced environment.

Along with this comes an inevitable degree of change, and one area of the industry that has seen great change in recent years is its clinical trials. Today these have become increasingly global operations, which means they are becoming both more and more complex and that patient groups are getting larger: all this brings a series of challenges to those involved in this process, and J&J’s Janet Flisak is no exception.

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“What we’re doing with J&J is that we have an organizational model where we’re tapping into our resources at a local level in different companies,” she explains when we speak with her in Pennsylvania. “One of our missions is to look to Eastern countries and we have more trials starting up in Eastern Europe and in Asia Pacific where we are using our experts in those local areas.”

While Flisak does acknowledge that there are some issues related to the GCP in those countries, and that the general standard of care may not always be the same as what we have come to expect from the Western world, she highlights how J&J is currently in the process of trying to standardize its trials and support sites to maintain a unified standard.

In addition to this, she points out several advantages in looking to Eastern countries for trials: “Firstly it costs less,” she says, “and that’s because those countries who have not been at the forefront of clinical trials are considerably more motivated and enthusiastic in trying to prove that they can do just as well as traditionally chosen Western countries.”

“I think a lot of companies are facing these issues and it’s a general industry-wide issue. If anybody has some magic cure, I’d sure be happy to hear about it”

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She also says that the Eastern countries often offer more patients, are more cost effective and provide more quality data.

This is very important as, in essence, a clinical trial is strictly all about data: conducted to allow for safety and efficacy information to be accumulated for new drugs or devices. Subsequently, both of these factors are very prominent within J&J’s efforts. “For the safety component we have a global safety unit located in Germany and everything we do floats through that unit.

“As far as reporting safety events go, that is all centralized,” she continues. “I guess that is easy because it enables us to report things easily and makes it attainable for reporting that information to the different health authorities and, also, it makes it easier having one central point of contact for all of sites.”

Flisak goes on to say that though there are different processes internally, every compound holds quarterly safety meetings: “I think that’s a policy of J&J to do that,” she qualifies. “We look at the ADR’s across compounds and although we start developing the safety profile as well as the efficacy, it is ultimately the safety that is the primary concern.”

The challenge of design

Another thing that J&J is trying to do is adapt design so it can shorten the time for trials to get to registration, and this remains something of a hot topic within the industry in general. Elsewhere for J&J, notably in terms of recruiting patients for clinical trials, Flisak points out several difficulties that are raised when conducting trials on the global stage.

“Recruitment is different in various countries,” she says first of all. “In the US and Western Europe, it’s really a case of getting the KOL’s on board as promoters of the compound and understanding the mechanism of action and then publishing it as quickly as possible.

“But what we have found is that if we move East, there’s better performance Janet Flisak is Clinical Program Leader, and we get more patients. They’re eager Oncology at Johnson and Johnson, within the to prove that they can do as well as the Global Clinical Operations (GCO) group. She West and you find that it’s not as difficult has over 14 years’ experience in the clinical to recruit patients for trial out there. development field. She has an international team “What’s really important is having made up of experienced global trial managers the data on the compound, and then prewho oversee the day-to-day activities of trial senting that data so that these sites can execution, reporting directly to her. be comfortable with the investigational product and comfortable in using it with their patients.”

A lot of what Johnson & Johnson is investigating at the moment is related to the generalized standard Johnson & Johnson: a quick history of care for patients and how, though with the Western formularies there’s a lot of process and regulation surrounding clinical trials, 1886: Founders Robert Wood Johnson, James Wood Johnson there’s not the same for the patients in Eastern countries. “The reand Edward Mead Johnson started a small medical products cruitment techniques are basically the same,” suggests Flisak, “but company in New Jersey. today the patient populations have been saturated. It’s difficult to get naive patients in some therapeutic areas, and that’s something that 1926 – 1946: J&J expanded into Mexico, South Africa, Australia, needs to be addressed.”

France, Belgium, Ireland, Switzerland, Argentina and Brazil.

Sadly, Flisak isn’t wrong. She illustrates her point by telling us about an instance in the US where J&J was looking for patients for a 1946 – 1966: Expansion continued in Zimbabwe, Austria, prostate cancer trail. According to Flisak, the trial went to 230 differSweden, the Philippines, Colombia, Puerto Rico, the Netherlands, ent sites but only ended up with five patients. “Obviously it took an India, Scotland, Pakistan, Zambia, Venezuela, Italy, Malaysia enormous amount of effort to evaluate all of those sites and to go up and Portugal. to them with questionnaires, to go through the necessary protocol and talk to them individually about the trial.” Yet despite all this, return on 1966 – 1986: J&J’s operating companies pioneered several the trial was still minimal. As a result, Flisak suggests that one of the important medical advances and in 1985 expansion continued biggest challenges facing the industry lies in getting to a place where to China. there’s a better return on effort.

“I think this is something that a lot of companies are facing right 1986 – 2009: Continued growth through acquisitions and now,” she concludes. “I’d like to hear what other companies are saying internally developed businesses that have given the firm and what they’re looking at. I think a lot of companies are facing these leadership positions in a number of areas. issues and it’s a general industry-wide issue. If anybody has some magic cure, I’d sure be happy to hear about it.” n

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INDUSTRY INSIGHT

Taking responsibility for innovation In times of severe economic stress, all sectors of all industries will be seeking to reduce costs, create efficiencies, and generally find ways to ride out the storm. As a consequence, innovation and market development will often be relegated to the ‘nice to do’ category that lives at the back of the collective corporate mind. The pharmaceutical industry is no exception.

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or a number of years, there has been increasing pressure on the industry to reduce costs, especially those created by outsourcing. Increasingly the sponsor needs to rely on the vendor to shoulder the responsibility for service innovation, and to efficiently provide the deliverables. This expectation can only increase as the service providers continue to mature and consolidate.

In recent years, the margins that had been previously enjoyed by the industry have been squeezed and eroded from a number of directions.

The drug development organization is continually under pressure to control its own spending from the market, from regulatory bodies, payers, and of course shareholders. The main drivers of this pressure include for example the regulatory bodies requiring greater due diligence and self scrutiny; health authorities and other payers applying downward pressure on the prices they are willing to pay; aggressive market entry strategies from generic companies, and the looming threat of drug companies only being reimbursed for successful treatments, i.e. positive responders. Chief amongst these must be outsourcing costs, a necessary and fundamental component of the drug development process.

This attention is turning the spotlight onto the providers to offer more cost effective solutions. Whether the provider is a supplier centralized ECG services, spirometry, central laboratory, data management, recruitment, site management, or any one of the myriad of other services required to plan and execute a clinical trial.

When a drug development organization looks to outsource a component of a clinical trial, what they look for in a vendor is largely dependent

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on what their own internal resources have available; or more importantly don’t have available. Everybody wants flexibility, but nobody wants the inherent difficulties that come with it; trial leaders dislike the rigidity of a well established process when it does not provide what they need, but like to sleep easy at night knowing that their trial is in a safe pair of hands that use tried and tested procedures. The incongruities of these needs are at the heart of the challenges.

Collaborations The era of true partnership between sponsor and provider is drawing to a close; it is debatable whether, in the pragmatic working environment, it ever really existed.

There were, without doubt, a few laudable examples of success, which of course provided benefits to each party. But alas, on the whole, the majority of relationships rarely stuttered beyond that of the client and the vendor.

The central laboratory providers, who have a more focused offering, will often struggle to secure large long-term contracts against the full service providers. A 30 site phase II study in five countries limited to North America and Europe is a very different animal to a 300 site phase III in 30 countries.

Sponsors rightly have a concern of risk, especially for those with limited pipelines.

Similarly, those with plenty to outsource often labor under the misunderstanding that the smaller phase II studies are the right ones with which to pilot a new provider. It could be argued, these are often the most complex, most demanding studies for a provider to manage and execute, and may only prime the relationship for an early failure. To place work with a vendor who has performed

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very well on the phase II, but may have limited capacity to deal with the phase III, the risk of failure is just too high.

Capacity in this context is not limited to the number of samples they are able to receive in a day, or the level of project and data management they are able to provide. These are a given. Capacity must, out of necessity, also include the value added services that will shoulder some of the burden of managing a large complex global trial, and give the trial leader that good night’s sleep. In these circumstances the full service provider should have the advantage, however it may be that vendors who are able to collaborate and innovate, and deliver this service without risk, will prevail.

But nonetheless, the pressure is there, and central laboratories must wrestle with the challenge of delivering these tests in a more cost effective manner.

The cost of shipping these samples to the laboratory continues to perplex many of the trial leaders and managers, and more often than not, is the major contributing factor to an exceeded budget. It is obviously possible to significantly reduce costs by using an integrated carrier as opposed to a premium courier. But in making this decision, the trial leader will need to wrestle whether the reduced cost is worth the elevated risk.

This is a case where it is not just the providers who have a key role in reducing costs, but the entire supply chain. Whether it is an

Cost

innovation in service, pricing, or the business model, this is an area that is certain to evolve in the near future.

Cost is always a driving factor, and the budget for a central laboratory service usually consists of three broad categories, laboratory testing, shipping and logistics, and the management services. Each of these, to one extent or another, would likely benefit

Model differentiation The central laboratory market is competitive; those providers that are already operating in the field are looking for ways

“When a drug development organization looks to outsource a component of a clinical trial, what they look for in a vendor is largely dependent on what their own internal resources have available; or more importantly don’t have available” from some innovative thinking that could either reduce the cost or increase the value for spend ratio.

There is an understandable desire to move laboratory tests that have to date been considered of high technical complexity and therefore high revenue earners, into the more routine and commodity driven areas of operation. This will of course always happen, as part of the natural evolution of a laboratory test. However it does also need to be driven somewhat by the market. But it is questionable whether it should be the process of conducting a clinical trial, which does this, or the need for cost effective patient care. Maybe they are just different aspects of the same goal?

to differentiate themselves from one another. On the whole, the core product data is similar from one laboratory to another, and the mechanisms of achieving that are also very similar. Likewise the challenges are similar, and for global providers, the business model will usually fall into one of three categories; the global network of affiliated laboratories, the network of wholly owned laboratories, and the core laboratories where samples are shipped to a limited number of owned facilities.

Of course the reality is that current vendors actually offer a combination of all three to one extent or another. The current trend appears to be moving away from the alliances of affiliate laboratories towards

Kevin JD Smith, M.B.A., is Director of Central Laboratory Operations at Eurofins Medinet, a global central laboratory service provider. He has a broad range of experience working in laboratories and clinical research facilities and most recently as the CRO Manager – Outsourcing for Novartis Pharma.

that of wholly owned facilities. The unanswered question remains: will the chosen model give anyone a real market edge? The key to any of these models succeeding is the mechanism by which they are managed, the added value, the ease by which the product, data, can be delivered.

Convoluted and complex internal mechanisms often create challenges for the sponsor, and it is these kinds of challenges they can do without; they just want it to work. The provider and their collaborators, who can make this easy and are transparent in their processes, may find themselves at an advantage.

As we speed towards the second decade of the 21st century, the onus is on the providers to collaborate together in order to offer better products, improved services and greater cost efficiencies for their clients, which are, after all, very often the one and the same. n

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MARKETING

PATIENT POWER Millennium’s Isabelle Mercier tells NGP about the rising power of patient influence on marketing’s delivery of information.

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s we continue stumbling through times of uncertainty and despondency, the call for transparency and accountability has been heightened throughout society, from senators who don’t pay their taxes, to over-the-top executive bonuses. The same is true for the coordination of marketing in the pharmaceutical industry, as the power of patient desire for information determines the way in which pharmaceutical companies operate.

“Patients have become much more aware of and assertive in finding information about their disease and their treatment options,” says Isabelle Mercier, VP of Marketing at Millennium. “What’s changing, from a marketing perspective, is the way in which we provide additional information and insights to the patients, allowing them to become more informed and educated about their treatment options.

“From a marketing perspective, we have to be prepared to engage them differently: traditionally it’s been more the healthcare team being the conduit of information to the patient, but increasingly you hear of the patient coming in with printouts from the internet, with information they heard on the radio or saw on TV, demanding more from their healthcare team. We as a pharmaceutical company have an opportunity to play a role in educating patients, which is probably the most striking change in pharmaceutical marketing.”

“Patients have become much more assertive in finding information about their disease and their treatment options” More responsibility Pharmaceutical companies are now facing the responsibility of providing patients with treatment information and must take on a more informative role than they have previously. “The most relevant trend is that of demand for full disclosure of information, which is becoming more stringent.

That full disclosure is an opportunity for the pharmaceutical company to enhance the understanding of the treatment options and/or the particular therapeutic option that the pharmaceutical company has to offer,” says Mercier. A greater role of responsibility, if seized upon with an opportunistic approach, can allow for pharmaceutical companies to approach healthcare with an element of creativity, as they provide more valuable and insightful information.

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MILLENNIUM HISTORY In her new role as Vice President of Marketing, Mercier will be leading and developing the US and global marketing strategy for the commercialization of late phase development products, along with oncology market products. “Millennium is specific to oncology and has a vision of developing and delivering first class therapeutic agents, aiming to offer more patients across the globe new innovative therapeutic agents to advance cancer care.

“When you look at the portfolio of pipeline agents, the late phase products, as well as currently marketed products, are either best or first in class, which speaks volumes to the engagement that Millennium has. This is done from a scientific perspective of understanding the specific mechanisms that lead to cancer genesis and targeting the ones that are the most relevant to counter cancer development, providing that option to offer more patients treatment across the world.” It is global visions such as this that provide the company with its methods for branding.

Millennium’s approach to branding is very different to that of other pharmaceutical companies. As its entire focus is cancer care, the link between the product and the company vision is inherent. “Due to the fact that we are solely focused on cancer care and interested in serving the patient with high level science therapeutic options, that potential conflict between corporate branding and actual therapeutic agents is not an issue, which it makes it a unique organization from that perspective,” says Mercier.

“If you think of the larger pharmaceutical companies, the struggle they always find themselves facing is due to them not focusing on a single therapeutic area: on a single disease, or disease state. Since every cancer is different from each other, they do face an identity barrier between the therapeutic options they offer and their organization as a whole. As a specific oncology company, Millennium is a therapeutic agent entirely dedicated to advancing cancer care, and therefore we avoid that identity barrier.”

Strategic decisions As a company that has demonstrated how to successfully build a corporate brand, Mercier advises that it is the strategic decisions the company has made that have allowed them to successfully project a specific image. “Branding is a question of what the company wants to be known for. We want to be known for having the ability to take high-level science and transform it into therapeutic options for patients, and we have already demonstrated this through currently marketed products, such as the delivery of Velcade. So the concept of bringing science from the bench to the clinic is something that’s very familiar to us.

“Other organizations tend to identify themselves more as pharmaceutical companies and do not necessarily have that sort of predefined identity of being a pharmaceutical company that is known for its science. We have transitioned already from that perspective because we are focusing on cancer care and stated this by naming ourselves as Millennium, the Takeda Oncology Company,” says Mercier.

As Mercier explains, the development of marketing strategies is not about to change in a dramatic way, either for the industry Millennium itself.

“Understanding to a greater extent your customers, understanding their

Millennium Pharmaceuticals, Inc., was established in 1993 as a genomics company applying world-class recombinant technology to the discovery and development of innovative new therapies in a broad spectrum of diseases.

Millennium has since grown into a fully integrated biopharmaceutical company with a pipeline of investigational drug candidates, as well as a commercialized medicine derived from Nobel Prize-winning science that is now approved in more than 87 countries worldwide.

In May of 2005, the company's leadership changed as founder Mark Levin turned the helm over to Deborah Dunsire. For the next several years, significant refocusing and reconfiguration took place within the company, as well as improvements in the scale and strength of its commercial operations.

In May 2008, Millennium was acquired by Takeda Pharmaceutical Company Limited. Takeda is the largest pharmaceutical company in Japan, and a global enterprise with an important presence in key markets.

Millennium now operates as an independent subsidiary, serving as the global center of excellence in oncology under its new name: Millennium: The Takeda Oncology Company.

needs, their wish lists, and designing and assessing how you can address those needs and wishes is what is subject to change.”

Specialized approach Mercier points out that what will evolve is the development of personalized medicine, especially in cancer care. “It’s a significant trend, so from a pharmaceutical company perspective our need is to be laser-focused on the disease, on the customer and on the patient, and the positioning of a brand will need to be there to address those needs. We’re going to take even more of a specialized, customized approach, just like medicine is evolving in that direction.

“A specialized approach is going to involve targeting specific diseases with specific characteristics, avoiding the over-treating of patients that probably would not benefit from the therapy, and instead providing maximum benefit with balancing the risk associated with any therapeutication for a better defined group of patients and/or diseases that your therapy might be best suited for.”

Such marketing techniques of specialized products and focusing on the development of personalized medicines have certainly benefited Millennium’s branding, as it continues to align its strategies on cancer care. “This is a tremendous opportunity for us to be part of the transformation of cancer care into a chronic disease.The evolution of cancer survivals has made great strides in the past 10 years; there’s a lot more to be done and certainly we are very much engaged in being part of making that happen and serving the patients.”

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Faking it Should pharmaceutical companies influence patient groups to create a grassroots demand for their products? By Natalie Brandweiner

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stroturfing is the name given to the behind-the-scenes funding of prominent patient representative groups by some pharmaceutical companies. Such relationships are often accused of creating a false grassroots demand for drugs, hence the term. But should the drug firms bear the brunt of all the negative press, or should patient groups be dealt just as much responsibility for accepting their funding?

As representatives of those affected by certain diseases, the function of patient groups is to offer support to the American public, with the patients as their primary concern, campaigning for treatments and sitting on advisory committees. But with many having little or no lobbying power, and a small membership in tow, there is a perhaps understandable temptation to accept the readily available funds from pharma companies to help fund these activities and prolong their existence.

And why shouldn’t drug companies seize upon these opportunities? They are looking to make a profit like other companies; their stock price on Wall Street will always remain one of their primary concerns.

Through filtering their marketing message into patient groups, drug firms can reach the public in a far more effective way. The trouble is that many Americans place their trust in those groups that they believe are representing them, and have limited awareness that a group’s agendas and actions may be influenced by its ties to a pharmaceutical company.

Timing The timing of the donations is often carefully planned by the drug companies to coincide with their marketing strategies. For example, Pfizer was a major fund provider to the Restless Leg Syndrome Foundation in 2003 and 2004.

However, after the company announced plans to stop manufacturing its candidate RLS drug in July 2004, donations to the patient group stopped.

A study undertaken by the New Scientist to investigate the extent of influence by drug firms on patient groups

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attempted to find out exactly how many dollars were being used to buy marketing power. In certain cases, the donation funds were huge; the American Heart Association, for example, was found to have received more than $23 million from drug companies.

The study found that in total, seven groups received more than 20 percent of their funding from drug firms: the Depression and Bipolar Support Alliance, the Restless Leg Syndrome Foundation, Children and Adults with Attention Deficit/Hyperactivity Disorder, Child and Adolescent Bipolar Foundation, C3: Colorectal Cancer Coalition, the Narcolepsy Network and the Hypertrophic Cardiomyopathy Association.

Allegations

One group that caused much ethical debate over its relationship to pharmaceutical companies was the Depression and Bipolar Support Alliance in the UK. Allegations of disease mongering were made following the revelation that the patient group had received more than half of its funding from the industry. The group remained vague about the exact figures, but when annual reports and tax return figures were combined, the amount was found to be equal to 77 percent of its revenue.

The questions that surround such partnerships center on the amount of influence gained by such funding, and whether this affects what the patient groups do.

Many groups are charged with producing treatment information for patients, which could obviously be influenced by which pharma company is funding them and what drug it is marketing. However, astroturfing is a term that is becoming much more well-known by patients, and as awareness grows, such relationships “Many groups are charged will begin to lose their power. with producing treatment If funding of patient groups by pharinformation for patients, maceutical companies is to continue, there which could obviously be should be transparency around how much is given to which groups, and patients influenced by which pharma should demand full disclosure before placcompany is funding them” ing their trust in any association supposedly advocating on their behalf. n

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TROUBLESHOOTER

BECOMING MORE FLEXIBLE Why the pharmaceutical industry needs to evolve to meet its current challenges.

W

e have all seen reports about how pharma must change its business model in order to deal with the contraction of the drug pipeline and increasing competition from generic drugs. In this new era pharma needs to better manage and exploit existing products throughout their entire lifecycle.

They must also address the needs of the increasing number of stakeholders who influence patients’ access to medicine.

The industry is looking for a miracle which is unlikely to materialize, but by taking a more strategic approach to sales force management the industry should be able to find the right mix of integrated and flexible sales solutions for success. Innovex’s multiple service offering helps biotech and small pharma to develop and implement sales strategies on a much greater scale than they could independently. This begins the product’s launch phase and adds value throughout the product lifecycle.

ProStrakan, a UK-listed company (LSE: PSK), sought a partnership to launch its Sancuso product and establish a long-term US commercial capability without incurring the full risk and expense.

Innovex, together with NovaQuest, was able to offer an immediate commercial infrastructure with 75 dedicated specialty representatives for launch that ProStrakan can convert into its own headcount within three years of the agreement.

“The industry is looking for a miracle which is unlikely to materialize”

Big pharma can also benefit from an integrated approach. A tailored, strategic sales support program to support launch can involve risk share deals and/or a range of sales options. In 2004 Lilly was facing a number of challenges, in-

cluding multiple launches of products, which were putting pressure on internal resources. A risk-share partnership deal with NovaQuest and Innovex was developed. Innovex hired and trained the sales team in around 10 weeks. Forty percent had more than two years of pharma experience and 60 percent had B2B sales experience. The result was an optimum sales force resource in preparation for launch and Eli Lilly was able to retain control of its commercial program.

When a product is at the tail end of its lifecycle, better return can often be realized for longer by outsourcing. In addition to sales forces, this can include the full spectrum of services required to support a product, such as regulatory affairs and pharmacovigilance.

Implementing these programs successfully does require a more strategic and diverse team compared to the traditional model of high numbers of reps with uniform geographic distribution,

Daryl Gaugler is the President of Innovex. He brings over 20 years of pharmaceutical sales and senior management experience to the position. Gaugler oversees the US commercial business for Innovex Americas with operations in the United States, Canada and Mexico and with service offerings including investment-based commercial partnerships, fee-based outsourcing and health management services.

In the middle years of a product lifecycle, big pharma still often looks to fee for service solutions to provide the sales muscle. This ensures fast mobilization of sales teams, reliable access to specialists in secondary care and therapy areas such as oncology, and the flexibility to respond to market dynamics.

Innovex worked with one top 10 pharmaceutical partner who wanted to expand, from three sales teams of 350 territories to four teams of 510, but was concerned that productivity could be lost during the growth.The solution included a phased recruiting and training program that ensured smooth sales team expansion. Key to this was involving the partner’s district managers in the final interviews and creating a hiring SOP with scheduled dates and feedback mechanisms.

and limited access to clinicians. Depending on the product and where it is in the lifecycle, this new team will be comprised of sales reps, specialty reps, nurse educators, medical scientific liaisons and telesales. With such a diverse range of skills distributed according to geographic potential, these teams are able to communicate effectively with the increasingly complex network of influencers, which goes beyond just clinicians to include payors, regulators and others. Determining the best mix of people relies on robust analytics drawn from Quintiles’ substantial experience in both commercialization and consulting.

For pharma to secure a successful future, they must focus on achieving better outcomes from less people and evolve to become more flexible in response to market dynamics and other challenges.

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EXECUTIVE INTERVIEW

NGP. Who is TARP Worldwide?

Christopher Giuliani. TARP Worldwide, located in Arlington, VA, is the world’s leading customer experience agency and research consultancy. We pioneered the science of quantifying, managing and optimizing the healthcare customer experience. TARP initiated the science of experience management decades ago when we stated it was five times cheaper to keep a patient than to get a new one. We combine customer satisfaction research and analytics with actionable programs that change employee behaviors and improve the quality of the customer interaction. This powerful combination creates quantifiable bottom-line results. Simply put, we “Release the Profit of Interaction”. Within our healthcare division, TARP’s products are designed to improve the physician-sales professional interaction.

NGP. Has TARP Worldwide always had a healthcare division?

CG. After more than three decades working with many of the top pharma and biotech companies and healthcare system organizations, we recognized a need to service these clients through a dedicated healthcare division. Within TARP exist decades of professional pharma and healthcare sales and marketing expertise leveraged through innovative and revolutionary product and service offerings. Our Healthcare division is operated from offices in the Midwest, equidistance from all of our clients around the country, making it much easier to provide personalized attention and customized work.

NGP. TARP Worldwide Healthcare recently announced the launch of a product for pharma companies with field sales forces. Can you tell us about this new product?

CG. In healthcare, the most prevalent, financially significant and highly scrutinized interaction exists between the pharmaceutical sales rep and the physician. The economy is demanding a higher ROI from sales resources.

Pharma needs more effective physician interactions to drive incremental performance, improve product standing and establish a dependable, meaningful relationship with physicians.

Considering the changes in the healthcare industry and the immense demands on physicians’ time, an innovative new approach is required in order to thrive in the new environment. Our Affinity Solution is innovative in that it is not just sales training, but interaction training. By studying and optimizing the physician/sales rep interaction we are creating a new way of selling – a new way of thinking really – that will have physicians perceiving sales professionals in a whole new light. Rather than a necessary drain on their time in return for samples, reps will be seen by physicians as knowledgeable consultants and partners in delivering healthcare to their patients. Sales professionals will quickly become the physicians’ favorites because they get it.

We get it – this is what we do better than anyone else. TARP’s Affinity Solution was designed with the specific purpose of improving the effectiveness of pharmaceutical sales professionals.

Product performance TARP Worldwide’s Christopher Giuliani explains the importance of physician interactions to improve product.

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NGP. What led TARP to developing and offering its Affinity Solution?

CG. Through our exhaustive research and product validation efforts, we had hundreds of physicians report to us that they are tired of pharma sending in sales reps, when they have continually asked for healthcare consultants.

This disconnect between pharma companies and their primary customers, physicians, led us to develop an innovative and revolutionary product, Affinity Solution.

Our Healthcare division has broad and deep experience in the pharmaceutical industry. As we have closely monitored the evolution of this industry over the past 10 years, we identified a significant unmet need where TARP holds more than three decades of expertise.

This unmet need lies in intensely measuring, analyzing, profiling and then improving the pharmaceutical sales representative-physician interaction.

targeted physicians and the sales representatives that call on them. From this, key driver and ‘gap’ analyses will be defined, providing actionable steps to improving sales force performance and effectiveness. We then move to TARP Practices to realize. We work closely with our individual clients to make change happen, leveraging our expertise and innovation in training and communication programs to close the identified ‘gaps’ and capitalize upon identified key drivers. Finally, we close the research loop and optimize. From a post-training scientific survey, we track our effectiveness, making clear the measurable increases in physician loyalty, thereby holding ourselves accountable as a business partner.

Based on a client’s pre-determined targets for improved effectiveness, we assess program performance. If targets have not been hit, we will work on our dime to make it happen. If targets are hit, we won’t hang around – capability transfer successful! That’s the difference in partnering with TARP.

NGP. Why did TARP feel that now was the right time for Affinity Solution?

CG. The industry needs this now more NGP. What has been the response to than ever. Look at the economy and the Affinity Solution so far? dramatic pressures pharma faces. A CG. We are thrilled to have hit the mark. The complete restructuring is under way; reaction from the pharmaceutical commusince 2007, major pharma companies nity has been outstanding as they recognize have laid off more than 70,000 employthis product as powerful and unique from ees, most in the sales force. This is sigany other offering on the market today. nificant and devastating to their once More specifically, pharma companies are exfailsafe business models. As every cited to see a product offering that can be pharma company looks to accomplish highly customized by disease state or medChristopher Giuliani has more than a decade of professional experimore with less, they must diagnose ical condition, physician specialty and type and treat the illnesses of their sales ence in healthcare sales and executive management roles responsiof sales force structure. Additionally, the models and sales forces. This begins ble for growing bottom-line revenues. He is an expert in leadership physician community is equally excited with taking a much closer look at the inskills, process and people alignment, relationship management, about the product, as it gives them a voice teraction between their field sales peostrategic planning and, most critically, listening to and understanding to pharma companies, as they desire a more ple and their targeted physician the needs of a business as it pertains to the customer experience. He reciprocal and consultative relationship with customers. In the old model, pharma held sales and management positions at Galderma Labratories and pharma sales reps. From the beginning, we would use metrics like reach, frequenCapital One before joining TARP Worldwide as the Vice President, knew we had developed something special cy, and number of samples delivered as Healthcare and Sales. and unique. Following our announcement of their primary sales force diagnostic the Affinity launch, we have been very tools. In the new model, that’s just not enough: an X-ray is limited compared pleased with the response. Pharma gets it and knows TARP does, too. We beto an MRI – we are talking about using an MRI. TARP’s expertise in the areas lieve this is revolutionary and will dramatically improve pharma sales force of diagnosing and treating unhealthy customer experiences and interactions effectiveness. is unmatched. We coupled that with our Healthcare division’s pharma expertise. Our Affinity Solution emerged and is perfect for today’s transformed NGP. How or where can people find out more about TARP and Affinity pharmaceutical industry.

Solution?

CG. The easiest way for people to learn more aboutTARPand Affinity Solution is NGP. What differentiates Affinity Solution from other product offerings on to contact me at cgiuliani@tarp.com, or Geoff Arbuckle, our Vice President of the market?

Healthcare and Business Development at garbuckle@tarp.com. You can also CG. Nothing like this exists in the market. This is an integrated research and visit us on the web at www.tarp.com, where you will find a link to our Healthcare practices program. We start with TARP Research to prioritize. We execute a division. Additionally, we maintain an active presence within social and profescarefully designed, aligned and integrated scientific survey completed by sional media networks and on our expert blog at http://blog.tarp.com.

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aSK tHe eXPert

Strategic commercialization The complexities of today’s financial markets, as well as growing FDA and market pressures, have made Rx drug introduction a riskier proposition than ever before.

David Stievater

primary care sales teams in place, while specialty medications can do quite well with smaller pharmaceutical companies with deep specialist expertise.

The right partner

D

espite the current financial turmoil, emerging and smaller pharmaceutical companies are finding that the value of their viable pipelines opens up many doors to commercialization.

Many companies pursue co-promotion deals with an established player as a way to share the risk of bringing drugs to market.

Such deals eliminate the need to build infrastructure or raise additional funds. As attractive as these deals can be – and there are many successful ones, such as Johnson & Johnson’s and Amgen’s collaboration on J&J’s Procrit and Amgen’s Erythropoietin, or ICOS and Eli Lilly’s joint venture on Cialis – co-promotion does come with its own set of problems. Culture clashes, lack of control, sacrifice of net present value (NPV) to shareholders, and the stifled development of independent relationships with certain physician targets are just some of the issues that tend to surface in these deals.

For many, outright licensing of their patented technology to another pharmaceutical company is the route to follow. Unlike those who pursue co-promotion, licensors are primarily interested in the research and development of viable products and the profit potential represented. They are not vested in the commercialization process, nor do they have an interest in developing the infrastructure to get there.

When licensing, finding the right partner and striking the best deal is key. Primary care products are generally best licensed to major pharmaceutical companies with strong

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Negotiated deals can include a productby-product option, payments throughout the lifecycle, R&D funding, and equity investment. In many instances, deals are being struck where the licensor maintains co-marketing rights; for example, marketing to specialists while the licensee markets to primary care.

“When licensing, finding the right partner and striking the best deal is key” Like co-promotion, licensing comes with similar drawbacks for pharmaceutical companies: a lower NPV than if they took the drug to market themselves, and lack of creative control and development of independent physician relationships.

Based on the risks associated with co-promotion and licensing deals, ‘going it alone’ may be the best commercialization option for many from both a cultural and financial perspective. Certainly going it alone offers the highest potential NPV; it allows companies to build a successful commercial capability; and it creates investor confidence and generates opportunities to pursue other deals. The inherent risks to this strategy are self-evident. In going it alone, financial resources are needed to absorb all the development and go-to-market costs,

and the company faces the commercialization risk alone, which is compounded when there is a lack of commercial infrastructure and expertise.

Mitigating risk One way to mitigate these risks is to work with an outsourced contract sales organization (CSO) for key needs. A CSO provides the immediate expertise needed to be successful with lower risk and more flexibility than a company has when building their own sales team internally.

CSOs can provide strategic resources for the rapid deployment of such key prelaunch and launch activities as market research, medical education and sales force development and management. Companies utilizing this approach leverage an existing infrastructure without losing control of their destiny and in some instances do so with the CSO bearing some of the costs on a riskshare basis. This enables companies to maintain a lean infrastructure while building both market and cash positions, with the option to eventually internalize CSO employees.

Although the outsourcing of product manufacturing and clinical research has been practiced and accepted by the industry for quite some time, the value a CSO brings to emerging pharmaceutical companies in the commercialization of their products is just now being fully realized. Not only do CSOs offer the advantage of saving time and money in the commercialization process, but management teams of emerging companies are able to tap into the vast knowledge base of their CSO partner, greatly expanding on their own industry experience and better equipping them to drive brand performance. n

David Stievater leads the new business development team for PDI Sales Services. He has worked with pharmaceutical sales forces for 10 years, including as a partner with the Monitor Group consultancy and VP, Sales at ImpactRx. He holds a BS from Georgetown and an MBA from the University of Michigan.

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MARKETING

Down out but not

Times are tough for marketers everywhere, and no less so in the pharmaceutical sector.

But take heart – the latest marketing priorities survey from Frost & Sullivan shows that marketers are not giving up the fight.

F

rost & Sullivan’s Growth Team Membership recently completed its 2008 marketing priorities survey. Marketing executives in North America and the European Union were asked to identify the most pressing challenges facing the marketing function for 2009. The results were as reported by directorlevel or above executives from companies with revenue of $100 million/€70 million or more.

Frost & Sullivan conducted the survey to better understand the business environment factors and the key issues facing marketing executives in 2009.

Current impact Respondents were asked to select the top two environmental factors. The top business environment factors were the global economic downturn (54 percent) and the increasing need for product/service innovation (10 percent). The secondary business environment factors were

decreasing customer demand (20 percent) and intensifying competition (17 percent).

In response to how the business environment factors are impacting marketing, the top three ranked factors were judged to have a negative impact – global economic downturn (80 percent), intensifying competition(70 percent), and decreasing customer demand (80 percent).

The survey contained 12 questions broken out into three sections: company demographics; business environment; and key marketing issues.

MARKETING FUNCTION EFFECTIVENESS EXCEPTIONAL OTHER 4% 6% POOR 2%

Company demographics The majority of North American respondents (70 percent) work for public companies and more than 90 percent operate in a business-tobusiness (B2B) environment. Sixty percent work for firms with revenues higher than $1 billion.

Conversely, 55 percent of EU respondents are from private companies and 98 percent of the EU work in B2B companies. Fifty-seven per-

FAIR 29%

GOOD 65%

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cent of respondents report working for companies with revenues higher than €700 million.

The healthcare and life sciences (20 percent), and information and communication technologies (18 percent) industries had the largest participation.

When asked about the effectiveness of their marketing function, only three percent of North American and four percent of EU respondents rated it as ‘exceptional’. Sixty-one percent of North American peers rated their effectiveness as ‘good’, and almost 30 percent rated it ‘fair’ or ‘poor’. Forty-five percent of EU marketers rated their effectiveness as ‘good’ and 51 percent consider it ‘fair’ or ‘poor’.

Challenges In both North America and the European Union, the survey data highlighted the negative nature of the business environment and its effects on customer demand and competition (see Table 1).

While there is some variation in the key issues shaping marketers’ decision making in North America and the EU, there are many shared challenges. Accordingly, marketing has to justify its expenditures yet create new sources of growth for the company (see Table 2).

Respondents were asked to identify whether their top three issues were primarily an issue of “staff, technology, or process.”

Overwhelmingly in North America, respondents identified ‘process’ at the crux of their top three issues. In the EU, ‘process’ and ‘talent’ were identified as the main factors.

Going forward The global economic downturn is having the biggest impact on marketing decisions. Marketers have to justify their budgets as companies squeeze spending in light of falling customer demand. At the same time, marketing is under pressure to spur growth opportunities whether through finding new markets or developing innovative products and services. This pressure will be telling as many respondents feel the effectiveness of their function could be improved.

As expected, the data highlights the negative nature of the economy and its effects on customer demand and competition. However, this recessionary environment also provides new growth opportunities in emerging markets, demand for enhanced products and services, and innovation in green and sustainable offerings.

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TABLE 1 TOP FIVE BUSINESS ENVIRONMENT FACTORS FACTOR

NORTH AMERICA

Global economic downturn Decreasing customer demand Intensifying competition Emerging global markets Increasing need for product/ service innovation

EUROPEAN UNION

64% 24% 21% 17% 14%

47% 19% 17% 11% 28%

TABLE 2 KEY MARKETING ISSUES ISSUE

NORTH AMERICA

Measuring market spend effectiveness and efficiency Identifying emerging customer needs and preferences Justifying the ROI on marketing budgets Enhancing the pace of new product and service introductions Identifying new, adjacent market opportunities Evaluating and prioritizing innovation investments Improving sales and marketing integration

EUROPEAN UNION

30% 30% 28% 25%

16% 21% 29% 24%

23% 18% 18%

24% 29% 26%

TOP SIX PRIMARY BUSINESS ENVIRONMENT FACTORS 60%

As can be expected in these turbulent times, the foremost business environment factor is the global economic downturn (54%). This is also reflected in the second business factor, the increasing need for product/service innovation to capture and retain market share.

54%

50%

40%

30%

20% 10%

10%

5%

0

Global economic downturn

Product/ Green/ service sustainability innovation initiatives

The top five key issues are focused on monitoring and justifying expenditures or creating new sources of revenue. The data highlights that although budgets are being scrutinized, marketing continues to be charged with catalyz-

5%

Emerging global markets

5%

5%

Intensifying Corporate competition restructuring

ing growth through identifying unmet customer needs, or speeding up innovation.

The research for the survey was carried out by Holly Lyke HoGland, Donald Savant and Keith P. O’Brien.

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INDUSTRY INSIGHT

Innovation and focus in healthcare Richard Vanderveer, Chief Executive Officer, GfK Healthcare, discusses a fundamental shift on the horizon, both in the practice of medicine and our approach to pharmaceutical marketing.

P

fizer recently announced it was terminating more than 800 drug discovery scientists and would release more than 2400 pharmaceutical sales representatives, each a significant percentage of its respective cadre.

What’s going on?

At the same time, newly inaugurated President Barack Obama seeks to provide healthcare to the approximately one-third of American citizens currently not covered. The only problem is that he plans to do this with a $75 billion opener that is neither available nor enough.

In brief, 2009 will be a year that continues the significant change in healthcare, pharmaceutical marketing and pharmaceutical marketing research.

TheInnovator’s Prescription,a new bookbyClayton M. Christensen, provides a clear understanding of many of the facets of these changes.

As for companies like Pfizer, which are radically downsizing, abandoning their research strategy and outsourcing as much as possible, Christensen points out that such organizations, originally designed to support blockbuster drugs, are now sinking under their own weight as mega-drugs go off patent and are not replaced by new agents.

Most serious conditions are well-controlled in only about half the cases, most probably because we have not become good enough at diagnostics to know which agent will work on which patients.

Exceptions to this pronouncement can be found in infectious disease, where specific antibiotics targeted at specific pathogens move us from ‘intuitive’ medicine to ‘precision’ medicine, with a similar phenomenon now being observed in oncology. Christensen tells us to look for significantly more emphasis to be placed on precision diagnostics in the future.

Greater focus As medicine moves in this direction, also look for greater precision and focus in service providers.

General hospitals that attempt to do everything for everybody are hopelessly inefficient, since they are not focused in staff, equipment, etc. Compare this

tablished in local pharmacies, using nurse practitioners to treat many simple conditions quickly and cost-effectively). This will help convert the cottage industry that currently constitutes healthcare into a far more organized and efficient entity, and change the question of how will we pay for the current costs of healthcare to how do we make healthcare affordable.

Progress in areas such as electronic patient records, which have failed to come to fruition not because of technical limitations but because of proprietary and protectionist interests among healthcare suppliers, will assist greatly in making order out of chaos.

Need for change

Richard Vanderveer has spent almost 40 years in the pharmaceutical industry and is recognized as one of the foremost thought leaders in healthcare marketing research. He is Chief Executive Officer of GfK Healthcare (www.gfkhc.com), the largest provider of fully integrated custom healthcare marketing research in the US, offering the broadest range of custom and multi-client research offerings as well as innovative proprietary approaches to meet a product’s needs across its life cycle.

with the Shouldice Hospital in Ontario, Canada, that does nothing but abdominal hernia repairs, but does so at significantly less cost and with far fewer negative outcomes.

Additionally, Christensen predicts that as medicine becomes less about the intuition of the practitioner and more about the rules and tools of practice, we will be able to use much less highly trained professionals to provide much of our healthcare and do so in entirely new and more efficient settings (such as the MinuteClinics es-

But who will make all these changes? The author is understandably schizophrenic in noting that market leaders and other established entities are usually the leaders in evolution, rather than in the kind of disruptive evolution called for here. But, he also writes that the small, upstart organizations – usually the best at disruptive solutions – will have a difficult time pulling all the pieces together that are necessary to generate efficient focus from chaos.

Finally, expect our role as marketing researchers to change fundamentally over the next few years. As medicine becomes increasingly rules-based, with less emphasis on the intuitive decision-making of the practitioner, we will certainly spend less time testing the types of promotion and persuasion currently practiced by pharmaceutical sales representatives and through other channels to influence practitioners, of which there will be fewer and fewer.

Rather, our focus will turn to the conduct of research that will help prioritize rule generation, to develop the rules and clear ways of communicating and applying them, and to investigate other ways in which we can make healthcare more precise, focused and affordable.

Dr. Vanderveer can be reached at 215.283.3200 x303 or richard.vanderveer@gfk.com

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CUSTOMERS AT THE CENTER John Moran analyzes the impact of promotional branding. its declining, commercial leaders must embrace multi-channel strategies as a tool to boost ROI. Responsiveness to new forms of promotion such as digital media can be effectively measured with a combination of cause-and-effect analysis, in which well designed, in-market tests are structured, and customer research that explains why physicians responded to certain forms of promotion and why they did not is used.

NGP. How will promotion strategy change as pharmaceutical companies move to more customer-centric operating models?

John Moran. As a first step, commercial leaders will seek to understand the impact of different promotion channels at a more granular level, such as customer segments, geographies and managed care, to name a few. Regionalization initiatives around the industry will lead marketers and sales executives to undertake these types of evaluations to more effectively plan and drive promotion strategy and local market sales force deployment.

The need to base promotion on the desires and interests of particular customer groups, as well as their responsiveness to different forms of promotion, will be key and result in differentiated marketing strategies driving more relevant information to customers. Companies undertaking this approach are already reaping the benefits in terms of stronger customer relationships. Equally beneficial, promotion differentiation will also help drive higher sales force productivity and improvements in ROI. Ultimately, commercial executives will model promotion spend by customer segment, not just at a channel or brand level, and develop more optimal segment level mixes that will result in higher productivity.

NGP. With new forms of promotion such as social networking, peer-to-peer communications and web-based education growing in use, how will brands measure their promotion impact?

JM. Today’s promotional mix is much more complex. With overall responsiveness to physician vis-

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NGP. How will brand teams set and implement an optimal promotion mix that takes advantage of the wider choice of promotion channels available today and in the future?

new promotion forms as well as market test some of these new promotion channels.

NGP. How can commercial organizations successfully implement an integrated view of the customer in order to drive greater sales force and marketing effectiveness?

JM. Through the alignment of customer promotions with the needs and responsiveness of customer segments, field force productivity is significantly increased. In many cases, dollars directed to the field force can be redirected to other promotional channels, offering stronger marginal rates of return and improved ROI.

“Ultimately, commercial executives will model promotion spend by customer segment, not just at a channel or brand level” JM. The future will require a more integrated view of companies’ sales and marketing investments to clearly identify how spending decisions can be improved – to drive higher revenue, reduce inefficiencies, or both. Companies will take advantage of new analytics that incorporate anonymized patient-level data, along with enhanced promotion data, to optimize brand and portfolio spending. By combining traditional promotional response analysis with strategic insights and benchmarks, companies will be better able to determine how customers respond to

Changing the traditional promotion allocation process to a customer-response based process is the critical first step. Helping marketing and sales understand promotional decision-making and how to improve it is key. At IMS, we recommend doing side-by-side comparisons of the outputs of the traditional promotion allocation process and the more advanced integrated channels approach. The incremental value identified is often significant to drive support for and willingness to make change happen.

John Moran is Global Leader for the Commercial Optimization Center of Excellence for IMS Health. He has more than 20 years of Rx, OTC, and consumer marketing and sales experience spanning a broad range of marketing and sales disciplines. Moran works with many of the world’s top pharmaceutical organizations, developing new commercial effectiveness models, with emphasis on strategies that enable greater customer focus and value.

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EXECUTIVE INTERVIEW

Velocity explain the categories needed for coaching

Coaching culture NGP. First of all, what is a coaching culture?

John Miller. When people at all levels of the organization consistently participate in goal focused, solution oriented strategic conversations that lead to faster decision making and better results.

NGP. What advice do you give executives who are interested in establishing a coaching culture in their organization, especially in light of the recent changes in the industry?

JM. My first piece of advice is: do it! Our research clearly indicates that companies with embedded coaching processes quickly see results on the bottom line, in some cases upward of 15 percent growth in productivity and/or direct sales. This is especially important when you consider companies are becoming leaner and expected to achieve more with fewer people.

Once a company makes the decision to create a coaching culture we generally focus on three things: First we want to develop the managers’ skills and ability to coach. Second we want to make sure that coaching takes place at every level of leadership. And third we want to have in place a solid process to ensure sustainability over time. I have seen several examples of pharmaceutical companies that went so far as to proclaim ‘the year of the manager,’ but after much fanfare very little changed because they had no system in place to pull through and reinforce the transformation.

NGP. Can you tell us first about the work you do to build managers’ coaching skills?

JM. We begin with an assessment based on four broad categories for coaching: commitment, focus, skills and approach.

In the commitment part of the assessment, we look at the amount of time a manager invests with his/her people. Most believe

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that they spend enough time on coaching. In fact, nine out of 10 employees want specific job skill coaching, but less than four in 10 receive it.

Next we look at manager focus. Has the manager worked with his/her employees to identify critical areas to work on that will have the greatest impact on the business? In sales organizations this often means increasing sales call effectiveness. Is the manager aligning the employee’s goals, objectives and development plans directly to the key initiatives of the organization and the overall strategy?

John Miller is the President of Velocity LLC, an international coaching and training firm specializing in supporting the pharmaceutical industry. In this article, he describes how and why to establish a coaching culture in sales organizations.

In our assessment we target seven skills.

We have found that managers are least proficient in what we call ‘clarify success.’ Most

managers make assumptions and give only general direction when it comes to coaching their employees and it is based on the managers’ own personal style. Seldom are they effective in jointly developing action steps and plans to achieve them. We are able to clearly see this need when we conduct audits of written correspondence.

In assessing coaching approach, we look at how the manager builds a relationship with employees. Managers need to recognize that the people they have more transactional relationships with, versus high value, are generally those who most need and can benefit from their coaching. Each manager receives coaching themselves that not only exponentially improves their own skills, but gives them a visceral example of what good coaching looks and feels like.

NGP. Is coaching more applicable in certain areas of an organization? How about in different cultures and countries?

JM. We have implemented our coaching programs around the world and have seen them transform business relationships and create better collaboration – even across multiple foreign cultures. Certainly there are some minor differences. For example, in China the manager is more likely to ask fewer questions of their employees and therefore do more telling, but even that is changing as coaching takes hold.

Organizations today demand crossfunctional collaboration and coaching can help cut across party lines and silos pretty much throughout the entire company. Creating a coaching culture opens and expands pathways to dialogue and debate among competing peers and helps to align support for the objectives everyone is trying to achieve. Creating a coaching culture improves business on every level. n

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Work happens through conversations.

What % of conversations in your company are strategic?

Shouldn’t they ALL be?

Check out Velocity’s learning programs: The Art of Strategic Conversations™ •Coaching •Mentoring •Accountability Training

Contact us: 800-545-1758 info@velocitysuccess.com or visit our website www.velocitysuccess.com

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EXECUTIVE INTERVIEW

Communication is key Paul Hilditch of Watermeadow Medical explains why using consistent vocabulary is important throughout a product’s lifecycle NGP. Why is it important to ensure that decision-makers are aware of a product’s attributes and benefits throughout its development and marketing lifecycle?

Paul Hilditch. The aim of medical communications, in an age of transparency and high ethical principles, is to give decision-makers the information they need to make informed judgments and to select the most appropriate therapeutic interventions. The challenges in this task are the changing nature of the therapeutic landscape over the timescale of a product’s development and marketing, and the constant flood of messages and communication from all sources competing for our audiences’ attention.

In the case of a product in development, our aims are to show how the product will fulfill an unmet need (while exercising care not to be culpable of ‘disease creation’) and to ensure that decision-makers have an awareness of the product and an understanding of how it will relate to other current and future interventions.

In the case of a more mature product, we need to show our audiences that our product is still relevant and that it fits into the current treatment paradigm, and we need to communicate any expanding applications and indications so that treatment decisions can be made in a wider context.

NGP. What tools and resources can pharmaceutical companies use to ensure this is achieved?

PH. Expert opinion is the pivotal tool, whether expressed via publications in the scientific literature, presentations at academic meetings, educational activities or simply in peer-to-peer ‘water-cooler’ conversations. Again, we need to be seen not to be manipulating that opinion – thus publications need to be prepared with full involvement, disclosure and transparency; presentations need to show objectivity and balance; and advocates, like all stakeholders, need to have been supplied with enough information to reach a balanced judgment. Clearly, the way we use these tools will change as a product progresses from the pre-approval, development phase to the post-approval, marketed phase of

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NGP. Why is consistent vocabulary so important when talking about a product, even before the brand development process officially starts?

PH. Clarity of communication is paramount in everything we do, and this requires us to use language and terminology that is both consistent and uncomplicated. Which is not to say that we should ‘dumb down’ our communications to professional audiences, but there are many examples of things being made overly complicated, and few of things being made too simple.

Paul Hilditch is Managing Director of Watermeadow Medical, a full service global medical communications agency with offices in New York, Oxford UK, and Manchester UK. With a PhD in protein biochemistry, Hilditch worked in healthcare research and marketing before joining the agency world as a medical writer, a job that after many years he still finds time to enjoy.

its lifecycle, when we have greater scope to discuss a product in a promotional context and to use field force to deliver tactical materials.

NGP. The development of new pharmaceutical products depends partly on revenue from current products. Why are communications activities pivotal in achieving an effective return on investment for a product?

PH. Revenue from a pharmaceutical product comes from treatment decisions made by prescribers and communications activities give them the information they need to make those decisions. Communications activities are also important in establishing the value proposition – in the most literal sense – for a product, facilitating market access and ensuring appropriate levels of pricing and reimbursement.

“There are many examples of things being made overly complicated, and few of things being made too simple” Consistency of language can overcome confusion, not by constraining language, but by resolving ambiguities, both internally within a pharmaceutical company and externally among its advisors and customers, about such topics as disease pathophysiology, mode of action and endpoint interpretation. A consistent brand vocabulary underpins all product positioning, supporting a unique and consistent brand identity.

We can also use the need to use consistent language to clarify and support our chosen place in therapy, and to establish our product as, for example, an advance within a class, or the first member of a new class. We can use it to clarify the definitions of medical conditions, patient groups or therapeutic interventions. What is important, however, is that our chosen vocabulary and terminology should be sustainable, evidence-based and credible – which implies that there is a substantial task in developing and validating this asset. This task needs to start early in the development lifecycle, since we will be communicating to our audiences with prephase III clinical data, in symposia and presentation assets well before any formal brand development occurs. n

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TECHNOLOGY

CIO Rich Williams has elevated technology from the sidelines to the center of AstraZeneca’s operations.

He tells NGP why information is the lifeblood of any organization.

Keeping the corporate heart beating

R

ich Williams, AstraZeneca’s Group CIO, is dramatically changing the role and importance of technology within AstraZeneca, transforming its operation from micro to macro to become the backbone of business infrastructure.

“Within the pharmaceutical industry, information services were traditionally focused on building technologies, managing data centers and developing applications. Our focus, what we call our new IS agenda, is a transformational change to shift the focus from internal operations to delivering business effect through technology, from data collection to knowledge management and intelligence, from a historical role of back office activities to being an integrated part of the business, ” Williams says.

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Richard Williams is Vice President and Group Chief Information Officer of AstraZeneca, responsible for the global information services strategy and operations, including company-wide application development, data management, technology infrastructure, data center operations and telecommunication networks worldwide. Williams joined the company in 1992, where he was one of the founding members of Astra/Merck, a new joint venture. Prior to the AstraZeneca merger, he was responsible for information systems for Astra Pharmaceuticals in North America.

Williams has been the group’s CIO since 2006, and explains how a background working in the commercial side of the business is behind his push to change technology usage to become an integrated component of the end product: “Whether it’s increasing R&D productivity, supply chain efficiency, commercial productivity all the way to how we reach and interact with the patient, if we keep in mind how each step ties in to achieving our business objectives, then we’ll make the right technology decisions and build the right capabilities.”

Technology, for Williams, is intrinsically linked to AstraZeneca’s business strategies. With the company’s overall strategy focusing on strengthening its pipeline of new products, reducing product development time and developing new sales and marketing practices, technology plays a pivotal role in providing an outcome that both differentiates AstraZeneca within the marketplace and improves patient health. “If I can make an investment that will improve quality, reduce the time to market or improve compliance to a life-saving medicine as it moves through the R&D cycle, through better analysis of drug usage and efficacy or through better understanding of the needs of physicians and patients then that’s tremendous value to our business and the patients we serve,” Williams notes.

On a corporate level, investing in a technology that allows for a reduction in overall costs provides AstraZeneca with greater time and resources in which further product R&D can be pursued. “We look at it a number of ways: is the investment in line with our strategic objectives, does it improve our interactions with our customers, and from a financial perspective, does it improve the efficiency of our operations and reduce our costs, given the pressures in the industry?”

“It’s really a fundamental belief that information is the lifeblood of the organization, from the discovery of new chemical entities to ensuring the speed and quality of the drug through the clinical process, to submissions to regulatory agencies all the way to information to the physician and patient regarding the disease, treatment and therapy.

Every day that we can shorten the development process moves us one day closer to making a difference in patient health.”

The result has been improved knowledge management solutions and a reduction in overall IS spend of 30 percent. The company was recently awarded the BIO-IT Best Practices Grand Prize for its pioneering use of SAFE electronic submissions that provide the FDA earlier access to the product submission for review.

Partnerships

According to Williams, AstraZeneca’s strategic partnerships with IBM, BT and Accenture have set new standards for pharmaceutical companies and their use of technology. He points to this shift in the traditional order of service providers and establishing partnerships as key to success. “The partnerships we have established have helped transform our internal organization from managing a particular Implementation technology or application to shaping the business But how exactly will AstraZeneca actualize impact it achieves. It also shifts their role and “If I can make an this implementation of technology into its busiraises the bar considerably in our expectations, as ness system? Williams’ shift of technology’s role they are truly linked into the achievement of our investment that will has been to dramatically change the organization long term success.” he says. improve quality then and its infrastructure, as well as increase its use of IBM’s role at AstraZeneca is to provide a global that’s tremendous value strategic partnerships. In July 2007, AstraZeneca technical infrastructure, linking the entire Astrato our business and the Zeneca organization and producing global results. expanded its partnership with IBM in a $1.4 bilpatients we serve” lion deal to streamline the company’s previously “It underpins our global services, and creates the fragmented technological services. The most funfoundations by which now we can start operating damental impact brought about by this agreement in a consistent way, which we could not do previis the standardization and expansion of the infrastructure itself. ously,” explains Williams. “The structure we created centers on a “When I walked in the door as CIO there really wasn’t anything concept of ‘service effect’, where IBM services and capabilities are global about our IS organization; it was all run independently along measured on the business outcome delivered and not on technology market and functional lines, with no consistency of operation,” alone. This strategy has now been applied with IS partners across Williams says. The rationale behind making a change of this magnithe company’s business, each managed to delivering the defined tude is that it drives greater consistency of information flow across business outcome “It comes down to focus, I want the internal team the business, and ultimately establishes a more efficient framework focused on the things that will truly make a difference to our business in which to achieve business results. and to use a small number of partners to deliver support services.

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ASTRAZENECA KEY FACTS • Active in over 100 countries with growing presence in important emerging markets. corporate office in London UK; major R&D sites in Sweden, the UK and the US. • More than 67,000 employees (55 percent in Europe, 30 percent in the Americas and 15 percent in Asia, Africa and Australasia).

• Sales in 2007 totalled $29.6 billion, with an operating profit of $9 billion.

• R&D spend in 2007 totalled more than $5 billion.

• Employs around 13,000 people at 17 principal R&D centres in eight countries.

• Has 29 manufacturing sites in 20 countries.

• Broad product portfolio includes: Arimidex (cancer), Crestor (cardiovascular), Nexium (gastrointestinal disease), Seroquel (schizophrenia and bipolar disorder) and Symbicort (asthma and chronic obstructive pulmonary disease).

However, these key partners are measured on delivering an outcome – not just on a set of technologies. ”

Acclaim It is not just the speed of transformation that has hailed Williams’ leadership as innovative. He’s also been highly acclaimed for his technology investments regarding physician and patient education. As a result, the company has produced pioneering capabilities using the digital environment to reach and educate patients regarding disease education, compliance programs and products.

AstraZeneca’s representatives have also benefited from this focus on leveraging technology through the use of their unique CRM technologies that deliver product knowledge to physicians in a highly interactive way that is uniquely tailored to the physician and their practice.

In recognition of his contribution to healthcare, Williams was awarded the IBM Global Public Sector Innovation Leadership Award in 2008, which he describes as a testament to the AstraZeneca IS team and the value and impact each member has had on the business. “Our work to link the organization, to help streamline R&D, and to educate physicians, patients and caregivers on disease, product and therapy has made a difference in patient health. What more can you ask for as a tangible reminder that what you do every day makes a difference?”

Transforming the function of technology to incorporate an entire global organization does not come without its challenges, however, and linking a business is challenging – especially one as diverse as AstraZeneca. Added to that are the increasing number of alliances, partnerships and acquisitions, including the recent purchase of Medimmune in 2007.

Previously, operations within the pharmaceutical industry have performed on an internal level; therefore AstraZeneca faces challenges in setting the precedent for third party partnerships and success of global communications. “Historically the pharmaceutical industry has been operating within this hard shell. Everything’s been done internally. What we’re moving to is more of a network model, and I think that adds complexity to the infrastructure – but will dramatically improve our business right across the value chain,” Williams explains.

Impact As CIO, Williams’ goal is to increase capabilities, providing AstraZeneca with the ability to operate with any partner or organization to deliver innovative medicines to the marketplace. Above and beyond Williams’ predictions of technological advancements in the pharmaceutical industry, he stresses the importance of collaboration, now and in the future. “Collaboration internally and externally is hugely important, and there is potential for major impact across our value chain as so many aspects of our business rely upon the intelligent processing of data from many sources. Often this can mean linking our internally developed information and collaborating externally to leverage the expertise, and insight externally, wherever it exists,” he says.

For example, AstraZeneca, the Karolinska Institute and other academic institutions in the Stockholm Brain Institute, are collaborating in a unique way of combining instrumentation (functional MRI and PET scan images), data analysis, visualization, modeling and simulation to develop major advancements in understanding the structure and function of the brain in order to develop new drugs by smarter research.

Likewise, AstraZeneca is working with a number of partners to explore alternative methods of meeting customer information expectations from modernday influences such as social networking or the potential cross-over into the personal technology markets leveraging consumer devices, such as the Apple iPhone, that may provide realtime access to personal health information, compliance and health support.

Williams’ services to technology and achievements as an innovative information leader can be attributed to his focus on technology not as a collection of wires in a dark cupboard, but as the opportunity that technology creates to drive business value and competitive differentiation. The view of information as an asset and the relentless focus on business outcome has fundamentally transformed the IS organization into a significant business asset – truly a new agenda for a new world. 

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THE NEXT BIG THING While there are a number of technologies to combat counterfeiting and diversion, a comprehensive system that provides protection of the product itself is required.

PROTECTING PRODUCT FROM PLANT TO PATIENT

P

atients place an incredible amount of trust in the pharmaceutical industry that the medications they are taking are indeed the exact medications prescribed by their physician. When a physician puts pen to pad, he or she is also not usually wondering if the medication to be dispensed is real or counterfeit. At least, it has not been a pervasive thought until recently, as both the threat and the reality of counterfeit medications has risen with each passing day.

Of course, not all integrity issues are the result of counterfeit medications. Diversion plays an important role in the demise of the pharmaceutical supply chain as well. The loss of profits is an obvious result of diversion activities but the problem goes beyond lost profits and in fact is much more than a manufacturers’ problem. Illegal diversion often serves as the catalyst for counterfeit product being inserted into the legitimate supply chain.

With an estimated $40 billion in counterfeits and perhaps an equally significant amount of diverted product entering the pharmaceutical supply chain each year, the stakes are high for the criminals who make large profits selling counterfeit medicine, as well as for consumers who are exposed to illegitimate, and at times dangerous, medicines.

The ideal protective solution is a multilayered approach incorporating overt, covert, on-package and on-dose technologies, which when combined, protect products and patients.

legitimately as in the case of dispensing by a pharmacist or via parallel trade, the protection provided by these on-package technologies is lost, as is the ultimate security of the product.

In order to better thwart counterfeiters and diverters, protect patients, and thereby raise the pharmaceutical supply chain to a higher level of integrity and confidence, manufacturers need to extend security efforts to on-dose (tablet, capsule or vial) technologies.

NanoGuardian’s NanoEncryption technology is the only on-dose, multi-layered, brand protection technology that enables manufacturers to trace and authenticate every single dose. NanoGuardian’s NanoEncryption technology possesses intrinsic layered security features at the overt, covert and forensic level and is applied directly to tablets, capsules and vial caps. These multi-layered security features provide a dual-protective benefit to manufacturers with a single technology. The overt and covert security features enable authentication at any point in the supply chain, while the forensiclevel NanoCodes provide comprehensive tracing information on each and every dose.

NanoGuardian’s NanoCodes can be associated with an unlimited amount of data, including but not limited to, product information, manufacturing information and distribution information. Since NanoEncryption technology always remains with the specific dose, even after numerous repackaging efforts, it provides brand integrity, protection and confidence that traditional, on-package More security needed technologies cannot alone provide.

Dean Hart serves as Executive Vice Traditionally, manufacturers have foManufacturers needs to implement protecPresident of NanoGuardian, a division of cused on securing product through package tive strategies to combat criminals who reap NanoInk, Inc. A pharmaceutical industry technologies; however, while these solutions profits by deceiving patients and in so doing, veteran with over 25 years of experience, provide a strong first level of defense, the cost tarnish the reputation of safety and quality Hart most recently served as Senior Vice of many medications has given counterfeitthat they have worked so hard to achieve. OnPresident Sales at Takeda Pharmaceuticals ers significant motivation to attempt to copy package technology initiatives are a must in North America, where he led a sales force any on-package technology. For example, a comprehensive brand protection strategy; numbering in excess of 2500 in successfully counterfeiters have become adept at copyhowever, they become ineffective when prodmeeting sales and profit goals. ing virtually all elements of pharmaceutical uct is repackaged. This gap in protection can packaging, including boxes, bottles and even often provide counterfeiters and diverters blister packaging. with the opportunity they need. Thus, a final While necessary tools in the fight against counterfeits and diverstep is needed to close this critical void and on-dose technologies sion, on-package technologies, including e-Pedigree initiatives such such as NanoGuardian’s NanoEncryption technology can provide the as 2D barcodes and RFID, fall short of a complete solution in that they protection required for manufacturers to protect the supply chain are applied to the package only. Once a product is repackaged, even from plant to patient. 

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HEALTHCARE IT

STAYING ON TRACK

When is a national electronic health record system like a railroad? When it faces the same challenges in ensuring all the pieces fit together. Nina Schwenk, VP for Integration and Chair of the Mayo Clinic’s IT Committee, explains.

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he election of an administration with a strong focus on healthcare reform can mean only one thing for Nina Schwenk: a faster, more dynamic system of patient care.

President Obama’s proposals to dramatically change the way in which health information is managed require the development of innovative technologies to support them, and as Chair of Mayo Clinic’s IT Committee, Schwenk will be one of hundreds of IT heads in hospitals and associations across the US attempting to implement the administration’s proposed establishment of a National Health Insurance Exchange.

But at what stage is the technology, and can it realistically cope with an expansion of information flow whilst still keeping patient health records secure? As one of the largest healthcare organizations in the US, Mayo Clinic cares for a high number of patients in several locations, and coordinating an increased flow of information could present challenges for Schwenk and her team.

Making tracks For President Obama to successfully achieve a transformation of the current patient medical health records (MHR), reform would need to take place across the entire US healthcare infrastructure. Given the time and funding needed for such a project, is it even possible to implement something of this size in the current economic climate, even with the delayed passage of the economic stimulus package? The withdrawal of Tom Daschle as Health Secretary certainly seems to have slowed down the process.

Schwenk believes that the way in which the infrastructure is to be developed is critical, and the creation of a uniform mandate of standards will be the key to successfully achieving a federal EMR system. Even with the correct implementation of procedures, she notes the challenges that still remain: “We can create more problems and increase the health risks and safety issues because we can’t specifically identify individuals, as we do not have a universal or unique patient identifier in the United States,” she says.

Identification by name only cannot make a successful infrastructure.

Without the creation of determining, specific factors, such as individual patient numbers, there will be a problem of patient differentiation. “If we can’t electronically exchange data, we won’t be able to make sure it’s the right person’s data we’re sending; a unique patient identifier is a key factor that the government will have to introduce. There will also be the need for the creation of a broad incentive to ensure the electronic system or clinical information data exchange follows certain guidelines.

“It’s similar to when we put the railroads in; if there wasn’t a common gauge, we wouldn’t have been able to get the railroad track from one side of the country to the other. We need something similar in healthcare information transfer, because without the standardization, we’re going to be hampered.”

Patient data Mayo Clinic is one of the few organizations that has unified patient medical records in its paper format. “We began this journey in 1907,” Schwenk explains. “If you were a patient seen at any of the sites at Mayo Clinic, for example if you were seen by a cardiologist in one of the hospitals, you were provided with a paper record in a plastic jacket that followed you around everywhere. Such a system doesn’t exist even now in

Nina Schwenk is VP for Integration and Chair of Mayo Clinic’s IT Committee.

many organizations, but we’ve had that for a long time. So, the tradition for information in a consolidated, integrated manner has been there for a century.”

With patient data at Mayo Clinic already operating at an organized level for a substantial length of time, the blueprint for data handling has been set. The technologies needed to consolidate patient information into digital form have been in the development process for a long time prior to the election of Obama and his subsequent healthcare reforms.

“We began the journey of consolidating and accessing data in an electronic format in the early 1990s, and in 2009 we find ourselves fully digital in the clinic and in the hospital. As a physician, I can see a patient in my office and have access immediately to all their medical data that’s collected in Mayo Clinic’s records via the computer. All their lab data, their surgical data, their radiology data, their radiology images; their past information all in sequential format. And this is available for every single patient for me now, both outpatient and inpatient.”

As Schwenk explains, the implementation of an electronic system is beneficial not only in terms of access to medical data, but also in terms of the consolidation of every single patient record. Mayo Clinic’s main site is located in Rochester, Minnesota; its precise situation is in a cornfield, described by Schwenk as “pretty much the middle of nowhere.” However, such a setting does not limit the number of those that are cared for by the Clinic or its influence within healthcare.

Mayo Clinic is the primary employer for the town, and expands its operations outside of Minnesota to care for patients across the US, and even

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across the globe. “The vast majority of our patients come from our fivestate or regional areas, and we do have extra regional clinics we are affiliated with; it’s called the Mayo Health System, and we now have the ability to electronically share data about those patients with those clinical sites as well,” she explains.

“If a patient is seen in Austin, Minnesota, the Austin physician, their primary care doctor in their community, is able to see all of the data on that patient that may have been provided at Mayo Clinic as a tertiary center.

Likewise, I can see that data when I see the patient at Mayo Clinic or any of the health system sites that we are connected with; I can see the data that’s collected there as well. Also, if a patient saw their primary care provider two weeks ago and had tests done, when I see them here two weeks later, I have access to all of that data, so repetition and inefficiency in terms of repetitive testing is unlikely to occur.”

Digital benefits The challenge that the Mayo Health System faces is not necessarily due to limitations within the organization, but rather to incompatibility between systems on a national level. As Schwenk explains, if patients come to the clinic from outside of the Mayo Health System, the lack of a federal uniform system of patient records slows down the processing of data.

“There’s not going to be an automatic sharing of the data because each individual organization is not connected. It’s still very much a manual process. We may fax it, we may give it to them in a paper format, or we can put it on a CD and give it to the patient before they go to their local site. But it doesn’t automatically populate it; somebody has to read it, decipher it and then change the formats to meet those of the electronic medical records of wherever they’re going to be treated.”

The biggest challenge facing Mayo Clinic is the same challenge facing Johns Hopkins Hospital, UCLA Medical Center and all other high ranking, innovative clinics: without the interoperability or the standards to be automatically exchanging that information, humans have to be intermediaries.

Schwenk explains that the two problems standing in the way of organizing patient data are two very different problems that must be dealt with separately and consecutively: computerizing all health records and then the sharing of this data between institutions. “These are two very different goals. If all health records are computerized, then that’s an advantage to the site that computerized them, but there’s a long gap between computerizing data and then being able to share that data.

“For example, we have other sites within Mayo Clinic, in Florida and Arizona. Because they have different electronic medical records, we still have to use other means to exchange data. Even within our own system, the standards and the interoperability aren’t there to automatically shift data across those lines, and this is often because of the differentiation in products from the different vendors who build the electronic medical records. Even if you give a computerized record to every physician in the

United States, it doesn’t mean they’re going to be able to talk to each other, and to me that’s one of the biggest challenges.”

Privacy concerns Schwenk notes the high value placed on the protection of individual privacy in the US as another potential problem factor. “Individuals don’t want their information shared and feel privacy is a human right, and are fighting a form of specifying identification via a number. The government has therefore put it on the back burner and hasn’t addressed it, and has gone so far as saying they will not address it. Again, if you look at it in terms of patient safety and healthcare, we’re going to need to readdress it to see how can we get there from here.”

The issue of privacy is always going to be intrinsically linked with patient fear of information safety: with more things becoming electronic, there are going to be concerns as to the likelihood of access to that information.

“Within Mayo Clinic, we deal with security in many ways,” Schwenk says.

“We have policies to keep a check on who has access to that data, and the appropriateness of that access. Also, if we’re transmitting data, we ensure that we’re using appropriate encryptions and that there is enough network security so that somebody can’t hijack the data. The exact storing of the data is also kept in check.

“Having said this, you can put in better security barriers to information theft in the electronic format than in the paper format. But unfortunately, if they break down in the paper format, you’ve lost one person’s record; in the electronic one, once you get in you can steal multiple people’s records. The risk is greater, although the security measures are probably tighter around the electronic data than they ever were in the paper data.

“Monitoring levels of security remains most important: tracking data, knowing what data is being viewed by others. Electronically we can do that, in the paper records we couldn’t. Stringent policies are also needed to enforce it if there are breakages, as well as audit functions to make sure that we’re keeping on top of that. So there are two issues regarding privacy: one is hijacking or theft of the data, where technical security and policies need to be in place, and the second is confidentiality.

“The public is also concerned about the ability of insurance companies to access patient health records. What’s in my record makes a big difference. If I do a genetic profile and find out I have a huge risk of cancer in my forties, who will insure me? Or, what if I find I already have HIV in my blood test result, who will insure me? I think that becomes a real valid point, and certainly then becomes an employability issue if my employer has access to that data. Those are two other privacy issues that are going to need to be addressed by legislation as opposed to technical security.”

“We can create more problems and increase the health risks and safety issues because we can’t specifically identify individuals”

Personalized medicine In his healthcare proposals, Obama has also pledged to promote public healthcare by requiring an increase in coverage of preventative services, such as cancer screenings. But, what will be the effect of personalized med-

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icine on EHRs? Schwenk advises that Mayo Clinic has been in the business of delivering individualized healthcare since the last century. “When you saw a patient, you took their life circumstances into consideration, you looked at their financial situation to assess what they could afford in terms of healthcare, and you looked at what their specific disease pattern or multiplicity of diseases was. Then you formulated a treatment or a management plan.

“The difference today is that we cannot continue in that paradigm, it’s simply not scalable anymore because of the volume of information. The amount of data is so huge that I don’t think any one person or physician or brain can synthesize all the information that’s available and bring it to bear for that patient; this is the benefit of EHR. How do we understand or synthesize genomic data, which is incredibly complex? We need algorithms to even understand what the meaning is, and then how does that apply to this particular patient?

“Clinical decision support is very important. From viewing all of the patient’s data in electronic format, as a care provider, I receive alerts regarding drugs and dosages, according to the patient’s medical background.

That’s the kind of individualized medicine that will help in the electronic era, so that’s one form of patient specific care.

“The other type is that once we start collecting this data in an integrated manner, we can go back and query it, viewing the treatment given to other patients within Mayo Clinic who were administered under the same disease. What were they given, and what were their outcomes? From com-

paring one patient’s genetic profile versus another’s, I can use that information to tailor the treatment for the patient in front of me. For that we need the capability of analyzing data in real time.”

It remains to be seen how the new administration will take those first steps to begin the transformation of the healthcare infrastructure, and whether the idea of computerizing all health records within five years is achievable. For Schwenk, it depends on how much money is invested.

“Dollars will get us there, but it’s also how the process flows and the buy-in. A two-physician clinic may ask why they should put the money in to computerize their records. Well, here’s the reason: What does that EMR actually do? Is it just collecting patient data, or is it helping you manage and solve clinical decision problems? This is the next step, and I believe that is Obama’s agenda. Once the information is in a digital format you can start using clinical decision support, as reminders and alerts for other physicians.

“There are all of those pieces; that’s where the value will be. The computerizing, we can probably get there by brute force, by giving dollars to go ahead and do it, but the real value will be in improving the quality of the care, and just by merely putting computers in, we’re not going to solve the problem.”

Just like with the building of the national railroads, it may take some time to get there, but the results will change our country immeasurably for the better. n

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SUPPLY CHAIN

he handling and transportation of perishable and temperature sensitive products has led to an increase in waste by those companies with an inadequate program of disposal.

As chairman of a non-profit association, Robert Arendal is focusing the organization’s strategies on ensuring improvement through partnering with pharmaceutical companies to produce better quality for the end user.

“We established the CCQI Master Table together with Germanischer Lloyd, the certification body for shipping and produced Master Tables for the perishables, mainly the foodstuffs,” explains Arendal. “We thought they would be a good PR company to look at this. We then invited in a representative from service providers, such as the airline industry, the handling companies, the trucking companies; all those companies involved within the cool chain procedure. We addressed the issues of shipment and transportation to meet the highest standards of the customers and improve the quality, reducing the waste.

“We then met with the pharmaceutical industry for their opinion of this and what specific requirements they might have,” says Arendal. The Cool

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Pharmaceutical event in Brussels provided the setting for a question and answer session between association and Pharmaceutical Company, both exchanging views and comments to examine the issue of waste disposal and provide a better solution.

“One of the things that we needed to do was to compare the CCQI Master Tables to what might already exist out there. The pharmaceutical industry said that they had looked at various programs and had established certain guidelines, and so our aim was then to analyze that and ensure there to be no and ascertain whether the CCQI will go much deeper into the handling and transportation of pharmaceuticals than what they have already.”

For Arendal, this remains to be seen as the analysis stage is currently in full swing. The event, being the first exclusive meeting between Arendal and the pharmaceutical industry, the association was able to explain the introduction of the Master Tables and CCQI. “It was based on the feedback from having presented this that we decided it was necessary to have a special CA event, focusing on the pharmaceutical industry and how to now proceed,” notes Arendal.

NGP talks to Robert Arendal, Chairman of the Cool Chain Association, about the issues faced by the pharmaceutical supply chain

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Standards Currently, companies only have their own corporate standards to follow, there being no general guidelines for the entire pharmaceutical industry to adhere to. “There are some stipulations, but they do not go as deep in it as the CCQI Master Table does. Each manufacturer or pharmaceutical company has their own specific requirements, adopting policies through the use of their service provider.

“We feel that it’s important to have a global vase. The use of service providers by pharmaceutical companies will continue, but it is important to have a baseline to start from. We can create a global standard, beginning first with Europe,” explains Arendal. This is the reasoning for the industry discussion between the companies and the association, to formulate a base standard that could be the CCQI. For Arendal, the importance of global guidelines for shipping and handling is the result of the ever-growing global relationship between the pharmaceutical industry and solution providers. “Shipment from A to Z

“We have now working together with Cargo 2000 to introduce temperature check during the transportation, temperature of the shipment is taken while it’s in transportation, to make sure that when let’s say the airline takes it over from the warehouse handling, it has the right temperature, and vice versa when it happens at the other end. When the airline delivers to a trucking company, it must make sure that it has the right temperature.

Guidelines “This is the role of the CCQI. Each Master Table explains exactly how a service provider should handle perishable or PTSP shipments, so each has a clear set of specific guidelines. The service provider can operate according to the guidelines as a certified supplier or not, but of course it has so much more value when it’s certified in terms of acquiring business,” explains Arendal.

“By applying the CCQI, you can also achieve an improvement in CO2 reduction, which of course is a very important issue these days, due to a far less amount of waste produced. Certain products, when they’re shipped by air, do emit CO2, we cannot avoid that, but we have to do it in the best possible way to the least possible environment.

Robert Arendal has been Chairman of the Cool Chain Association since it was founded in 2003. Previous to his position at the CCA, Arendal held a management position with cargo airline company Cargolux; he founded the Luxembourg Air Cargo Club (LACC) in 2001, together with other industry leaders in Luxembourg 2001, and was appointed Chairman of the Club.

goes through various phases. It starts with maybe a manufacturer of pharmaceuticals in South Africa. He then harvests the shipment to turn it over to a forwarder, who then takes care of it, prepares the documents, trucks it to the warehouse, either in the harbor at the airport. It’s shipped by air or sea, and then at the other end does the same kind of procedures in reverse. So you have here a range of six to 12 different service providers in order to handle one shipment from.” This demonstrates the importance communication between service providers and the guidelines upon which they must deliver.

“For example, if the shipment of berries or fruits from South Africa is not in the correct packaging from the very beginning and therefore is not at the right temperature, it’s very difficult to correct that temperature during transportation. You might, just after harvest, go into a blast cooling facility to get the temperature down, but if it’s not at the right temperature once it has started the transportation chain, it’s not easy to correct it. We need to make sure that each of these service providers know exactly what they have to do from the beginning, and we will then with the CCQI check that they have done that.

“We haven’t finalized this certification as of yet, we are currently in the process of checking what other guidelines the pharmaceutical industry has, and once we have that, we will sit down and make the exact agenda,” adds Arendal. The amalgamation of various company guidelines into a uniform system is due to start before 2008 ends, with the workshops operating during the first quarter of next year.

The specifications of the pharmaceutical industry provide more complexities and challenges when attempting to bring together a set of certified guidelines than most industries due to its special needs. “Most pharmaceutical products are shipped in a container and you have to be very careful not to open that container unless specifically authorized to do so. So what you have to do is to check that the container, at least from the outside where you can read that the temperature inside is within the range that they have requested, which will require the container to be supplied with electricity while waiting for it to be loaded. Once it’s loaded, there is nothing else that can be done to control the temperature, so ensuring all is done beforehand is imperative,” explains Arendal.

“Another challenge is that these containers have to be stored in a certain temperature also, which can often be within two to eight degrees.

Some of these containers can withstand the short periods of external temperature, but most containers will be affected. For example, cooler contain-

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ers will be unable to retain their desired temperature if they were standing outside in the sun for several hours; so consequently, there’s a specific care for and handling there.

“The pharmaceutical companies also do not usually want their products to be stored with those products that are not pharmaceuticals, such as food. In the setting of an aircraft, there will undeniably be one container with pharmaceuticals stood directly next to another of food, which is unavoidable.

“Certainly there are times when the forwarder is asking if the container could be loaded in a specific position on the aircraft on behalf of the manufacturer. This is often very difficult because an aircraft needs weight and balance, and consequently, it’s almost impossible to do that. You could certainly argue that if you load the containers in the lower belly, you could keep a certain temperature down there during the transportation. However, it’s more difficult to do that on the main deck due to the volume of the container. Also, if there are some pallets that have been standing in the sun and they are then loaded together with some containers or other products that are to be of a cooler temperature, one will affect the others,” explains Arendal.

The various factors that pose problems for the service providers is what is currently being addressed by the pharmaceutical industry and the service providers themselves. “We try to find solutions to this, so we at least need to know what are the sensitive parts of the pharmaceutical shipments when it’s being transported,” adds Arendal.

Shipments Pharmaceutical shipments are often very high value and have increased security requirements, providing further challenges to service

“The use of service providers by pharmaceutical companies will continue, but it is important to have a baseline to start from. We can create a global standard.” providers. “Many pharmaceutical companies prefer that their boxes are neutral boxes without labels, so as not to give away what it is.

Consequently very important in all this is to stipulate the temperature that is required during transportation on the shipping documents, as well as on a label, and that’s why we have worked with IATA trying to develop a specific label for PTSP shipments where we want the shipper or the forwarder to write down the temperature that this shipment should be maintained at during transportation.

“The reason for this is very simple in that why the temperature might be mentioned on the airway bill or the shipping documents because some airlines, especially US airlines, do not always like or accept that there’s a temperature specified on the airway bill, so it could be in some other part of the shipping documents. However, the shipping documents are not normally seen by the warehouse people, so how should they know that this is a shipment that has to be mentioned at a specific temperature? This is why a specific label with the temperature stated is very important.”

For Arendal, the effects of rising food prices due to the current economic crisis and potential food shortage provides a setting in which there is a greater need for protection of products, both food and pharmaceuticals.

“What we are doing here is becoming increasingly more valuable as people are wanting a better quality of their product. If we can help by applying the CCQI standards and Master Tables, then it can produce a longer shelf life, better quality for the end user, and less waste.” n

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PROJECT FOCUS

Combined competence Bürkert Fluid Control Systems and BBS Systems combine to make one of the most comprehensive partnerships in the hygienic processing segment.

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ccording to Mike Rodd, Segment Manager – Hygienic Processing (HP) at Bürkert Fluid Control Systems and Director of BBS Systems, “Understanding the business of our customers and the end-users of our products in very great detail is decisive for both Bürkert and BBS. We teamed up to improve our analysis of the market and customer needs, with the aim of improving client profitability.”

The new alliance delivers fluid control systems and components for an industry which depends more crucially on time and space factors than many other segments.

“The major players in the pharmaceutical business calculate with an ROI of months sometimes when building a new plant,” explains Rodd.

The pharmaceutical industry is driven by • • • • • •

Product yield Flexibility of the process lines Efficient maintenance Process efficiency Optimised process performance Fast and flawless cleaning cycles

concerns, Bürkert and BBS provide process efficiency and higher yields by offering unlimited process modularity. End-users profit from the combined experience of both companies.

And in addition to convincing functionality and cleanability, all instruments and components are not only good-looking, they are also flexible and can be used in many different processes – for even easier operation, internal processing and preventative maintenance.

It’s all about control In hygienic processing industries, measuring and controlling the flow of liquids and gases demands superior instrument performance and networkability. Standard connectivity with modular, decentralized monitoring, intelligence and diagnostics are the platform for flow control networks which provide reliable productivity data from the plant level flow network.

Control can be deployed when and where it is needed: whether centralized in a control cabinet with communication via

Bürkert and BBS see themselves as vital partners for this industry, offering a complete range of services, from consulting and engineering to installation, testing, and after sales service. “When we develop new products, our first goal is always to improve the business parameters of the end user,” says Mike Rodd.

Hygienic processing Bürkert is continuously involved in elaborating the latest specifications and requirements, and works in special interest groups – e.g. as a member of ASME BPE – to push the hygienic processing industry towards higher standards and greater value for their customers.

In the world of hygiene, where compactness, smart communications, plant footprints, cleaning and sterilization, dead legs, crosscontamination, and validation are everyday

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Mike Rodd is Segment Manager Hygienic Processing for Bürkert Fluid Control Systems. Rodd joined the German company Bürkert as responsible for the UK in 2001. He is also director of BBS AG, a leading manufacturer of piping components and solutions for the HP segment.

profi-bus, device net or field-bus or locally in the plant. Bürkert’s process control centres, valve mounted PID controllers, or valve tops for remote control, are flexible regarding to I/Os and communication protocols. According to Rodd: “Bürkert and BBS can deliver whole customized control cabinets or just a single control device.”

Connectivity Bürkert’s experience lies in linking all parts of the production process via electric signals. BBS links all the parts mechanically: sterile weld unions or quick connectors, flanges, fittings, hoses, and pipes are the world of the Swiss manufacturer. And where Bürkert stands for process design, flow, and instrumentation, BBS completes the offer with a huge number of special valves like check valves or point-of-use valves, sampling systems, flow indicators for process visualisation and heat exchangers – to name just a few of the wide range of components.

Rodd explains: “BBS delivers all the mechanical parts which perfectly complement our product range. Moreover, the cooperation with BBS gives us more flexibility when using exotic materials like hastelloy for example.

We can also supply hoses, approved for sterile use, as flexible connections between the various processing devices. The BBS hose is of exceptional quality; it is platinum cured silicone with optional types of reinforcement and has the advantage of working with the BBS re-usable unions which means the modularity and flexibility is transferred to our customers bringing major benefit and cost efficiency when exchanging them.”

Together, the Bürkert and BBS alliance offers all the mechanical and instrumentation components needed in a HP plant as well as complete process control solutions and systems “The combined product range of BBS and Bürkert is like a very large Lego kit – everything fits perfectly. This is unique and makes us stand out from our competitors,” as Rodd points out. n

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REGULATIONS

Worlds

apart

at different responsibilities. In Europe, we have a regulatory affairs department, which is structured around our business units in therapeutic indications, and each one of them has a group of people who support the content, the science and the strategy of their products. Then there’s my group which supplies services to those groups. If you take a typical regulatory affairs department, they need support for their submissions, so there’s regulatory publishing and regulatory operations in my group.

We supply some support for general principles of advertising and promotion. We leave the therapeutic areas, the regulatory people in those groups to review and deal with the content of scientific issues and then we provide support in how the regulations work and how the market works. We’re not enormous, so in a company this size you often play other roles.

We also work on process improvement projects where we are trying to build what you could call a chain of data that runs from the clinic in the trials through to the summary tables and the marketing authorization which would be six, seven years later. We work with processes with other groups in my division, the development division, biomedical and regulatory affairs, to make sure that what is submitted to the agencies is what we collected in the clinic.

Through that, we develop and we work with messaging standards and with databases. We provide knowledge management services. We manage an internal database that allows us to track regulatory status, track activities, support project planning activities and then my group works very closely with quality assurance to work on things like healthcare compliance and processes between our departments.

Genzyme’s Raun Kupiec on the regulatory challenges of a global market

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enzyme is a fairly large company in the biotech world, perhaps not up there with big pharma, but we’re probably second to Amgen in the independent biotech companies. We’re a very global company and we try to harmonize globally, so we have corporate support for our business units in therapeutic areas that are split between Europe and the US. There is a regulatory function in the US and a regulatory function in Europe that are meshed as one but

The chain Clinical supply chain is related to the marketing supply chain. We support the clinical group and so become involved a little bit there.

We are a frequent purchaser of small companies, so we have a lot of acquisitions and one of the critical things with acquisitions is making sure that you have data and product history available.

We work with incorporating those acquisitions and getting that information back from smaller companies, which may disappear out of the acquisition or may have been virtual. We have to bring in what they were doing from their CROs so that we have an actual dossier and dataset. This often involves a lot of work because we have a fairly structured and regimented knowledge management system, while many of the small companies that we acquire don’t.

My group works to take these documents in and to put them in a named and structured environment that matches our corporate requirements so that our project teams can work with it. Genzyme is a very unusual company in that one of our senior management

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develop strategies that can maximize or improve the chance of the product reaching the global market.

That becomes quite a challenge when you’re building a regulatory strategy and a development strategy that needs to meet these multiple endpoints and requirements. The data that’s required by the authority is not always exactly the same request, so that’s a very large challenge for the company.

There’s also a regulatory intelligence function. Genzyme is very active with industry associations. The company believes it’s very important to be involved as early as policy and develop regulation, both so we can proactive but also so that we can shape what’s developing with our own knowledge from experience and not be caught by surprise.

That’s a challenge for us because Raun Kupiec joined Genzyme in 1996. He has held the regulations are always lagging various positions in Genzyme’s regulatory affairs and behind practice and technology. quality assurance departments and currently directs While most of the more experienced Going global the Process Management group within the Regulatory companies know what they’re doing, Globalization and the harmonizaAffairs function. RA Process Management incorporates there are often small companies that tion of different processes is a major publishing, records management, regulatory intelligence don’t and so crises can come up. challenge. There’s a great deal of comand aspects of quality systems, labelling, advertising and We try to keep up with regulamunication between regulatory authoripromotion as well as IT support. tory intelligence and make sure that ties, but there are many reasons why Kupiec is a leading authority on regulatory our strategies are applicable for the they come to different decisions and operations and has served on multiple industry and way regulations develop. We learn different approaches, some very valid. professional organizations’ panels, committees and from other companies in the indusThere’s also a lot of difference in clinical editorial boards – including TOPRA, RAPS, EFPIA, try, through industry association practice between countries and so the EuropaBio and the ICH. best practices. We are also trying to regulatory group has a challenge workimprove our project planning proing globally and working with the US to cesses, so that we can really measure ourselves against things like CMR benchmarks and make sure that we’re still developing products Genzyme: key figures in the most efficient way.

For Genzyme in particular, a large focus of what we do is orphan The company has 80 locations in over products and sometimes even what they call ultra-orphan, which 40 countries. are very, very small indications. In clinical development, it can be challenging in these kinds of indications. We tend to focus on seriThese include 17 manufacturing facilities and ous and life-threatening disorders, which means a separate set of nine genetic testing laboratories. challenges.

As the company grows and we have more and more products and Genzyme products are available in nearly more lifecycle, the knowledge management of all that becomes very 90 countries. difficult, my group works in partnership with people in corporate IT and divisional IT, and other parts of the development and manufacturIn 2007 the company had revenues of ing environment. We collaborate to come up with systems so that we can have a good grasp on what we’ve done, what we’re doing, where $3.8 billion and spent $640 million on R&D. we’re going and where problems may crop up. n describes it as technologically agnostic, so we work with a variety of technology platforms and products.

We have medical devices. We have diagnostics. We have medicinal products. We have recombinant proteins and we have monoclonal antibodies.

We have cell therapies. We have a very large gene therapy research program, one of the largest in the world. We manufacture some conventional devices, diagnostic reagents, some small molecules and polymers.

As a result, we need to support all of that. The science and processes underlying that sometimes vary and certainly the project teams work in different ways and with different regulatory client issues and national requirements.

Therefore, we work with the regulatory group as a whole to bring that all together and keep the products moving through development. I think development is one of Genzyme’s strengths.

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COMMENT

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Business in the Year of the Ox At first glance, Pfizer’s plan to swallow Wyeth may look like a good strategic move, but closer examination reveals it to be a missed opportunity. By John Singer

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ccording to the Chinese zodiac, 2009 is the Year of the Ox. The sign of prosperity through fortitude, the Chinese say the ox works methodically, a born leader possessing an innate ability to achieve great things. A good time then, for natural leaders to step forward and make big, creative moves on behalf of their companies – much like Pfizer buying Wyeth.

Despite its size, however, Pfizer’s plan to swallow Wyeth feels more routine than imaginative, more tactical than strategic. The deal looks like a linear move at the operational level.

And its center of gravity – the focal point for overall competitive capability – is still squarely sitting on a commercial model whose success depends on promoting the features and benefits of individual drug brands in an operating environment that sees little value in, and does not trust, pharmaceutical promotion.

Pharmaceutical companies face an adaptive challenge to a interconnectivity, the chaotic, and the nonlinear. They will know changed context for business. The whole framework for getting how to build whole new forms of collaboration, like P&G and new medicines approved is evolving, the amount of revenue Google, who recently exchanged employees in a move to spark generated by new drugs is dropping, and atomizing ‘custommarketing innovation. ers’ are awash in information and competing data claims. The The future of the pharmaceutical industry is broader than marketplace is moving away from accepting laboratory meapharmaceuticals; it also lies in servicing health. More spesurements as evidence of real clinical benefit, focusing instead cifically, it lies in transitioning from an industrial-era view of a on improving health outcomes. business focused on manufacturing and promoting physical For example, there are five classes of drugs that all control products (i.e., drug brands), to a model based on organizing inblood sugar effectively, yet the incidence of adults with diabetes dustry environments around shared marketspace. This is about has tripled from 1980-2005. There are more than 150 drugs for creating new wealth by forging new business ecosystems: Pfizer high blood pressure. From the perspective linking with Dole Foods to invent a new stanof the insurers (these are the customers, dard of care in diabetes; Pfizer connecting John Singer is the founder of like states and the federal government, that with Apple to design a unique aggregation Blue Spoon Consulting, a strategy buy in bulk), many medicines are commodity of health information; Pfizer aligning with and marketing consultancy that inputs to electronic treatment algorithms, IBM to develop a new health infrastructure helps clients innovate their tactics, which are being used by huge integrated in Africa. These are the kinds of creative differentiate their strategies and delivery networks to standardize care. strategic moves that will address the unmet create at a system level.

The meltdown in the world economy, as it needs of patients, physicians and custommoves from link to link, engulfing industries and commercial relationships from which no one seems immune, reveals the potent networking effect that encompasses economic and technological connectivity. It also highlights a central feature to strategy in an advanced economy: the concept of separation – between people, between markets, between governments, between countries, between ideas – is bankrupt. Everything is connected to everything else in complex systems of behavior. The winners will know how to work with all this

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ers around the world.

There is opportunity in this Year of the Ox to transform the pharmaceutical industry, as Pfizer claims in its news release announcing the Wyeth acquisition, and the new even-bigger company has the resources and positioning to do it. But it will take a different kind of strategy and action, an evolutionary leap to adapt to a new world where there are no easy answers, no proven routines and no straight lines. This is the strategic challenge for Pfizer. 

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TRAVEL Growth market Home to three of the world’s biggest pharmaceutical companies, Germany is the third largest pharma market in the world.

ocated in Central Europe, Germany holds 82 million inhabitants and is the largest populated state within the European Union. It is the third largest pharmaceutical market in the world, and is by far ahead of the pack in terms of other European states.

Although recent EIU statistics show German economic growth to be minimal, pharmaceutical exports are continuing to increase. The domestic conception of

pharmaceuticals within Germany however, is very much constrained by government policy. This is imposed through severe price constraints, and as a result of this decrease in VAT, the pharma market is expected to experience moderate growth in the coming years.

With its pharmaceutical roots in the 19th century, Germany enjoys a reputation of being the ‘world’s pharmacy’. German rooted companies are both global and active pharmaceutical giants like Bayer

Schering Pharma, Boehringer Ingelheim and Merck KGaA. What’s more, the global pharmaceutical market is expected to grow about fi ve percent in 2009, with Germany expected to grow three to four percent, alongside the remaining top fi ve EU countries.

Growth is expecting to be driven by the ageing of Europe’s population and the rising demand for preventative care, along with the decentralization of government healthcare budgets. 

MAJOR GERMAN DRUG FIRMS Bayer AG Boehringer Ingelheim Merck KGaA

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BERLIN

Bode-museum of Berlin, Germany

As the capital city and one of the 16 states within Germany, Berlin hosts a population of 3.4 million, gaining the title of second most populous city in the EU. The metropolis is a major center for science and is home to world-renowned universities and research institutes, with a total number of 62,000 scientists working in research and development.

As a center for scientific advancements, Bayer Schering Pharma and Berlin Chemie are the major pharmaceutical companies headquartered in the city.

Berlin is a metropolis teeming with culture and is noted for its reputed institutions. Historically, the city has a very diverse art scene and holds around 420 galleries, drawing numerous young Germans and international artists to the city, establishing itself as a center of youth and popular culture in Europe.

The city is also an important center for the European film industry, housing more than 1000 film and television production companies and 270 movie theaters. Berlin is also the home of the European Film Academy and hosts the infamous Berlin Film Festival. Created in 1951, celebrations have been annually hosted since 1978, and with over 430,000 admissions, it is the largest publicly attended film festival in the world. 

FRANKFURT The fifth largest city in Germany, Frankfurt has a population of 670,000 and is situated on the Main River. The city is renowned for being the financial and transportation centre of Germany, and in continental Europe. Located within the city are the European Central Bank, the German Federal Bank and The Frankfurt Stock Exchange, along with the headquarters of other commercial banks.

Frankfurt is also home to chemical industries; due to the previous pharma giant Hoechst AG, Frankfurt is often referred to as the ‘Apothecary of the world’. Hoechst’s industrial park in Frankfurt is one of the three largest locations for the pharmaceutical industry in Europe.

As a significant business center, Frankfurt is the only German city with a high number of skyscrapers, housing buildings over 150 meters tall. Most of the buildings are located in the western part of the city center, known as Bankenviertel. Alongside the skyscrapers are numerous other tall structures, such as Europaturm, a telecommunication tower known as the Frankfurt TV tower. Henninger Turm and Goetheturm are also tall structures to see. 

Skyline of financial center, Frankfurt, Germany

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PHARMA EVENTS INTERNATIONAL EVENTS A selection of upcoming conferences and symposia around the world

Biotechnology for Non Biotechnologists Radisson SAS Hotel, Nice, France 22 Apr - 24 Apr 09 Organizer: Management Forum Ltd T: +44 1483 730071 | F: +44 1483 730008 E: info@management-forum.co.uk www.management-forum.co.uk/animalhealth/eventid/801 Injectable Drug Delivery - Devices, Technology & Development Le Meridien Hotel, London, UK | 23 Mar - 24 Mar 09 Organizer: Management Forum Ltd T: +44 1483 730071 | F: +44 1483 730008 E: leigh@management-forum.co.uk www.management-forum.co.uk/medical/eventid/963

10th Drug Discovery Leaders Summit 2009 Montreux Palace, Switzerland 15 Jun - 16 Jun 09 Organizer: Oxford Global T: +44 1865 304925 | F: +44 1865 304935 E: info@oxfordglobal.co.uk www.drugdiscovery-summit.com

11th Annual European Supply Chain and Logistics Summit Swissotel Dusseldorf, Germany | 8 Jun - 10 Jun 09 Organizer: World Trade Group T: +44 (0)20 7202 7560 | F: +44 (0)20 7202 7600 E: laurence.allen@wtgevents.com www.supplychain.eu.com

Preparing & Implementing an Effective Change Control System Toronto, Canada 26 Mar - 27 Mar 09 Organizer: International Pharmaceutical Academy T: 416 410 7402 | F: 905 472 1819 E: enquiry@ipacanada.com www.ipacanada.com/viewcourse.php?id=cc0309to

DUPHAT – Dubai International Pharmaceuticals and Technologies Conference and Exhibition Dubai International Convention & Exhibition Centre 29 Mar - 31 Mar 09 Organizer: INDEX Conferences & Exhibitions Organisation Est. T: +971 4 362 4717 | F: +971 4 362 4718 E: duphat@index.ae www.duphat.ae

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P-MEC Japan Big Sight Tokyo, Japan 21 Apr - 23 Apr 09 Organizer: CMP Information T: +31 346 559444 | F: +31 346 573811 E: pmec@cmpi.biz www.pmec-japan.com

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IN REVIEW

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On the shelf These are interesting times for pharma. What do the latest crop of pharmaceutical and life sciences books have to offer in the way of advice?

Our Daily Meds

How the Pharmaceutical Companies Transformed Themselves into Slick Marketing Machines and Hooked the Nation on Prescription Drugs, By Melody Peterson Former New York Times reporter Petersen takes an in-depth look at questionable practices within the pharmaceutical industry, and suggests reforms aimed at making big drug companies more accountable. Covers everything from copycat drugs and the environmental impact of drug residues in drinking water to marketing practices aimed at doctors.

NGP says: A thorough inside look at controversial aspects of the pharmaceutical industry not usually accessible to the general public. Read it and decide for yourself.

The Generic Challenge

Understanding Patents, FDA & Pharmaceutical Life-Cycle Management

By Martin A. Voet Explains the role of patents, FDA regulations for generic drugs and the Hatch Waxman Act on conventional and biological drug product development, and how directed innovation can result in enhanced care for patients while extending the commercial lives of the drugs. Of interest to pharmaceutical executives and managers; regulatory, legal, business development, R&D and strategic marketing professionals; and anyone with an interest in the future of the leading American pharmaceutical and biotechnology industries and the high value jobs they provide.

NGP says: Concise, easy to read, and helps to simplify the complex subject of pharmaceutical patent regulations.

Business Development for the Biotechnology and Pharmaceutical Industry

By Martin Austin

Business development in the biotechnology and pharmaceutical industries accounts for over $5 billion in licensing deal value per year. The scope of the job can be huge, and it can require a broad range of knowledge and skills from practitioners. Austin’s book is based on the international training program he delivers to pharmaceutical executives.

NGP says: A practical guide to developing a career in business development in the pharmaceutical industry. A must read for anyone thinking of entering the ďŹ eld.

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Final word

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Proof positive results Clinical Resource Network takes protocol visits to the patient to accelerate patient recruitment and significantly lower dropout rates.

“Insanity: doing the same thing over and over again and expecting different results.” Albert Einstein. Have we been conducting clinical studies the same way over and over again, expecting different results?

Patient recruitment problems Timely patient recruitment is the Achilles heel of the clinical trial process. Even with the most efficient site selection processes, sophisticated trial designs, outreach programs and advertising campaigns, patient recruitment accounts for over 25 percent of the median cycle time for clinical trials. Making matters worse, approximately 20-30 percent of patients drop out from phase II/III trials resulting in 90 percent of studies missing targeted completion dates.

The hassle factor Everyone reading this article has probably directed, managed, reviewed or analyzed a clinical trial, but have you ever been a patient involved in a trial? If so, you know firsthand about the ‘hassle factor’ of clinical trial participation: • Scheduling challenges • Distance to the PI’s location • Challenges due to disease state • Disruption from school schedules, work responsibilities, travel plans, etc.

• Caregiver burden Every potential patient, considering whether or not to enroll in a trial, thinks about many of these issues when making the clinical trial enrollment decision. Once the trial begins, patients will drop out if the hassle factor caused by trial participation becomes overly burdensome. So what can be done differently?

Taking visits to the patient Clinical Resource Network’s service model is based upon a ‘patientcentric’ approach to implementing clinical trials. Rather than requiring patients to go to the investigator’s site for protocol visits, CRN takes selected visits to the patient – at home, at work or on vacation.

Since 2003, CRN has been offering access to their mobile clinical network of over 15,000 highly skilled nurses, pharmacists and clinicians, supporting hundreds of studies in multiple therapeutic areas and in all age groups and phases of development. How it works: • Study sponsors contract with CRN, a national homecare management organization; homecare services are made available

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to participating sites to use as needed for protocol visits.

• Physician orders and homecare source documents are standardized; the site completes the order for homecare services once a patient is enrolled in a study.

• Local CRN homecare clinicians are selected based on where the study patients reside, clinicians are trained by CRN on GCP’s and study-specific and regulatory requirements.

• Local clinicians contact the study patients and schedule and conduct the ordered services; source documents are completed by the local clinicians at each visit and provided to the site, CRN oversees the day-to-day homecare activities.

Case study: accelerated patient enrollment Making study participation convenient for patients through NDA compliant in-home or alternate-site protocol visits has proven results.

This was a phase II, safety and efficacy study of a cancer drug for the treatment of patients with glioblastoma. The dosing regimen required one-hour infusions three times weekly for six months. Patient recruitment was significantly behind schedule after six months of enrollment. Study-specific nursing and pharmacy homecare services were implemented for the administration of study drug and safety blood draws. As a result, enrollment nearly tripled over the next six months and was completed. Seven of 10 sites recruited patients from out of state.

Conclusion and summary CRN’s innovative and proven trial model is available for patients, sponsors, CROs and clinical sites and can provide an important alternative to the traditional study logistics. More patients are willing and able to participate in trials via this model. Additionally, more patients are retained, resulting in decreased development time. n

Gail Adinamis is President and CEO of Clinical Resource Network, LLC, a diversity company specializing in the provision of in-home nursing and pharmacy services to facilitate all phases of clinical trials throughout the US, Canada, UK, Europe and Israel. Adinamis has 29 years of comprehensive clinical trials experience, including over 12 years of global clinical trials management at Abbott Laboratories and Astellas Pharma US.

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