NGP US 18

www.ngpharma.com • Q1 2010

BRAVE NEWHOW THE INDUSTRY’S MOVE INTO EMERGING MARKETS WILL RADICALLY

CHANGE THE PHARMACEUTICAL LANDSCAPE PAGE 34

TOUGH CHOICESWhy pharmaceutical R&D

must reinvent itself PAGE 40

LIVE LONG AND PROSPERJohn Lechleiter’s take on the human

dimensions of medical innovation PAGE 52

WORLD

THE H1N1 CONTROVERSYPAGE 60

TOWARDS A GREENER INDUSTRYPAGE 92

FIXING THE FAILURE RATE PAGE 100

COVER NGPUS18 FINAL_feb10 18/02/2010 14:11 Page 1

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According to PricewaterhouseCoopers’‘Pharma 2020’ report, the real GDP ofthe E7 countries will triple from $5.1trillion in 2004 to $15.7 trillion in

2020, whereas that of the G7 countries will grow byjust 40 percent, from $25.8 trillion to $36.1 trillion.

Our cover story looks at how these sevencountries – Brazil, China, India, Indonesia, Mexico,Russia and Turkey, along with other under-ex-ploited areas of the globe – represent a huge oppor-tunity for the pharmaceutical industry. Pressure athome from patent cliffs and dry pipelines has eventhe big players looking for ways to increase theirbottom lines while at the same time bringing newtreatments to previously unserved populations. Itseems like a win-win situation.

Other significant opportunities in emergingmarkets include the chance to further develop newproducts and establish manufacturing, R&D orother facilities, as well as taking advantage of localskill sets and accelerating time to market.

There are pitfalls to beware of, however. The

velopment is a long-cycle business and that in theend innovation will be rewarded.

We also hear Eli Lilly CEO John Lechleiter’stake on medical innovation and the critical role itplays in lengthening lifespans and providing liveli-hoods. He points out that people are innovation’screators as well as its beneficiaries, and that inorder to foster it we need to encourage improvededucation, increased immigration and more fund-ing for research.

As pharmaceutical companies continue toadvance into new markets, they would do well tokeep these points in mind. Smart people, good re-search and a healthy dash of innovation are thebasis of a successful operation in any market, be ittraditional or emerging. n

Marie Shields Editor

potential for political upheaval and other unfore-seen events is arguably higher in certain of thesecountries than in the West, and could prove par-ticularly challenging for companies unfamiliarwith the local markets. Concerns also exist aboutthe solidity of the infrastructures in place, IP con-siderations and whether proper compliance andregulatory standards can be established.

Such challenges seem unlikely to prevent theindustry’s continued expansion into these areas.PwC’s report also predicts that in 10 years’ time,the E7 emerging economies will account for 20percent of sales in the $1.3 trillion pharmaceuticalmarket. What company is going to let that oppor-tunity get away?

Elsewhere in this issue, Joe Miletich, Amgen’sSenior Vice President for Research andDevelopment, explains why pharmaceutical com-panies should continue to innovate, even in thesefinancially straitened times. According to Miletich,while an increase in short-term costs may be un-avoidable, it’s important to remember that drug de-

“Emerging markets are playing apivotal role in how establishedcompanies will move forwardand in their growth potential forthe future” Simon Friend, GlobalPharmaceuticals Leader,PricewaterhouseCoopers(Page 34)

“In the long term, what wefundamentally need as asociety and human beings willprevail and the truly innovativethings will be rewarded” JoeMiletich, Senior Vice Presidentfor Research and Development,Amgen (Page 40)

“We need to get away from thenotion that every drug hittingthe same target is equivalentand communicate the potentialdifferentiation of our molecules”Paul Matthews, Vice Presidentfor Imaging, GlaxoSmithKline(Page 108)

EDITOR’S NOTE7

Out from the shadowsWhy the rapid rise of emerging markets willchange the pharmaceutical world as we know it.

ED NOTE_feb10 19/02/2010 10:52 Page 7

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Towards a greener futureMark Rhodes examines the levelof environmental awareness inthe pharmaceutical industry

34

40

CONTENTS9

Curing the world’s ills?How the so-called ‘pharmerging’ markets willchange the future of the industry

When the going gets toughJoe Miletich explains why innovationin R&D is more important than ever

92

52

Lifespans and livelihoods The human dimensions ofmedical innovation, according toJohn Lechleiter

CONTENTS_feb10 18/02/2010 11:42 Page 9

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60 Who influenced WHO? The controversy surrounding the H1N1pandemic

70 Business mindedRaafat Fahim explains why an efficientbusiness model is needed to cope withindustry challenges

78 Leading the wayWhy California is the worldwide headquartersof biomedical R&D

100 Fixing the failure rateKamal Shah looks at why most new compoundsfail to progress beyond clinical trials

60

CONTENTS11

58

128

ASK THE EXPERT

64 Lorne Davies, Olympus America Inc.74 Christina Shasserre, EMD Chemicals90 Lynn Zieske, Singulex96 Patrick Lucy, Pfenex Inc.112 Michael Morales and Bruce Hillman,ACR Image Metrix124 Alfred Sherk, SherTrack136 Ethan Smith, Metastorm144 Chuck Russo, Corbett AccelHealthcare Group

Who influenced WHO?

The Lean solutionImproving enterprise-level productivity

48 Craig Dobbs, Waters50 Andrew Thompson, Eurand68 Nitin Sood, Agilent AutomationSolutions80 Matt Sawtell, GE Healthcare88 Brandon Pence, Thermo ScientificHyclone Products150 Tom Haskell and John Moran, IMSHealth

EXECUTIVE INTERVIEW

PROJECT FOCUS

114 John Hall, Quintiles116 Grace122 Debra Shumar, 3P Partners134 Paul Dupont, Ropack

TROUBLESHOOTER

106 Amy Furlong, ERT142 Bruce Jones, Disney Institute

ROUNDTABLE DISCUSSION

85 SoftwareWith Amos Dor of Umetrics and PatrickFlanagan of Tripos International


138 Putting people firstCharles Depasse on the importance of payingclose attention to your staff’s needs

146 Feel the forceWhy sales force effectiveness is taking toppriority

CONTENTS12

50

48

118

154 Travel156 Events158 Snapshot160 Final word with Byron Hill

IN THE BACK

In the driving seat

Andrew Thompson, Eurand

Craig Dobbs, Waters

INDUSTRY INSIGHT

46 John McCarthy, Symyx58 Kim Shah, Thermo Fisher Scientific98 Scott Dixon, Phase Forward104 Christene Leiper, Onorach Clinical126 Grant Howes, Accuri Cytometers Inc.132 Rebecca Vangenechten and IvoBackx, Siemens

NEXT BIG THING

82 Richard Kurtz, Bio-Rad Laboratories, Inc.152 Eric Opron, Walt Disney World Swanand Dolphin Resort

Photo finish

108 Wedded bliss?Paul Matthews looks at the challenges posed bythe marriage of imaging and drug development

118 In the driving seatRene Labatut stays in control of SanofiPasteur’s vaccine manufacturing processes

128 The Lean solutionCarmen Doran and Domingo Traver explainhow Lean and Six Sigma are bringing aboutperformance improvements


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UPFRONTTHE BRIEF16

Then Dolly the sheep wascloned from an adult cell in 1997,

showing that a specializedcell could act like an

embryonic stem cellunder certain con-ditions. In 2007,researchers an-

nounced the cre-ation of induced

pluripotent stem (iPS)cells from human skin cells byinfecting them with four stem-

first into branches and then intoindividual leaves, the cells werebelieved to be consignedto one developmentalfate by physicalmodificationsadded to theirDNA. Accordingto this line ofthought, a skin cellcould no more become anerve cell than a leaf could movefrom branch to branch.

scientists involved are confidentthe same technique would workwith human tissue.

Until recently, it wasthought that cellular specializa-tion, or differentiation was aone-way path: pluripotent em-bryonic stem cells give rise toall the cell types in the body, butas the daughter cells becomemore specialized, they also be-come more biologically isolat-ed. Like a tree trunk splitting

BRAIN CELLS FROMMOUSE TAILSScientists at Stanford Universityhave turned skin cells from thetails of mice into neurons that areable to form connections crucialto brain function. The research,which was published in Nature,shows once again that the basicfunctions of cells can be radicallyaltered by turning on or insertingthe right genes in their DNA. The

Until recently, it was thought

that cellular

or differentiation was a one-way

path

specialization

UPFRONT NGP US18:25 June 18/2/10 14:57 Page 16

UPFRONTTHE BRIEF 17

cell-associated proteins calledtranscription factors.

One interesting aspect of theStanford study was that it wasaccomplished without the needto first turn the skin cells intothe equivalent of embryonicstem cells. A similar method de-veloped four years ago by ShinyaYamanaka of Kyoto Universityin Japan originally showed thatskin cells from mice or humanscould be made into stem cellsand manipulated again to be-come any cell in the body.The new work provides amore efficient way tomake neurons fromthe skin of peoplewith Alzheimer’sand Parkinson’sdiseases.

The Stanfordstudy was led by MariusWernig, Assistant Professor ofPathology at Stanford’s Institutefor Stem Cell Biology andRegenerative Medicine. Wernigand his team identified 19 genesthat are active in neurons andinserted them into skin cellstaken from the tails of youngmice, using a lentivirus to carrythe genes into the skin cells.

A month later, several of theskin cells appeared to haveturned into brain cells. Threegenes were identified using atrial-and-error process fromamong the 19 that could do thejob on their own. Using thesethree genes, Wernig’s teamfound that 20 percent of the skincells had changed into neuronsin just two weeks.

“We actively and directly in-duced one cell type to become acompletely different cell type,”Wernig said. “These are fullyfunctional neurons. They can doall the principal things that neu-rons in the brain do.” That in-

cludes making connectionswith and signaling to othernerve cells – critical functions ifthe cells are eventually to beused as therapy for Parkinson’sdisease or other disorders.

“This study is a huge leapforward,” said Irving Weissman,Director of the Institute. “Thedirect reprogramming of theseadult skin cells into braincells that can show complex,appropriate behaviors like gen-erating electrical currents andforming synapses establishes

a new method to studynormal and disor-

dered brain cellfunction. Finallywe may be ableto capture and

study conditionslike Parkinson’s or

Alzheimer’s or herita-ble mental diseases in the labo-ratory dish for the first time.”

The research suggests thatthe pluripotent stage, ratherthan being a required touch-stone for identity-shifting cells,may simply be another possiblecellular state. Wernig specu-lates that finding the right com-bination of cell-fate-specificgenes may trigger a domino ef-fect in the recipient cell, wipingaway restrictive DNA modifica-tions and imprinting a new de-velopmental fate on thegenomic landscape.

Wernig and his colleaguesare now applying the sameprocess to human cells andStanford has applied fora patent on the process.Researchers could use themethod to turn skin cells froma patient with Parkinson’s orAlzheimer’s disease, for exam-ple, into neurons with thegenetic defects that causethe condition.

Wernig’s team found that

of skin cells hadchanged into

neurons in just two weeks

20%

The Bud medical marijuana dispensary in Boulder, Colorado. Since the policy onmedical marijuana changed, Colorado’s dispensaries have more than tripled

Swiss drugmaker Novartis appointsformer Head of PharmaceuticalsJoe Jimenez as Chief Executive

The Military Sealift Command hospitalship USNS Comfort anchored off the coastof Haiti, following the recent earthquake

NEWS IN PICTURES

Demonstrators call for the release of 43 arrested health workers outside theCourt of Appeals in Manila, Philippines


UPFRONTPROFILE18

James Cornelius was named CEO inSeptember 2006 and was elected chairman ofthe Board by the company’s Board ofDirectors on February 11, 2008. Prior to join-ing Bristol-Myers Squibb, he served as chair-man emeritus of the Guidant Board ofDirectors upon closing of its merger intoBoston Scientific in April 2006. He previous-ly served as Chairman and CEO during themerger process and was responsible for thecompany’s initial public offering and subse-quent split-off from Eli Lilly in 1995.

“Our vision for Bristol-Myers Squibb is to be-come a healthcare leader for the future,” saysCornelius. “By uniquely combining the best ele-ments of a leading-edge biotech company with thereach and resources of a major pharmaceuticalcompany, we are transforming into a new kind ofenterprise – a next-generation BioPharma leader.”

Since 2002 the company has brought ninekey products to market for the treatment ofserious disease, including two new biologicmedicines. “Our focus is helping patients pre-vail,” says Cornelius. “Moving forward, ourstrategy will be unwavering.”

Cornelius was a member of the Board ofDirectors of Eli Lilly, a member of itsExecutive Committee and Chief FinancialOfficer from 1983 to 1995. From 1980 to 1982,he served as President and CEO of IVACCorporation, previously an Eli Lilly subsidiary.

He attended Michigan State University,where he earned a BA magna cum laude in ac-counting in 1965 and an MBA in 1967.Cornelius has received several honorary doc-torate degrees in recognition of his civic andphilanthropic activities in Indiana.

JAMES CORNELIUS,CHAIRMAN AND CEO,BRISTOL-MYERS SQUIBB


Counterfeits of weight-loss drug Allihave reportedly been found on sale onUS-based websites, includingrenowned auction site eBay.The genuine article, which ismanufactured by UK-basedGlaxoSmithKline is cur-rently available over thecounter in Britain and claimsto help users lose more weightthan dieting alone. However, thecounterfeit version has been found notto contain

orlistat, as it should have done, and insteadcontains sibutramine, a substance that wasremoved from use by the European

Medicines Agency, after early datashowed it may increase the risk

of heart attacks and stroke.The websites selling

the counterfeit drug arebased in the US, but thecounterfeit packets may

be available to interna-tional patients online. The

UK Medicines and HealthcareProducts Regulatory Agency has

warned against the “trend of self-diagnosingand self-prescribing,” calling this prac-

tice “dangerous”.

FAST FACT Medicines purchased from

illegal internet sitesthat conceal their

physical addresseshave been found in

of cases to becounterfeit

50%

THE REAL ALLI

Despite declining sales, Pfizer reported a26 percent jump in third-quarterprofits last year, as cost cutsoffset massive industrylags. Pfizer Inc., alreadythe world’s largest phar-maceutical company, hasbeen a hot topic in thenews recently thanks to thecompletion of its $68 billionacquisition of Wyeth, whichclosed in October. Now, with reportsshowing net income in the firm’s most re-cent quarter at $2.88 billion – up from$2.28 billion a year earlier – Pfizer is ridinghigh again.

PFIZER MERGER CLOSES

The counterfeit version has been

found not to contain

as it should have doneand instead contains

sibutramine

orlistat

With the acquisition complete, Pfizer nowemploys 4500 former Wyeth employees at facil-ities in Collegeville and Great Valley. Though

Pfizer has already made moves to con-solidate quickly now that the

merger – announced in January2009 – has been finalized.

The company says thatit plans to announce whatprojects will stay in its re-

search program and whatgets cut more quickly than the

six to nine months companiesoften take; the time period is expected to be

considerably shorter than the painful, drawn-out integrations following Pfizer’s buyout ofPharmacia Corp. in 2003 and Warner-Lambert Co. in 2000.

UPFRONT19

The FDA has approvedGlaxoSmithKline's drugArzerra (ofatumumab) as atreatment for chronic lym-phocytic leukemia, a slowlyprogressing cancer of theblood and bone marrow.

The news of the ap-proval comes as part of theFDA’s accelerated approvalprocess, which allows earli-er approval of drugs thatmeet unmet medical needs.According to reports onReuters pertaining to theaccelerated process, prod-ucts may receive this kind ofapproval based on a surro-gate endpoint – for exam-ple, the reduction in the sizeof a tumor or the decreasein the number of cancerouswhite cells.

The approval ofArzerra patients with CLLwhose cancer is no longerbeing controlled by otherforms of chemotherapyillustrates the FDA’s com-mitment to using the accel-erated approval process tohelp those patients who oth-erwise have limited thera-peutic options.GS

KAP

PROV

AL

Pfizer reported a

jump in third-quater profits

26%


UPFRONT20

AUTISM ARTICLE DISAVOWEDMERCK PROFITS approve Merck’s plan to buy NewJersey neighbor Schering-PloughCorp. That sale alone saw thecompany reap an impressive $1.7billion (after tax), but even without

it, profits would stillhave been up 58

percent from theyear before.

As a result ofits profitable year,Merck is movingup from number

eight to numbertwo on the pharma

power ladder, thanksin part to its $41 bil-

lion acquisition ofSchering-Plough. Other

successes for Merck havebeen the company's new dia-

betes drugs, Januvia and Janumet,which brought in a combined totalof $664 million. MeanwhileSingulair sales increased five percentto $1.1 billion.

Merck & Co. has posted a hugeprofit margin due to higher thanaverage sales and the sale ofa business.

The company,whose range ofproducts in-cludes choles-terol drugsand vaccines,along with theasthma and allergytreatment Singulair,posted a net income of $3.42billion, triple the amount it made atthe same time last year.

A large part of that in-come came from the saleof half of the Merialanimal health busi-ness so that regu-lators would

GATES PLEDGES $10 BILLION FOR VACCINESbecause of the “incredible impact” theyhave on children’s lives. Bill Gatesadded that the next 10 years must bedefined as “the decade of vaccines”.

The boost comes after a modelused by the Foundation and developedby a consortium led by the Institute ofInternational Programs at the JohnsHopkins Bloomberg School of PublicHealth stated that significantly scalingup the delivery of vaccines in develop-ing countries could prevent the deathsof some 7.6 million children.

At the reccent World EconomicForum in Davos, Switzerland, reveredbusiness tycoon and founder of com-puter software giant Microsoft, BillGates, announced with his wife thatthey will commit $10 billion over thenext decade to help research, developand deliver vaccines for the world’spoorest countries.

According to Mrs. Gates, whoannounced the initiative last Friday,the vaccines are now the “numberone priority” of the Gates Foundation

A prestigious medical journal hasdisavowed an article it publishedmore than a decade ago linkingautism in children to a commonchildhood vaccine. The original arti-cle raised widespread concernabout the safety of thevaccine, promptingmany parentsworldwide tostop vaccinatingtheir children.

In 1998, ahigh-profile articlepublished in the Britishmedical journal, The Lancet,announced a link between autismand the MMR vaccine, used againstmeasles, mumps and rubella. Therehad been no established cause shownfor autism, a disorder that affects ayoungster’s social skills and ability tointeract with the outside world.

In the original paper, Britishgastroenterologist AndrewWakefield described a small sampleof 12 children, eight of whomshowed evidence ofautism shortly afterreceiving the vaccine.However, subsequentinvestigations by Britishregulators led to chargesthat Dr. Wakefield falsi-fied data and was paid bythe parents of autistic chil-

dren. In 2004, as scrutiny and criti-cism of the study intensified, ten of13 co-authors of the 1998 autism ar-ticle publicly disassociated them-selves from it. Paul Offit, a vaccine

researcher at Children’sHospital in Philadelphia,

says at least 12 studieshave been doneworldwide con-cluding repeatedlythat the MMR

vaccine does notcause autism.

“We’ve reached themany hundreds of thousands

mark of children who did or didn’t re-ceive MMR to see whether risk ofautism was greater in the vaccinatedgroup and it wasn’t; consistently, re-producibly, redundantly,” he says. “Ithink the problem is there are peoplewho simply don’t believe the science.They hold on to this notion thatMMR causes autism or that vaccines

cause autism much as one holds areligious belief.”

Source:voanews.com.

co-authors of the 1998autism article publicly disassociated

themselves from it

10 of 13

of children aged 3 to 17 in the US have an

autism spectrum disorder

1%

FAST FACT

The sale alone saw the

company reap an impressive

after tax$1.7 billion


UPFRONT21

MALARIA BREAKTHROUGHsharing its scientific data and lab-oratories to help fight the

good fight against tropicalcountries. According to

reports, Andrew Witty,Chief Executive of

the firm and thedriving force be-

hind the initia-tive, said the

drug com-pany

has a“gen-

uineappetite to change the landscapeof healthcare for the world's poor-est people.”

In the Q3 2009 issue of NGP, Chris Viehbacher, CEO of sanofi-aventis, ex-plains his controversial appointment to the position and the need he foundto reshape the company’s image.

Go to www.ngpharma.com to browse ‘Past issues’ and click on Issue 16,June 2009 and read of Viehbacher’s plan to “bring the outside world intothe company and open it up to what’s out there”.

The number of product recallsand safety alerts for pharma-ceutical products and medicaldevices more thanquadrupled in theUK between2004 and 2008,a new studyby customermanagementagencyBlueview Groupreveals. The study,which pulls together UK gov-ernment and European Unionfigures, shows that over thefive-year period starting in2004, recalls and product alertsin the pharmaceutical sectorrose from 22 to 94.

Nearly two thirds of theseactions are down to defects inthe manufacturing or perfor-mance of a medical device with62 percent of recalls or alerts inthe sector being issued for thisreason. Another 12 percent of

pharmaceutical recalls are dueto incorrectly labeled or pack-aged goods, and nine percent

are due to compromisedsterility owing to

packaging errorsor poor struc-tural integrity.

In 2007 theEuropean

Commission re-leased figures re-

vealing a five-foldincrease in fake pharmaceuticalsacross Europe, with 2006 seizureshitting an all-time high of 2.5million items. The worrying in-crease in the incidence of coun-terfeit drugs and the growingsophistication of the lengths thatcounterfeiters are now preparedto go to are a constant source ofconcern for drug manufacturers,prompting ever more researchinto new technologies and strate-gies to protect the pharmaceuti-cal supply chain effectively.

US regulators have reportedly can-celled a review meeting set to decideupon a proposed new indication forEli Lilly‘s blockbuster antidepressantCymbalta. According to a notice onits website, the Food and DrugAdministration (FDA) has nowcancelled the review meeting thatwas due to take place in light of “newinformation”, in hope that this newinformation may prove to be rele-vant to the benefit/risk balance forthe proposed new indication.

However, the FDA also main-

tains that it intends to “continueevaluating the application” and islikely to announce future meetingdates for the FDA’s Anesthetic andLife Support Drugs AdvisoryCommittee to reconvene and con-sider whether Cymbalta (duloxe-tine) should be recommended forapproval for the treatment ofchronic pain. The drug is alreadyapproved for depression, anxiety,diabetic nerve pain and fibromyal-gia, and had third-quarter sales of$790.2 million, up 10 percent.

LILLY REVIEW CANCELLED

FROM THE VAULT

RISE IN PRODUCT RECALLS

Scientists across the globe havelong hunted for a vaccine againstmalaria – a disease that claimsroughly one million liveseach year. But now, afterdecades of searching,the creation of amalaria vaccinebegan to lookmore andmore likely.UK-basedphar-maceuti-cal giant GlaxoSmithKlineannounced it would take the sig-nificantly unprecedented step of

of pharmaceutical recalls are due to

incorrectly labeled orpackaged goods

12%


UPFRONT22 INTERNATIONAL NEWS

DRUG INFO PLEDGE

A call for new initiatives to completeCommission proposals that wouldliberalize European controls on theprovision of prescription druginformation to patients has comecourtesy of Europe’s new HealthCommissioner-designate.

John Dalli, who is the Commissioner-designate for Health and ConsumerPolicy (SANCO) in President JoseManuel Barroso's new Commission,has told ministers that the currentdraft directive needs to be reassessed.According to Dalli, “Patients have theright to have access to proper infor-mation on prescribed medicines. Wehave to reassess the proposal and puta better one on the table.”

If successful in his nomination, Dalliwould also be taking on responsibilityfor the European Medicines Agency,and in his written answers to theENVI panel he says he is looking for-ward to the upcoming evaluation re-port on the Agency’s functions.

GSK JOB CUTSPharmerging GlaxoSmithKline isexpected to announce thousands ofjob losses. The UK-based pharmaceu-tical giant is reportedly likely to followin the footsteps of other drug compa-nies, including key rival AstraZeneca– who announced similar cuts recent-ly – by announcing cuts at the end ofthis week.

Like many big pharma companies,GSK is facing the harsh reality thatseveral of its blockbuster drugs are ei-ther about to lose, or have already lost,their patent protection in Westerncountries, with the US and Europeangovernments continuing to beardown on medical costs. The an-nouncement is likely to continue thepush by GSK to reduce the workforcein the US and Europe, while continu-ing to expand in Asia.

TEVA HITS HIGH

Teva Pharmaceutical Industries Ltd,the world’s largest generic maker ofdrugs, has announced that trading hashit a 15-year high and that annual rev-enue will double to $31 billion by 2015.As the company has reduced its de-pendency on the Copaxone multiplesclerosis treatment, its biggest sellingdrug, it has seen its more profitablebranded business more than double.

The company’s growth has also beenattributed to more opportunities incountries where generics account for asmall amount of drug sales, as well asgreater government reforms empha-sizing cost savings. It hasn’t hurt that$150 billion worth of brand namedrugs will be losing their patent pro-tection in the next five years. Teva hasalso projected a net income of $6.8 bil-lion in 2010.


23INTERNATIONAL NEWS

FAKE ADVERTISING

The Ghana Medical Association(GMA) has called on stakeholders tohelp it eliminate the practice of fakedrug advertising and the reckless useof medical titles, which has character-ized the sector of late. The Associationhas pointed out that The Ministry ofHealth, Food and Drugs Board, theNational Media Commission, and theMedical and Dental Council, shouldwork together to enforce the laws reg-ulating the use of titles, and ban theunregulated ad information available.

The President of the Association, Dr.Emmanuel Adom Winful, remindedthe general public to be mindful ofsome of the false claims contained insome of the advertisements being car-ried by those claiming to be doctors.Consequently, it has reacted againstthe unnecessary doctorial titles manyGhanaians, especially herbal medicalpractitioners, have conferred onthemselves.

TOP SPOT

Sanofi-aventis, France's largest phar-maceutical company, is reportedly ontrack to secure the top spot in the dia-betes area, aiming to steal it from cur-rent leader, Danish firm NovoNordisk.

Reports have surfaced that suggestsanofi has identified diabetes as a toppriority in pharmaceuticals and hasnow established a global division tohelp the firm achieve its aim of be-coming the number one firm in thedisease.

The move comes after the firm's best-selling drug for 2009 proved to beLantus (insulin glargine), with full-year revenues reaching €3.08 billion($4.2 billion), up 22.5 percent fromthe year previous. Sales of Apidra (in-sulin glulisine) were also up 38.8 per-cent to €137 million ($188 million).

OUTSOURCING

Leading British-Swedish pharmaceu-tical company AstraZeneca has an-nounced that it is to cut 8000 jobsworldwide as it embarks on one of thebiggest shake-ups seen in the indus-try’s history.

According to analysts, the job cuts arelikely to result in the loss of 1500 jobsin the UK, where AstraZeneca has re-search and development (R&D) oper-ations in several locations. Analystshave also speculated that the pharma-ceutical giant will shed as many as3500 posts from its R&D facilitiesacross the globe as it tries to cut costs.

The reasoning behind the cuts is tosave money. The overall plan is to out-source more of AstraZeneca’s researchand development function – a divisionlargely defined as the heart of anypharmaceutical company – topharmerging markets such as China.

UPFRONT


On 12January, Haiti wasrocked by the largest earth-quake ever recorded in the area.The incident sparked a call foremergency aid across the world,and now, thanks to Novartis, thepharmaceutical industry is gettingon board too. According to reports,Novartis is, through its local organi-zations in countries throughout theregion, set to provide the equivalentof over $2.5 million in immediateemergency aid for victims of the disas-ter. Reports show that this support willinclude both direct financial aid to re-lief agencies working in Haiti, as wellas donations of essential medicines,including antibiotic and pain reliev-ing drugs.

NOVARTIS GIVES TO HAITI

Biggest threats to men’s health,according to the Mayo Clinic

TOP 10

32

54

1

87

109

6

Heart disease

Cancer

Injuries

Stroke

COPD

Type 2 diabetes

Flu

Suicide

Kidney disease

Alzheimer’s disease

UPFRONT24

ACADEMIC-INDUSTRY COLLABORATION

An international consortium of scientists, led byH. Lundbeck A/S and King’s College London, haslaunched one of the largest ever researchacademic-industry collaboration pro-jects to find new methods for thedevelopment of drugs for schizo-phrenia and depression.

‘Novel Methods leading toNew Medications in Depressionand Schizophrenia’ (NEWMEDS) isa unique project, bringing together topscientists from academic institutions with a widerange of expertise, and partnering them withnearly all major global drugs companies.

The main objective of NEWMEDS is to de-velop new models and methods to enable noveltreatments for schizophrenia and depression. The

project will focus on developing new animalmodels which use brain recording and behavioral

tests to identify innovative and effectivedrugs for schizophrenia. It will also de-

velop the hardware and analysistechniques to apply brain imag-ing, especially MRI and PETimaging, to drug development. It

will examine how new geneticfindings (duplication and deletion

or changes in genes) influence the re-sponse to various drugs and whether this in-

formation can be used to choose the right drugfor the right patient. And finally, it will try to de-velop new approaches for shorter and more effi-cient trials of new medication – trials that mayrequire fewer patients and give faster results.

The project will

techniques to applybrain imaging to drug

development

develop


Japan’s leading pharmaceutical company,Takeda, has revealed today that it has signedup Pfizer as a partner to co-promote its block-buster diabetes drug Actos in China.According to the Japanese drug maker, thepact will increase the number of medical rep-resentatives supporting the sales and market-ing of Actos (pioglitazone) in the region. Theagreement is set to expand the product’s reachby “utilising the territory coverage of Pfizer, thelargest multinational pharmaceutical compa-ny in China.” Statements on Takeda’s websiteexplain how the drug, used for the treatment oftype 2 diabetes, has been sold in China since2004 by Tianjin Takeda Pharmaceuticals, ajoint venture of Takeda PharmaceuticalCompany Limited and Tianjin LishengPharmacetical Co., Ltd., a Chinese company.

According to the International DiabetesFederation, the diabetes epidemic has the great-est potential to increase in China, because of itspopulation size, rapid urbanization and eco-nomic expansion, meaning that a wider use ofActos in China is critical to overcoming thefight against the disease. In fact, the potential toexpand the use of Actos is considerable, giventhat China is estimated to have more than 50million diabetics by 2025. The deal also high-lights Pfizer’s own strategy of expanding its op-erations in the country and comes less than amonth after it announced plans to establish anew R&D centre in Wuhan.

Oregon Freeze Dry, Inc, and its partnerEnerG2 have been selected to receive aDepartment of Energy stimulus grant of $21million to design, build and manufacture aunique carbon electrode material. The plantfunded by the DOE grant will be the first US-based large scale manufacturing operation forthese materials making up the key com-ponent in ultracapacitors for usein applications such as elec-tric vehicles. The facility isproposed for constructionon the site of OFD’s exist-ing campus.

OFD’s innovativethinking and experiencecoupled with the flexibility ofan elegant preservation processprovided the right blend of contract servicesEnerG2 needed to rapidly develop and providea proposal to the DOE. The breadth of OFD’scapabilities and experience manipulating thelyophilization or low-temperature, low-pressurepreservation process provided EnerG2 a hugeadvantage in savings from proof-of-conceptthrough to commercialization. A unique set ofintellectual property assets is required to enabledevelopment of defensible products or process

that crossover from a variety of commercial areas.Lyophilization is consitently utilized in the

development and preparation of drugs, medicaldevices and food products. This successful appli-cation of lyophilization is another example ofhow two companies took advantage of their cryoand lyo preservation knowledge to customize for-mulation to maximize the preservation of form

and functionality. Lyophilization expe-rience with materials ranging from

active pharmaceutical ingredi-ents, quick dissolve tablets, ad-vanced wound care products,stabilized platelets, vaccines anddiagnostic kits provides a foun-

dation to investigate new deliverysystem concepts.Creating or retaining high surface

area, bioavailability and solubility can be en-hanced with the appropriate expertise inlyophilization. Materials that have sensitivities toheat, shear, oxygen and shelf-instability at certaintemperatures and finished weight are candidatesfor taking advantage of this technology.

At OFD the passion is to utilize its over 45years of lyophilization application in diverse areasto find solutions and develop clients’ productsrapidly through Quality by Design (QbD).

EXPANSION INTO NEW REALMSTEAM-UP IN CHINA

New reports have warned that the pharma-ceutical industry may have to pay out morethan the $80 billion it agreed to con-tribute to President BarackObama’s health overhaul ef-forts. The news reportedly re-flects pressure from theDemocrats and their support-ers for more money, neededto cover older and low-incomeAmericans. It comes amidst re-ports that both Obama and theDemocrats are desperate to keep the drug in-dustry on-side, as a crucial ally in the health-care debate. This is largely because of thepharmaceutical industry's influence in stateswhere it is a large employer, particularly NewYork, New Jersey, Connecticut and Indiana.

PHARMA TO PAY UP

Oregon Freeze Dry, Inc., and its

partner EnerG2 havebeen selected to receive a grant of

$21

million

In fact, according to insiders, the healthpackage the House requires approximately$140 billion from drug companies to pay addi-

tional healthcare costs over the nextdecade. What’s more, officials

within the pharmaceuticalindustry have warned thatthe version of the bill theSenate is debating may al-ready pluck close to $100

billion from drug makers.However, it has also been re-

ported that proposals that wouldrequire drug makers to pay out even more

money will prove to be a real test for one ofWashington’s richest lobbies. ManyDemocrats believe the industry will profitwhen roughly 30 million uninsured Americansgain coverage for prescriptions.

UPFRONTCOMPANY NEWS 25

The House requires

approximately

from drug companiesto pay additional

healthcare costs

$140 billion


UPFRONTCOMPANY NEWS26

FAST FACT

More than

Americans stutter – about 1%of the population

3 million

RISING TAXESA new report by leading consultancyfirm PricewaterhouseCoopers (PwC)has warned that factors including chang-ing market dynamics and rapidly evolv-ing healthcare reforms are likely to pushup the effective tax rate for the pharma-ceutical and life sciences industry.

According to the study, Pharma2020: Taxing Times Ahead, rising taxrates will also be dictated by the impactof the global financial crisis and the di-minishing reliance on the blockbusterdrug model. The findings of the reportwarn that such changes in the industrywill make tax planning more complicat-ed and challenging for tax executivesworking for pharmaceutical companies.The survey is based on a poll of 35 se-nior tax executives from pharmaceuti-cal, biotech and medical devicecompanies and warns that six in 10 taxleaders agree that an increase in the ef-fective tax rate for the pharmaceuticalindustry is inevitable.

In addition to these findings, nearlytwo-thirds of respondents (63 percent)agreed that the cost of increased taxes ontheir organizations might be passed on toconsumers, unless they find ways to op-erate more efficiently and transform theirapproach to R&D and sales and market-ing. A total of 62 percent of respondentssaid they are looking to maximize taxcredits and other incentives for R&D.

The head of Almac, Sir Allen McClay, has diedaged 80. Sir McClay, who qualified as a pharmacistin 1953, established his first business, Galen, in 1968and made it one of the world’s leading pharmaceu-tical and biotech companies. When he retired asPresident of Galen Holdings, which later changedits name to Warner Chilcott, in 2001 he establisheda new company, Almac which integrated drug de-velopment services, research and manufacturing toabout 600 clients. The company quickly establisheditself as a leading pharmaceutical firm and employsthousands of people in the pharmaceuticalindustry.

ALLEN MCCLAY DIES

Nanotechnology coupled with proteomic analysesoffers the pharmaceutical industry new opportuni-ties to optimize the drug discovery and drug devel-opment process. The miniaturization of assays in thenanoscale range will improve cost effectiveness byrequiring substantially less sample for any giventechnique, improve result reproducibility and sensi-tivity due to the precision of the automation and lownonspecific binding, reduce assay time since the re-actants are confined to femto or atto liter vol-umes, and allow for important new tests thatwere previously not possible due to insuffi-cient sample material.

Dip Pen Nanolithography (DPN) isan established method of nanofabricationthat is ready to impact the biologicalsciences. Using DPN, biomaterialssuch as proteins, cell extracts orwhole cells can be depositedon to surfaces at nanometer res-olution. The resulting nanoarraysare made with far less sampleand use femtoliters of reactantsper spot compared to traditionalmicroarrays, bringing precision,cost effectiveness and high repro-ducibility to proteomics.

NANOTECHNOLGY INCREASES OPTIMIZATION

Combining DPN generated nanoarray with thelatest generation of fluorescent detection technolo-gies has resulted in the NanoDiscovery FluorescentSystem, a new approach to protein analysis and de-tection developed by the Nano BioDiscoveryDivision at NanoInk. It is compatible with high-res-olution fluorescent scanners and easily accommo-dates existing assay protocols. The uniformity of thenano features combined with the low volumes and

extremely low non-specific binding substan-tially improves the sensitivity of these assays.This ultimately permits the detection of verylow abundance biomarkers from smallamounts of biofluids or other precious clin-ical samples, as well as the detection proteinsburied deep in the proteome, with very lowor no expression profiles.

The NanoDiscovery Flu-orescent System opens thedoor for exciting opportuni-ties towards experiments thatwere previously not possible,as well as more cost- and time-efficient approaches to drugdiscovery and development.

For more information, please visitwww.nanoink.net

Sir Allen was knighted in 2005 and for aman of his wealth, was a very generous philan-thropist. He set up the McClay Foundation tounite industry and academia, which has aturnover of £167 million ($264 million). Healso personally donated £20 million ($32 mil-lion) to Queen’s University in Belfast.Ironically, for all his success in the pharmaceu-tical industry, Sir McClay often described him-self as “one of the world’s worst pharmacists.”


NANOINK AD.indd 1NANOINK AD.indd 1 9/2/10 09:16:099/2/10 09:16:09

UPFRONTCOMPANY NEWS

Researchers have discovered a gene linked to stut-tering, a speech disorder that afflicts an estimatedone million adults worldwide. Scientists believe thefinding raises hope that a drug might someday bedeveloped to treat this disabling condition.

Researchers say the speech impediment ap-pears to stem from a defect in the gene that regu-lates the way brain cells break down and recyclewaste products. This abnormality interferes withthe brain’s ability to process speech.

Stuttering causes sufferers to get stuck re-peating or prolongingsounds, sylla-bles or

words that interrupt the normal flow of speech.Experts say most children who stutter seem tomagically outgrow the disorder.

But for people who continue to stutter intoadulthood, researcher Dennis Drayna of the USNational Institute on Deafness and OtherCommunicable Disorders says stuttering can beprofoundly disabling.

“I think in some cases it is hardly evenviewed as a legitimate disorder,” said Drayna.“People dismiss it all the time when in fact it’s aclear biological disorder that has very big influ-ences on affected individuals.”

The researchers homed inon a single gene, known as

GNPTAB, which wasdefective in 46 members

of a large Pakistani fami-ly. The abnormal gene also

was found in 77 unrelatedPakistanis with the speech impediment.Source: voanews.com

STUTTERING GENE FOUND

Today, containing costs and maximizing thevalue of each development dollar is critical toassuring that the industry continues to pursuepromising new technologies and therapies.However despite our best efforts, as an indus-try the cost of discovering drugs, developingnew therapies and conducting clinicaltrials continues to soar. If a compa-ny can focus on a particularasset, such as a drug candidateat a particular phase, it will beable to more specifically definethe skills needed for develop-ment as well as how long they arerequired, and thereby more accu-rately gauge costs.

Additionally, if the exit is something otherthan developing into a fully integrated devel-opment company, it makes little business senseto hire full-time personnel. It would be difficultto predict the level of involvement needed fromthe new hires while also ensuring sufficientbandwidth to deal with inevitable challenges ofa development program. Yet many companies

make this mistake and unnecessarily hire spe-cialty expertise or bring them in too early, re-sulting in a loss of time and money.

What if this asset were paired with sever-al other assets in a similar stage of develop-ment? It is easy to see how a virtual team

could be constructed with experts whodo not require full-time employ-

ment but can be dedicated tothe firm for some period oftime. It becomes easier tomake decisions on each asset

based on data rather than tiedinto the context of a company’s

survival or long-term stability. A vir-tual team could improve program efficiencyand considerably reduce development costs.Such gains in efficiency could lead to more so-phisticated financial models with which tomanage risk across product portfolios whilehelping promising therapies reach patientsmore quickly.

For more information please visitwww.hallorancg.com

eClinical is ill-defined in today’s marketplace. Manyuse ‘eClinical’ to simply mean an electronic technolo-gy, i.e. EDC; others further differentiate eClinical tomean technology solutions working together to createintegrated process-driven solutions.

Considering this latter definition, as our clinicaltrials environment has changed, we can consider threestages in our current evolution of eClinical.

Firstly, clinical trials typically employed multipletechnologies which meant some data and functionali-ty overlapped. This led to repeated activities and datain multiple solutions, and the requirement to checkand reconcile the data contained in each. The first evo-lutionary step developed was point-to-point data inte-grations to ensure that data entered in one system wasautomatically replicated into others – eliminating dataduplication issues and redundant activities. Commonintegrations include provision of study progress datafrom EDC and RTSM (randomization and trial sup-ply management) systems to CTMS applications.

Point-to-point integrations, whist effective, arecomplex to support and deploy when there are multi-ple solutions that require connecting. Utilizing a clini-cal technology integration platform – or middlewarehub – is an evolutionary step that enables integrationsbetween multiple solutions to be implemented andsupported quickly and efficiently. This approach re-quires only a single connector between each applica-tion and the middleware hub and provides centralcontrol and visibility of all integrations in play.

We’re seeing further evolution of eClinical in re-sponse to the complexity that site and sponsor usersface when using multiple technology solutions. A studymanager, for example, must access and review reportsin multiple solutions to understand the true status andprogress of their study. A site user must log in and outof multiple solutions to perform basic workflow. Thenext adaptation is to focus on how solutions and datacan be combined to simplify their use. This can beachieved through product convergence: making func-tionality that resides in one product available throughanother. For example, enabling an EDC user to accessRTSM functionality – randomization, dispensation,pack replacement –through that product interface, re-moving the need to access multiple solutions.

eClinical will continue to evolve by making theprocess of running clinical trials simpler.

For more information, please visitwww.perceptive.com/eclinical

eCLINICAL EVOLUTION

A virtual team could improveprogram efficiencyand considerably

development costs

reduce

SEARCH FOR THE BEST DEVELOPMENT MODEL

28


PERCEPTIVE AD.indd 1PERCEPTIVE AD.indd 1 9/2/10 09:17:399/2/10 09:17:39

UPFRONTCOMPANY NEWS30

EXPANDING PRODUCT SECURITYAUTISM/AGE LINK “We know that it is a risk factorbut we can’t attribute the rise inautism to the shifting trend to-wards having children later in

life,” she says.. Oldermothers are known

to face increasedrisks for havingchildren with ge-netic disor-ders,

andgenes

are thoughtto play a role in theentire autism spec-trum.

Source: voanews.com

Autism is a complex disabilitythat affects a person’s ability tocommunicate and in-teract with others.There aremany theoriesabout whatcauses it, andthe latest hasto do with amother’s age.

Researchersfrom the University ofCalifornia looked at millions ofparents, and found that womenwho gave birth after age 40 werenearly twice as likely to have achild with autism as a womanunder 25.

But the increased risk issmall: only five percent of the in-creased risk is attributed to ma-ternal age. Researcher JanieShelton was the lead author.

Given the growing sophisticationof pharmaceutical counterfeitersand illegal diverters, it is becomingmore apparent that multi-layeredapproaches to protecting medica-tions are becoming a necessity forpharmaceutical manufacturers. Inan article titled ‘FakePharmaceuticals’ from the January4, 2010 issue of Science andTechnology, David Shore, AssistantDirector of Global Securityfor Europe at Pfizer,said, “Any new se-curity features forpackaging onlylast about 18months beforecounterfeiters canproduce mimics.”Additionally, counter-feiters are adding smallamounts of the correct active ingre-dient to their counterfeited versionsin an attempt to fool API detectionmethods. These are the extremes towhich counterfeiters and illegal di-verters will go to fool authorities,healthcare professionals, manufac-turers and patients.

These disturbing trends merit anew approach by pharmaceuticalmanufacturers to extend pharmaceu-tical security features beyond the pack-age and on to the medication itself.

NanoGuardian’sNanoEncryption technology is an

on-dose, multi-layered, brand pro-tection technology that enables man-ufacturers to authenticate and traceevery single dose. NanoGuardian'sNanoEncryption technology pos-sesses intrinsic layered security fea-tures at the overt, covert and forensiclevel and is applied directly to tablets,capsules, vial caps and prefilled sy-ringes. Since NanoEncryption tech-nology always remains with the

specific dose, even after nu-merous repackaging ef-

forts, it providesbrand integrity,protection andconfidence thattraditional, on-

package technolo-gies cannot alone

provide. Although pack-aging security features provide a

vital barrier to counterfeiters and ille-gal diverters, there is mounting evi-dence supporting the need to protectpatients, brands and companies byimplementing new strategies that in-clude on-dose security features. Byimplementing a technology likeNanoGuardian’s NanoEncryptiontechnology, manufacturers can au-thenticate and trace each and everydose from plant to patient and there-by significantly increase their defenseagainst the costly, and potentiallydeadly, consequences of counterfeitand illegally diverted medications.

Any new security feature only

lasts about

before counterfeiterscan produce

mimics

18 months

Women who gave birth after

were nearly twice aslikely to have a child

with autism

age 40

Stuttering affects

as many males as femalesfour times

FAST FACT

J&J RECALLS PRODUCTSstatement, J&J stated that someconsumers had experiencednausea, stomach pain, vomitingand diarrhea. The recall, whichwill involve calling back prod-ucts from all over the world in-cluding the United ArabEmirates and Fiji, will also in-volve the Benadryl allergy drugand St. Joseph’s Aspirin.

According to J&J’s McNeilConsumer Healthcare division,the smell is caused by the pres-ence of trace amounts of achemical called 2,4,6-tribro-moanisole (TBA), which can re-sult from the breaking down ofa chemical found in wood pal-lets and other packaging andtransport materials.

The world’s largest consumerhealthcare company, Johnson& Johnson has voluntarily re-called more than 500 productsthat are available over-the-counter, including brands suchas Tylenol, Motrin and Rolaids.The recall was issued after re-ports of an unusual odor ema-nating from the products. It issimilar to the issue that saw amass Tylenol recall last year,damaging the product’s repu-tation.

The odor has been de-scribed as an “unusual moldy,musty, or mildew-like odorthat, in a small number ofcases, was associated with tem-porary and non-serious gas-trointestinal events.” In a


NANOGUARDIAN AD.indd 1NANOGUARDIAN AD.indd 1 9/2/10 09:15:569/2/10 09:15:56

Companies in this issue are indexed to the first page of the article in which each is mentioned.3P Partners 122, 123

Accuri Cytometers, Inc. 126, 127

ACR Image Metrix 112, 113

Aerotek 8, 149

Agilent Automation Solutions 68, 69,

OBC

Ambit Biosciences IFC, 77

Amgen 40

Aventis Pasteur 70

Bio-Rad Laboratories, Inc. 82, 83

BioProcessing Inc. 45

Celgene Corporation 100

Corbett Accel Healthcare

Group 144, 145

Disney Institute 142

Eli Lilly and Company 52

EMD Chemicals 74, 75

ERT 106, 107

Eurand 10, 50, 51

European Vaccine Manufacturers 60

Finesse Solutions, LLC 66, 67

Frost & Sullivan 146

GE Healthcare 80, 81

GlaxoSmithKline 60, 92, 108

Grace 2, 116, 117

Halloran Consulting Group 15, 28

IMS Health 150

Meettheboss 76

Metastorm 136, 137

Missouri Partnership 160, IBC

Nabi Biopharmaceuticals 70

NanoGuardian 30, 31

NanoInk, Inc. 26, 27

New Jersey Economic

Development Authority 159

Norwich Clinical Research 103

Novartis 60

Novartis Pharma Technical

Operations 128

Nycomed 34, 138

Olympus America Inc. 64, 65

Onorach Clinical 104, 105

Oregon Freeze Dry, Inc 25, 33

PACE 60

Perceptive Informatics 28, 29

Pfenex Inc. 96, 97

Phase Forward 98, 99

Pilgrim Software 6

PricewaterhouseCoopers 34, 78

Quintiles 63, 114, 115

Roche 60

Ropack 134, 135

SAGE 60

Sanofi Pasteur 118

SanMed 146

SherTrack 124, 125

Shire 34

Siemens 132, 133

Singulex 90, 91

Symyx 46, 47

COMPANY INDEX Q1 2010

FAST FACT

UPFRONTCOMPANY INDEX32

Thermo Fisher

Scientific 13, 58, 59

Thermo Scientific Hyclone Products

88, 89

Transgenomic 73

Tripos International 84, 85

Umetrics 85, 87

University of Florida 141

Waters 4, 48, 49, 121

Walt Disney World Swan and

Dolphin Resort 152, 153

World Health Organization 60

Autism is the fastest-growing developmental

disability, with a

growth rate1148%


OREGON AD.indd 1OREGON AD.indd 1 9/2/10 09:17:259/2/10 09:17:25

CURING THE WORLD’S ILLS?

COVER STORY

34 www.ngpharma.com

MAin Article_emerging.indd Sec1:34MAin Article_emerging.indd Sec1:34 18/2/10 13:25:3418/2/10 13:25:34

China, India, Brazil, Mexico, Russia, Turkey, Indonesia – these are the top so-called ‘pharmerging’ markets, and they and others like them could hold the key to the future growth of the international pharmaceuti-cal industry.

Two years ago, PricewaterhouseCoopers pro-duced its ‘Pharma 2020’ report, analyzing industry trends for the next 10 years, and these seven countries

– called the E7 – play a crucial role in that vision of the future. According to the report, “Th e real GDP of the E7 countries will triple from $5.1 trillion in 2004 to $15.7 trillion in 2020, whereas that of the G7 countries will grow by just 40 percent, from $25.8 trillion to $36.1 trillion. Th eir wealth relative to that of the G7 will rise from 19.7 percent to 43.4 percent over the same period.

“In 2004, the E7 countries spent 0.94 percent of their GDP on prescription medicines (although the precise percentage varied from one state to another). Th ey collectively accounted for eight percent of the $518 billion global market.Th e G7 countries, by contrast, spent 1.31 percent of their GDP on medicines and accounted for 79 percent of all sales.

“If all 14 countries continue to spend the same proportion of their GDP on medicines as they do now (and if their GDP grows as we have projected), the global pharmaceuticals market will be worth about $800 billion in 2020, and the E7 countries will account for about 14 percent of sales.”

Simon Friend, PwC’s Global Pharmaceuticals Leader, confi rms that this view has not changed. “Th e industry has been in a watershed mode for the past few years, and to some extent is starting to work its way out of it. But there are huge pressures on it from a number of diff erent angles, and the most critical or funda-mental is, where are the new products coming from?

“Compounding the pipeline issue, you’ve got patent expiries. We predicted two years ago that $157 billion of sales would come off patent by 2015. We’re now some way into that. It’s very real and companies are struggling to work their way through it in the absence of signifi cant new products coming through.”

Th ese challenges are forcing pharma companies of all sizes to change their business models – exploring the potential of generics and how to leverage the biotech space, for example – and one of these new models, perhaps the most im-portant one, is expansion into emerging markets.

Ann Brady, Vice President of New Market Development for Shire, confi rms that her company is moving in this direction. “Th e traditional model within

With emerging markets poised to contribute more than 50 percent of the pharmaceutical industry’s growth in the next year, many companies are looking to expand their international presence. Marie Shields takes a look at what this means for the future of the industry.

www.ngpharma.com 35


36 www.ngpharma.com

pharma has been dominated by Western developed markets, treating Western diseases. In recent years we’ve seen a trend for big pharma, as they have come under pressure with regard to patent expiries and a lack of pipeline, to move commercialization activities beyond the developed markets.”

Shire is a specialty biopharmaceutical company focused on help-ing people with serious diseases, wherever they are in the world. Brady continues: “Th e world is becoming more connected and as an industry, we do need to look at global development, and specifi cally for Shire, that’s where we are directing our business. We’re looking beyond just what will service the developed Western market.”

Dealing with diversityIt’s one thing to say you’re moving into emerging markets, and quite

another to deal with the practicalities involved. Th e seven countries that make up the top of the emerging market list are obviously vastly dif-ferent from each other in terms of geography, population, culture and political situation. Th ere is no such thing as a generic ‘emerging markets policy’ – each country requires its own specifi c plan, which brings with it its own challenges.

How then, does a company choose which new market to invest in? As Nycomed’s Jostein Davidsen points out, the top 10 companies will most likely invest in all of them, while for mid-sized and smaller com-

panies, it’s oft en a matter of history. “It has to do with the his-tory of the diff erent companies, the history of Nycomed being, for

example, active in the Soviet Union for 20 years. We had a footprint there from an early stage and we automatically built on that.

“When it comes to countries like Turkey or Mexico, if you were not there in the early days, maybe you’re reluctant to go in later. It will cost much more, of course, and in some of these markets you may well have to go in and acquire local companies, only by that time there is not much left to acquire, so it is much more diffi cult.”

As General Director for Nycomed Russia-CIS and Senior Vice President, Nycomed, Davidsen has been involved with the company’s operations in the country since the Soviet days, and has seen the region rise to play a key role in Nycomed’s growth strategy; so much so that the current aim is to have Russia-CIS represent 38 percent of the company’s growth in 2013.

Th at doesn’t mean there won’t be challenges along the way, as Da-vidsen explains: “Entry costs are high, although there is relatively less expense on the registration of products and on clinical trials. But offi ce premises are much more expensive here than in other parts of Europe, and the cost of media campaigns and TV campaigns for over-the-coun-ter products has risen dramatically. And then are unforeseen events that can have a negative impact.”

Unforeseen events are indeed a potential downside of moving into any new market, but particularly so in markets where the political situ-

Jostein Davidsen is General Director for Nycomed Russia-CIS and Senior Vice President, Nycomed.

Ann Brady is Vice President of New Market Development for Shire.

Mark Rothera is Vice President for Europe, the Middle East and Africa for Shire’s Human Genetics Therapy business.

Mazen Darwazah is Vice Chairman of Hikma Pharmaceuticals.

Simon Friend is Global Pharmaceuticals Leader, PricewaterhouseCoopers.TTHHEE PPAANNEEELLLLLLLLLLL


www.ngpharma.com 37

being designed for the future, away from the traditional model of going out to the physicians and leaving samples.

“Th e infl uence of physicians has declined, because the buying pro-cess is becoming increasingly binary. You need to get to the payer and get behind the payer’s mindset and understand what the payer’s eco-nomics are. And that applies equally in the emerging and the developed world; you need to know who are the real infl uences and what sort of sales forces you need in the future.

“One of the interesting things for domestic companies in countries like India, China, Brazil and Central Eastern Europe is that the best thing they can do is not to follow the western model. If the view is that the western model is broken, why would you try to replicate it?”

Looking for advantagesGiven the number and nature of the challenges involved, you may

wonder why companies would bother moving into emerging markets at all. Th e benefi ts do, however, outweigh the challenges. “Th ose markets are becoming increasingly attractive in a number of diff erent ways,”

ation or other factors may be unfamiliar to the investing company. As Mazen Darwazah, Vice Chairman of Hikma Pharmaceuticals, puts it: “You need to understand the local culture. Oft en, when you’re a multinational company, you think globally and you act globally. Work-ing in this part of the world you have to think globally and act locally.

“You have to understand the barriers of entry. You have to understand the perception that the healthcare community has in a par-ticular country, so you have to work with them on the basis that these are local requirements in terms of dosage forms, pricing and delivery of goods.

“You also cannot work in a country, and then when there’s a crisis or a civil war, leave

that market. Th is is what happened for example in Algeria, when there was a civil

war and all of the multinationals left . You cannot go into a market in the good times

and leave when there’s a crisis. You have to stay in a long-term partnership.”

Hikma started out as a Jordanian com-pany 32 years ago, so its perspective is a little diff erent from that of European or US-based companies. Having concentrated on the imme-diate surrounding markets of Lebanon, Syria, Iraq and Saudi Arabia for its fi rst 10 years, the company then expanded into other parts of the Middle East and further afi eld, and has a pres-ence today in 42 countries in 18 markets.

Th is history of moving from an emerging market outward rather than the other way around has given Hikma an interesting insight into the complexities of doing business in diff er-ent parts of the world, as Darwazah explains: “Egypt, for example, is a $2.2 billion market, while Bahrain is a $40 or $50 million market. To make a fi le for registration for a product takes the same time in terms of preparation for both countries. You cannot say, ‘I want one fi le for all the Arab countries.’ It’s an accumulation of the registrations and an ac-cumulation of the time that you spend in countries where you get your market share and you gain your footprint in those markets.”

PwC’s Simon Friend points out that this tremendous variation is not something that is unique to emerging markets: “Th e reality is that this is also the case in developed parts of the world: the US market is very, very diff erent from the markets in Europe, for example. It may be changing in the US at the moment, where you will end up with a much greater percentage of the industry being funded by government, but right now US healthcare is still largely private, whereas in the UK and other economies, it is very heavily a government-funded market.

“Th e other thing to bear in mind is, who is actually buying? Th at is transforming the way in which the sales and marketing functions are


38 www.ngpharma.com

frastructure improvements that may help to draw the big international companies in: “Th e domestic companies are building and growing and establishing themselves in the larger world. Th ey’re no longer small off -

shoots. Th ey’re starting to become well-established companies with well-established products that are competing against others in

the more developed environment.“Th e infrastructure that is starting to be put in place

to support domestic companies provides great support for the Western companies to come in behind and have a more security around what is happening. For example, in India where they put in new IP legislation in 2007 or

2008, the issue there around policing it is still exists. Does that mean you wouldn’t go there? I don’t think it does.

What we’re seeing with many companies building a pres-ence there, is that you just have to go in with your eyes open. “In China, we know that from a counterfeit perspective, the

authorities are working hard and have identifi ed the pharmaceutical industry as one where they need to ensure that the IP is protected. Th ey are taking steps in the right direction.”

Th ese potential pitfalls will not be enough to stop the industry’s major and niche-market players from making the move overseas. Shire, for one, has set itself a goal that will be driven by expansion into non-traditional markets: it aims to be the most valuable specialty bio-pharmaceutical company in the world by 2015. “An important part of achieving that goal is the diversifi cation of our revenues across a bigger

geography globally,” underlines Mark Ro-thera, Vice President for Europe, the Middle East and Africa for Shire’s Human Genetics Th erapy business. “Th is means not just the revenues that we’re generating, but the qual-ity of those revenues and the sustainability of them that will build value.”

“We have a broad ‘rest of world’ defi ni-tion,” adds Shire’s Ann Brady. “Today our rev-enue base is very heavily weighted to the US, and we need to diversify that. We need to look in geographies beyond the US, Canada and the major European markets. Our defi nition is ex-tremely broad in that it encompasses Central and Eastern Europe, Latin America and Asia Pacifi c. So we have a huge opportunity to in-crease our presence in many of the developed markets within this ROW defi nition.

“In addition, the traditional emerging markets are a signifi cant component of our ROW activity. As a business, we will be tar-geted in our expansion here. We’re not saying we’re going to every one of these markets, and nor are we saying that we are going to invest directly in these markets. We need to target our rollout into new geographies on the basis of our portfolio and how we may best optimize value for our global business.”

says Friend. “Emerging markets are playing a pivotal role in how estab-lished companies will move forward and in their growth potential for the future. Part of that is in terms of where the money sits, and if there is a growing purchasing power in some of these emerging markets there in itself lies a market potential. Th at’s why companies are looking to build their footprints in those marketplaces, where the demand for branded drugs will start to increase in the same way that it has done in the developed world.

“Equally, there are other signifi cant opportunities in emerging markets from an industry perspective – whether it is around the further development of new products, or establishing manufacturing, R&D or other facili-ties. Th ese environments are increasingly attractive because of the skill sets that exist there, and the speed at which they can accelerate and get to market.

“Th ere are still concerns about the infrastructures in place, about the IP considerations and about the ability to properly establish compli-ance and regulatory standards in these areas, which will require proper monitoring and resources to ensure that companies are not exposing

themselves to undue risk.”Friend cites the rise of homegrown companies in

these markets as the force behind regulatory and in-

Opportunities for orphan diseases

Mark Rothera, Vice President and General Manager for Europe, Middle East, and Africa for Shire Human

Genetic Therapies, explains how specialized therapies are making inroads into new markets.

The division that I’m in is specifi cally focused on very rare diseases, and we’re very much involved with products that benefi t from the the orphan

drug legislation, where you’re looking to bring products to market for a very small patient population as compared to some of the broader specialty products.

In this context, it’s interesting to look at the Europe and Middle East and Africa arena, because of the enlarged European Union with 27 markets, and the fact that there is this umbrella intention related to the orphan drug legislation. Countries in the Central and Eastern European regions that are now part of the EU are looking to adopt some of the practices that Western European countries have had in place for a while. This includes the implementation of rare disease plans for those countries, and the opportunity is for patients with these rare diseases to have access to premium-priced but very innovative and very targeted products for these conditions.

Places like Poland and the Czech Republic and others within Central and Eastern Europe are playing an increasingly important role. We’re also opening up in Turkey and we have an offi ce in Russia. These are countries where it is also possible to bring in premium-priced products for very rare disorders, where the health authorizes are willing to entertain that for a small patient population set.

Th e global pharmaceuticals

market will be worth about $800

billion in 2020


www.ngpharma.com 39

tive earnings potential of emerging areas, will drive further investment into these new markets. Aft er all, according to the forecast by PwC’s ‘Pharma 2020’ report, in 10 years’ time, the E7 emerging economies will account for 20 percent of sales in the $1.3 trillion pharmaceutical market. Any company worth its salt won’t be able to sit back and let that opportunity slide away. n

Nycomed’s Davidsen also foresees emerging markets playing a big role in his company’s future. “In terms of Russia-CIS, we have a tough year behind us in 2009,” he explains. “Russia was very negatively af-fected by the global fi nancial crisis – GDP was minus nine percent. It is expected that this year we will achieve a GDP of between one and three percent. Th e oil price is helping here, and, of course, any industry in Russia is very much dependent on macroeconomic elements; much more than in any other Western country. Many things are oil-price de-pendent, which is now looking much more stable.

“Th e prediction for the Russian pharma market is that we will have slight growth this year. Th e challenging factors for this market are the state regulations and the new laws related to medicine and the price regulations that are in the later draft stages, about to be accepted and decided in the national assembly and signed off by the president. We don’t know exactly what the impact of these regulations will be, but again it is a major move toward a more regulated marketplace.

“Nycomed is also strong in some Latin American and South Ameri-can countries like Brazil, Argentina, Mexico and Venezuela. We are also looking at China, and attempting to get a better foothold in India and in Asia, although for the near future, Russia-CIS and Latin America will play the most dominant role.”

Despite the challenges involved, it seems clear that increased pres-sures on pharmaceutical companies at home, combined with the attrac-

E7 countries

The seven major emerging economies as defi ned by PricewaterhouseCoopers, with their predicted economies in 2050 (US$)

People’s Republic of China: - 70,710,000,000,000India: - 37,668,000,000,000Brazil: - 11,366,000,000,000Mexico: - 9,340,000,000,000Russia: - 8,580,000,000,000Indonesia: - 7,010,000,000,000Turkey: - 3,943,000,000,000

Europe vs the USDo European companies have an advantage over their US counterparts when it comes to seeking out new markets?

Mazen Darwazah, Vice Chairman of Hikma Pharmaceuticals:European companies sometimes are more fl exible in terms of their size. The MENA market, for example, represents only two percent of the dollar value of the fi nal market worldwide, and it’s divided into 18 different countries, so it’s very fragmented.

If you’re a very big company and you want to go into this market, you have to decide whether it’s worthwhile investing and putting in all that infrastructure. European companies tend to be smaller and they know how to work in small markets, where big companies may work better in bigger markets.

This’s why we’ve seen more European companies in this part of the world than American companies. That’s the basic difference, and because the US market is currently 40 percent of the dollar value of the world market, why should they spend time on a two percent dollar market when they have a bigger market in their own backyard?

Jostein Davidsen, General Director for Nycomed Russia-CIS and Senior Vice President, NycomedIt’s diffi cult to say. Historically, when it comes to Russia-CIS, in Soviet times there were no American companies active here at

all. There were mostly European companies: German, French, Italian. European companies still have perhaps a closeness to this emerging market.

Today, of course, all the big US companies are here and they have had good business development over the years. But I think that in the Russia-CIS marketplace, the European companies have an advantage in being a frontrunner because of that history.

Simon Friend, Global Pharmaceuticals Leader, PricewaterhouseCoopersI don’t think one can draw any particular conclusion that a US-headquartered company is at a disadvantage from a European-headquartered company, because they’re all pretty global in outlook and approach and have footprints all over the place.

If you’re moving into a new market and you’re leveraging relationships there, the more fundamental issue is, do you trust the people you’re working with? You only need to get burned once or twice before you think, ‘I’m not going to go there. I’ll go somewhere else.’ The more an environment becomes developed and the more experience a company has in building trust there, chances are that if that trust is built, it will go back.


40 www.ngpharma.com

THE BIG INTERVIEW

When gets

going the

tough

Miletich ED_4August 18/02/2010 13:29 Page 40

oe Miletich is clearly a man who loves his job. His enthusiasm shinesthrough as he talks about his current responsibilities as Senior VicePresident for Research and Development at Amgen, and also whenhe talks about his past positions. Miletich certainly boasts a variedcareer background: after completing an MD and a PhD in molecu-

lar biology at Washington University, he trained in internal medicine at theUniversity of California, San Francisco, then went back to WashingtonUniversity where he was a faculty member for 18 years.

In 1999 he moved into the pharmaceutical industry, taking a position atMerck in the toxicology group before heading up the company’s worldwidepre-clinical development. Miletich joined Amgen in 2002, and for the firstfour years was responsible for discovery research all the way through thefirst introduction of medicines into people. Since 2006 he has focused ontranslational medicine. To top it all off, he is also a board-certified clini-cal pathologist.

This wealth of experience should come in handy as he shepherdsAmgen’s R&D through what are shaping up to be some turbulent yearsfor the industry. Like most top 20 pharma companies, Amgen rode thewave of blockbuster success in the late 1990s and early 2000s, but nowfinds itself staring at the twin threat of patent expiries and a lack of bigearners coming out of the drug pipeline. Amgen’s answer is to “reignite”its innovation engine. But what does this actually mean?

In its broadest sense, any change can be labeled as innovation. AsMiletich points out, you’re not going to get very far by doing things thesame way they’ve always been done. In this way, innovation is essential toa company’s survival.

His definition of the term ‘innovation’ as it is used in the current con-text of drug discovery means not just bringing in change but bringing inchange at a very significant level: changing the practice of medicine andchanging what people understand and believe about what can be done indisease conditions.

“That’s the highest level of innovation when you’re in the drug dis-covery and development business,” says Miletich. “You want to changethe way people think about a disease and make things possible thatweren’t possible before.

“I think society truly wants our industry to focus on the highestlevel of innovation, but in our current climate there are a couple of

Joe Miletich tells NGP why it’s more important than ever for pharmaceuticalR&D to pursue the highest levels of innovation.

J

This is an unusual time tobe in the pharmaceutical

industry: our fears and concernsare at a peak at the same time thatour hopes and aspirationsare also at a peak

Joe Miletich

things that are acting against that larger goal. The first is a fear of beingreckless and having an insufficient regard to safety; and the second is a con-cern about how we are going to pay for it, because it’s very costly to be thisinnovative.

“The only reason people might be reluctant to be highly innovativenow is because of a worry that we’re at a temporary phase where the con-cerns about safety and reimbursement have become so prominent in ourthinking that what we would normally expect as rewards for innovationmight not be there.”

Against the oddsMiletich believes it is more important than ever to be innovative in the

current climate. He underlines the obvious fact that discovering and devel-oping drugs is a long-cycle business: the time from an original idea until adrug reaches the market might be 12 or 15 years. Companies work constant-ly to reduce that time, yet at the same time ever more stringent safety and effi-cacy requirements act to increase it.

He remains optimistic, however, that the need for innovation will winout in the end. “In the long term,” he says, “what we fundamentally need as asociety and human beings will prevail and the truly innovative things will berewarded. When you think about this as a long-cycle business, as a companywe need to pay attention to that and bet heavily on it.

www.ngpharma.com 41


translate that original idea. You also have to understand how to make a mol-ecule at large scale, how to formulate it and what the attributes are that willbecome important in human biology, and how you would recognize if youneeded to change something.

“You have to incorporate all you learned from your pharmacokineticsand drug metabolism studies to know and appreciate the characteristics of

those molecules and how they behave, and you certainly have to un-derstand all of your toxicology assessments so that you can

clearly make a weighted judgment about what risk you willexpose patients to and become very convincing and fluent

and provide appropriate scientific evidence about thesafety factor that you’re employing when you embark onthose experiments.

“Even more than all of that, when you integrateyour learning from all of these different sciences that go

into what molecule you want to make and how it performs,as well as what actually happens when you do this in biology,

you can learn a great deal more. You can learn a great deal abouthow things work in the human body.”

Miletich and his team work to integrate the different sciences needed tomove a candidate molecule forward and develop it with the optimal proper-ties for a potential human therapeutic, in order to learn as much as they canabout what goes on in human biology and to carry out the most informativeexperiments. They then use that information to make judgments about how

“That doesn’t mean we won’t do anything that isn’t the most highly in-novative thing we can think of. There are very practical benefits to being in-novative on a less expansive scale, and we do make improvements tomedicines. We’ve done this in the past, and we’ll continue to do so where itbrings benefit.

“It’s all in how you weight your portfolio. We weight our portfolio so thatroughly two-thirds of what we’re doing are highly innovative things.It’s a conscious choice. We make the choice to do that and thenset ourselves up so that we can find people in our own re-search labs and in all the connections we make with smallcompanies and with academic collaborators around theworld – find those innovative insights that will helpchange the practice of medicine.”

A major focus of Miletich’s role at Amgen is to over-see the translation of drugs from discovery through earlystage clinical trials. He points out that at Amgen, transla-tional medicine is not limited to early clinical trials and bio-marker research.

“Of course we have a terrific medical sciences group that places an enor-mous emphasis on biomarkers and we concentrate on our experiments inpeople to discover whether that fundamental idea that we started with backin the research labs actually does have enough impact in human biology to letus change the practice of medicine.

“But that’s not the only thing that’s important when you’re trying to

42 www.ngpharma.com

MORE THAN17

MILLIONPATIENTS HAVE

RECIEVED AN AMGENMEDICINE


what your likelihood of success is, and about what your potential for doinggood in how many people might be. My firm belief is that you should adjustyour investment to those opportunities as you see them in real time.

“You don’t just set up a drug discovery and development organizationand turn a crank. You learn how to turn the cranks very efficiently where it’simportant, but you continuously review your portfolio and continuouslymonitor what the opportunity actually looks like relative to your original ideaand adjust your investments accordingly.”

Miletich says that when this is done well and a good stable of candidatesis selected at the very beginning, a fraction of these emerge quite early as hav-ing very promising characteristics. These can then be invested in heavily andpushed aggressively and quickly, thanks to the conviction that this drugshould be developed and made available as fast as possible.

“With some, another fraction, you find the idea simply wasn’t goodenough or your molecule wasn’t good enough, and when you find that earlyyou can stop that investment, rethink what you want to do, and see if there’san adjustment you can make. Then there’s a group in the middle, which canencompass 40-50 percent of the molecules, where you discover that there’ssomething else that you need to understand before you can gage the value ofthe opportunity. For these candidates, you adjust and modify your investmentand decide what that next piece of information is to allow you to make a de-cision about whether it’s worth investing in or not.

“You have to manage this portfolio in a very dynamic way. When you dothat, you’ll increase your overall success rate, and you’ll increase the efficien-

to weight the portfolio and where to make the investments that are the mostlikely to pay off with the greatest benefit to people.

Forging aheadProducing breakthrough drugs that radically change the way we look at

disease might be every R&D team’s dream, but what about the challenges inbringing that drug to market? Only about one in every 10 drug candidates thatenter clinical trials are eventually approved by the FDA, and the cost of allthese failed drugs is another major challenge for the industry. How can phar-ma companies raise their success rates and cut down the amount of moneyspent conducting trials for drugs that never come to market?

“Companies may understandably try to reduce drug discovery and de-velopment to a methodology that can be repeated for project after project,”Miletich says. “There is great efficiency in doing that so you don’t relearn howto do things, and we do that when it is appropriate as well and have no qualmsabout it. Where things are repetitive and we can learn to do them in a repeat-able, efficient fashion, we do that at every opportunity.

“Every one of these innovative projects, however, is a new adventure. It’sa pioneering discovery, and in order to optimize how much you can do withthe resources you have you need to make decisions all along the way aboutwhat your level of investment is going to be.

“That means that when you integrate all this information that’s comingin in real time as you’re in this early stage of drug development, you shouldhave a sense, if you’re paying attention to all the information you have, about

www.ngpharma.com 43


cy of the resource base you use. I’m optimistic that in another five or six yearswe will be able to point back and say it did result in an improved success rate.”

Although Miletich makes this process sound quite straightforward, in re-ality it is anything but. He explains that for a typical project at this stage therecan be as many as 1000 different work streams. Histeam could be working on 30, 40, or 50 differentprojects and many of those work streams are inter-connected, so that one that’s about to begin dependson the results from another one that has just beencompleted. This makes managing this resource basein real time an incredibly complex project manage-ment task.

On targetThe use of biomarkers is often touted as an es-

sential weapon in this struggle to cut waste by en-suring more drugs hit their targets, but Miletich isquick to point out that biomarkers are not magicbullets. “Biomarkers are just tools,” he says. “Theyallow you to gage whether you’re doing what youwanted to do and whether it’s as impactful as youwanted it to be.

“Sometimes when people talk about biomark-ers, they make it sound as though they can solve allour problems, and that it’s the biomarkers them-selves that are important. But in fact the importantthing is deciding what you want to do, what youridea is, whether it works and whether it is impact-ful. Biomarkers help you determine whether you’redoing that or not, and you have to have a full toolsetof biomarkers to do that.

“One of the things that might not be evident topeople who aren’t familiar with the business is thatwhile in human medicine we have a large numberof tests that are available through physicians andhospitals and we have a lot of imaging tools, thosetools, assays and tests were developed for very spe-cific purposes and often don’t answer the questionswe’re asking now.

“So we have to set up new assays, new tools, new tests, and we have to un-derstand how they perform in populations of people. All that work has to startvery early on because it can take years to set up. Our goal is to always havethose tests and assays in place by the time we are ready to do that experimentin people.”

All of this hard work has resulted in some interesting drug candidatesmoving through Amgen’s pipeline, including an osteoporosis drug known asAMG-785, which is now in phase II trials and about which Miletich is veryexcited. “We’re investigating AMG-785 along with our partner UCB, to findout what dose and schedule of this new therapeutic will enable us to restore agood level of baseline bone health to women with moderate to severe osteo-porosis, and we’re also studying it in a phase II trial where we’re looking atvery hard-to-heal fractures. In particular, we’re looking at fractures that hap-pen in the tibial plateau, the top of the lower leg bone.

“Fractures there can often be problematic, not healing adequately or tak-ing too long to heal. We’re investigating AMG-785 to see if we can improvethe speed or quality of healing in that setting.”

Amgen has a large number of therapeutic candidates in phase II trials inoncology, as well as a portfolio of molecules beingstudied in a variety of inflammatory and autoim-mune diseases, including an extensive program ofmolecules in asthma. The company recently licenseda molecule from Cytokinetics and is studying pa-tients with severe congestive heart failure to improveheart function.

“We’ve also recently introduced an antibodycalled AMG-145, which helps us lower cholesterollevels in patients that can’t otherwise reach target,”Miletich says. “We’re in phase I studies with thatmolecule. So we’re making some meaningful ven-tures into the cardiovascular arena, again where we’reusing mechanisms that have never been explored inhuman biology, to do things in ways that were neverpossible. We continue to have new efforts in dia-betes, such as the deal we concluded in Decemberwith Array BioPharma to license their glucokinaseactivator, which is a very promising molecule that, ifit is successful, will allow treatment of diabetes in anew and meaningful way.”

When asked how he sees pharmaceutical R&Ddeveloping over the next couple of years, Miletichsmiles, and calls it an intriguing question. “In onesense if you take the pulse of the industry, there arepressures there that are unprecedented: concernsaround safety, around reimbursement, around theproductivity of the industry as a whole.

“At the same time, from someone in my positionthe prospect of doing important things for patientswho suffer from grievous illnesses has never, everbeen better, and it feels like a very unusual time to bein the pharmaceutical industry: our fears and con-cerns are at a peak at the same time that our hopesand aspirations are also at a peak, and no one knows

how this will play out.“If you look at previous examples of how humankind has reacted in other

situations that are even remotely parallel to this, I would say that there will betremendous advances, and there will be some things that we can’t predict thatwill take place in ways we can’t foresee. My guess is that some time over thenext 10 years we might see some consolidation in the industry, but we’ll alsosee some winning scenarios emerge out of the next four or five years of effort.Those companies that are nimble and can adapt and that aren’t afraid of theopportunities will manage to be highly successful even though there are greatconcerns about the pressures on the industry at the moment.

“I hope, and will work diligently with all of my colleagues here at Amgento ensure, that we are one of those companies that emerges with the successrate that’s necessary to move on to even greater things.” n

44 www.ngpharma.com

Happy anniversary In 2010 Amgen celebrates its 30thanniversary, having beenestablished as a corporation onApril 8, 1980. Since then, thecompany has grown to become oneof the world’s leading independentbiotechnology companies.

• More than 17 million patientshave received an Amgenmedicine

• The company has a presence innearly 50 countries

• Its focus is on discovering,developing and making humantherapeutics

• It specializes in innovativemedicines for serious illness andis a pioneer in proteintherapeutic manufacturing

Joseph Miletich is Amgen’s Senior Vice President for Research and Development.


BIOPROCESSING AD.indd 1BIOPROCESSING AD.indd 1 9/2/10 09:09:169/2/10 09:09:16

46 www.ngpharma.com

Life scientists and lab managers are increas-ingly embracing electronic lab notebooks (ELNs) for many reasons. First and fore-most, today’s highly confi gurable ELN supports the diverse needs of the many

life science disciplines that must collaborate to bring small molecule drugs and biologicals to market, and the right ELN does this without requiring expensive customization. Th e ELN has proven itself vastly supe-rior to the paper notebook as a truly eff ective tool for se-curely documenting the design, execution, analysis and reporting of experimental information in the context of researchers’ workfl ows. Furthermore, centrally acces-sible and searchable notebook repositories enable life scientists to share information and improve experiment design by taking advantage of their colleagues’ insights. Today’s ELN consolidates experimental data, reduces errors, enhances workfl ow productivity by driving consistent processes, simplifi es regulatory compliance, protects intellectual property (IP) and drives collabora-tion within and across labs.

In a time of shrinking budgets and constrained resources, the ELN is helping life sciences R&D groups of all sizes do more with less. Scientists with whom we are working claim a 20 percent increase in productivity is through effi ciency gains in experiment setup, calculations, planning and documentation, along with the ability to fi nd information instantly and ‘clone’ previous experiments. Most importantly, deploying a single ELN across many disciplines – and the entire R&D spectrum – improves R&D productivity by letting all scientists collaborate in an orchestrated workfl ow process. Given the shift ing priorities within today’s R&D en-vironment, a rapidly deployable, highly confi gurable ELN also provides the operational fl exibility to start new projects, defi ne new processes and transfer resources rapidly and easily.

Deployment and collaborationR&D organizations have traditionally relied on a conventional

license-based soft ware model for acquiring ELN applications, but today’s economic and competitive pressures are leading many organizations to consider a new model in which the ELN is hosted off site and accessed as a subscription-based service online. Under this model, all that scientists need is an internet connection and a password to gain instant access to a shared ELN that is fully supported and maintained by the supplier.

Th e hosted ELN is a great option for small and mid-size life sci-ences labs, biotechnology companies and academic project teams. Th ey do not have to purchase expensive soft ware licenses or manage exten-sive server banks with security, redundancy, data backup and main-tenance. Th ey also do not have to support resource-draining system administration teams and the change control documentation required by system auditors.

Th e research expenditures required to carry out specialized test-ing in today’s market are burdensome. As a result, to reduce costs and

shorten the path to more robust, promising pipelines, life science teams of all sizes are partnering with outside organizations that off er specialized expertise. In essence, this move to collaborative outsourcing is enabling labs to do more with others.

Th e hosted ELN is especially valuable in sup-porting transparent partner engagements. When a partner performing initial screening or animal studies for an R&D lab returns its results in a shared, hosted ELN environment, the R&D lab doesn’t just receive a spreadsheet of data. Th e lab also accesses the protocol, methodology, sample preparation and other related in-formation used by the partner, thereby gaining a much broader and deeper view into the overall context of the outsourced project. By linking into a shared, hosted informatics environment, multi-disciplinary virtual teams can quickly and easily access the same informa-tion, use the same methodologies and work together more eff ectively.

For further discussion, please see our longer online article on today’s fl exible ELN for multidisciplinary life science teams at www.ngpharma.com For more information about the company visit, www.symyx.com

INDUSTRYINSIGHT

John McCarthy is VP Product Management Strategy with Symyx’s software business unit. Symyx electronic laboratory notebook, decision support, scientifi c database and hosted informatics offerings give researchers immediate access to critical workfl ow applications and information. Symyx powers R&D laboratories with information that generates insight, enhances collaboration and drives productivity.

A hosted electronic notebook for life scientistsHow an online hosted ELN helps scientists do more with less in the lab. By John McCarthy

Symyx.indd 46Symyx.indd 46 18/2/10 14:08:0318/2/10 14:08:03

SYMYX AD.indd 1SYMYX AD.indd 1 9/2/10 09:20:199/2/10 09:20:19

48 www.ngpharma.com

analysis on the manufacturing fl oor with the PATROL UPLC System. PATROL UPLC is the fi rst and only real-time LC system specifi cally designed for this environment.

How can PATROL UPLC technology address manufacturing business pressures? CD. In the current Six Sigma environment of manufacturing, facilities are constantly searching for process improvements to drive overall effi ciencies and productivity. Because of the throughput challenges that LC presents as described above, as well as resource and cost issues, the technique is not usually considered an appropriate candidate for manufacturing fl oor deployment. Realizing these limitations but desiring the many analytical benefi ts of LC, the PATROL UPLC System began as a col-laborative eff ort between Waters and a major pharmaceutical company to deliver real-time speed, sensitivity, specifi city and accuracy to the manufacturing fl oor, with a focus on making it reliable and rugged with a simpli-fi ed operator interface appropriate for the environment. Th e fl exibility and automation engineered into the system was implemented to address existing SOPs, provide a continuum of real-time UPLC technologies across the entire drug development cycle, and convert a once considerable manufacturing bottleneck into a competitive advantage. n

For more information on the PATROL UPLC System, visit www.waters.com/patrol

laboratory to monitor reaction progress, or to specifi cally measure individual parameters like IPM purity or concentration. During a single in-process LC analysis, a remarkable breadth of information can be extracted: raw material consumption, IPM purity, IPM concentration, even the presence of low-level or trace concen-trations of impurities can be measured and quantitated down to 0.01 percent. If a trace compound negatively impacts a critical quality attribute of the IPM, LC is the ideal technology for monitoring its presence. Leveraging all of this information is critical to understanding where your process is relative to the defi ned design space within a QbD strategy.

Are there limitations in applying traditional LC as a PAT tool? CD. What generally keeps traditional LC from being adopted directly onto the manufacturing fl oor is that it simply takes too long to generate a result. LC may produce data with unrivaled breadth, specifi city, sensitivity and accuracy – but off -line QC Lab sample-to-answer times are typically in excess of four to six hours. Th at reality is rapidly changing. With new at-line and on-line analytical LC tools, manufactur-

ers can make a measurement, generate infor-mation and make a decision in real-time or in less than fi ve minutes. Real-time LC capability was realized in 2004 when Waters Corporation introduced UltraPerformance LC, or UPLC technology. Th e ACQUITY UPLC System was the market’s fi rst real-time LC, followed by ACQUITY UPLC H-Class System for easy LC to UPLC migration in discovery and develop-ment labs. UPLC technology now extends to automated direct on-line and at-line IPM

Of all of the analytical techniques that are currently applied as process analytical tech-nology (PAT) tools in solid-dosage manu-facturing, why is liquid chromatography of particular importance in drug develop-ment? Craig Dobbs. Several analytical techniques can be used in PAT – liquid chromatography, mass spectrometry, near infrared spectros-copy and Raman spectroscopy to name a few. Th roughout a therapeutic compound’s lifecycle, liquid chromatography (LC) is the only advanced analytical technology that is routinely used in every phase of the process: in discovery, research, development, manu-facturing, qc/release and post shipment sta-bility monitoring. Th e amount of meaningful information produced by LC systems during this process is nothing less than a gold mine of data. It is imperative that such LC analytical data is secured, easily archived and searchable, can be quickly cross-referenced and overlayed, and is instantaneously available to support decision-making processes. Th e concept of a long-term, historical database focused specifi -cally on full characterization of a therapeutic molecule is at the central core of the USFDA’s

Quality by Design Initiative (QbD). LC is the single analytical technique that supports QbD by consistently producing the same type of easily referenced and interpreted data from anywhere in a drug product’s lifecycle.

Th e manufacture of an active pharma-ceutical ingredient is invariably a solution phase based process, which is the ideal sample matrix for LC analysis. Analytical LC testing of inprocess material (IPM) is routinely per-formed today in an off -line manufacturing QC

Real-time data for manufacturingCraig Dobbs describes defi nitive technologies for PAT and QbD initiatives.

EXECUTIVEINTERVIEW

As a Senior Manager for both Biopharmaceutical Business and Process Analytics at Waters, Craig Dobbs partners with industry experts to develop technology solutions that address process analytical needs in manufacturing, as well as in the development of biotherapies.

“In the current Six Sigma environment of manufacturing, facilities are constantly

searching for process improvements to drive overall effi ciencies and productivity”

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Despite increasing similarities to the devel-oped world, emerging markets present their own unique challenges. What other consid-erations must companies make before plan-ning to enter an emerging market?AT. Review of emerging markets is a very dynamic process, and perceptions and direc-tion can oft en change. Companies seeking to succeed in these markets must be armed with substantial information, prepared to create local partnerships for the long term, and will-ing to be fl exible and creative in their planning.

Eurand’s experience has led to the develop-ment of an intensive process for assessing each market, working closely with local partners to leverage their understanding of market dynamics. Key factors in this process include assessment of the region’s healthcare system, trading environment and taxation issues; the local competitive landscape, therapeutic class analyses; as well as a review of regulatory, pricing and reimbursement practices. With the right information, the right products and the right partners, companies that make the investment now can successfully tap into the great potential of emerging markets. n

As economic, demographic and social changes sweep through the developing world, pharmaceutical companies are look-ing beyond the leading industrial nations (the ‘G7’) to the growing potential of emerg-ing markets. What is the potential for phar-maceutical products in emerging markets?Andrew Thompson. PriceWaterhouseCoopers estimates that the GDP of the ‘E7’ – the seven major emerging countries that include Brazil, China, India, Indonesia, Mexico, Russia and Turkey – will triple over the next decade, and by 2020 could account for close to 14 percent of a projected global pharmaceutical market of $800 billion. Further, disease profi les in emerging markets are evolving to more closely resemble those of developed countries, shift ing from infectious disease control to management of more chronic conditions such as cancer, diabetes and respiratory and cardiovascu-lar disease. According to the World Health Organization, in the US only 12 percent of deaths from cardiovascular disease occur in working-age people, compared with 28 percent in Brazil, 35 percent in India and 41 percent in South Africa. Th ere is a growing market for products that address unmet medical needs in these countries – and those that also enhance therapeutic benefi ts such as dosing regimens and targeted dosage forms (such as via drug delivery technologies) greatly increase the po-tential for commercial success.

Pharmaceutical companies seeking to market their products in the fi rst world generally face a stringent approval process. How does the regulatory environment in emerging markets compare, and how can companies prepare? AT. Generally, regulatory dossiers such as a US Food & Drug Administration (FDA) approval or a EU Certifi cate of Pharmaceutical Product (CPP) meet the standards of developing coun-tries, and could over time become the bench-mark for regulatory approval in emerging markets. With more than 20 products sold in

over 50 emerging countries since 2002, Eurand has demonstrated success and experience in providing technologically advanced products to partners addressing unmet medical needs in these markets. Eurand’s successful record with the FDA, including recent approval of several products, has resulted in strong data packages that can help streamline registration timelines for these partners. Th e launch of a once-daily formulation of the muscle relaxant cycloben-zaprine in Korea in September 2009, for ex-ample, came just 17 months aft er fi nalizing the

licensing deal with a major local pharmaceuti-cal company, Daewoong, in April 2008.

Approved by the FDA in 2007 and mar-keted in the US by Cephalon as AMRIX (Cyclobenzaprine Hydrochloride Extended-Release Capsules), the product uses Eurand’s Diff ucaps technology and reduces the need for patients to take multiple daily doses of cyclobenzaprine while improving the safety profi le and tolerability of the drug by reducing the levels of somnolence associated with the standard immediate release (IR) drug formu-lation. In addition to Korea – a pharmaceutical market that increased 8.5 percent from 2007-2008 – Eurand has also fi nalized deals with local companies to market cyclobenzaprine ER in Turkey, South Africa and Israel, where growth over the same time period was 12.9, 7.8 and 5.3 percent, respectively.

Andrew Thompson is Vice President of Commercial Operations at Eurand. He has 25 years of experience in international marketing and operations in the pharmaceutical industry, including increasingly senior positions at ICI Pharmaceuticals, Glaxo Wellcome and Spanish pharmaceutical group Almirall. In 2007 he joined Eurand, where he is responsible for the company’s pharmaceutical technology business outside the US.

Understanding emerging marketsAndrew Thompson shares his thoughts on preparing for success in emerging markets.

EXECUTIVEINTERVIEW

“Disease profi les in emerging markets are

evolving to more closely resemble those of developed

countries, shift ing from infectious disease control

to management of more chronic conditions”

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As we embark on a supposed fresh start in this newdecade, we bring some baggage with us. We face im-mediate problems such as double-digit unemploy-ment and fiscal crises at the state and federal levels,long-term challenges that include the rising costs ofhealthcare and retirement in an aging population,and growing pressures on the underpinnings of the

American economy. Some pundits and prognosticators say America’s declineis inevitable. Of course, a decade ago, people predicted that Y2K would bringon the Apocalypse, and as we meet here there are always those predicting the‘big one’ that will finally send a big chunk of California into the Pacific.

But I’m optimistic about our nation’s successful journey through the‘teens’ and beyond, as long as we carry with us and safeguard the key to somuch of our prosperity and health… and that’s innovation. It’s no exaggera-tion to say that innovation is the wellspring of California’s – and our nation’s– greatness. Whether cars or airplanes or rockets; or agriculture, computersor medicines; innovation has fueled unprecedented prosperity. California it-self has brought the world the high-tech wonders of Silicon Valley – the ‘rightstuff’ that fueled our aerospace leadership – green technologies, a boomingbiotech sector, and of course, the movies!

At Eli Lilly and Company, we’ve staked our future on innovation. Ashealthcare undergoes radical transformation, we’re in the midst of the most

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Lifespans and livelihoodsIn this address given to Town Hall Los Angeles in January, CEO of Eli Lilly and CompanyJohn Lechleiter looks at the human dimensions of medical innovation.

FEATURE STORY

LECHLEITER_4August 18/02/2010 11:44 Page 52

sweeping changes in our company’s history, which in-volve a new structure and new ways to do R&D, all aimedat speeding the flow of new and better medicines to pa-tients. It’s no exaggeration to say that every single daywe’re intensely focused on cracking the nut of medical in-novation.

But I’ve learned that we also have to keep makingthe case for innovation, to sustain an environmentwhere new ideas can flourish, where innovative solu-tions can make life better for everyone, where creativethinking is nurtured and invention is rewarded, whichall raises the question: Why do I have to defend inno-vation? What’s not to like?

It’s not that people oppose innovation, but they takeit for granted – or unwittingly undermine the ecosystemrequired for innovation to flourish. I can tell you, basedon the experience of a company that invests some $4 bil-lion a year in R&D, that innovation doesn’t just happen.And the conditions must be right – starting with the es-sential aspect of a society that appreciates and rewardsinnovation.

We tend to think of innovation in terms of technol-ogy, science, labs, but innovation is essentially the appli-cation of human ingenuity to improve human life. Tofully appreciate innovation, we have to see and under-stand clearly its benefits for humankind.

I want to draw your attention to those human di-mensions of innovation. I’ll focus on bioscience innova-tion – speaking from the perspective of a research-basedpharmaceutical company – but I believe my remarks willalso apply more broadly to innovation of all kinds.

Transforming livesLet me begin with the first human dimension of in-

novation – lifespans. We’ve added a decade to lifespans inthis country, just in my lifetime. Has there been any moreimportant accomplishment in this period? A key reasonwhy we’ve gained this extra decade is innovation. In fact,an independent study found that just one area of medicalinnovation – the launches of new medicines – accountedfor 40 percent of the increase in life expectancy during the1980s and 1990s.

Indeed, throughout the past century, medical innovation transformedthe basic expectations of human life that had prevailed since the dawn of civ-ilization. More and more death sentences were lifted: think of antibiotics forinfections, vaccines for conditions such as polio, and more effective treat-ments for a growing number of cancers.

For example, the five-year survival rate for all cancers diagnosed between1996 and 2004 is 66 percent, up from just 50 percent in the mid-1970s. Morethan 11 million Americans with a history of cancer are alive today.

Other dread diseases became manageable chronic conditions, such as di-abetes, heart disease and HIV/AIDS. Between 1995 and 2005, annual deathsfrom HIV/AIDS dropped 70 percent. And countless maladies barely under-

stood or described in 1900 – things like severe sepsis, osteoporosis, schizo-phrenia and auto-immune disorders – are being brought to heel by medicalinterventions.

Six years ago, my predecessor, Sidney Taurel, spoke to this forum on thesocial implications of longer lives. Sidney made the point that we’ve added notonly to life spans but also to what some call “health spans,” that is, years of lifewithout a disabling condition. This means more people who are active, en-gaged, working, contributing to social progress in myriad ways.

We’re determined to keep this progress going. Today, America’s bio-pharmaceutical companies, including Lilly, have a robust pipeline of poten-tial new medicines – nearly 3000 compounds in development, some 40

www.ngpharma.com 53

“We know when budgets are tight, there’salways a temptation to cut R&D. We also knowthat our future depends on innovation and we

try to resist that temptation”


scientific inquiry and innovation, and free markets where innovators can ex-pect to be rewarded for the risks they take and the value they create.

The second element – the nutrients for innovation – come in the form ofmonetary investments. For investors to take the risks associated with innova-tion, they must have a fair shot at earning a return if the work is indeed suc-cessful. That requires solid protection of intellectual property and a fair,rigorous and transparent system of regulation.

In addition to better prepared teachers, we need to give them more sup-port, beginning with curricular materials based on sound research. Lilly issupporting research by the National Science Resources Center – an affiliate ofThe National Academies and the Smithsonian Institute – to develop a hands-on, inquiry-based approach to teaching science in Indiana. And we’re work-ing with I-STEM to improve science kits and make them available to teachersthroughout the state.

The third and most important element – the seeds of innovation – equateto talented people and their ideas. Ultimately, innovation grows from thehuman mind. So far, I’ve spoken of people as the beneficiaries of innovation,but it’s equally important to understand that we are the source, as well. Weneed to remind ourselves that human beings, with their talent and energy,their creativity and insights, are a priceless resource – but a resource that iswoefully underdeveloped in this country, even as we congratulate ourselvesfor maintaining – still – the world’s largest knowledge economy.

Better educationIn keeping with my focus, I want to call attention to three policies neces-

sary to allow these seeds of innovation – human talent and ideas – to take rootand grow. Those three policies are: broad improvement in science and math ed-ucation in our grade schools and high schools; immigration laws that allow and

percent more than we had 10 years ago. These molecules hold the potentialto treat some of our most pressing unmet medical needs, and to increase‘health spans’ even more.

Leading in biosciencesThere’s a second human dimension of innovation, the importance of

which is on par with health – and that’s livelihoods. Just the one area of inno-vation I’ve been discussing – bioscience – provides good jobs to 1.3 millionAmericans. Bioscience is a 21st century knowledge-based industry paying anaverage salary of around $75,000.

When most people think of Los Angeles, science might not be the firstthing that comes to mind, but LA boasts one of the largest concentrations ofbioscience employment in the country. A study by Battelle MemorialInstitute, based on 2006 data from the US Bureau of Labor Statistics, count-ed 70,000 bioscience jobs in the Los Angeles metropolitan area.

The study estimated that every job in biosciences supports nearly five ad-ditional jobs in the economy; so, with the multiplier effect, as many as 400,000jobs in the LA metro area are tied to bioscience.

Today the US biosciences sector leads the world. In fact, it is just thekind of knowledge-based industry we need to build our economic future.But leadership can be lost. Absent policies that maintain the right condi-tions for innovation to flourish, we risk losing our advantage and squan-dering our potential. The pursuit of innovation is a very difficult, veryhigh-risk venture. If innovation is to take root and grow, it requires a com-bination of elements I referred to earlier as an ‘ecosystem’ – and I believethis is a good analogy.

The first element of this ecosystem is an atmosphere in which innovationcan thrive – the air and sunshine – a society that understands and appreciates

54 www.ngpharma.com

When compared with studentsin 57 countries around theworld, US 15-year-olds rank23rd in science literacy and32nd in math literacy


encourage top scientists to choose to work in the United States; and a well-fund-ed basic research infrastructure within academic and government labs.

Let’s begin with science and math education. No matter how you look atthe statistics, the United States is falling short, especially at the high schoollevel. In international comparisons, American 15-year-olds perform poorlyin science and math literacy. When compared with students in 57 countriesaround the world, US 15-year-olds rank 23rd in science literacy and 32nd inmath literacy.

And we’re not meeting our own goals for student performance in thesefields. On the National Assessment of Educational Progress, only half of 12thgraders are at or above a basic level of achievement in the sciences, and aver-age scores for 12th graders in the sciences actually declined nationwide from1996 to 2005.

A recent review of science education ranked California – along with myhome, Indiana – among states with what was described as “middling perfor-mance”. California is among relatively few states that showed improvementin science scores between 2000 and 2005.

The ACT admissions test reported that fewer than one-third of studentswho took the test in 2008 were ready for college-level biology – both nation-wide and in California. These kids are the future scientists we’ll need to dis-cover new treatments and cures for our toughest medical problems. But, notsurprisingly, the number of US students pursuing bachelor’s degrees in sci-ence, technology, engineering and math – the so-called ‘STEM’ fields – is farbelow what will be needed to meet future demand.

Broad understanding of math and science is essential, first of all, sothat young people across our society have an opportunity to participate in

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MORE IMMIGRATION

An important policy to promote innovation isimmigration policy that allows and encourages topscientists to choose to work in the US.

Let me explain why this is so important. In pharmaceuticalresearch, only one molecule in 10,000 ever makes it to themarket as an approved medicine. One discovery, one insightover the course of years can mean the difference betweensuccess and failure for an entire research program.

So, just as we look for the most promising molecules, wealso look for the very best scientists. Today, many of the topcandidates are not US citizens or even permanent residents.This includes candidates emerging from US graduate schools –and, again, it’s not surprising in light of US science education.To stay and work in this country, skilled foreign nationalstypically need H1B visas, but the number of those visas hasbeen subject to impossibly low limits in federal law.

Since Congress last raised the annual cap in 1990, US GDPhas grown by nearly two-thirds, and the demand for skilledworkers has risen commensurately.

We’re not talking about big numbers. At Lilly – a top 10global pharma company – we currently employ a grand totalof 230 people in the US on H1Bs and other temporary visas;that’s about one percent of our US employee population. Yetthose folks are vitally important. They account for asignificantly larger percentage of our senior-level scientificwork force, and they make vital contributions that otherwisewould not be made.

At Lilly, we’ve typically had success with only about 75percent of our H1B visa applications, because once the lowlimit has been exceeded, we’re subject to a lottery like everyother potential employer.

And that’s not all. It takes an average of five years for theLilly employees we sponsor for residency status to obtain agreen card. This kind of delay causes a great deal of anxiety anduncertainly for prospective immigrants, including promotionsand careers on hold, and significant difficulty traveling outsidethe US while green-card applications are pending.

We believe that the uncertainty and frustration of the

immigration process are driving away prospective candidatesbefore we ever see them. In fact, our nation is experiencing atrend where a significant number of talented foreign nationalswho come to our universities and corporations simply returnhome, which is what you’d expect under these conditions.

Whether or not Congress takes up comprehensiveimmigration reform, we must fix the policies that are drivingaway talented people who want to live here and contribute toour economy. This does not require drastic changes, just asensible increase in visas for these highly skilled immigrantsand a shorter, simpler process to get a green card.

To those who argue that these immigrants are taking jobs

from Americans, I respond that they’re contributing to strongbusinesses that help create jobs and drive innovation righthere in this country. According to the Wall Street Journal,between 1990 and 2007, 25 percent of US companies startedwith venture capital had an immigrant founder.

It surely beats the alternative: talented people returningto their native country or going elsewhere to start or help aforeign firm to compete against us. You want a job-killer?That’s a job killer.


Research fundingAnother policy imperative is a well-funded basic research infrastructure

within academic and government labs, through increased funding for theNational Institutes of Health, the National Science Foundation and otheragencies that pursue and support basic research, as well as the training ofyoung scientists. Academic and government research has historically operat-ed synergistically with the private biopharma sector, often supplying the rawmaterial, such as insights on disease processes and leads on promising mole-cules, which industry works to translate, develop and commercialize.

Real federal funding for research declined over the past five years – andthe decline hit basic research in government and academic labs. During thissame five-year period, by comparison, R&D spending by biopharmaceuticalcompanies grew 22 percent in real terms. The American Recovery andReinvestment Act – the ‘stimulus bill’ – provides substantial funding for theNational Institutes of Health, the National Science Foundation and otheragencies involved in health research. While that infusion of funding is wel-come, what’s more important is sustained federal support for basic research.

At Lilly, we know when budgets are tight, there’s always a temptation tocut R&D. We also know that our future depends on innovation, and we try toresist that temptation. We need the same commitment at the federal level.Inconsistency in funding means that grants dry up, projects are cut short, andprogress is disrupted. In addition, too many prospective research scientistssee the attendant uncertainties of a career in basic science, and look for otheropportunities.

Our nation’s innovation engine works best when we’re firing on all cylin-ders. The indispensable role of government is to support basic research, along

the high-tech economy of the future. Further, as the technology sectorgrows, the Baby Boom generation retires, and shortages emerge in partic-ular fields, we will need a large cohort with basic scientific skills to preparefor these jobs.

Meeting these needs will require continued significant attention to im-proving K-12 science and math education across our country, and I believethat both the public and private sectors must be involved.

Let me cite just one key imperative: Better preparation and support forteachers in STEM subjects: teachers who know their stuff and can get studentsexcited about math and science. In too many schools, teachers lack strongsubject-matter knowledge in these fields. When I think about my own deci-sion to pursue a career as a chemist, it was two devoted high school teacherswho inspired me and put me on the right path.

Yet even the best-prepared teachers too often lack necessary curricularsupport, beginning with materials based on sound research. To that end, Lillyis supporting an effort by the National Science Resources Center to develop ahands-on, inquiry based approach to teaching science in Indiana.

President Obama recently announced a public-private initiative to im-prove STEM education, building on existing philanthropic programs to ex-pand teacher training, and to place math and science teachers with advanceddegrees in hard-to-staff schools. This is just what the doctor ordered.

Ultimately, what we need is not an intensive program to produce anelite cadre of brilliant scientists, but a common effort as a society to devel-op whole new generations of Americans with knowledge and skills in mathand science – a large pool from which great scientists and breakthroughideas will emerge.

56 www.ngpharma.com


with translating and transferring knowledge to the private sec-tor. US companies, in turn, apply that knowledge to developand commercialize innovative products that create value in themarket.

What’s required is not some new Manhattan Project butrather a long-term commitment to funding for basic research,to attract more outstanding scientists to that research and keepthem engaged in productive work throughout their careers,whether those careers take root in academia, government labo-ratories, or the private sector.

A few years ago, a business reporter offered a startling de-scription of the business that Lilly is in: “Drug research,” he said,“is quite possibly the least efficient endeavor in the world ofbusiness. It’s the equivalent of hiring thousands of art studentsand funding decades of work in hopes that once in a while onewill paint a ‘Mona Lisa.’”

Now that comes across as a sobering thought, except thatLilly scientists do produce those Mona Lisas! And the portraitthey paint is the face of every patient who benefits from themedicines they create.

We’re determined to paint more masterpieces – longerlives, healthier lives – through medical innovation. Clearly, at atime when we’re up against some big economic and fiscal bar-riers, protecting innovation might be seen as a luxury. Yet whoamong us can witness the impact of cancer, Alzheimer’s disease,and other scourges and say, “We have all the medical innova-tion we need”? In fact, innovation may help us overcome fiscalas well as medical and technological challenges; in a world of in-creasingly constrained budgets, scientific innovation is likely tocreate new and less expensive treatment alternatives.

Furthermore, bioscience innovation is truly an active in-gredient in the economy of our nation; a source of enhanced livelihoods andof good jobs and incomes based on American economic and technologicalleadership in this high-tech field. It can and must also be an active ingredientin any recipe for healthcare reform, representing as it does a huge part of thesolution to our healthcare challenges.

Without innovation, we’re not going to be able to provide more effectivehealthcare to a rapidly aging population; we will be defenseless againstscourges such as Alzheimer’s disease; the staggering health crises that lingerin the developing world will get worse, not better, and America’s most fun-damental competitive advantage will indeed decline.

Optimistic outlookFortunately, I’m an optimist. Being involved in the hard, often frustrat-

ing work of innovation requires optimism. But it generates optimism, too, be-cause we’ve seen diseases conquered, pain relieved, lives saved by our work.

One of the most inspiring aspects of my job is the chance to meet face-to-face with patients whose lives have been touched by Lilly medicines. In aChristmas photo on my desk is the face of a young man, a Lilly employee, whohad been saved from imminent death not two months ago by a Lilly medicine… and the faces of his wife and son.

We stand on the brink of an enormous opportunity to harness new sci-entific knowledge that could make a further, substantial contribution to

human health. It is no understatement to call this the ‘Century of HumanMedicine’. And medicine is just one of many fields where dedicated peopleare pursuing exciting innovations to improve life for people around the world.

We’re fortunate to live in a time and place where we can choose to de-vote substantial resources to such endeavors. We owe it to future generationsin this country, and to people around the world, to ensure that we create andsustain a viable ecosystem for innovation as a matter of highest priority.

We must continue to build a society that appreciates and rewards in-novation, maintains a strong legal and regulatory infrastructure, and mostof all, prepares and encourages talented people to pursue innovative science.All of us who care about innovation should be insistent about high-qualityK-12 education, especially in math and science; immigration laws that allowskilled scientists to work in the US; and steady long-term funding for basicresearch.

Through a commitment to innovation, founded on a deep appreciationfor what innovation contributes to human lives, we can overcome the very se-rious problems that face us today and prepare for the challenges of the future:securing livelihoods and enhancing lifespans for Americans in this newdecade and for generations to come. n

www.ngpharma.com 57

© 2010 Eli Lilly and Company. Reprinted with permission.

John C. Lechleiter is Chairman, President and Chief Executive Officer, Eli Lilly and Company


In an environment of extreme cost containment, integrated informat-ics solutions contribute significantly to today’s pharmaceutical manu-facturing laboratories that require increased product quality andcompliance with strict regulations, as well as improved efficiencies that

can lead to reduced costs. Modern LIMS (laboratory information management systems) serve as

common platform frameworks that other informatics solutions, instrumen-tation, enterprise systems and enterprise communications tools can plug intoto share common functions, without having to build them from scratch foreach product. These systems are capable of storing data and methods in a safeand consistent way, thereby ensuring ultimate data security and integrity aswell as effective processing distribution.

As a consequence, scientists and researchers are able to easily access datain order to make better-informed decisions in a faster and more reliable fash-ion. Adopting a comprehensive enterprise-level integration approach tostreamline business processes can alleviate some of the challenges facing mod-ern pharmaceutical manufacturing laboratories.

In response to market growth indicators, Thermo Scientific CONNECTShelps bridge the gap between laboratory-generated data and the enterprise-level information that is required for mission-critical management decisions.Because our company is uniquely positioned to offer this enterprise-level so-

lution set, Thermo Scientific CONNECTS allows our customers to more fullyintegrate the work of the laboratory across the organization and to expand thebusiness of science from the lab throughout the enterprise.

We are also able to capitalize on our ongoing partnership with industryleaders such as Microsoft and Oracle, as well as newer entrants to the inte-gration discussion, like secure document management systems or ELN re-sources. CONNECTS provides both the integration of instruments andsystems, and the interoperability necessary to transform laboratory data intorelevant business drivers.

In facilitating this enterprise-wide integration of systems, managementwill have the information they need for early insight into how pipeline drugsor compounds are progressing on a routine basis, as well as the critical datathey need before, not after, any point of crisis that may affect operations,shareholder value or the safety of the consumer.

Improving enterprise-level productivity

58 www.ngpharma.com

By Kim Shah

INDUSTRYINSIGHT

“Adopting a comprehensive enterprise-levelintegration approach to streamline business

processes can alleviate some of thechallenges facing modern pharmaceutical

manufacturing laboratories”

THERMOFISHER_co proof 18/02/2010 11:48 Page 58

We are engaging with our customers in dialogue that will facilitate man-agement-level discussion about the necessity of integrating all of the sourcesof potential data, including the laboratory and all related instrumentation, en-terprise systems like MES (manufacturing enterprise systems), PIMS and ERP(enterprise resource planning), and enterprise communications tools likeSharepoint, BizTalk or document management systems.

In the ideal situation, this end-to-end integration of the entire enterprisewill facilitate better data correlation and collaboration, end-to-end report gen-eration, and more secure data exchanges, with the goal of providing manage-ment with a dashboard view of the key business metrics essential to runningthe business.

Pharmaceutical manufacturing operations, contract manufacturing or-ganizations (CMOs) and active pharmaceutical ingredientmanufacturers (APIs) are highly regulated and required tocontrol the quality of their analyses according to specific FDAguidelines, which apply to electronic format records that arecreated, modified, maintained, archived, retrieved or trans-mitted in their laboratories.

These regulations are valid even for records that are notused in a submission, such as training records and SOPs. Asa consequence, one of the major challenges facing the in-dustry is the need to use validated CDS (chromatographydata systems) and LIMS that enable compliance with stan-dards and procedures enforced in this highly regulated en-vironment.

For pharmaceutical manufacturing companies today, akey business driver is the availability of a coherent strategythat can integrate data from LIMS, CDS, ERP, MES, ELN(electronic laboratory notebooks) and other sources acrossthe enterprise.

SolutionsGlobal Pharmaceutical Supply Group (GPSG) Brazil, a

unit of Janssen-Cilag Farmacêutica Ltda., Johnson & Johnson,has taken advantage of the latest connectivity opportunities inits São José dos Campos laboratory complex in São Paulo.GPSG Brazil has adopted Thermo Scientific CONNECTS, anintegration solution that provides the connectivity for laboratory instrumen-tation and informatics software, enterprise systems and document manage-ment tools, enabling a fully integrated pharmaceutical manufacturingenvironment.

Every month, GPSG Brazil’s manufacturing plant processes more than10,000 analyses to assure the quality of nearly 2000 samples of raw materials,packaging materials, semi-finished and finished products, water and stability.The site is fully equipped with an incoming laboratory plus microbiologic,chemical, analytical development and research and development laboratories.The manufacturing plant handles both solids and liquids, including Tylenol750 mg tablets, Tylex tablets, Nizoral tablets, Tylenol drops, Nizoral cream andshampoo, and imported products such as Eprex, Risperdal tablets.

GPSG Brazil selected a Thermo Scientific LIMS solution to deploy in itslaboratories to ensure integration with corporate enterprise resource plan-ning package, SAP R/3. Between the production plant and the laboratory thatanalyzes data from production, there is a need for regular exchange of infor-

mation about quality and analysis values. In order to leverage the full benefitsof modern ERP solutions, GPSG Brazil needed a solution to interface theLIMS with SAP so that the LIMS feeds data into the ERP.

By interfacing the LIMS with its ERP, GPSG Brazil can expedite the dataflow between the lab and the manufacturing functions, streamline data han-dling, and integrate data collection and reports. GPSG Brazil needed a validat-ed product that provided sufficient flexibility to deliver all the requirementsthat a pharmaceutical plant has, such as data security and consistent qualitydata; a centralized repository for the quality management data; fast and accu-rate data storage and recovery, and all the industry functionality.

Seamless integration of laboratory instruments to the LIMS and of theLIMS to the existing ERP systems at GPSG Brazil ensures full regulatory com-

pliance at a lower cost. CDS/LIMS integrationalso supports and enables the periodic auditingof the supplier certification system utilized by thecompany to guarantee the quality of its raw ma-terials.

The LIMS/CDS solution achieves quick andaccurate transfer of high volumes of data, in-creasing sample throughput and improving lab-oratory productivity. Since the LIMS providesincreased traceability, the system enables easyand quick access to background data associatedwith batches, allowing for automated batch con-trol. In the case of failed data, CDS/LIMS inte-gration allows scientists to track both the originalfailed result and the actual chromatograph in thesystem. This enables users to find out if there wasan operator error or a serious issue that wouldimpact the quality of the product, so as to take allof the appropriate action to protect consumers.

The integrated system detects changes in theproduction line, determining new analyses to bemade. Chromatograms can be viewed during theanalysis and the workbook can be customized, inorder to view the analytical results. All requiredmodifications may be performed in advance,

preventing unnecessary and time-consuming rework. The integration of laboratory and enterprise systems has enabled GPSG

Brazil researchers to view information that was previously only available indata reports. As a result, delivery of results has been accelerated since fewersteps are required within the analysis process.

Enterprise-level integration is crucial in today’s business climate, wherenear instantaneous response is required by pharmaceutical companies to pro-tect the public and the environment. With CONNECTS, our goal is to bringkey business knowledge originating in the laboratory to management at alllevels of the organization. The integration of the entire enterprise will facili-tate better data correlation and collaboration, end-to-end report generationand more secure data exchanges, with the ultimate goal being to provide man-agement with a dashboard view of the key business metrics essential to run-ning the business. n

www.ngpharma.com 59

For more information, visit www.thermo.com/connects

Kim Shah is Vice President, Marketing andBusiness Development, Thermo FisherScientific. Shah has more than 20 years’experience in high tech marketing andmanagement. Prior to joining ThermoFisher Scientific in November 2006, heserved as Vice President of Marketing andChannel Development at Convoq. He hasheld leadership roles at Inso Corporation,Lotus Development and Micrografx, andco-founded e-tractions, Inc., a provider ofstrategy and implementations of onlinemarketing campaigns.

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In April of last year, the World Health Organization (WHO) was informed of human infections caused by a new H1N1 virus. Th e report was classifi ed as being of ‘immediate concern’ because the genes contained in the virus were from animal infl uenza viruses, es-tablishing that the virus was very diff erent from the usual seasonal human infl uenza viruses.

On 11 June 2009, WHO announced that the virus would now be classed as a pandemic, because the virus had spread through 120 countries. It was

predicted that the H1N1 virus would aff ect billions of people, and kill thousands. To date, there have been more than 14,000 laboratory-confi rmed deaths worldwide.

Media speculation In recent months, however, there has been speculation that due to

WHO’s ties with the pharmaceutical industry, the extent of H1N1 was exaggerated. It has been suggested that there was no need for WHO to call the virus a pandemic, an action that resulted in many countries changing their health priorities to accommodate the thousands of patients that were expected as a result. Th is, in turn, prompted govern-ments to spend millions on contracts with drug companies to procure large quantities of the H1N1 vaccine.

But, as argued by Dr. Keiji Fukuda, Special Advisor on Pandemic Infl uenza to the Director General of WHO, “Th e H1N1 pandemic is not the same as seasonal infl uenza and diff ers in major respects. Large outbreaks occurred outside the usual season for infl uenza. Th e virus caused a striking and unusual pattern of severe illness and deaths in younger people, with many deaths caused by viral pneumonia: an espe-cially aggressive form of the condition – and this pattern is not typically

Who infl uenced Is it better to overestimate the threat of a virus and spend millions on vaccines that may not be needed, or make a misjudgment in the other direction and cause millions of unnecessary deaths? By Jodie Humphries

COMMENT

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WHO?

Profi tsYet there can be no denying that the pharmaceutical industry has

seen a rise in profi ts as a direct result of the H1N1 pandemic and the resulting sudden demand for vaccines. CSL Limited saw its profi ts rise 63 percent above 2008 levels by June 2009, while GlaxoSmithKline had benefi ted from a 30 percent jump by the third quarter. Roche, maker of the preventative drug Tamifl u, enjoyed a 12-fold leap in profi ts from the second quarter of 2008 to the same period in 2009.

What’s more, and perhaps most critically, at the hearing Dr. Wolf-gang Wodarg, a medical expert specializing in epidemiology and the former Chair of the PACE Sub-committee on Health, stated, “WHO basically held the trigger for the pandemic preparedness plans; they had a key role to play in deciding on the pandemic. Around $18 billion was spent on this worldwide.”

Th ere is some debate over whether this is an issue of blame. At the hearing, and speaking on behalf of the pharmaceutical industry, was Dr Luc Hessel from the European Vaccine Manufacturers, who said, “Th e vaccine industry merely did what it was asked to do. Th e industry’s role is to produce safe vaccines in a timely manner and respond to governments’ requests. It is governed by stringent international health regulations and rigorous safeguards against confl ict of interest. Decision-making regarding vaccine needs can only be based on the best available data at the time.”

Nonetheless, swine fl u has ended up being one of the most expensive public health crises ever, as – in the midst of a global recession – gov-

seen during seasonal infl uenza.” Fukuda’s arguments came on behalf of WHO at the Council of Europe hearing ‘Th e handling of the H1N1 pandemic: more transparency needed?’, held in late January.

Ultimately, WHO’s collaborations with the industry provide better access to high-quality and aff ordable medicines, vaccines and diagnos-tics. Medical interventions, including antiviral drugs, vaccines and di-agnostic tests, have long been recognized for their role in mitigating the health impact of an infl uenza pandemic. In fact, WHO itself states that “pharmaceutical companies play an essential role in this regard and WHO has engaged with them to pursue its public health objectives.”

As such, in responding to the pandemic, WHO drew on advice from a standing body of experts, the Strategic Advisory Group of Experts on Immunization (SAGE), which advises WHO on vaccine use. Members of SAGE are likewise required to declare all professional and fi nancial interests, including funding received from pharmaceutical compa-nies or consultancies or other forms of professional engagement with pharmaceutical companies. Th e names and affi liations of members of SAGE and of SAGE working groups are published on the WHO website, together with meeting reports and declarations of interest submitted by the experts.

H1N1 Facts and fi gures

FranceOrdered 90 million // used 5 million

United KingdomOrdered 90 million // used 23 million

United StatesOrdered 251 million // used 160 million

Vaccine Orders and Consumption

Number of cases have slowly been declining, resulting in governments having a huge surplus of the vaccine and cutting their initially large orders from the pharmaceutical companies.

Estimates vs. The Actual Number of Deaths

The United States The United Kingdom

Actual3,068

Actual392

Est.

90,000Est.

50,000 It was estimated that up to 30-40% of both the UK and US would become ill within six months of the situation of a pandemic being announced. Official figures of confirmed cases were much lower.

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have spent billions of dollars on vaccines that are seemingly not needed, some politicians and health professionals are looking to hold someone accountable.

Dr. Fukuda, however, argues that, “WHO is confi dent of the scien-tifi c validity of its recommendations. Th e labeling of the pandemic as ‘fake’ is to ignore recent history and science and to trivialize the deaths of

over 14,000 people and the many additional serious illnesses experienced by others.”

He certainly has a point: while the number of cases might be declining, the fact remains that more 14,000 people died as a result of the virus. In the US alone, initial es-timates put the projected death toll at 90,000, while in the UK the fi gure was expected to be 50,000. While the actual fi gures haven’t reached these numbers, the eff ects of swine fl u are still very real.

Was the seriousness of the swine fl u pandemic exaggerated? Perhaps, but it would be wrong to jump to the conclusion that this was done to line the pockets of the world’s drug-makers. On the contrary, the speedy development and delivery of vaccines could be one of the main reasons that the pan-

demic hasn’t reached the dizzying heights of infection that were initially expected. Aft er all, a pandemic remains a pandemic whether it results in 14,000 deaths or – like the Spanish Flu in 1918 – 50 million. n

ernments spent millions on vaccines that now may not be needed. And because of this, drug companies are reaping the benefi ts.

Far from over Despite the fact that WHO says the pandemic isn’t over yet, with

more infections – and deaths – still to come, many nations are never-theless attempting to cancel pending orders for H1N1 vaccines. France, for instance, which had ordered 90 million doses of the vaccine, more than was needed to inoculate its entire popula-tion of 60 million, has so far used only fi ve mil-lion doses and now wants to cancel 50 million and sell the rest. Similarly, the Netherlands has a 19 million-dose order on sale to other countries, while Germany is in talks with manufacturers to halve its order of 50 million doses and sell off millions of others.

Switzerland, Spain and Britain are also con-sidering giving away or selling the millions of doses that they have received or have on order, while the US, which has so far only distributed 160 million of the 251 million doses it purchased to doctors, hospitals and other healthcare pro-viders, has yet to make a decision on whether it will have an overfl ow and what it will do with any surplus.

Th e main reason for the extra vaccine is simply that demand fell far short of what was originally expected. And now, aft er governments

Sources: WHO, ECDC, BBC, Financial Times

United States

113,690 cases // 3068 deaths

Canada

25,339 cases // 426 deathsUnited Kingdom

28,456 cases // 392 deaths

Brazil


Turkey


India


China


Russia


Argentina


Mexico


The 10 countries with the highest number of swine flu deaths(confirmed cases // confirmed deaths)

“Many nations are nevertheless

attempting to cancel pending

orders for H1N1 vaccines”

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Pharmaceutical and biotechnol-ogy laboratories are under in-creasing pressure to help bring drugs and healthcare treatments to market faster. But the process

of isolating and testing lead candidates is fraught with difficulty. Digital pathology and virtual microscopy are valuable during every key step of the discovery process and are being adapted more and more by companies doing pharma and biotech research.

The first research area that can be stream-lined using virtual microscopy is the examina-tion of hundreds or thousands of animal slides that are generated for each study. Until recent-ly, a pathologist or other clinical professional prepared each slide, put it on a microscope, decided which area to review first, looked into the eyepieces, counted cells or made other ob-servations, and finally, recorded the findings in a spreadsheet, analysis tool or LIS system. The user then moved to the next area of the slide (or next magnification) and repeated the sequence. This process was repeated with each animal, slide and region.

Today, using new virtual microscopy tools like the Olympus VS110 slide scan-

ning system, glass slides are delivered to a technician who scans them once. Numerous pathologists can review the slides simultane-ously, each at various magnifications, with automatic logging of batch, animal, slide, location, magnification and other metadata, along with each reviewer’s findings. The slides are instantly accessible, so instead of deliver-ing boxes of slides first to one pathologist and then to another, any number of pathologists anywhere in the world can be called upon to review them, vastly increasing the potential for rapid and expert review and analysis.

Adding the capacity for parallel review to the workflow has saved some companies enough time to allow for additional pathol-ogy reviews. Furthermore, since original glass slides are not passed around, they can be ar-chived, while accurate, clear digital images are available for future research without the risk of breakage or loss. Each pathologist’s review is also streamlined. Onscreen whole slide review using multiple magnifications and areas of the sample allows for greater speed, less risk of error, enhanced data archiving and retrieval, fewer ergonomic issues, and access to expert pathologists wherever they are located.

Virtual microscopy offers additional benefits beyond the laboratory. For instance, it offers the company the potential to more easily deepen and draw on the knowledge they have amassed about the compounds or treat-ments they are considering. They can now go back to review a molecule or a whole class of molecules, using the database to relate their findings to other studies. In addition, digital imaging and review allow both qualitative and quantitative analysis. Image analysis, for instance, adds data points to help minimize subjectivity and reduce the number of inde-pendent analyses needed to arrive at an end result. Whole slide stereology is a technique that allows the rigorous quantification of lung alveoli, brain neurons or other features as part of the research process. Both image analysis and stereology provide more than data end-points; they also can help save valuable time in the research process. At the Osteoarthritis Research Society International (OARSI) meet-ing in Chicago in 2004, one major interna-tional pharmaceutical company reported that it took 15-30 minutes to annotate each image using traditional microscopy tools, but with the virtual microscopy system, they were able to shorten review time to under 30 seconds per image, giving the company a remarkable 30-60x time saving over the older method. Automated data management tools also help reduce repetitive and manual processes, even as they increase data traceability.

Virtual microscopy and digital pathology are helping today’s pharma and biotech compa-nies bring new products to market with greater speed, enhanced connectivity, stronger valida-tion based on scientific principals, improved quantification and increased traceability. The next frontier in digital imaging in the field may be the development of multimodal systems that will deliver brightfield, fluorescence, darkfield, differential interference contrast (DIC) and more in an integrated package. n

Helping bring products to market fasterLorne Davies explains the importance of digital imaging in research.

ASK THEEXPERT

Lorne Davies is Group Manager, Strategy and Product Management, Clinical Digital Imaging at Olympus America Inc. He is responsible for virtual microscopy research and planning throughout the US and Canada. A veteran of two decades in the microscopy, pharmaceutical and scientific instrumentation fields, he has been with Olympus since 1998.

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Today, there is a great deal of mar-keting noise touting the 5000 L single-use bioreactor. Th e direc-tion of single-use vendors (in

increasing vessel size) appears to be in direct contrast with the evolution of market needs.

Consider that the landscape of biotech-nology-based drugs is evolving from a small number of high-volume blockbuster cancer drugs to larger numbers of more targeted drugs for smaller populations. Focusing on large therapeutic areas such as cancer, but ac-quiring approvals for multiple related orphan indications, has proven to be a good strategy for many drugs. Th e result of this diversifi ca-tion in monoclonal antibody drugs is a need for fl exible manufacturing facilities capable of rapid product changeover at smaller volumes, as opposed to high-volume, capital-intensive facilities focused on the high-volume produc-tion of a single drug.

Similarly, facilities built to develop and manufacture biosimilars can benefi t from high-yielding, robust new cell lines and there-fore do not require the same production vol-umes. Moreover, biosimilar product facilities must minimize capital expenditure, and di-versify the risk with multi-product capability. Th ese drivers, namely multi-product capabil-ity, rapid scale-up and capital effi ciency, have driven the adoption of single-use systems by the cell culture community.

Because single-use bioreactors are still a relatively ‘new’ area, vessel design continues to evolve, as do new processes such as perfusion. Furthermore, single-use automation systems are designed to be fl exible in both hardware and soft ware for easy product changeover, so that they naturally lend themselves to the incorporation of new sensors, new types of vessels, new control algorithms, and new cell culture methods. It is precisely this fl exibil-ity and ease of use that is expected to propel single-use system adoption in the future.

Th e recent proliferation of single-use bioreactor designs has focused primarily on aeration methods, as well as optimizing the uniformity of mixing and temperature. Th is becomes more and more diffi cult to achieve in volumes of 2000 L or more, whereas it is rela-tively straightforward and low risk in smaller size vessels.

Th e advent of new sensors will allow additional data about the bio-process to be obtained and new algorithms to be developed for improved control and titer. In contrast to electrochemical sensors that vary up to four times in length depending on vessel size, the same optical pH and dissolved oxygen sensors can be used in 1 L or 2000 L single-use vessels using a clever port design.

Moreover, single-use optical sensors such as Finesse’s TruFluor pH and DO sensors can be manufactured to a well-defi ned set of tol-erances that assure reproducible and predict-able performance parameters. As a result, all measured values are obtained using the same sensor and the same performance specifi ca-tions, so that the bio-process engineer can be assured that the measured process values in scale-up and scale-down studies are com-pletely consistent, and any variations between the processes are a result of fl uid mechanics in diff erent sizes of vessels. In this case, literally, size won’t matter.

Additionally, because single-use bags allow easy modifi cations and additions of new ports, it is much easier to introduce new mea-surement technologies in the process as they become available in the market. As a result, it is anticipated that the process analytical tech-nologies (PAT) initiative will be much more useful for single-use technologies than for traditional stainless steel platforms. Because the measurement technologies will be inde-pendent of reactor type and size, their testing and validation should actually become much easier, with greater repeatability of results and consistency in measurement during scale-up and scale down.

Finally, owing to more robust cell lines, whose productivity can yield tens of grams of product per liter, bioreactor size of single-use vessels for the production of most biologicals is not expected to exceed 2000 L. Most single-use production systems today are a 1000 L stirred tank confi guration that mimics a stainless steel reactor in geometry, but can be designed to have a more homogeneous cell culture envi-ronment. Th is size of reactor allows manage-able handling of the bioprocess bags, while matching (with the increased titer) the capac-ity of a typical production Protein A chroma-tography column. Realistically, handling bags larger than 2000 L carries signifi cant risks to both the product and personnel involved.

In the end, size will matter. What will matter is that the bioreactor is ‘just right’. To that end, with further increases in titer and the downstream bottleneck in chromatography, the industry may indeed fi nd that ‘small is beautiful’. n

Does size really matter in single-use applications?By Barb Paldus

Barb Paldus was most recently the CTO of Picarro, a company she founded in 1998. At Picarro, she was responsible for technology strategy, research and business development, which led to a solid-state Cyan laser product in 2003 and cavity ring-down spectroscopy products in 2004. Paldus is currently a partner at Skymoon Ventures. She received both her PhD (1998) and MSEE (1994) degrees in electrical engineering from Stanford University, and her BS (1993) in electrical engineering/applied mathematics from the University of Waterloo.

ASK THEEXPERT

“Focusing on large therapeutic areas such

as cancer, but acquiring approvals for multiple

related orphan indications, has proven to be a good

strategy for many drugs”

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Which are the best methods for companies to use in automating their genotyping workfl ows and their siRNA screening?NS. Th at’s the beauty of a fl exible automation platform. Th e science drives the automation, not the other way round. If it is feasible and sound scientifi cally, we can fi nd a way to adapt and advance the automation to work with the application. And the automated methods we have already developed to support PCR and next generation sequencing are being leveraged by our customers to support the increasing in-vestments in pharmacogenomics research.

How do you see automation developing within pharmaceutical R&D in the next few years?NS. We see that there will be a continued emphasis on developing quality targets and biologic therapeutics. Th at will mean auto-mating a variety of applications in genomics and protein analysis – something we already do but which we expect will take up the bulk of our business in the next few years as HTS investments level off . And we see public-private partnerships playing an increasingly important role, as more target development unfolds in universities and private research institutions. We’re looking forward to the challenges and innovations that this will drive in the near future. n

Can you explain current automation trends within the life sciences sector?Nitin Sood. Th e automation trend we are seeing is a shift in emphasis away from small molecule lead identifi cation with its larger and more static automation systems toward fl exible, bench top stations to support target identifi cation and the development of new biologic therapeutics, or NBEs. Th is is consis-tent with the broader industry move toward biologics and the need to have high qual-ity and well-characterized targets. Biological drugs off er greater target specifi city, improved safety profi les and open up new possibilities in disease treatment and prevention not address-able with conventional therapeutics. As such they are an attractive addition to the pharma portfolio, commanding a premium price with reduced competitive pressure, especially from the generic threat that looms for small mol-ecule drugs.

Within fi ve years, half of marketed drugs are expected to be biologics, and the industry is moving to sustain and expand NBE discovery. We expect to see our business shift accordingly, moving to the earliest stages of drug discovery. Automation will be a key component in reduc-ing cycle time, developing high quality targets and getting quality biologic candidates into the pipeline faster.

What are the challenges and benefi ts of expanding automation beyond HTS work-fl ows and what tools can pharmaceutical companies use to achieve this?NS. Th e challenge is in being able to under-stand the fundamental diff erences between screening for active chemical entities versus developing quality targets and viable NBEs. In order to address target ID and biologics discovery, automation companies need to begin thinking beyond simple throughput concerns to the more sophisticated idea of re-ducing cycle time. Reducing cycle time means a greater emphasis is placed on the quality and

certainty of results, on the science that is driv-ing discovery. Th at science changes rapidly and the automation must have the fl exibility to respond. At Agilent, we are known for robust, low-footprint automation that can be easily repurposed as the need changes.

Another challenge is that reducing cycle time means having a deeper understanding of the science and the steps involved to getting a sound result. Th at pushes us to consider new applications and assays. In traditional lead identifi cation, we essentially address one step of a workfl ow. Th e basic operation is plating

compounds, transferring compounds to assay plates and reading. Now consider what goes into a target ID workfl ow. We have a customer doing functional genomics using a lentiviral system. Th ey create vector libraries, produce virus, transfect cells and assay the cells. Th ey use an Agilent BioCel system to automate the whole process, so the system does nucleic acid prep on the Agilent Bravo liquid handler, man-ages the pipetting and incubations involved in the transfection, through to high-throughput fl ow cytometry. Th e system has to orchestrate those various steps at the level of both hard-ware and soft ware, which is quite impressive. Th is customer has cut their project time, gets high-quality data from the system and uses be-tween one and two resources per project when they previously used eight to 12. And they were able to redirect those resources to develop the science that will give them a competitive ad-vantage in the marketplace.

Nitin Sood is the General Manager of Agilent Automation Solutions and has served in this role since July 2009. Sood brings a wealth of business experience and market expertise to his role. He has held leadership positions in leading life science companies, including Applied Biosystems and Agilent Technologies.

Nitin Sood explains the expansion of automation trends in life sciences.

Rise of biologics

“Automation will be a key component in reducing cycle time,

developing high quality targets and getting quality biologic candidates

into the pipeline faster”

EXECUTIVEINTERVIEW

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DRUG DISCOVERY

Raafat Fahim has long been a fi xture in the phar-maceutical industry. Prior to his role at Nabi Biopharmaceuticals he held a 14-year tenure with Aventis Pasteur before it became a part of sanofi , and it was here in the leading vaccine manufac-turer of the world that he cultivated his concept of developing research to market. By converting

research fi ndings into manufactured solutions and implementing them into the market, Fahim found a more effi cient business model to cope with the rising industry challenges.

He attributes much of his thinking to his time at Aventis Pasteur: “It certainly provides a wide scope of experiences that I’m using today in my current role as Chief Executive of Nabi – a biotech with a vaccine develop-ment pipeline. In this I am able to interact and use my experience in the many areas that Nabi needs, both research and development, as well as from a business development perspective,” he explains.

ChallengesNow is the time a wealth of experience is needed to respond to the

industry’s challenges. Bioinformatics are enabling researchers to identify more numerous and complex targets than ever before, and pharmacies are fi nding that they’re also unusually constrained in their ability to turn research fi ndings into manufactured solutions through the market. Al-though R&D is much further ahead in its game than manufacturing and not facing the constraints of regulatory processes, it still has its hindrances. Fahim explains that on a daily basis certain things may work in a good way but are oft en unable to be applied in practice due to regulatory constraints; the rigorous side to this is ensuring that manufacturing continues consis-tently and in a compliant way.

“Compliance is one of the biggest elements facing biotechs. Th ey in-novate very well, but then when it comes to regulations and compliance the brakes are put on their development simply because of the need for a rigor in manufacturing. Th ese are the kind of things that one faces on a daily basis. Having the technology is one thing, but what you can do with it is another. For the most part pharmaceutical companies, and in my case vac-cine companies, have understood, digested and accepted that it’s a reality and are coping with it reasonably well.”

Fahim points to the example of this occuring: a concept can be in-vented in a short period of time but then it oft en takes fi ve or six years to go through the various stages of regulatory and compliance process. “You can have an idea of what works or what you’ve tested in the lab and in small animals and maybe discovered in a couple of years, but then it takes you another six years to get to the stage where you can apply for marketing authorization,” he explains.

Th is is usually a problem for small biotech companies and this is oft en an area in which they don’t excel, he says, as the company is unlike-ly to be developed for manufacturing or engineering but for discovery and research; what Fahim describes as “the fun part.” Th e problem is a practical one that all biotech companies face and each must endure the necessary length of time to go through the regulatory process to arrive at the fi nal stage.

“Th e best advice one can give is to realize what you don’t know very early on,” says Fahim. “Most companies, when they get early successes in research and discovery, think and believe that now they can do anything and don’t recognize that getting through the next stage of manufacturing, compliance and the regulatory process is actually a completely diff erent set of expertise that you need to start preparing for earlier. Th at is probably one of the biggest problems facing most small biotech companies, that they don’t realize early enough what they don’t know and the experience they lack within the company.”

Th is is not the only challenge facing small biotech companies; the pharmaceutical industry also has to face problems within pharmacies’ supply chain. Fahim notes effi ciency as one challenge. Th e pharma indus-try, although it has grown substantially in recent years and is recognizing it is now well established, still remains far less effi cient than other indus-

Raafat Fahim of Nabi Biopharmaceuticals explains why a more effi cient business model is needed to cope with the increasing challenges of the industry.

Businessminded

“So many companies have gone bankrupt, even though they have a very good product, because they are unable to continue to develop”

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tries. He points to the automotive industry, as well as the chemical and food industries and the success in these in getting the supply chain down to the minor details.

“For a long period of time, the pharmaceutical industry enjoyed a rea-sonable return on investment and a reasonable margin for their product, and they were less concerned about cost and effi ciency. Th ey recognized that a few years back, but are not yet at the stage that they could be or should be, from my perspective anyway,” he says. “Th ere is no doubt it will change. Th at I can guarantee you because with the pressure on the pharmaceutical industry to control costs, they are now recognizing and facing quite a bit of a challenge to become more effi cient. Th ey are actually coping with it now and addressing it in a big way. Th ey are taking the right steps, maybe a bit later than they should have; but nevertheless they are doing that now.”

Effi ciency Driving effi ciency within Nabi is of primary importance to Fahim.

Still in the development stage, the company is preparing itself for consis-tency in manufacturing and preparing for commercialization. Th e fi rst stage is ensuring the drug can be produced correctly and with equality.Th e second stage is then to drive consistency. Nabi has not yet had to face the second stage, but Fahim has already begun examining it; his previous role with Aventis Pasteur taught him to approach such issues very carefully.

“I started to look at that and see how we can do it in the future but I don’t have to face it for another two-to-three years or so, fortunately for me. Th e most important thing for us now is to make sure we can do it and to make sure that I can produce the material. Effi ciency becomes a second-ary issue at this stage but planning for effi ciency is defi nitely important.

“We’re now looking at the supply chain, what is the best way to handle the various contract manufacturing organizations that you’re working with to make them more effi cient then to be responsive to the needs that we have in the future. So you can consider that we are in the planning phase, as opposed to the implementation phase today,” says Fahim.

Economic recessionTh ere are certain challenges that face every pharmaceutical company,

regardless of size or stage of development. Th e economic recession im-pacted the ability of companies to ensure the security or consistency of supply chains and has driven home the need for effi ciency in a big way. Pharmaceuticals and biotechs may be two completely diff erent industries but the challenges they face both derive from the same fi nancial dilemma. Th e pharmaceutical industry has seen the big issue of control of costs and pricing of pharmaceuticals whereas within the biotech industry this is much more dramatic. Th e pharmaceutical industry is still reasonably profi table but the biotech industry is less so.

“To me innovation is about meeting a huge unmet medical need with huge market potential”


72 www.ngpharma.com

Raafat Fahim is President and Chief Executive Offi cer, Nabi Biopharmaceuticals. He most recently served as Chief Operating Offi cer and General Manager. His career includes 14 years with Aventis Pasteur where he developed several vaccines from early research to marketed products.

“Th e pharmaceutical industry is one of the industries that has been least impacted, so to speak, by the fi nancial crisis, although they are facing the challenges themselves. For biotech, however, it is dramatic,” says Fahim. “If a biotech company now wants to raise money for the next stage of development or discovery they are doing, it is almost im-possible to get anybody to back it up now.

“So many companies have actually gone bankrupt, even though they have a very good product, or sold their companies or products at a signifi cantly reduced price simply because they are unable to continue to develop. Th at’s a major problem that we’re currently facing. We were fortunate that we had cash in the bank so I didn’t have to go and raise money otherwise I could be facing the same fate as others have.”

Without money in the bank Fahim explains that the situation is nothing other than a crisis. He advises that if a company has prod-

uct but no cash, the most feasible move would be for them to partner with larger pharmaceuticals that may be interested in their technology. Th is is oft en easier said than done, with large pharma companies wanting to take advantage of the smaller company is dilemma and wait for the price of such a deal to become cheaper. Without public funding or private backing there is little option other than a partnership.

One big issue shaping the industry is the number of acquisitions that have been conducted recently, Pfi zer and Wyeth being just one example. But is this proving to be a help or a hindrance during these dif-fi cult times? Fahim states that he prefers to be the optimist, advocating that the trend is not necessarily a bad thing and not one that will necessarily stifl e in-novation. “It may actually make it more effi cient,” he says. “And in the current realities of price control of pharmaceuticals, that is a very good thing. Th at’s one way to cope because the pharmaceutical industry has been ineffi cient so far.

“To drive effi ciency is very good. Now, does it impact negatively on innovation? It potentially may have a negative impact, but the overall impact would be positive, in essence, and would drive more effi ciency in the pharmaceutical industry. It’s not a bad trend. It depends how far it goes. You don’t want to end up with one huge phar-maceutical company in the world, and we have regulations in place to prevent that from happening.”

Ensuring that smaller companies can still compete against these merged giants is innovation, says Fahim. He notes that there is no longer any doubt that large pharma’s ability to drive innovation fast or wide enough is stunted compared to the past. “Each one of them was fully

dependent on their own organic growth for innovation. It is clear that they have failed miserably.

“Th ey have a huge infrastructure that makes the cost of innovation very, very high, stifl es innovation with the various committees, and the various triage of projects that they have. On the other hand, the biotech has shown, categorically, that it can develop very fast and in a nimble way. Th at’s why they’ve been gobbled up by the big pharmaceutical com-panies, be it the products or the companies as a whole. So there is no doubt that biotech has driven innovation over the past 15 years and will continue to do that in the future.”

InnovationInnovation is essential for a company to stay ahead of the game:

it has proved to be a critical piece of the drug discovery model. Fahim explains that at the center of Nabi’s innovation is a drive towards areas that are of signifi cant unmet medical need and that are unique. “I can go and discover the next antibiotic, but guess what; there’s a lot of other companies doing the same thing.

“Th e best way for a biotech to be unique, and survive and strive is to get into areas where there’s still signifi cant unmet medical need but is not very crowded. Th e vaccine that we are looking at within Nabi, which I consider to be a very good example of that is a nicotine vaccine.

“Th ere are still 1.3 billion people smoking in the world and we know how bad smoking is. And, therefore, a nicotine vaccine, which is a unique technology and a unique drug is a huge unmet medical need with huge market potential. We are the leaders; so obviously, we have found that area to be attractive very early on.

“Th e other vaccine we have is against the fl u coccus aureus, which is the super bug everybody hears about. Again, there is no vaccine on the market for it, so it’s a huge unmet medical need, has huge market potential and is not in a crowded area. To me innovation is about meeting a huge unmet medical need with huge market potential, so you can make your mark in the fi eld.”

Driving and managing that level of innovation throughout the company is Fahim’s responsibility as CEO. Th e best way to do this, in his opinion, is to ensure that the scientists have enough freedom to develop the concepts and ideas they have, although this is oft en prohibited by the constraints of costs and resources. If possible, this is the model he believes to work well. A very heavy structure will stifl e innovation, which is to

be avoided at all costs. Fahim explains that effi ciency is the future; the most important

development for the pharmaceutical industry over the next few years is to drive effi ciency and become lean in the supply chain. He argues that the examples of extracting a lot more cost out of the current state of ineffi ciencies are plentiful. “It’s a wise thing for the pharmaceutical industry to start paying even more attention than they are today to the current potential for more price controls over the industry. Th at becomes, probably, one of the biggest things they need to look at care-fully,” concludes Fahim.

“Th e best advice one can give is to realize what you don’t know very early on”


TRANSGENOMIC AD.indd 1TRANSGENOMIC AD.indd 1 9/2/10 09:20:469/2/10 09:20:46

ASK THEEXPERT

Biological markers, or biomarkers, are measurablecharacteristics used to distinguish normal biolog-ical processes from altered ones. In the clinicalsetting, protein biomarkers present in serum or

plasma are often measured using one of the traditionalELISA/EIA-format tests. Results from these routine tests areused in diagnosis, prognosis, determination of disease stage,risk assessments, and in determining whether the subject willrespond positively (or negatively) to a planned course oftreatment.

Disease-associated biomarkers identified by primary re-search are typically altered in only a subset of patients, andmost are modulated in multiple diseases or biological statesand so lack the specificity required for a diagnostic or prog-nostic test. The poor utility of most single analytes as diag-nostic biomarkers has led researchers to seek disease-specificprotein distribution ‘fingerprints’. Used together, a panel ofbiomarkers has the power to better discriminate a specificdisease and can potentially do so at an earlier stage.

The application of biomarkers at the point at which itmakes a tangible difference to human health and wellbeinghas its roots much earlier in the drug and diagnostic devel-opment process. Multiplex biomarker assays have key ad-vantages in that they require less sample material, providetime and cost saving through parallel throughput and pro-vide a level of flexibility that fits into many discovery and de-velopment workflows.

Drug developmentIn the research environment, the use of single and mul-

tiplex technologies is critical to the success of most projects.The analysis of key biomarkers involved in specific biologi-cal pathways or processes gives researchers a rapid and ac-curate snapshot of the disease state and whether a candidatecompound is effective. More specific tests can give rise tomechanistic insights on the mode of action of compounds,as well as the condition itself.

Safety profilingEvaluating the safety aspects of lead compounds is an es-

sential step in drug development.

Multiple organ and system toxicities, including hepato-toxicity, cardiotoxicity, immunotoxicity and nephrotoxicity,are evaluated prior to use of a potential therapy in humans.Due to their potential utility, the use of biomarkers in drugsafety testing was included in several projects under the aus-pices of the Critical Path Initiative (CPI), which is the“…FDA’s national strategy for driving innovation to mod-ernize the sciences through which FDA regulated productsare developed, evaluated, manufactured and used.”

One of the first successful projects was the developmentof a set of biomarkers that can effectively detect whether acompound of interest can cause damage to the kidney ornephrotoxicity. Through collaboration with the public-pri-vate Predictive SafetyTesting Consortium(PSTC), both the FDA andEMEA have listed sevenbiomarkers for kidneydamage as being useful indetermining kidney dam-age. As more CPI projectscome to fruition we canlook forward to firmerguidance on biomarkeridentity and application insafety testing, with the ultimate goal of lowering the cost ofdrug development and reducing the number of late develop-ment/post-marketing failures due to toxicity concerns.

Time brings technological advances, new ideas andshifts in our understanding of biological systems, and so thenumber and biomarkers that are available will increase. Justas the use and type of biomarkers have progressed fromage/height to blood pressure and heart rate and on to mole-cular biomarkers, we can expect novel parameters to be dis-covered, validated and ultimately put to effective use. Welook forward to the evolution of biomarkers and their in-creased application. Perhaps they are the vanguard into ourpersonalized medical future – but for that we need more thanone haystack. n

74 www.ngpharma.com

Needles and haystacksIndividual parameters often do not meet the usability criteria that wouldmake them ideal candidate biomarkers but by combining multiplecharacteristics, it is possible to develop a firm basis for decision-making,both in drug development and the clinic. By Christina Shasserre

For more information on CPI please visit www.fda.gov

Christina Shasserre isGeneral Manager and Headof Global Biosciences atEMD Chemicals, aninternational organizationserving the global marketby providing specialtychemicals forpharmaceutical, biotech,cosmetic, automotive,plastics and variousindustrial applications.

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California is the world headquarters for biomedical research anddevelopment. The state is home to the largest concentration ofbiomedical companies in the world and one in six of the 1.6 mil-lion biomedical jobs nationwide. Its companies, universities and

research institutes are dedicated to delivering biomedical innovation in thegreatest areas of unmet medical need. The California biomedical industryspans the full range of technologies and entities whose ultimate goal is the im-provement of public health, human therapies and the quality of life for pa-tients around the world.

California entered 2010 with its highest unemployment rate in postwarhistory, 12.5 percent, and economists and political leaders worry that payrollswill not bounce back to 2008 levels for years to come. California’s biomedicalindustry delivers high-wage jobs that drive the economy and are crucial to thestate’s economic recovery. The average annual wage for the biomedical in-dustry across the state in 2008 was nearly $75,000, as it was in 2007.

The biomedical industry continued to add jobs in 2008, employing near-ly 274,000 Californians and growing by approximately 24,000 jobs since 2004.The industry was not only a pillar in the overall state economy but a signifi-cant player in local communities throughout the state as well. The largest con-centration of industry-related jobs was in the San Francisco Bay Area.Companies and academia there employed nearly 54,000 people. Los AngelesCounty companies and institutes employed more than 44,000 people, whileOrange County recorded over 30,000 biomedical industry jobs. San DiegoCounty rounded out the top four clusters with 23,000 industry positions.

Examined by sector, the overall biomedical employment in the state in-cluded approximately 112,000 people in the medical devices, instruments anddiagnostics sectors. That number represented about 41 percent of the overalltotal jobs. Biopharmaceutical companies employed the next largest segment,with more than 81,000 jobs or about 30 percent of the total. The state’s acad-emic research centers employed more than 43,000 people in life sciences po-sitions for approximately 16 percent of the total. Wholesale trade accountedfor nearly 32,000 personnel or about 12 percent of the state’s biomedical em-ployees. The remaining 5400 employees or two percent worked in the labo-ratory services sector.

Product developmentCalifornia remains an important source of the scientific innovation that

creates the commercial value of biopharmaceutical products and the benefitsthey bring to patients around the world. At the end of August 2009, there weresome 869 products in the California biopharmaceutical pipeline.

The state’s pipeline includes products that California companies origi-nated or invested in to address a broad range of diseases. The California bio-pharmaceutical pipeline represents about 15 percent of the total worldwidebiopharmaceutical pipeline of 5850 products.

Global sales of all biotechnology and pharmaceutical products reached$719 billion in 2008, reflecting growth of 5.4 percent over the prior year.Of this total, biologic products contributed about $120 billion. Biologicscan include products such as vaccines, blood and blood components, genetherapy, tissues, monoclonal antibodies and recombinant therapeutic pro-teins created by genetic engineering.

The top six disease focal areas comprised 86 percent of the Californiapipeline, with oncology research and development remaining on top with 272products. Central nervous system disorders were next with 117 products, fol-lowed by immunological and inflammatory disease (110 products), infectiousdisease (109 products), cardiovascular and blood diseases (70 products), anddiabetes and other metabolic disorders (66 products).

Leading the way

78 www.ngpharma.com

The highlights presented here from PricewaterhouseCoopers’ California BiomedicalIndustry 2010 Report outline why the state is the worldwide headquarters ofbiomedical research and development.

SPECIALREPORT

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www.ngpharma.com 79

InvestmentCalifornia’s life sciences companies continued to expand

through 2008 (most recent data available). Total revenues from thestate’s biomedical sectors of $75.9 billion marked a nearly two per-cent increase over the $74.5 billion generated in 2007. Most of therevenues were attributed to product sales by such California head-quartered biopharmaceutical powerhouses as Genentech, Amgen,Gilead Sciences and Allergan, as well as medical technology leadersEdwards Lifesciences, Gen-Probe and Illumina.

Venture capital drives many of the country’s innovative newcompanies. All told, venture capital investments in the UnitedStates totaled $28.1 billion in 2008 and $17.7 billion in 2009. Inboth years, half of the national total was put to work byCalifornia companies. Venture capital fueling the state’s indus-tries in 2008 totaled more than $14 billion through over 1600deals involving more than 1300 companies. In 2009, nearly $9billion was put to work via more than 1100 deals and over 900companies. The largest beneficiaries in the state were thebiotechnology, medical devices and equipment, semiconductor,media and entertainment, and telecommunications industries.Yet the biomedical industry, which combines biotechnology andmedical devices and equipment, secured the bulk of the invest-ment dollars at approximately $3.5 billion in 2008 and $2.6 bil-lion in 2009.

Opportunities and challengesThe biomedical industry is one of the most recession-re-

silient sectors in California’s hard-hit economy and a criticaldriver of innovation, job growth and revenue that will helplead the state to economic recovery. In fact, among respon-dents to the most recent California Healthcare Institute (CHI)and PricewaterhouseCoopers (PwC) California BiomedicalIndustry Survey, most (64 percent) had expanded or sustainedtheir workforce over the previous year.

Looking forward, the respondents to this year’s CHI-PwCSurvey remained confident in their ability to sustain and growtheir California-based operations over the next two years.

California remains a magnet for grants from the NationalInstitutes of Health (NIH). In 2008, California received NIHgrants worth more than $3.15 billion. The Golden State’s sharewas approximately 40 percent more than that of Massachusetts,the next highest recipient. California has averaged approximate-ly 15 percent of the total NIH grants over the past decade, andwas awarded 15.1 percent of the total in 2008. n

California Biomedical Average Wages by Sector (2008)

Source: Bureau of Labor Statistics Quarterly Census of Employment and Wages andCompany Specific SEC filings.

Biopharmaceuticals

Wholesale Trade

Medical Devices, Instruments & Diagnostics

Laboratory Services

Academic Research

$108,93

$80,130

$57,314

$55,958

$54,213

California Biomedical Employment by Sector (2008)

Medical Devices, Instruments & Diagnostics

Biopharmaceuticals

Academic ResearchWholesale TradeLaboratory Services

Source: Bureau of Labor Statistics Quarterly Census of Employment and Wages andCompany Specific SEC filings.

Number of Biopharmaceuticals in California Product Pipeline

Source: IMS Health R&D Focus, July 2009

400

350

300

250

200

150

100

50

07

194

369

217

69

13

Preclinical Phase I Phase II Phase III RegisteredPre-registration

The figures

“The biomedical industry isone of the most recession-resilient sectors in California”

California Biomedical_4August 18/02/2010 13:18 Page 79

80 www.ngpharma.com

ing of their value if unused, to support deci-sions around redeployment or disposal. In addition, insight into fi nancing options and advice on asset purchase enables companies to really maximize CAPEX.

How do you see the area of laboratory asset management developing in the future?MS. Th e current economic environment is forcing pharmaceutical companies and their suppliers to think diff erently about how to drive performance and make their business model more agile. With M&A activity showing no signs of easing off , all companies are look-ing to redefi ne their business practices in order to address both present and anticipated future market challenges.

Laboratory asset management providers need a deeper and faster adoption of learnings from other industry sectors such as the aircraft industry through reliability centre mainte-nance, IT outsourcers’ service agnostic ap-proach and industry partnerships to enable IP

creation. Service organizations are morphing into ‘services’ solution providers, off ering consultative tools, technologies and change processes to become a more integral part of the pharmaceutical operating model. In this environment, strong organizations will thrive under the challenge of producing more aligned services and solutions. As Darwin once said, “It is not the strongest of the species that will survive, or the most intelligent. It is the most adaptable to change.” n

Matt Sawtell is Director of Global Operations, Scientifi c Asset Services – Life Sciences at GE Healthcare.

Although R&D is project-based and therefore more diffi cult to process map than manufacturing, there are many opportuni-ties for improvement. Th e key initially is to gain visibility of every process and laboratory asset, including a complete understanding of where all assets are, how oft en they’re used and moved, and the workfl ows they’re used in.

At GE Healthcare we have created an ef-fective life sciences services solution, built around a change acceleration program (CAP) enabling fast and eff ective change, combined with data-driven decision making which provides a roadmap of when, how and where to drive that change. In addition, as these programs cover the entire lifecycle of an asset, support is off ered right through from purchase planning to disposition.

What tools can companies use to optimize the management of their laboratory assets?MS. Although many pharma companies have already adopted measures on a low level, such

as asset tracking, spend and asset utilisation analysis, they have certainly not maximized the benefi t these tools can bring. Going over and above this, GE Healthcare’s asset manage-ment service programs off er resources such as analysis of workfl ow and waste, data analyt-ics designed to measure service quality, and benchmarking data to ensure spend, service levels and other variants, which are best in practise.

Rather than supplying simple service level analysis, business intelligence gives insight into how assets are used, and an understand-

Pharma companies are striving to reduce costs without affecting quality, yet few have capitalized on the optimization of their laboratory assets. Why is this the case?Matt Sawtell. Th e pharma and biotech in-dustries have for a long time focused on driv-ing cost out and continuous improvement in manufacturing, through widespread adoption of Lean and IT initiatives. However, there has been minimal focus on adopting these best in class approaches in R&D, leaving pharma companies at the ‘early adopter’ stage when it comes to laboratory asset management.

On the vendor side, companies in this space have been slow to evolve away from the standard service delivery structure. Th e step change needed now is to adopt an outsourcer/Chief Technology Offi cer approach. Th is would enable pharma companies to realize the value of a combined technology, IT, Lean, pro-cess and business intelligence off ering in the management of laboratory assets in R&D.

Once this approach is adopted both the vendor and pharmaceutical company can form a true strategic partnership, ensuring each op-erational project makes an impact not only on hard cost savings and simplifi cation of oper-ating models, but also signifi cantly improves the effi ciency and productivity of scientists to focus on core activities.

What benefi ts does a complete laboratory asset management program offer? MS. Th e industry is being advised to stream-line R&D groups to small focused teams with more emphasis on ensuring R&D dollars are spent on drug development rather than non-core activities. Pharma is looking to out-source more of these non-core activities and a complete lifecycle laboratory asset manage-ment service will enable them to take advan-tage of integrated services, technologies and tools, going way beyond an extended service contract.

EXECUTIVEINTERVIEW

GE Healthcare’s Matt Sawtell looks at the tools pharmaceutical companies can use to ensure they maximize their R&D dollars.

Optimizing your laboratory assets

“Once this approach is adopted both the vendor and pharmaceutical company can form a true strategic partnership"

GE HEALTH ED P80.indd 80GE HEALTH ED P80.indd 80 18/2/10 14:10:4718/2/10 14:10:47

GE AD.indd 1GE AD.indd 1 9/2/10 09:14:119/2/10 09:14:11

Over the years, polymerase chain re-action (PCR) has evolved into areadily automated, high through-put quantitative technology. Real-

time quantitative PCR (qPCR) has become theindustry standard for the detection and quantifi-cation of nucleic acids for multiple application,including quantification of RNA levels.

But a lack of consensus among researcherson how to best perform and interpret qPCR ex-periments presents a major hurdle for advance-ment of the technology. This problem isexacerbated by insufficient experimental detailin published work, which impedes the ability ofothers to accurately evaluate or replicate report-ed results.

In extreme instances, incongruous pre-assayconditions, poor assay design and subjective dataanalysis methods have led to the publication of ir-relevant or misleading data. The original 2002paper on measles, mumps and rubella (MMR)provided evidence that supported a link betweenthe MMR vaccine and autism. Later examinationestablished the original conclusions were basedon flawed real-time PCR data. Subsequent publi-cations have convincingly demonstrated there isno plausible link between the vaccine and autism,but the debate and doubt continues outside of thescientific community and MMR vaccination rateshave dropped in several countries.

Accurate qPCR testing can help companiesavoid pursuing the wrong compound or target.Providing sufficiently detailed reports of experi-mental design in early stage drug discovery re-search can potentially save millions of dollars bynot wasting man-hours or reagents. TheMinimum Information for Publication ofQuantitative Real-Time PCR Experiments(MIQE) standards can help companies and re-searchers avoid these drug development pitfalls.

MIQE’s goal is to restructure the currentapproach to qPCR data reporting into a consis-tent format that encourages detailed auditing ofexperimental processes, analysis and resultswhereby the technical quality of the work and

reliability of the conclusions can be evaluated.Implementing these guidelines is imperative incontinuing the growth of qPCR into an accu-rate and reliable nucleic acid quantificationtechnology.

MIQE promotes the careful examination ofqPCR results to enhance integrity of submissionsto peer-reviewed journals, consistency betweenlaboratories and experimental transparency.Adoption and compliance of these guidelines willhelp researchers more accurately report data andreplicate experiments, ultimately saving time andmoney.

When it comes to providing scientists withthe tools to be MIQE-compliant, Bio-RadLaboratories, Inc. is paving the way. Recently,

Bio-Rad entered into an arrangement withBiogazelle to exclusively distribute the qbasePLUS

data analysis software with its CFX96™ andCFX384™ real-time PCR detection systems, a pro-gram that enables users to annotate their experi-ments with MIQE-compliant experimentaldetails. The qbasePLUS software in combinationwith these real-time PCR systems provides cus-tomers with improved accuracy in their qPCR ex-periments and speeds up standardized dataanalysis.

qbasePLUS software allows for the eliminationof erroneous data, normalization to remove sam-ple-specific non-biologic variation, and inter-runcalibration, which can remove the technical vari-ation between samples analyzed in different runs.By enhancing the reliability of the qPCR data,qbasePLUS conforms to MIQE.

Using the CFX96 and CFX384 real-time de-tection systems with qbasePLUS software acceleratesresearch through automated, fast calculations and

direct import of data from the system to the soft-ware. The combined solution provides re-searchers with the flexibility to handle both smalland large experiments as well as combine datafrom different experiments using qbasePLUS soft-ware as the repository database.

As the industry continues to recognize theimportance of the MIQE guidelines it will be-come increasingly necessary to ensure that lab-oratories and corporations are following them.Simplifying compliance facilitates not only drugdiscovery and development, but basic biologicalresearch. Investing in a qPCR system and fail-ing to follow guidelines that will ensure thatquality data is being produced may result in awasted investment.

It can be anticipated that additional qPCRvendors will soon offer solutions to assist re-searchers in maintaining MIQE compliance.Top instrument makers and reagent vendors aresupporting the thought leaders working to ex-pand MIQE awareness and compliance. Bio-Radhas trained sales and support staff to help re-searchers comply with the guidelines. Theyshare this training through educational meetingsfocused on MIQE.

Quality data is paramount for the successfuldevelopment and potential approval of a drugcandidate. Following MIQE will help strengthenthe quality qPCR data needed to move a candi-date forward. Plus, it may avoid the devastation offinding out the focus was on the wrong target orhaving a drug candidate fail. n

Step up to the MIQEWhen it comes to real-time PCR in drug discovery, Richard Kurtz believes

that MIQE guidelines will help create a clear path.

82 www.ngpharma.com

NEXT BIGTHING

Richard Kurtz is Senior Marketing Manager at Bio-RadLaboratories. Prior to joining Bio-Rad, Kurtz served asField Applications Manager for MJ Research Incorporated.Kurtz earned his PhD from Northwestern University anda BA in Molecular Biology from Colgate University.

“Quality data is paramount for thesuccessful development and potential

approval of a drug candidate”

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www.ngpharma.com 85

As the pharmaceutical industry changes in response to unprecedentedchallenges, how must the information technology supporting the drugdiscovery process evolve and be redefined in order to improve researchproductivity and success rates?Amos Dor. As the pharmaceutical industry changes, the information tech-nology supporting it must be able to keep up. Advanced sensors are neededto gain information about the materials being used, the process they gothrough, and their results. This investment in sensors, however well inten-tioned, doesn’t add value without the means to collect, store and understand

the data they provide. IT must be able to support this data explosion withdatabases, networks and advanced data analysis tools. The analysis tools es-pecially need to be trustworthy and intuitive to maximize benefits from theiruse. Multivariate analysis becomes even more important when the number ofvariables being considered increases. Correlations between variables must beconsidered, and it is very difficult to see correlations between more than fouror five variables at a time when they are looked at individually. To truly opti-mize productivity and success, the majority of time and resources should befocused on decision-making based on relevant information, instead of on howto collect and plot the data.

Patrick Flanagan. All pharmaceutical organizations have their own datastores and data access applications. Standardizing on an extensible productthat fulfils their data requirements reduces costs and allows internal IT groupsto focus on adding value rather than supporting the base platform.Introduction of data standards makes data more readily capturable, sharable,and understandable and ultimately valuable.

The tangible benefits of adopting/moving to a product-based solution arestraightforward: reduced cost of ownership, focus of internal resources on de-livery of higher value scientific capabilities, and reduced burden on the scien-tist of tedious data manipulation tasks. The less tangible benefits offer a vastlyhigher value and productivity gains to the scientist and project leadership: in-creased focus of scientists on the meaning of their data and delivering the nextprogression in their project rather than on how to move data around theircomputers, and improvement in the use and interpretation of data.

In the current climate, pharmaceutical drug development must increaseits productivity. How can the more widespread use of technology sup-port tools help streamline and improve discovery processes?

ROUNDTABLE

Amos Dor is the Umetrics US Manager atMKS Instruments in San Jose, California. Hemanages marketing, businessdevelopment, application, operation, andsales for North America, South America andIsrael. He has 20 years of broad experiencein management, marketing, businessdevelopment and engineering in start-upsand large organizations.

Patrick Flanagan is Chief Operating Officerfor Tripos International and leads theorganization’s commercial efforts. Prior tojoining Tripos, his career included strategicsales and business development forleading companies in the healthcare,software, and consulting fields includingBaxter International, Allegiance Healthcareand A.T. Kearney and Oracle.

THE PANEL

NGP gathers some of the industry’s leading experts to discuss how information technologycan support and develop the discovery process.

Using IT to improve success rates

Software RT_4August 18/02/2010 13:52 Page 85

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PF. Technology support tools, made available across the enterprise and uti-lized in daily workflows, can enable true knowledge management. Scientistsneed to get to their data as soon as it is available, so timely data entry and sim-ple delivery are critical requirements. Data must be presented in the way sci-entists want to see it, so analysis tools must be a click away, and require nofurther complex data manipulations, avoiding the need for data transferand loss of context, and data access and analysis capabilities must be inte-grated with all the applications that are required for an entire workflow.Logistical data such as synthesis and test dates need to be accessible to bet-ter understand and improve research processes, and cross-project datasetsneed to be readily accessible so progression decisions can be made earlierwith greater objectivity. Capabilities to mine corporate information be-yond the scientists’ current project provide the key to realizing corporateknowledge.

AD. When drug development includes Quality by Design (QbD) from the be-ginning, resources can be focused where they will be the most beneficial.Umetrics’ Design of Experiment (DOE) software, MODDE, can be used toreduce the amount of experiments needed, while at the same time, provideas much information as possible from those few experiments. DOE helpsdecide which variables to control, find the optimal setting, and ensure theprocess is robust enough to keep quality consistent. It also helps to trans-fer the product from development to production. Knowing the range ofsettings that will keep quality consistent before handing the process tomanufacturing can reduce the time it takes to qualify and validate theprocess. Also, the data from the design can be combined with historicaldata from manufacturing to monitor the process and to do quality predic-tions in real time.

What software tools can discovery scientists use to help organize, ana-lyze and visualize ever-increasing amounts of data, enabling them tomake better, faster decisions?AD. Advanced multivariate analysis tools like Simca-P+ from Umetrics canhelp increase productivity in several ways. First, you can quickly create anoverview of all the data showing trends, groups and outliers. You can use thisoverview to see which observations are similar to each other (or to the groupaverage) and which are not. Second, you can look for correlations in the data.Using the variable plots, you can see which variables are positively or nega-tively correlated with each other or with your quality measurements. If yousee groups or outliers in the data, you can quickly drill down to the variablecontribution plot, which shows which variables are causing the groups to sep-arate or the outlier to be different from the main population. Within minutes,you can get an overview of the data, compare two populations of data, or seewhich variables are predictive of quality.

PF. Tripos’ Benchware Discovery 360 (D360) is a powerful system that allowsevery researcher in a life science organization to access and analyze discoverydata and easily share their findings with project teams. Using D360, scientistsgain simple access to everyday logistical data queries, as well as in-depth datamining and analysis capabilities. In addition to productivity gains achievedby reducing the amount of time spent formatting, manipulating and manu-ally transferring data, D360 users report that they are able to perform analy-ses they simply couldn’t do prior to implementing D360. Pfizer recentlyglobally adopted D360 under a unique agreement where we are adoptingvaluable elements from their organic system (RGate) and adopting them intoD360, providing a leading technology to Pfizer scientists while leveraging in-vestment in their legacy system to reduce cost and create a modern, best-of-breed platform for drug discovery and development. Previous to itsacquisition by Pfizer, Wyeth selected D360, and worked extensively withTripos over a five-year period to develop the application to meet the needs ofWyeth scientists.

How do you see the use of software in pharmaceutical R&D developingover the next five to 10 years?PF. We believe that use of software that provides improved capabilities in theability to predict successful outcomes – like optimizing lead compounds, pre-dicting off-target effects, and managing attrition – will play an increasinglyimportant role in pharmaceutical R&D. Additionally, the integration of datafrom discovery through clinical and beyond should allow the process of dis-covery and development to become more cohesive and efficient, moving to-wards informatics support of translational efforts from hypothesis through topatient outcome.

AD. In five to 10 years, drug discovery will rely even more on data and the in-formation you can get out of that data. The ability to collect data from com-plex experiments will increase, and it will become even more imperative tobe able to quickly understand the story that data is trying to tell. Processanalytical technology (PAT), including online multivariate process moni-toring, will take a larger role in drug manufacturing. With online processmonitoring, batches are supervised to see if any measured variables are dif-ferent than normal. If so, an alert is automatically generated so action canbe taken to prevent the batch from being lost. Companies will be able tomonitor products from research and development all the way through todelivery to customers. They will be able to provide a complete history forall delivered products. Because of this and other benefits mentioned previ-ously, the FDA will be even more encouraging about implementing pro-grams like QbD and PAT. Companies who haven’t implemented this typeof process and quality control will be the exception and will have a moredifficult time competing with those who have. n

“In five to 10 years, drug discoverywill rely even more on data”

Amos Dor

“Technology support tools can enabletrue knowledge management”

Patrick Flanagan

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EXECUTIVEINTERVIEW

In your opinion, what are the main challengescurrently facing biopharmaceutical drug de-velopment?Brandon Pence. Moving products to marketquickly remains the challenge of any company, inparticular those developing biotherapeutics andvaccines. Additionally, as new biologics are devel-oped for more specialized applications, the demandfor yesterday’s large manufacturing plants with tensof thousands of liters in bioreactor capacity is di-minishing. The ability to quickly manufactureproducts in a cost-effective manner, and in manycases locate the manufacturing facility in the regionwhere the end-product will be supplied, is becom-ing key to the market performance of the biologic.To accomplish this, more biopharmaceutical man-ufacturers are turning to single-use systems for liq-uid preparation and handling, cell culturemanufacturing and bulk intermediate storage.

The advantages of single-use systems havebeen widely documented over the past few yearsand include manufacturing cost reduction, rapidproduction turnaround timelines and maintain-ing a consistent contact surface throughout themanufacturing process flow. With the expandedrange of applications for single-use systems, easeof implementation is another critical factor. AtThermo Fisher Scientific, we are placing technol-ogy experts in the field capable of working direct-ly with our clients on identifying opportunities toutilize single-use systems all the way from the de-velopment of initial application protocolsthrough their integration and qualification.

How can biopharmaceutical companies in-crease the productivity of their protein-baseddrug production?BP. Matching cell expression systems with the rawmaterials consumed and the equipment used inthe bioproduction process can significantly im-prove titers, elevating overall efficiencies for man-ufacturers. However, achieving this productivityimprovement requires a balance between provid-ing the right nutritional components in the form

of complete cell culture media and feed supple-ments for the cell platform selected with the opti-mization of the bioreactor production process. Inmany cases, titer improvements are a function ofcustomizing the nutritional components for thespecific cell clone and then developing the rightstrategies for delivering those nutrients.

We believe that having subject-matter ex-perts with the right process monitoring technolo-gies enables us to analyze thecomplete cell culture processand provide customized re-sponses to our clients’ needs. Inmany cases, these customizedresponses influence the type ofcell culture media and supple-ments used, as well as the pro-tocols for operating productionbioreactors. Through practicalapplication of this approach,we’ve been successful in part-nering with biopharmaceuticalmanufacturers to achieve pro-ductivity improvements greaterthan two-fold compared to tra-ditional production systems.

What should companieslook for when choosing anexternal partner to help op-timize cell culture perfor-mance and achieve maximum results fromtheir research?BP. Having the right technologies and applicationsresources is obviously important. We have taken aleadership position in the bioprocessing industry byintegrating cell culture nutrients (sera, media andsupplements) with single-use handling and pro-duction systems, including the Thermo ScientificHyClone Single-Use Bioreactor. This enables us topartner with companies in developing complete cellculture systems.

Another critical factor to be considered forachieving maximum output from process opti-

mization collaborations is the ability to take resultsand implement them globally. This includes select-ing a partner with global manufacturing sites and ahistory of providing and supporting productsplaced into various regions. One important elementthat is often overlooked is identifying a partner ca-pable of providing the right degree of collaborativeactivity. This activity may involve onsite technicaldiscussions and support, project management and

communication, and coordinat-ing studies at research facilitieslocated at the partner’s head-quarters.

How do you see the area ofcell culture-based biothera-peutics developing over thenext few years?BP. An emerging trend in cellculture science will be the de-velopment of more personal-ized biotherapeutics instead oflarge blockbuster drugs. Thesewill require smaller produc-tions systems as they will takeadvantage of existing cell cul-ture productivity improvementtechnologies as well as have re-fined dosing requirements for asmaller patient population. Assuch, personalized biothera-

peutics manufacturers will require an ability tocustomize the delivery of key raw materials andproduction systems to ensure robust and efficientprocesses.

Additionally, the emergence of biosimilars aspatents expire on existing blockbuster biothera-peutics could have a profound impact on the bio-pharmaceutical industry. Utilizing strategicpartners capable of providing the right technolo-gies will enable both biosimilar manufacturersand novel biotherapeutics developers the abilityto constantly be at the forefront of their respectivedomains. n

Optimizing cell culture performance Brandon Pence talks to NGP about achieving maximum output

from process optimization collaborations.

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Brandon Pence is the AssociateDirector of Market Managementfor Thermo Scientific Cell Cultureand BioProcessing. In his currentrole, Pence is responsible forglobal strategic business effortsprimarily aimed at improvingthe tools utilized inbioprocessing systems,biotherapeutics and vaccinesmanufacturing.

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Biomarkers are indispensable toolkitsfor drug discovery and development,covering nearly all classifications ofanalytes such as proteins and metabo-

lites, genetic markers, DNA, RNA and many oth-ers. They are widely used in virtually alltherapeutic areas including cardiovascular (car-diac troponin I), neurology (amyloid beta 40, 42),oncology (VEGF, Akt-1, PSA), metabolic (in-sulin, GLP-1), and inflammatory (cytokines andchemokines) diseases. Researchers need respon-sive biomarkers to serve a variety of differentpurposes.

During drug discovery, biomarkers are usedto identify and qualify drug candidates, determinepotencies, validate targets and to determinemechanisms of action (MOA). During pre-clini-cal development, biomarkers are used to demon-strate PK/PD and to evaluate drug safety andefficacy, enabling early decisions on drug candi-dacy to be made with more reliability. Duringclinical trials surrogate biomarkers are used toidentify and track disease progression. It is im-portant that these biomarkers discriminate anddistinguish between study populations and thatmethods used to measure them can quantify sub-

tle changes caused by drug intervention.Biomarkers are also used to develop diagnostictools or to validate another surrogate biomarker.Some biomarkers can identify populations forrisk stratification that can be used for diagnosticmonitoring and predictive tests.

The preeminent goal during drug discoveryis to optimize the balance between drug efficacyand toxicity. Reproducible and sensitive surrogatebiomarkers are instrumental in devising an opti-mal therapeutic index. Surrogate biomarkers areneeded as indicators of disease severity and drugefficacy. Additionally, specific markers responsiveto drug toxicity can be monitored in relation tothe efficacy of dosage. Knowledge of the stabilityof these biomarkers in normal populations helpsto provide a framework for comparison. With anaccurately established baseline of the biomarker,one can observe significant changes over baselinebeyond underlying biological variation.

Many biomarkers can be used to monitordisease progression, however it is important thattechnology capable of measuring these biomark-ers in a healthy population exists. Significant con-centration changes compared to baseline are thenindicative of deviation from normalcy. By longi-

tudinally monitoring the progression from ahealthy to diseased state, then conversely from adiseased to healthy state, one could determine theefficacy of a given therapeutic intervention. Thusbiomarkers can serve as valuable indicators of dis-ease severity and can be measured to provide clin-ical evidence for drug efficacy.

Technologies used to measure biomarkersspan across a wide range of platforms. For exam-ple, Singulex has developed ultra-sensitive im-munoassays for many proteins such as cytokines,chemokines, growth factors, transcription factors,hormones, regulatory proteins such as troponin,and metabolites such as cAMP. Development ofsuch ultra-sensitive immunoassays addresses thelack of sensitive detection methods commerciallyavailable on the market. Without the requisite

assay sensitivity, it is not possible to accurately es-tablish baseline levels of specific biomarkers pre-sent in the sub-picogram/mL range. Furthermore,small incremental concentration changes (ap-proximately 50-250 fg/mL) possibly linking to dis-ease progression cannot be measured withstatistical confidence. Increased assay sensitivitythus enables the clinical utility of biomarkers, em-powering the researcher with the ability to gathervital data in evaluating drug efficacy, dosing ortreatment regimen. n

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ASK THEEXPERT

An indispensable toolkitLynn Zieske explains the importance of biomarkersin the drug development process.

Lynn Zieske serves as Vice President of CommercialSolutions for Singulex, where he promotes the adoptionand innovation of Singulex technology in the life sciencemarketplace. Zieske brings over 20 years of experience inlife science product development and marketing strategy,helping to bring innovative products to customers.

“Many biomarkers can beused to monitor disease

progression, however it isimportant that technologycapable of measuring these

biomarkers in a healthypopulation exists”

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SUSTAINABILITY

GSK’s Mark Rhodes examines the level of environmental awareness

in the pharmaceutical industry.

GREENER FUTURE

Towards a

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As we become increasingly aware of our impact on the planet, environmental consciousness is grow-ing across many sectors. Big pharma may not im-mediately spring to mind as having the greenest of business models, but Mark Rhodes, VP Sustain-ability Pharmaceutical and Consumer Healthcare

for GlaxoSmithKline, believes the industry boasts quite a high level of awareness around environmental issues.

“I think there is quite a high degree of awareness,” he says. “We’re a very compliant industry, so pharma tends to follow things like envi-ronmental regulations and health and safety regulations. Th ere is strong knowledge around compliance and policies and procedures.

“Th e gap that we have that makes us diff erent to other industries, such as the car industry, is that we need to ask ourselves how we can be more sustainable when we don’t have a customer demanding sustainable products. It’s very diff erent to somebody buying a car and wanting some-thing with a low fuel consumption and low emissions. We don’t have anybody saying to us, ‘We want your pharmaceuticals, but we want them greener.’ It has to be driven internally.

“Generally, people tend to trust their doctors. If a doctor says, ‘Th is is what I’m going to prescribe you for your illness,’ they accept it and don’t question whether there’s an option that has a better environment profi le. A good example is dry powder in respiratory devices versus aero-sols. Th ey have very diff erent environmental profi les, but the patient will tend to be very conservative and want to stick with what they’ve got. And the doctor will not necessarily prescribe based on environmental impact. Even though the molecules might be the same, it’s just the way they’re presented that is diff erent.”

Th is can pose a challenge to those charged with making their busi-ness more sustainable, but they do have one advantage: as Rhodes puts it, everyone who is internal to the company is also a member of the public.

“Everyone has their own per-sonal feelings about recycling. Th ey may recycle at home; why shouldn’t they do it at work? Or they may choose a low-emission car at home, so why are they working in a factory with very high emissions? Th ey’re not diff erent people when they’re at work. You have to harness that enthusiasm and channel it and get everybody together to share their ideas. In fact, sometimes they want to go further than perhaps we in the environmental group want to go, because we see the challenges and we know the problems.”

When asked whether he thinks there will come a time when phar-maceutical companies will promote themselves based on their envi-ronmental records, Rhodes points to the UK’s National Health Service as an example of a higher consciousness within the health sector. “Th e NHS has published their own carbon footprint, and they’ve shown that pharmaceuticals are a major part of that,” he explains. “Th ey have to take 80 percent of the carbon out of their system, which includes the supply

chain. Th ey’ll be asking us about the options for a low-carbon respira-tory medicine, and then we can have a discussion with them around dry powders versus aerosols and so on. Th ey will then have to think about how they will transition from aerosols to dry powder, for instance.”

Yet making these kinds of changes is not necessarily going to be easy, and involves instituting some long-term thinking from the very beginning. “If we were going to develop new molecules in the respiratory arena,” Rhodes says, “we need to ask whether we should be developing them in the future in aerosols, or should we stick to dry powder because we know carbon is going to be an issue? We’re going to be constrained, we’re going to be taxed, there are going to be issues with cap and trade. We have to realize that the choices we make now in R&D can have an enormous impact on our product portfolio in fi ve or 10 years’ time.

“So irrespective of the supply chain, there’s the whole point around what delivery mechanisms you’re going to have. In the supply chain, it’s a question of asking the right questions of the suppliers; for example, asking them what the carbon footprint is of the service they provide, or of a certain packaging material. Th en we need to start asking what the options are to reduce or improve it.

“It’s quite possible they’ve got something sitting on the shelf that they off ered us fi ve years ago and we said, ‘No, we don’t want that.’ And now we’re saying, ‘Actually, we might want that. We’ll have a discussion about it now.’”

Rhodes points out that in some cases it may take suppliers a few years to develop more sustainable options. Th is may result in the off er of exclusivity for a certain period of time, and then the option to open the new product or material to everyone else. Because there is an upfront investment involved, they need to see some returns. Th is again ties into the idea of taking a more long-term view, rather than just viewing it as a one-time transaction.”

Strategic movesIn his role, Rhodes fi elds queries from colleagues working to make

improvements in environmental sustainability. “Th ey may say, for ex-ample, ‘We’re reducing the amount of packaging we use in a carton. Can you help us describe the environmental benefi t of that change? We know how much cardboard it is, we know how much we’ve saved, but how does that equate to the carbon we produce, or the amount of trees or water we use?’

“Our brands are now also starting to work on sustainability strate-gies, because clearly people don’t go into a shop and buy two pounds of GSK. Th ey go in and buy Aquafresh toothpaste, or a pack of Panadol.

“We’re a very compliant industry, so pharma tends to follow things like environmental regulations and health and safety regulations. Th ere is strong knowledge around compliance and policies and procedures"


94 www.ngpharma.com

Th is puts more pressure on the brands to think about their sustainability strategies, which could be from how to design their packaging, what in-gredients they’re using, where they’re sourcing them from, and whether they are sustainable. Th ey may aske: What’s the diff erence between FSC-certifi ed cardboard versus SFI-certifi ed cardboard? Which one is better? Which one do we want? Can you help us with that?

“We help with the technical aspects. Th ey manage the projects, be-cause it’s their brand, and clearly they’re the ones who own the budget and it’s their PNL. Our role would be to guide them in that, give them the tools and advise them on things such as: recycled equals so much, virgin might be something else, what the diff erence is between cardboard and plastic.”

Rhodes says the VP Sustainability role within GSK is quite new, although he himself has been doing environmental management since 1990; the main diff erence being that this once consisted mainly of an auditor visiting the factories, writing policies on the environment and checking that they were being followed. Th e auditor would look at whether the factories were putting waste in the right place, managing effl uent, and complying with the laws.

“Th e shift in terms of this role is that now it’s much more around the product,” Rhodes underlines. “Environment health and safety manage-ment is one group in terms of operation, but now we’re also looking at

the impact of the product on the environment. Th e upstream impacts the downstream impacts which supplies are we using, are they ethical, are they not ethical? Th at’s the diff erence.”

Th e other change, of course, is the much greater awareness among the general public about environmental issues, such as climate change, and the eff ects of excess carbon being created at all stages of the manufac-turing process. As Rhodes points out, back in the 1990s, ideas about the environment tended to focus on “the smokestacks” – the direct impact of factories on air quality. Now things have become much more strategic.

“We can see the beginnings of the need to internalize the external costs of carbon, where we’re going to have to start paying for carbon, whether it’s in the packaging that we use, the ingredients we buy, the increased cost of oil and so on. We have to be much more strategic with the environment – again, it’s looking longer term.

“A project for the environment might have a payback of fi ve to seven years. In the past, we wouldn’t have approved that. We would have said, ‘Two years is our criteria.’ But now we’re saying actually, spend it now, because it will save you an awful lot of money later on.”

Ironically though, Rhodes says that when it comes to tackling cli-mate change, it’s oft en the smaller things rather than the big, newsworthy projects that make the diff erence – the boring things that no one sees and no one wants to talk about: turning lights off , improving air handling, improving air conditioning, changing boilers.

“Th ose are things that people don’t interact with and don’t get very excited with. You put a couple of solar panels on the roof and they all think you’re doing a great job. Th at will cost you $90 a ton to recover the carbon, whereas you get your sales fl eet to drive a little more effi ciently and it will cost you 10 cents a ton. And you’ll get that saving instantly.”

Nutritional goalsIn addition to its pharma division, GSK also has a consumer divi-

sion, and within that a nutritionals business, and each of these is in a

“Within its consumer division, GSK has created a 100 percent recycled plastic soft drinks bottle, and several consumer facilities have achieved zero percent to landfi ll”


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Greater awarenessIn terms of the future, Rhodes predicts that the big shift will be in

transferring this awareness of sustainability from the consumer side, where the link with the brands already exists, into pharma. He allows that there will be hurdles, including the oft -mentioned regulatory as-pects, but he counters that by pointing out that GSK has good engineers and good scientists. His feeling is that a lot of it comes down to just saying, ‘Th is is how we’re going to be.’

“Th ere are some things that will help us along the way, and one of them is partnering,” says Rhodes. “Some of the key leverages are partner-ing with diff erent suppliers and seeing how we can close the loop. Saying that if they provide this material, and we’ve got all these off -cuts, how can they take it back and use that somewhere in the process? Trying to

push it and say that there has to be a solution. Chucking it in a landfi ll is just not sustainable. Th ere’s got to be a better way out there.

“It may mean we have to spend a bit of money on research; for example, we’re spend-ing some money at the moment with someone who’s got some start up technology. If it works, then we’ve got an outlet for one of our waste streams that currently goes to landfi ll.

“We’re also kicking off a trial in the US to look at recycling some of our medical devices back from the patient. We wouldn’t put them back into the medical devices, but if they end up as a car bumper, well that’s better than just fi lling a hole in the ground.”

Regulatory hurdles are oft en cited as a bar-rier to increased environmental sustainability. While Rhodes concedes that there are hurdles, he believes there are not as many as some might suggest. “And whether the height of the hurdle

is quite as high as we say it is is another question,” he says. “We tend to exaggerate. And some-times we don’t ask the question, we just say that the regulations will never allow it, instead of going back and saying, ‘Actu-ally are you sure that’s really what you want?’

“If you get it right in the R&D phase when you register it and you’ve got the design in there, then that shouldn’t be an

issue later on. It’s addressing how many changes you make as a product comes up to patent loss in terms of processing, ingredients, packaging, because you realize it’s not going to be cost eff ective any longer. If you can do that when you’re worried about the patent hurdle, why not do it at the beginning?” n

diff erent place when it comes to an environmental strategy. Th e nutri-tionals division began work on its environmental strategy a few years ago, setting targets not only on energy and water, but also on working towards making their packs 100 percent recyclable, as well as having 50 percent recycled material in their packs and looking generally at sustain-able sourcing.

“You take a product like the drink Ribena in the UK,” Rhodes says, “which is a very old product and has a strong heritage. Consumers want to link to that product and feel that they can trust it. And, of course, they’ve got a choice. When they get to the shelf in a supermarket they could have Ribena, they could have Robinsons, they could have own-brand labels. So you want to build that trust, which is why it makes sense for nutritionals to move quicker on some areas than say consumers.”

Within its consumer division, GSK has made two key achievements: a 100 percent re-cycled plastic soft drinks bottle, and several of its consumer facilities achieving zero percent to landfi ll. “With the bottle,” says Rhodes, “we were using 20 percent recycled plastic and then we went to 30 percent, then 40. Each time we made a step change we had to do all the stability trials again. We had to look at the color of the bottles and we had to see whether anything was leeching out. And in the end they said, “Right, let’s go for 100 percent, and then we’re done. We’ll do the stability and then we’ll know. And if we can’t get enough we’ll go back to 90.”

“It was great because it was iconic. It was a barrier, a bit like the solar panels on the roof. We just said, ‘Let’s do it, let’s go for it.’ And a lot of that is then having the drive and ambi-tion. Wanting to be ambitious and take a lead as opposed to just being part of the pack. And it worked. And so they can say, ‘Great, we’ve done it now. We don’t have to worry about that any more.’

“Th e zero to landfi ll starts with somebody at the top saying, ‘We’re going to do this. And when we come to those diffi cult decisions, we’re going to fi nd an answer.’ You get strange things happening, like in the cafeteria we had a par-ticular type of coff ee machine that produced very nice coff ee using these laminated pouches, but the pouches weren’t recyclable.

“Suddenly we had a waste stream we couldn’t recycle, so we changed them. Th en we get people ringing up and saying they don’t like the coff ee, and we have to tell them they can’t have it any more, until they can come up with a recyclable pouch. So you do end up getting down to the minutia of trying to solve something.”

Mark Rhodes is VP Sustainability Pharmaceutical and Consumer Healthcare, GlaxoSmithKline.

“A project for the environment might have a payback of fi ve to seven years.

In the past, we wouldn’t have approved that. But now we’re saying actually,

spend it now, because it will save you an awful lot of money later on”


ASK THEEXPERT

At the heart of most, if not all, bio-logic drug development programsis the ability to express humanproteins in their proper three-di-

mensional state. Whether the protein is re-quired for structural studies, analyticalassessment, or per se is the therapeutic/vaccinecandidate, it is imperative to rapidly producehigh quality protein of interest in sufficientquantities for evaluation. The cost of delayeddrug development is estimated at $1 million perday and the cost of each day of delay is the same,regardless of the source of the delay (due to in-ability to synthesize protein) during the drugdevelopment lifecycle.

The traditional approach to protein expres-sion is to seek a host perceived to be inexpensive,facile to use and accessible. Recent research sug-gests that this type of approach results in a 75percent failure rate, with success being definedas high titers of soluble, active, high qualityprotein. Once the initial failure has occurred,most efforts will involve seeking alternativehosts in a linear, iterative and extremely costlyprocess, until finding a solution, or in somecases, altogether abandoning efforts for ex-pression and product development.Experience from a myriad of biotechnologycompanies suggests a recombinant proteinhost strain requires typically between six to 18months of development time, to ultimately ar-

rive at a host that will meet near and long-termneeds. This development effort typically does notoccur in one continuous effort, but rather duringperiods of increased and intense product demandduring the development process. While this type ofapproach is extremely common, it results in sig-nificant opportunity cost and manifests in delayedprograms, inefficient use of resources, and overallpipeline stagnation.

What if there was a single platform inwhich one could screen hun-dreds to thousands of uniquehost strains using a highthroughput, parallel approach,which demonstrated a successrate of greater than 95 per-cent, and routinely delivered arobust production strain capa-ble of producing high titers ofsoluble, active protein withineight weeks? This performancewould enable the drug develop-er to express approximatelythree-to four-fold more pro-teins, and arrive at a produc-tion strain in one-seventh thetime. The Pfēnex ExpressionTechnology platform providesthis type of success and speedto drug developers. The plat-form consists of a vast library ofexpression components in-cluding novel proprietary plas-mids and host strains. Thesecomponents combined withPseudomonas fluorescens’ obligate aerobic natureand a robotic, parallel screening process results inunprecedented protein expression speed and suc-cess rate.

As an example, consider a vaccine develop-ment program for which the innovator compa-ny has identified 10 putative antigens for avaccine formulation. The ideal approach to

down selection is to test each antigen in vivo tomeasure immunogenic performance. If a devel-opment team approached this program in thetraditional linear and iterative fashion, it wouldinitially attempt the expression of each antigenin E.coli. On average only two to three of the 10candidate antigens will be produced in solubleactive form. The remaining antigens requirescreening in additional expression strains, atlarger scale, in alternative hosts or refolded,

which presents significantproduct quality/reproducibil-ity risks in addition to long-term cost of goods challenges.Alternatively, if the researcherexpressed the same set of 10antigens in the PfēnexExpression Technology, eightto 10 soluble, active antigenswould be available for evalua-tion within five to eight weeks.Hence, as opposed to usingthe most efficient technology,the traditional E. coli ap-proach to protein expressionwould incur significant op-portunity cost, at an extremecompetitive disadvantage.

Protein expression is atthe core of every pharmaceu-tical development effort, withthe challenges experienced byprotein expression scientistssignificant. Antiquated tech-nologies with limited tools

simply cannot meet the challenges posed bytoday’s next generation drug developmentprograms. The Pfēnex Expression Technologyplatform provides a robust solution to thechallenge of efficient, high quality protein ex-pression, and enables drug development withthe avoidance of millions of dollars in oppor-tunity cost. n

The real value driverPatrick Lucy explains the benefits of protein expression and opportunity cost.

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Patrick Lucy is the Vice Presidentof Business Development ofPfēnex Inc. He played a leadershiprole on the original team thatdeveloped Pfēnex ExpressionTechnology and subsequently ledthe successful commercial launchof the platform. Lucy isexperienced in the areas ofalliance management, licensing,intellectual property,biopharmaceutical operations andbiopharmaceutical facility design,construction and validation.

“The cost of delayeddrug development is estimated at $1 million per day”

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In December 2009 the Food and Drug Admin-istration (FDA) released its fi nal guidance for industry on patient-reported outcome mea-sures to help the biopharmaceutical industry understand what the agency will be looking for when it reviews new drug applications

that include patient reported outcome (PRO) data. Th is guidance has been under review for the last three years and has become increasingly anticipated with the rise in post-approval drug surveillance and the growing need for quality data gathered directly from patients across all phases of drug development.

In the guidance, the FDA affi rms that the federal code (21 CFR 312 Subpart D) outlining the general re-sponsibilities of sponsors applies to PRO regardless of the technology (including paper) employed. Within these responsibilities are strict mandates for detailed record keeping and providing access to the FDA to conduct source verifi cation on the data. Th is traceability require-ment recognizes the limitations of paper-based data col-lection methods, particularly the lack of an audit trail. Further, the FDA wants to ensure that study participants are adhering to trial protocols, meaning if they are sup-posed to be completing a diary at specifi c intervals they are complying with that protocol rather than sporadically entering historical data. Again, this acknowledges the restrictions of paper, as there is no ability to track when and where a patient enters data. Th ese assertions provide validity to electronic PRO (ePRO) as there is a time stamp, and hence an audit trail, when data is collected electroni-cally. Th e experience of many providers has shown that the data collected by ePRO is more accurate, more timely and more comprehensive than traditional paper models.

Along these lines, the guidance also provides direc-tion for moving from various modalities and validating the modal change. An example would be moving from paper to electronic, be it web, personal digital assistant (PDA) or interactive voice response (IVR) systems. When the technology moves from paper to electronic there is a substantial change to the structure of the instrument and the FDA wants to ensure this technology shift does not impact the validity of the data entered. Th e closer the new mode can approximate the previous structure, the more easily the format’s adequacy can be confi rmed.

With web-based ePRO, an entire form can be dis-played, and font size, color schema and so on can more closely match the paper form than what is possible with a PDA or an IVR. A PDA device only allows for review of one or two questions at a time, resulting in context being lost, which could impact how a subject completes a form. Additionally with IVR, the technology itself can limit the type of answers a patient could provide. For example, with multiple choice questions, paper, web-based ePRO and PDAs allow more than one answer to be selected, giving a range of data. An IVR, however, is oft en limited to only accepting a single answer, aff ecting the scope and accu-

racy of the data. Th e validation doesn’t simply go away when shift ing from a paper instrument to a web-based ePRO, but it can become more straightforward.

Th e focus of this guidance, in essence, is the need for sponsors to follow accepted development models and good documentation practices and ensure adequate validation is in place, as well as to consider various patient-reported outcome options. It requires sponsors to be able to clearly demonstrate the documentation, validation and change control, and have adequate records of all the development testing and validation. All of this is consistent with and further re-emphasizes previous FDA guidance and regu-lations; including 21 CFR Part 11 and other guidance for computerized systems and clinical investigations. Th is guidance extends earlier instructions laid out by the FDA and conforms to the general regulatory framework it has established for collecting clinical trial data. n

Quality dataUnderstanding the fi nal FDA guidance for patient reported outcomes. By Scott Dixon

Scott Dixon is Vice President of OutcomeLogix Group and Global CRO Partnerships. He has more than 18 years experience in the healthcare, life sciences and pharmaceutical industries. Prior to this role, he was Chief Operating and Strategy Offi cer at ePRO provider Maaguzi LLC, which was acquired by Phase Forward in July 2009.

INDUSTRYINSIGHT

“Th e experience of many providers has shown that the data collected by ePRO is more accurate, more timely and more comprehensive than traditional paper models”

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CLINICALRESEARCH

Celgene Corporation’s Kamal Shah looks at why most new drug compounds fail to progress beyond the clinical trial stage.

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Despite all the scientifi c advances made over the past couple of decades, one of the main challenges in the pharmaceutical industry remains the failure of many drugs to reach success-ful registration and approval. According to Kamal Shah, Head of Global Trials Safety Surveillance for Celgene Corporation, the number of drugs that progress from discovery to approval

hasn’t changed much, in terms of the failure rate still being very high. “Th e pharmaceutical industry needs to come to a consensus and perhaps learn from

the past and fi gure out where the biggest failures are occurring,” Shah says. “Th ere are usually ample warnings from discovery all the way to the registration and approval pro-cess, but somehow the people working on these projects are missing them. Th is could be because they are focused on their own career aspirations.

“If you look at the development of a compound, most of the people who start working from phase I or earlier are in charge of that compound, and the failure of that compound could affect their career development. The f lipside of that is that they may hype up the compound rather than thinking more scientifically and per-haps more critically about its chances of success or failure. If the drug succeeds, of course, everybody working on it gets the rewards, so it’s a Catch 22 as to how to get away from that model.

“I’m sure other scientifi c areas have the same problem, and they have found a way of lessening it. If there was an independent review in the middle of or at every stage of the trial, it might make this process more successful. We can’t eradicate the failure rate completely, of course, but if it could be reduced by only 10, 20 or 30 percent, that’s a huge amount of research money going somewhere else.”

Th e other challenge Shah points to is that the US is paying for a lot of the innova-tion in research and discovery, which is not necessarily compensated when the resulting drugs move into other markets.

“In poorer countries where government resources are stretched, this is understand-able,” he says, “but for developed countries there is a need to share the burden of de-velopment rather than it being placed on only one or two countries. Th ere are a lot of countries that can aff ord to pay, and they need to come together, just like the EMEA has become one body. I’m sure if the organizations like the FDA, the EMEA and the Department of Health worked together, they could come up with some formula of how to divide the expenses.”

Safety fi rstPatient safety is obviously a critically important consideration in clinical trials, and

awareness is certainly not a problem within the industry, as Shah points out: “It’s not a question of whether people are aware of safety in clinical trials, because if somebody’s living in today’s world, I’m sure they’re reading the paper, looking at the compound and probably most of them are involved in answering the questions from the regulatory agency about safety.

“Th e challenge on the clinical trial side is that effi cacy is the driving force. Safety brings bad news occasionally to the table, and that’s one of the reasons it has not been accepted as a member of the core team, maybe just by default. Th e bearer of bad news is never welcome anywhere, but the teams need to look at this and the critical approach of how can you ignore safety, because drugs are approved now based on the benefi t-risk ratio rather than just effi cacy.

“In order to reach an acceptable level of safety, you have to make sure that safety is fully in tune and working right from phase I trials into human, all the way through. Th ere are a lot of challenges involved in improving safety and listening to the dose selec-tion as well as all the risk mitigation strategies that make a potential failure down the road less likely.”



trial population, making it easier to get drugs accepted worldwide. However, he also points to the challenges that de-velop through the need to satisfy local agencies and regulations and practices, which can occasionally throw a wrench into proceedings.

Despite this, Shah sees the inter-nationalization of clinical trials as a continuing trend within the industry. “A lot of companies are trying it. It allows them to get good enrolment from a lot of areas outside of tradi-tional, research-based centers. Th ey also get exposure to patients who are not controlled in the same fashion and so might help indicate how the drug might react when it gets marketed, so you have better population exposure.”

Another thing that Shah sees evolving in the next fi ve or 10 years is the development of more collaborative

partnerships with local expertise, either internally or acquired through partnerships with service providers. He predicts that service provider industries are going to continue to grow in terms of being the source of doing a lot of trials.

“Th e question is whether they will be able to maintain the talent pool, which keeps changing,” Shah says. “Quality of service is never guaranteed for the duration of the trial, even with the best companies.

“Personally, I also feel there is a strong need for collaboration be-tween academic centers and pharmaceutical companies, because most of the targets are being developed or invented or discovered at academic

centers, and then the development of the com-pound goes to the pharmaceutical industry.

“Th ere needs to be stronger, more collabor-ative eff orts between the academic centers that can bring a lot more science to the table, rather than just a faster approach to the development process, and maybe can help in selecting the best candidate, rather than just a candidate. Th ere are academic centers that can bring more partnership to the table, even for conducting trials, which is right now one of the biggest reasons for failure. Trials could be conducted either in collaboration with or maybe even in-dependent of the pharma industry, which gives

the potential for a better success rate.“Th e active involvement of large academic centers, the involvement

of good research physicians and the people who are at the forefront on the treatment side of the disease, would bring a lot to the drug develop-ment and clinical trial process.” n

It has become almost impossible to separate safety from effi cacy in clinical trials, because regulatory agencies now ask for a benefi t-risk as-sessment as a combination. “Th e problem there is that the assessment of acceptable risk is never well defi ned,” says Shah. “For many major diseases it’s not very diffi cult, but there is no consensus amongst diff erent regula-tory agencies in North America, Europe and Asia, for example.

“Th e regulatory agencies worldwide are attempting to come up with a formula for assessing and giving a number to the benefi t risk, but that’s another big challenge. You can put a number on effi cacy, and if you reach that, you succeed. With safety, things need to be considered on an in-dividual basis: drugs have idiosyncratic reactions and some behave diff erently in, say, a patient who is compromised in liver function or renal function. Th is has to be individualized and acted upon. It will be very diffi cult to come up with a fi xed number where you say, ‘Okay, this is the benefi t-risk ratio, and if the number is one, then the drugs get approved or not.’ It’s an evolving sci-ence in terms of how to perfect it.”

International outlookAnother change in the clinical trial

landscape has been the number of trials being conducted internationally. In Shah’s view, international trials are a very good way of making sure the drug is exposed to varieties of populations and individual country practices and habits as well as individual genetic considerations that may be brought in by diff erent parts of the world.

He underlines the fact that the opening up of certain areas, such as Latin America and Southeast Asia, has brought more diversity to the Kamal Shah is Head of Global Trials Safety Surveillance at Celgene Corporation..

“Trials could be conducted either in collaboration with or maybe even independent

of the pharma industry, which gives the potential for

a better success rate”

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THE DRUG DEVELOPMENT PROCESS

BasicResearch


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Any clinical trial is only as good as its weakest component, and ad-dressing this makes for a stron-ger, more robust project. Poor

site selection and poor site management can be costly in terms of resource and time alloca-tion, and also the clinical trial budget. Any effi ciencies that lead to quicker completion of studies will provide an oppor-tunity to bring a drug to market quicker, or at the very least make a decision on the suitability of a drug for market easier and reduce trial costs. Recognizing this, pharmaceutical companies are partnering with innovative CROs to manage site selection and management.

For any study to succeed, it is essential to choose the right investigator. A principal investigator (PI) should have a formidable knowledge in the therapeutic area of the trials and also strong knowledge of how clinical trials are conducted to FDA requirements. It is critical that the PI’s resumé is adequate for the trial undertaken.

However, there is more to selecting a PI than just these criteria. A PI must be the right one for your trial. Th ey need to have the right re-sources available and must be ready when you want to start the trial.

Some PIs are so much in demand that a clinical trial start date is delayed. It then becomes a trade-off : do you wait for the investigator or choose someone who is less in demand?

For day-to-day running of a trial, sub-investigators play a major role, but it is the PI who is the responsible leader of the team. Once again, the chal-lenge is to select the right site and look at the whole team, not just the PI.

Subject recruitment is also crucial. Th ere needs to be a proper search of patient records to justify selecting a site. In the past, sites have been selected that have said they have suffi cient numbers for a study, when in reality the

subjects have not matched the criteria needed for inclusion. Where the subject population

INDUSTRYINSIGHT

Effective site managementChristene Leiper explains how identifying key challenges and improving site management can save time and reduce costs.

has been minimal and the evaluable number not reached, this has led to poor results and in some instances a failed study.

While any one site might be performing well in a clinical trial, others may be falling behind in areas such as patient enrollment or data collection, or there may be other issues that prevent an individual site from perform-ing well. It is in your interest to identify the issues quickly, before they become a sig-nifi cant block to trial results. A good project management team can help here and ensure your trial stays on track.

Clinical trial management by a CRO that understands the importance of good site selection can assist in the navigation of the clinical trial project, taking the burden off investigators so that they can focus on the patient, and ensuring that the study is conducted at the highest standards of quality, ethics and performance. Th is support ensures collection of the robust, high-quality study data necessary for regulatory and product ap-proval submissions.

By making the right choices in site selec-tion and management, pharma companies can reduce risk, reduce cost and reduce the time taken to complete a clinical trial.

Key site management tipsIdentify, qualify and select the right sites

Negotiate good site contracts and budgets

Get supporting sites in local or central IRB/IEC submissions right

Design/produce training materials to ICH-GCP standards

Conduct site training on key aspects and on ICH-GCP requirements for the trial

Establish toll-free help lines with 24/7 access

Track/document project communications for Trial Master File compliance

Provide sites with regular study updates

Professor Christene Leiper has over 25 years of experience in clinical research. She is President of Onorach Ltd., a CRO located in Scotland with a global focus. The company philosophy is to engage with clients as a clinical trial partner and it has experience in site selection and management. Prof. Leiper can be contacted at [email protected]

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Increasing cardiac safety concerns have re-sulted in heightened regulatory scrutinyand the requirement for quality electro-cardiogram (ECG) data to be provided in

the early stages of drug development. Currently,a decentralized ECG study model is used in manyclinical trials to monitor a new drug’s effect on theelectrical functions of the heart. A decentralizedsystem involves ECG studies being carried outacross multiple investigator sites using local ECGmachines. However, this approach has a numberof limitations, including poor accuracy, consis-tency and efficiency of ECG data. A centralizedapproach has been found to overcome theseshortcomings.

Centralizing the collection of quality ECGdata, using digital ECG systems at a core labora-tory, accelerates the analysis process. Using highresolution digital methodology allows for moredependable data to be generated, as transcriptionand misinterpretation errors associated with a de-centralized approach are eliminated. The im-proved reliability of data collected using thisapproach leads to significant cost reduction andreduces the need for re-testing.

Some digital ECG systems offer the addi-tional benefit of automatically checking for miss-ing visits or changes in demography. A qualifiedcardiologist at the core laboratory evaluates eachECG, which ensures maximum data quality andconsistency. Not only does centralization reduceinconsistencies that may occur from site to site, italleviates laboratory and site workloads.

Additionally, the centralization of ECG analysiseliminates unnecessary over-read fees and re-duces site technical fee payments. Using central-ized equipment is an integral feature of a corelaboratory, requiring no extra expenditure formachine rental.

To enable trial sponsors to take full advan-tage of these centralized ECG model benefits, in-novative new instruments are necessary toprovide improved accuracy, reliability, space effi-ciency and cost effectiveness. Conventional ECGmachines can weigh between seven and 10 lbsand be of substantial size,making them expensive totransport and store, as well astime consuming and difficultto prepare for use. Averagerental costs for such machinesgenerally vary between $100and $150 per month.

Recent technological ad-vancements will see the intro-duction of highly compactECG instrumentation, pro-viding full ECG functionalityat a fraction of the size of tra-ditional systems.Revolutionary new instru-ments that will substantiallyreduce the costs of centraliza-tion are being developed.These small hand-held de-vices are easier to maneuverand significantly less expen-sive to ship and store, makingit easier for companies to adopt a centralizedsystem. Integration of these new instrumentsinto computer systems will enable informationto be automatically downloaded before a trial,saving staff time and costs associated with pro-gramming correct algorithms and patient de-mographics. Utilization of this advancedinstrumentation, with the process enhance-ments and reduced site and sponsor burden, willresult in measurable cost savings.

Conventional ECG systems produce paperprintouts of key ECG data, which are transcribedin order for results to be analyzed. Transcriptionerrors often occur, leading to inaccurate resultsand impacting the overall validity of trials. Thesenew modern instruments work by directly up-loading data onto the core laboratory computersystem, eliminating transcription errors and in-creasing data accuracy.

Although not officially mandated in currentlegislation, regulators often request that digitalECG data are submitted to a central digital sys-

tem, known as a data ware-house. All data stored on thesystem can then be accessedby regulators, facilitating andaccelerating inspections. Thelatest centralized digital ECGsystems enable clinical trialsponsors to easily complywith this requirement as theystore all data centrally andsimply transfer them to thedata warehouse.

Advanced softwareplatforms have also been de-veloped to enable seamlessintegration of new instru-ments into existing comput-er systems. This isparticularly beneficial interms of both staff time andcost, especially to sponsorsand CROs where the inves-tigator site is not familiar

with ECG systems. New centralized digital ECGsolutions, which will feature the new instrumen-tation, demonstrate clear benefits over tradi-tional decentralized methods, ensuring patientsafety and regulatory compliance while reducingsite burden and increasing accuracy, reliabilityand usability. n

Streamlining dataAmy Furlong explains why a centralized data system is more reliable.


For more information, please visit www.ert.com

For further information, please contact Amy Furlong atERT. Email: [email protected]

Amy Furlong is Executive VicePresident of Cardiac SafetyOperations for ERT. Furlong holds aBachelor of Science degree inBiology and a Master of Sciencedegree in Quality Assurance andRegulatory Affairs from TempleUniversity’s School of Pharmacy. Shehas more than 10 years of clinicalresearch experience, specializing inregulatory compliance andcomputer system validation.

“Not only doescentralization reduce

inconsistencies that mayoccur from site to site, italleviates sponsor/CRO

and site burden”

TROUBLESHOOTER

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Being the Vice President for Imaging at GSK is not just a job for Paul Matthews. Speaking to him, it is immedi-ately clear that he is passionate about the opportunity to bring chemical imaging to the heart of drug develop-ment. As he explains, this is not because it is just another test, but because it creates greater confi dence in drug

development, particularly at the early stage. He notes the current challenges of a high attrition rate in the industry

– when attrition is late in the drug pipeline it’s both extremely expensive and time-consuming, and is not doing either the patients or the industry itself any good as a result. “We’d like to bring confi dence in decision-mak-ing early and we can do this by trying to study pharmacology in humans in the same ways that we’ve become accustomed to and with the same detail of information we’ve been accustomed to getting in pre-clinical species. In order to do this, we need to have powerful non-invasive approaches to quantitative physiology and pharmacology. Th is is what imaging is really all about,” explains Matthews.

“While I speak of imaging in the context of drug development, it’s not about developing pretty pictures, although that’s a side benefi t. It’s

IMAGING

NGP talks to GSK’s Paul Matthews about the unique challenges posed by the marriage of imaging and drug development.

about providing quantitative information related to where a molecule might move in the body in a biodistribution study, molecular interactions of a putative drug with its target, or about physiological responses of the human tissue. Th is is what imaging can bring to us and its confi dence in decision-making is the impact.”

He describes the current relationship between drug development and imaging as an “interesting period of marriage”. Matthews adds that the technology connecting the two has been missing for some time, at least in principle, but what has really been missing is the connection of drug devel-opment in the hands of people who understand how to use the information that’s derived from investigation and those with an expertise in imaging.

“Bringing imaging to drug development isn’t just about going down a checklist,” he says. “It’s about developing powerful questions and then fi nding the technology that answers those questions and not diff erent ones. Previously, the limits placed on the ability of the imaging to have an impact on drug development happened through parties that were not engaged with the same agenda. A company would go to an academic site or an external CRO, who had a limited understanding either of the problems of drug development or the specifi c problems of a molecular series.


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“By communicating the results of trials and the rationale leading up to them in an open public forum, we can increase the quality of the science”

GSK Imaging Centre

In partnership with Imperial College and the UK Medical Research Council, GSK has built a Clinical Imaging Centre (CIC) at Hammersmith Hospital in London, UK. The CIC houses leading imaging scientists and state-of-the-art PET and MRI equipment. The imaging center partnership is one of the largest industry-university collaborations.

The goals of the CIC include to:

- Accelerate effective drug discovery and development in GSK- Establish a center of excellence with a critical mass of

imaging expertise- Develop and utilize imaging methods for novel molecular

targets from the GSK portfolio- Characterize the distribution and pharmacokinetics of novel

drug candidates in man- Characterize key human diseases represented by the GSK

portfolio- Develop and implement novel methodologies for the above




(CEDDs), have been divided up into these DPUs. Th e size of each unit ranges between 40 and 70 people, all of whom are located on single sites, and this allows for face-to-face communication on a regular basis. Howev-er, although this brings many advantages to the communication process, by dividing up a big organization into smaller units the risk remains of failure to communicate between each DPU.

“To some extent, this is helped by organizing clusters of DPUs together as CEDDs, or units as in oncology,” says Matthews. “For our pharmaceu-ticals, where the leadership regularly meets together with a leader of the CEDD or unit in order to develop coordinated strategies and provide a communication strategy that, again, is limited to a relatively manageable number of players who can meet regularly, face to face.

“You can understand that I’m a great fan of trying to get human-to-human contact to make those communications. Now, fi nally, what we’re trying to also do is create structures that move across DPUs and CEDDs and begin to share what is learned from one with the others. Th ese take a variety of forms; they’re suited to the problems that they’re trying to ad-dress.”

ChallengesMatthews provides an example of GSK’s peer review forum – a group

of senior clinical scientists who meet on a weekly basis to review new pro-tocols coming through drug discovery. Th e review is voluntary, although it is taken up by almost every unit moving protocols forward, and provides feedback on the science and attempts to help create the strongest protocols possible. In doing so, the hope is that expertise is brought across from one unit to bear on the problems of another.

Another challenge that continues to increase is the identifi cation of disease areas that are being pursued across DPUs or CEDDS. Matthews notes that discussion groups are coming together to look at the strategy for the company in terms of the science and the relatively autonomous units that lie beyond that.

He also notes that there are a number of higher-level mechanisms that are set up to provide scientifi c feedback in the form of scientifi c ad-visory boards that sit above the CEDDS and DPUs, in which learnings are shared so the best science can be produced, as well as to allow a good accountability for safe clinical practice and trials. “It’s not a solved prob-lem. It has to be addressed at multiple levels using diff erent approaches. One of the things that we’re trying to grasp is making person-to-person contact the foundation of this, because that’s ultimately what’s so much more eff ective,” says Matthews.

Internal communication is essential for better science and employs an equally critical role for the wider public – more information commu-nicated on the same level of effi cacy and depth of R&D has the potential to cut down on health scares. Matthews explains that some recent ex-amples of this have been generated by the pharmaceutical industry itself which failed to communicate the science well to the news media, who misunderstand as a result.

So how is this to be remedied? Matthews believes that it will be a slow process, but one in which GSK can be confi dent and successful. “First, we’ve got to create an open, transparent industry. We have to be able to communicate why we’re pursuing the areas that we are. We have to com-municate the importance of science and objective thinking being at the

“Here, what we’ve been able to do is actually merge clinical teams developing drugs with teams delivering this high-level pharmacological and physiological data, so the two have a common language. Th e ques-tions can be translated across. Th e tools can be suited to the problem. And that’s what is beginning to make these studies impact rapidly. To give you a fl avor for this, in the last seven months we’ve done as many studies with the opening of the imaging center and bringing it up to full speed, as GSK did in a similar area over the previous couple of years, and that’s because we can make things move much faster, do studies that count and bring value to the company and, ultimately, to patients.”

CommunicationR&D is one of the key functions in which science and the business

of pharma are merged, and ensuring communication between the two is essential. However, this is no easy task. Matthews explains that commu-nication is the number one challenge facing any large organization among the three issues that each organization must face. “One is communication across R&D itself to help this very broad organization learn to optimize its ability to work together, so that we don’t have individual drug units pursu-ing similar problems without knowing about each other.

“Th e second area of communication is perhaps even more critical if we’re to transform the industry, and that’s to communicate the needs of late-phase development into early phase and to merge the problems that late phase will encounter in the clinic into the early development decision-making. And, in turn, to use the science from early development to trans-late out to late phase, to help defi ne the populations that are targeted for a new treatment, the way studies are designed and also the way in which the potential benefi ts are communicated.

“Th at leads to the third communication problem. Making drugs is fundamentally a very complex scientifi c eff ort. We need to get away from the notion that every drug hitting the same target is equivalent and com-municate the potential diff erentiation of our molecules, which we’re work-ing towards from the very beginning of discovery way out past the stage at which it’s marketed.

“We need to help physicians and patients understand the diff erences between drugs within the pharmacopoeia, but also the diff erences be-tween the way drugs may act in diff erent kinds of people. Th is is a new type of agenda that we’re going to have to grasp. I’ve mentioned three: communicating with R&D, communicating between early and late-stage pipeline and communicating the science of drug development to the user population. But they’re all wrapped up together. It’s about making science the core of drug development and being transparent about how the infor-mation is used in the process,” he says.

Matthews explains that actively promoting this course of communi-cation throughout the organization is something that the senior executives within GSK’s R&D department are attempting to do. He notes that one key element that has been taken into account is to create working teams that are small enough to speak together, are co-located and have a limited agenda, which allows issues to be fully aired and done so openly amongst larger segments of the group. Th ese groups have been named development performance units, or DPU.

Matthews explains that the major drug development units, either the larger units or the former Centers for Excellence in Drug Discovery



basis of our decision-making. And, fi nally, we have to be able to commu-nicate this science, the results of clinical trials for example, in a fully open and transparent fashion.

“At the same time, we have to be willing to engage our scientifi c com-munity and even the public in very open feedback. We have to get away from KOL meetings that are stacked with people who we think are going to provide us the right answers. We have to go out and fi nd the people who are going to be able to comment the most robustly and provide the strongest opinions on what we’re trying to do. Th at’s GSK’s commitment now. By having open science, by communicating the results of trials and the rationale leading up to them in an open public forum, we can increase the quality of the science, because now it’s being tested against the best the scientifi c community has to off er.

“We can also help the public have more confi dence that decisions aren’t being made behind the backs of everyone, that things aren’t being hidden. Finally, we have to continue to address the issues of scientifi c ethics and business ethics throughout the process. We have to make sure that the motivations of the people we have involved, both within the company and outside, are transparent and appropriate.

“We have to appreciate the tremendous responsibil-ity that has been vested in the pharmaceutical industry to be the primary bringers of new therapies to the public. We have to recognize that we have a pact with the public who depend on our drugs, with the shareholders who are supporting the company, to be ethical in everything we do. If we begin to stray from that, we’re only going to hurt ourselves.

“GSK has taken these values very strongly to heart; they’re a core of what we’re all about. An example of this is our peer review group that vets every early stage protocol going through, trying to provide good scientifi c input. Th is group includes not just GSK staff but also external scientifi c advisers, who are independent of the drug pipeline of progression and who can openly look at our science and provide us with the clearest docu-mented feedback that we can get from them,” he says.

TechnologyGSK has a track record of turning such fi ndings into powerful and

marketable drugs; Matthews explains that drug development must not only have strong communication to be successful but also be collab-orative. “We’re in a very special place; we’re at the interface between pre-clinical science and clinical science, trying to translate the fi ndings from our pre-clinical colleagues into pharmacology in humans to help provide confi dent decisions moving forward.

“We see that as our space. Again, we try to be fi rm, open scientifi c critics of the development program; we try to ensure that we’re asking powerful questions that will either help a molecule move forward, if it’s appropriate, or kill a molecule if there is good reason to stop the development.”

To take on this challenge, GSK has a range of scientists participat-ing in development; this range is varied and they do not all share the same scientifi c agendas. Th is allows the project to be objective rather

than being carried away by the need to move a molecule on to the next stage. Bringing together scientists from diff erent backgrounds is vital so that they don’t carry the same biases to the problem. GSK’s aim is to create an independent development unit, contributing to drug eff orts in multiple CEDDs, DPUs and units.

GSK’s overall strategy is divided into three priorities – to grow, deliver and simplify each specifi c role in each area of responsibility. Matthews explains the importance of simplicity: “When companies grow, there is an eff ort to address many problems – communications, governance, coordination – but what they inevitably do is create more and more rules, so it becomes increasingly byzantine.

“Our goal, as a group within GSK that is trying not just to conceive clinical trials, but to execute them, and not just ordinary clinical trials, but trials that put a premium on speed and effi ciency, our job is to try to identify the hairballs that we can throw out of the mix to try to help us

move more quickly. So simplifi cation is something that becomes critical to our business case.

“We depend on being able to move rapidly from solutions to one problem to the challenge of solving an-other. If we’re mired by bureaucracy and unnecessary complexity, our mission is going to be severely limited. So simplifi cation is something we’re taking to heart. We’re continuously re-examining all of our processes and the way we relate to our partners; we’re trying to bring out unnecessary elements to do all the simple things like cutting meetings, making meetings more focused, but also to try to make all of our processes as simple, transparent and needs based as possible.”

Growing the company is also important – trans-lating value into growth is the company’s strategy. By growing in quality rather than quantity, GSK can bring greater value to the market. Matthews explains that

the focus is on making more rational, early-phase decisions, which will drive better drugs for patients.

He envisions delivery as having a sense of urgency, which permeates throughout the organization. Interactions between DPUs and CEDDs are fast-paced, making the drug development timeline signifi cantly shorter. “We’re trying to bring more patients into the organization in regular discussions about what the patient needs, so that we can show the bench scientists what it is like to have the disease that we’re trying to work on.

“We’re also trying to bring an intelligent plan to drug development so that we don’t repeat things that don’t need to be repeated. So urgency, and bringing science and a considered development approach to the problem, are how we’re trying to bring delivery.

“Our belief is that with a rational development process, with a sci-ence-based development process and with a very open and transparent approach to that science, we’re going to ensure that the molecules that we’re moving forward deserve to be moved forward, and that we ad-dress effi cacy and safety issues that need to be highlighted at the earliest stages possible. Th is limits the amount of resources, ultimately, that we may waste. And in the end, it is going to deliver products of real value to the market.”

Paul Matthews is Vice President for Imaging at GlaxoSmithKline and Head of the GSK Clinical Imaging Centre.



contemporaneous, original and accurate, some method of archival must also be established.

ACR Image Metrix utilizes a proprietary system, TRIAD OA, for the anonymization, re-identifi cation, analysis and archival of

image data. TRIAD represents the data management changes that imaging has eff ected in the development program en-vironment because it supports seamless, rapid management of data through the use of the web. Where sharing images once involved multiple steps, now data can be uploaded onto a secure site to promote instantaneous action. With-out delays in image transfer, the image can be QC’d by the imaging technologist for read-ers to perform interpretation and quantitative analysis more quickly, without information getting lost between steps.

Henceforth, imaging will continue to play a larger role in development programs, from start-up to post-marketing activities. As this technology continues to be refi ned, its role in clinical development will only increase. Already, its benefi ts boast streamlining the decision making process and necessitating stronger operational data management processes. Clearly, imaging’s contributions to success jus-tify its inclusion in your study today. n

waiting. One application of this exists when changes in glucose uptake in cells over time are critical to the recognition of drug activ-ity; including a conventional PET scan using F18-FDG eliminates the wait as FDG more quickly mimics the actions of glucose. Likewise, DCE-MRI allows earlier estimates of drug effi cacy by examining the vascular changes in a tumor, which begin more quickly than actual tumor shrinkage.

However, imaging solu-tions would lack relevance without cohesive data manage-ment, which actively demands standardization in data acqui-sition, management, quality control, archival and analysis. Th e fi rst step in standardized data acquisition is validation, which examines and qualifi es the utilized technology as a whole, including the comput-ers and users. Because image acquisition involves an inher-ent risk for human error, users must be trained in accordance with SOPs and GCPs while the technology is being tested to create an environment of control. Image management must establish means of source documentation in accordance with HIPPA regulations and must ensure the integrity of the image collected during in-terpretation and quantitative analysis. Because source data must be attributable, legible,

The capabilities of imaging today possess far more extensive ap-plications than existed 100 years ago. With conventional proce-

dures being replaced or enhanced with more advanced novel imaging or nuclear modalities, researchers are gaining a wealth of resources for various functions. Th us, imaging plays a far more active role in the development process. Moreover, the integration of the appropriate imaging technique in a development program reduces necessary time and costs, thereby in-creasing its effi ciency.

In selecting the most appropriate modal-ity, several considerations must be made. Each development program possesses distinct attri-butes and goals that must be addressed before imaging can be integrated. How will the imag-ing be utilized? Will the information serve as a biomarker, endpoint or marketing tool? In each of these situations, imaging operates in a diff erent capacity. As a biomarker, imaging provides a more comprehensive analysis of therapeutic eff ects and pathways of action; in early phases, imaging can be incorporated to elucidate mechanisms, reveal drug activity and assess the value of a new medical device. As an endpoint, imaging shortens the time to reach conclusions. During certain situations, data may be collected that will not contribute to the regulatory application; this imaging is oft en useful in marketing functions aft er approval has been received. Th us, imaging plays a role in every step of the development process.

If properly employed, imaging reduces time and cost expenditures primarily by low-ering variability in decision making. With earlier results in safety and effi cacy, research-ers can make go/no-go decisions sooner with-out consuming unnecessary energies while

ASK THEEXPERT

How the integration of appropriate imaging modality increases the effi ciency of clinical trials

By Michael Morales and Bruce Hillman

Bruce Hillman, MD, is the Chief Scientifi c Offi cer for ACR Image Metrix. He has been selected for Who’s Who in Medicine and Healthcare and Who’s Who in the World. Prior to his experience with ACR Image Metrix, Hillman was the Chair and principal investigator of the American College of Radiology Imaging Network (ACRIN).

Michael Morales holds the position of General Manager with ACR Image Metrix. As such, Morales has responsibility for strategic, tactical and fi nancial operations. His accrual of over 30 years of experience in organizing and coordinating large-scale clinical research to accelerate drug development programs involving imaging is critical to the success of his position.

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There is a new health landscape inwhich the rules are changing on allfronts. Patients are taking more con-trol over decision-making regarding

their treatments, with access to a wealth of infor-mation available at their fingertips on the web.There is also a greater emphasis on safety on thepart of both regulators and consumers.Furthermore, there is a greater value conscious-ness on the part of both patients and payers. Thismeans that there is a heightened need for differ-ent types of data for the changing stakeholdergroups that goes beyond the data traditionallygathered for the regulatory authorities. It is nowvitally important to consider these needs and todo so early in the drug development process.

These drivers have contributed to ‘the per-fect storm’ for biopharma companies. Goingforward, it is easy to envision how the impend-ing ‘patent cliff’ that is unfolding will serve toheighten the pressure that the biopharma indus-try faces. Specifically, from 2009 through 2014,an estimated $128 billion of branded revenueswill go generic. At the same time, funding for

biotechs remains under heavy pressure in a cap-ital constrained environment. Pharmaceuticalcompanies need to re-examine the way theymanage the lifecycle of theirdrugs, in particular the role oflate phase studies if they are todifferentiate their productsand build a comprehensivevalue proposition in an in-creasingly saturated andpayer-dominated market-place. If they don’t take up thischallenge, the payers them-selves will be only too happy tostep into the breach and, in theend, it will largely come downto price.

Ultimately it comes downto real lifecycle development.The concept of value haswidened to encompass not justwhether a drug is safe and‘works’ but other key factorssuch as how it performs against

the current gold standard of care, cost-effective-ness, long-term risk management and satisfyingreimbursement criteria. While elements of valuecreation, such as patient-reported outcomes(PROs) or quality-of-life measures, can be incor-porated into phase II or III clinical trials, the realgoal of these studies remains getting the drug li-censed and it is imperative that this goal is notcompromised by building in too many more ob-jectives. Hence the need to have a longer termstrategic clinical plan that includes post-market-ing studies.

These studies are concerned with what theproduct actually looks like in real life, rather thanin the highly selective context of a mainstreamclinical trial. For example, in a real-world settingpatients may have several diseases and be takingseveral therapies at once. To pursue late-phasedevelopment effectively, though, requires specificexpertise that goes beyond that employed in thetraditional phase III setting. Expertise is requiredin areas such as PROs, health economics, statis-tics and outcomes research and, as with all formsof research, the key success factor is designing thestudies correctly from the outset.

Nurses and patients can also help to fill out adrug’s profile post-approval. Sponsored nurses notonly play a crucial role in patient education andcompliance with therapy, they can also collect out-comes data from hospital databases under con-tract. Patients can also contribute through mediasuch as the iGuard online medical monitoring ser-

vice, which was launched in2007 with start-up funding fromQuintiles. The service now hasover two million users.

Ultimately however whatis required is a major change inthinking to ensure there is acontinuum of studies, whichencompass both the more tra-ditional and the more innova-tive approaches, which willprovide the right data at theright time to satisfy the needs ofthe increasing stakeholdergroups. It is only by thinkingstrategically early on in the de-velopment process that the bio-pharma industry will be able tocontinue to develop new andbetter medicines that deliverreal patient benefits. n

The perfect stormJohn Hall tells NGP about the burning issues inthe biopharmaceutical industry.


PROJECTFOCUS

John Hall is Vice President, GlobalMedical Affairs, Epidemiology andOutcomes Research for Quintiles.A former practicing physician,Hall brings over 25 yearsexperience in development andcommercialization strategy,having served in medical affairswith Eli Lilly, Glaxo, Allen andHanburys and an independentconsulting company.

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Few people genuinely enjoy change, butthe pressure is on for pharmaceuticalcompanies to change the way they doR&D, to more efficiently produce new

drugs in a post-blockbuster world. A visionarymight approach bottlenecks in their process bydeveloping a custom solution such as specializedsoftware or equipment platforms. While the em-phasis on new technologies and innovations iscommendable, such custom solutions are oftencomplex and risky, adding significant time andexpense. Thankfully, ready-made commercial so-lutions, such as the Reveleris flash chromatogra-phy system, are available to address bottlenecks inthe drug discovery and development process.

As discussed in a recent Chemical andEngineering News article, the days of feeling flushwith cash are over, and the pharmaceutical in-dustry must begin making simpler, more effectivechanges. Recent attempts to reduce overall drugdevelopment costs have included drastic cost cut-ting and ‘merger mania’. However, the industry’sattention has now shifted to examining and im-

proving processes to shorten R&D time and fuelthe pipeline. This is a critical time to consider thedifference between customized and commercialsolutions to productivity opportunities.

The productivity of the pharmaceutical in-dustry is often measured by the quality and quan-tity of new drugs in the development pipeline.Those companies that commit to effective trans-formation will reap the benefits of a rejuvenatedpipeline both short and long term.

There are many paths to strengthen apipeline – diversifying with biologics, focusing onfewer disease targets, in-licensing more therapies

and adapting to offer other products (such asgenerics and other health products). However,pharmaceutical companies must focus on theircore business – discovering and developing newmolecular entities – to drive long-term, sustain-able growth. In many cases, this requires an over-haul of their internal drug discovery processes.

Good operations management addressesbottlenecks to improve overall performance,quality and throughput. This new emphasis on‘process’ means drug discovery must be stream-lined to quickly deliver high quality NMEs with-out sacrificing quality. To address attritionconcerns, companies must have more confidencethat NMEs will perform better with less risk offailing in phase II. Leads must be advanced quick-ly, or failed early.

Adopting new technologies to achieve theseprocess improvements is critical. For many years,the industry has chosen the path of customizedsolutions for these improvements, such as pro-prietary hardware or software developed inter-nally or co-created in external collaborations.These projects may be born of an innovative spir-it, but they can often fail.

Large teams, typically including the scientistsin the affected labs, are chartered to develop andimplement the customized technology ‘efficiencyproject’. These projects take much of the scien-tists’ time in designing, planning and testing. The

result can be a negative effect on drug discoveryoutput since the scientists’ time and energy,which should be focused on developing and test-ing NMEs, is instead focused on the efficiencyproject. The drive to continuously advance NMEsis diluted, and progress is slowed. Later, upon re-view of the new custom technology, the projectmay be deemed an expensive failure or aban-doned due to a lack of measurable productivityimprovement.

The pitfalls of customized solutions can beavoided by implementing commercially availablesolutions without the distraction of lengthy, com-plicated projects. Such solutions, whether instru-mentation, software or consumables, aredeveloped with productivity in mind and can beimplemented quickly and cost-effectively.

As the world’s leading supplier of silica gel tothe pharmaceutical industry, Grace recognizesthe challenges of NME purification. The Revelerisflash chromatography system was designed to ad-dress one of the most common bottlenecks indrug discovery: purification. Along with our so-lutions in process media, packing systems andcolumn packing services, Grace can help phar-maceutical companies improve productivitythroughout the R&D process. n

Turning pipelines into profitsHow drug discovery bottlenecks can be addressed, according to Grace.


PROJECTFOCUS

This article was written through the collaborative effortsof Grace’s Marketing, R&D and Six Sigma teams. Pleasesee www.ngpharma.com to read our editorial on thepurification bottleneck.

“The pitfalls of customizedsolutions can be avoided byimplementing commercially

available solutions”

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PROCESSIMPROVEMENT

In this excerpt from an interview with NGP’s sister media channel, MeettheBoss TV, Sanofi Pasteur’s Rene Labatut tells Victoria Newing the secrets to staying in control of your vaccine manufacturing processes.

IN THE DRIVING SEATTh is also involves being in charge of continuous improvement for

any manufacturing process, as well as technological innovation. Th at’s my primary responsibility. Besides that and within that, there is all the techno transfer between internal sites and also between Sanofi Pasteur and our partners.

Sanofi Pasteur is the largest company in the world devoted entirely to human vaccines. How do manufacturing processes differ across the globe?RL. Sanofi Pasteur’s manufacturing processes use the same standards but have diff erent processes for the same therapeutic queues. We have three Tetanus processes, for example: one in Canada, one in the US and one in France, and now because of the recent acquisition we have one in India too.

You have 22 years of experience in biotechnology across 9 variety of disciplines. How does this insight help you in your current role?Rene Labatut. My experience has helped me in two ways. First, to have the right level of humility – there are a lot of things you have to learn and you can be surprised every day; the biotech world is like that. And also to always be looking at the big picture; sometimes I need to go into very detailed things, but I must always have the ability to go back and forth between the diff erent levels of vision, as well as to build a vision of what’s next based on experience and extrapolation between things.

My key mission is to be the guardian of industrial knowledge for the company. To be a guardian is a dynamic thing and not a passive one; not keeping things as they are, but moving them into what they should be in the next 20 years. It’s transferring new products from R&D to manufac-turing: taking them from phase II up to commercial launch.


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Th e diff erence in these processes is historical: they come from the original companies. Now when we are develop-ing a process, even if we have several manufacturing units, at the end it’s no-tably true in formulation. Th e processes are the same; the challenge in this fi eld is to keep it the same because along the life of a process in a diff erent unit, you always have circumstances where people make minor changes. So you have to be very strong on your change control policy.

Th ere is a system called a process book, which is an electronically orga-nized reference where people fi nd the detailed description of what they have to do. It is web-based, so any informa-tion can be accessible in less than six minutes; and there is exactly the same reference for people who are run-ning the same process in two locations.

It’s anticipated that the demand for new and existing vaccines will double by the year 2012. What measures are you taking to ensure that Sanofi can deliver and meet market demands?RL. Four or fi ve years ago we engaged in a strong investment policy. On a yearly basis we invest between €350 million to €400 million [US$480 million to $550 million], and have built a huge inactivated polio vaccine capacity in Lyon, France. We have more than doubled our fl u capacity in the US for seasonal fl u and the formulation/fi lling in the US has also been extended. We have invested close to $200 million in this unit and we have also invested very heavily in Normandy, France, to do formula-tion, as well as fi lling and packaging for distribution of vaccines on a worldwide basis.

Now we are also leveraging all the capacity we have at the group level, notably in packaging because it’s less specifi c for vaccines. We have a plan to invest more than €250 million [US$34 million] to build a new dengue unit; and there is also an ongoing plan to develop new vaccines for diseases which are not yet covered by vaccination programs.

What new approaches are needed to drive manufacturing processes more effi ciently and to overcome the complexities of new vaccines?RL. New vaccines for new diseases can be more complex to produce be-cause they have processes that are more complicated, such as new conju-gates or new formulation types, which are more diffi cult to manage. Th e other way around is to design your product approach – this can be more complex for something like the dengue vaccine, which is a vaccine for a

chimera,– but the management of the process itself is not so complex. Th e way you manage your cell and the interaction between the cell and the virus is diffi cult, but in comparison to a classical inactivated polio vaccine, the process itself is simpler because the complexity has moved into the product itself and the construct will simplify aft er the process.

A vaccine is a preventative medicine; when you inject a vaccine into someone they are not sick yet, and the worst thing you can do is to make them sick using the vaccine. So the level of attention you must pay to safety is very high.

Th is ties in with the trend of moving to a more preventative type of medicine from a curative one, and requires a diff erent way of thinking. Th e only area where the risk/benefi t ratio is very high is in therapeutic vaccines – but mostly these type of products are the last line of defense – or therapeutic use where the risk is death within six to nine months, so it’s a diff erent story.

You’re an advocate of the software solution process. Can you elabo-rate on the benefi ts that this can offer a company like Sanofi ?RL. We want to drive our processes instead of following them; when you drive you are in control. When you are following, you are just reporting what’s happened, which is not really the mindset we should have. We want to go to a QBD-type approach and have a consistency of output of our process; consistency of results versus the classical consistency of settings. Th ere is a lot of classical approach in secure process control.

Following critical parameters step-by-step independently of each other assumes that if you take a given step the result of this step will not infl uence the step aft er. In our process there is a lot of diffi culty, and it’s not mathematically accurate to say that the steps are independent. We have to consider the process as a rule, with interconnection between steps; and the result of what happened in step one will have an eff ect on what will happen in step six or eight and can be corrected by what will happen in step 10.

But you need to have the overall behavior; and this type of soft ware is trying to address that, looking at the overall process and how it be-haves and interlinks. And instead of having a critical parameter only on

Rene LabatutMeettheBoss TV

“We want to drive our processes instead of following them; when you drive you are in control”

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What drives the performance of the process, in terms of product and making yields? Th e huge leverage it yields. If you understand very well how your complex biological system is working, then you can apply a method or attune the way you drive your process to increase. Just by managing the biological organism we handle its physiology very closely and see how it behaves when it becomes invasive in the body, then use the defense mechanism as a leverage to obtain the product we want versus when it is in a comfortable situation doing regular things.

How is innovation formalized and managed at Sanofi Pasteur?RL. In order to manage innovation, we have had to sort out what the fi elds of innovation are. We are looking at what we have in the pot from discovery down to commercial. What is the overall portfolio of products in the company, the ones that are at the early stages, as well as the ones we are manufacturing? We’re working on the type of processes and the technology we are using from the early microorganism down to the fi nal box – looking at where the needs for technology are in the company and also in terms of order of magnitude in the market.

First, we are looking at needs we have not covered by existing tech-nology: where we have developed something, where it applies and what is the value for the company according to the span, focus or depth into a certain product. Th at’s the needs part.

We are also scanning what’s going on in diff erent areas of the industry, not only in pharma, but also food and microelectronics. We are scanning what’s going on in universities and at the very early stages, looking at where it can apply and where it can make a diff erence; in doing so, we want to develop technology. Our technical teams are evaluating continuously with biotech teams or with universities, several of which we have contracts with.

What role do issues such as the relationship between development costs and drug prices play in the transfer from R&D to operations?RL. If you take too long in transferring from R&D to operations costs will increase: any time you take will be costly and this will have an impact on the cost of the goods. If you fi nd ways to speed up this transition or transfer, normally you will reduce the cost at the end and you have more leverage to be able to negotiate or provide the services with a better price.

Th at said, to be able to transfer quickly from R&D to operations, you need to have a very specifi c approach on the R&D development level be-cause things that are a little bit fuzzy or not totally developed will induce a lot of rework during the transfer or just aft er the transfer, and that doesn’t help to keep costs at an optimized level.

Sanofi ensures that we’re optimizing that process by mostly impos-ing a quality by design mindset, starting in phase I. Th e pharmaceutical development of new products is jointly managed by the VP of R&D and myself, and to ensure the team diagnoses in phase I or phase II the critical quality attribute of any product, the critical process barometer associated with the system.

Th en there is also preparing the scale-up algorithm: starting to opti-mize upfront as much as we can yield reliability and the capability of pro-cesses to eliminate what can be damaging for the operation aft erwards; and also to help minimize the investment needed. n

one step, you have a cluster that are on diff erent steps. But it’s based on a mathematical model like genetic algorithm, which is a learning-type process. And the way we use it, notably on high frequency products, enables us to look at what happened in the early stages of the process for some parameters. We must then predict – based on all the models – where it will end if we don’t correct the settings and diagnose what will be the appropriate corrective setting we have to put in place before the end of the process. Th en we can be sure that we are very close to the point where we want to end in terms of product quality and product yield.

How does the manufacturing process help drive the need for innovation?RL. Th e innovation I’m focusing on centers on discovery work in vaccines. We now face the challenge of being able to do this in an economically viable way and also in a volume way, in terms of the number of doses produced at a reasonable cost. Th ey must be aff ordable on a worldwide basis, which is not a niche market for most of these products. We need to innovate to make this possible, to extrapolate directly what’s done at the lab bench scale. We cannot do it at the large scale that we need, so there is some innovation there to be driven by us.

We also need to improve processes and assure process performance. We need to think about doing it diff erently – changing and applying new technology or a new way of thinking, leading into new manufacturing technology even for existing products. Th e big drive behind that is that you can manufacture a certain way, and put the cost of goods at a value of 10. Th e number has no real value, it’s just to give an order of magnitude. If you want to sell that in Western Europe, that’s fi ne. But if you want to address it on a worldwide basis and encompass developing areas, you have to bring your 10 down to under one; and to do this you have to have a technology breakthrough.

Th ere are diff erent ways to achieve this. First, you think of the classi-cal approach of applying Lean to your manufacturing process or getting rid of things that don’t make sense or are just there because of history or habits. Th e second step is to maximize the value of what you get out of the things that it still makes sense to do. Rene Labatut is Vice President of Global Manufacturing Technology at Sanofi Pasteur.

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PROJECTFOCUS

Achieving sustainable performanceDebra Shumar explains the importance of knowing where and how to use Lean and Six Sigma.

“Problem detection and performance review processes can help guide where Lean and Six Sigma projects may be best suited to achieve sustainable growth for the company”

Each year, companies set out to align their organization with its strategic plan. Nonethe-less, the execution of the plan is, far too oft en, misaligned or out of sync with the company’s

overall values, mission and vision. Consequently, the leadership of the company, including the board of direc-tors, must possess and share a singular vision that not only allows them to create expectations but also to hold everyone to them. Since managing a company without risk is impossible, the next best thing is to manage a company with controllable minimal risk. Th is can be accomplished by setting up a comprehensive system called problem de-tection and performance review. In this regard, pharma-ceutical companies present a unique set of circumstances. Th ey have the ability to research and to develop drugs that enhance the lives of people, but they must do so in a cost-eff ective, effi cient manner so that the drugs being developed can be sold to the consumer at a reasonable cost. Th is is where goals and objectives that incorporate Lean and Six Sigma thinking are most eff ective.

Th e drive to succeed is both a company and an indi-vidual goal. Th erefore, the company must have a mindset that insures that the company’s processes both facilitate and foster an atmosphere in which the newest technician in research believes that his/her thoughts and suggestions are valued just as much as those of the CEO. Problem detection and performance review processes can help guide where Lean and Six Sigma projects may be best suited to achieve sustainable growth for the company. But serious questions remain: does this company have a process in place for sharing failures and successes among departments when developing a drug? Does this company communicate (through the written word and the use of metrics) what has fostered an effi cient, cost-eff ective method for conceiving new drugs?

Since the primary concern for the management team is how to deal with mounting pressure to reduce the costs associated with the development of new drugs, making certain that the requisite skills are in place becomes para-mount. For example, a study was conducted to understand the strategic control approaches used by major cancer cen-ters in the country and to relate these practices to fi nan-cial performance. According to the Journal of Healthcare Management, “Th e results suggested that high performing cancer centers use more sophisticated analytical tools and approaches, and invest greater fi nancial resources in

performance analysis and performance reviews than low performing organizations”. Consequently, if (and it’s a big ‘if ’) corporate goals establish the need to reduce costs, to eliminate waste and to encourage individuals to take own-ership of their work, the company will then be well along on its way to sustainable growth.

Vital to this transformation is making sure that Lean and Six Sigma objectives, goals and metrics are aligned from the top to the bottom to demonstrate consistency of purpose. Th is translates into sustainable performance across departments, functions, regions, divisions and cor-porate boards. In his book People and Performance, Peter Drucker states, “Any business enterprise must build a true team and weld individual eff orts into a common eff ort. Each member of the enterprise contributes something diff erent but they must all contribute toward a common goal.” Transform-ing the way companies work requires the creation and appreciation of a kind of workforce that (to a single person) understands their contribution to the company as a whole. Managing Lean and Six Sigma projects in support of these objectives requires them to become embedded into the overall business system so that the necessary behaviors are second nature – no one even thinks about ‘achiev-ing objectives’ anymore. Or, as Peter Drucker concludes, “Business performance therefore requires that each job be directed to the objective of the whole business.” Th is, then, is the vanguard to the success of any company because it is real and it is sustainable.

Debra Shumar is President and Founder of 3P Partners, a DL Shumar & Associates Co. LLC. 3P Partners provides innovative approaches, services and software solutions in quality, cultural transformation, Lean and Six Sigma management, and supply chain risk management for improving business, operational and workplace performance.

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The application of predictive analyticsto extend the use of the Lean pullprocess into complex manufacturingprocesses offers great potential for

improving the responsiveness and efficiency ofglobal pharmaceutical manufacturing chain op-erations. Predictive analytics are substituted forthe Kanban method used in assembly operationsto provide the demand signal for the pull process.

Predictive analytics is the application of sta-tistical data analysis to capture relationships usedto predict future trends and behaviors. Creditcard companies use predictive analytics in so-phisticated fraud detection systems and leadingretailers and e-tailers use predictive analytics tosuggest additional items that may be of interest tothe customer based on past behaviors and demo-graphics. In process manufacturing, RockwellAutomation uses predictive control models thatenable process systems to adjust more quicklyand accurately than with actual measurements.Applying these predictive control techniques sig-nificantly improves performance.

The Lean pull process dramatically im-proved Toyota and Dell’s assembly operations byeliminating dependence on inaccurate forecasts.The Lean pull process uses firm orders as a de-mand signal and propagates it along the produc-tion chain. However, manufacturers with high

structural complexity require reasonably longproduction runs to achieve acceptable productioneconomics. Accordingly, production-schedulingdecisions need to be made before a complete de-mand signal from customers is available. In suchenvironments, it had been assumed that the Leanpull process could not be used.

SherTrack’s research on demand patternshas enabled the successful application of predic-tive analytics to the order-to-fulfillment process.SherTrack’s predictive analytics algorithms pro-vide an accurate, synthetic customer order signalin the operational time horizon of the next two tothree production cycles, enabling application ofthe very efficient Lean pull process in operationswhere it was thought too complex to use.

The traditional approach to coping withpoor demand visibility is to forecast demand, setinventory targets that incorporate safety stocksthen optimize the production response.Unfortunately, forecast error renders this processincapable of handling the structural and dynam-ic complexity of multi-product facilities. Acrossall industries, best-in-class forecast error (such asdemand variation) exceeds 40 percent mean ab-solute deviation, which means that while forecastsare appropriate for tactical planning issues, theyreally can’t be effectively used in execution. Mostadvanced planning and scheduling (APS) solu-

tions were developed to meet the needs of theproduction planning process with finite schedul-ing capabilities added later. However, the needsfor very efficient execution level order fulfillmentprocesses are markedly different than those re-quired for tactical planning.

In complex production processes, the mostdifficult constraints to resolve are the needs ofcompeting products for the same production re-source. The dynamic fluctuations in demand forindividual products stress forecast-based process-es beyond their capability limits. The most com-mon operational response to complexity is tocarry more inventories and to require extendedlead times. Long end-to-end throughput timesand operational complexity are critical barriers tooperational excellence.

The combination of predictive analytics withinnovative probabilistic inventory and schedulingsolvers provide effective control of complex man-ufacturing, enabling performance close to thephysical process limits. New predictive modelingcapabilities use proven data based decision sup-port methods to quantify process capabilities andidentify improvement opportunities critical forattaining operational excellence. This approachalso provides the ability to balance customer ser-vice, inventory levels and production costs to en-hance operational excellence, and reducesoperational risk.

Today, innovations in predictive analyticsand probabilistic inventory and schedulingsolvers provide practical tools for the deploymentof the Lean pull order-to-fulfillment process inthe pharmaceutical industry. In industries withsimilar characteristics, innovative manufacturershave recently leveraged the new hybrid of Leanpull and probabilistic algorithms to help trans-form their business processes and gain competi-tive advantage. n

Predictive analyticsAlfred Sherk discusses new developments thatcan help enhance Lean capabilities.


ASK THEEXPERT

Alfred Sherk is the founder and CEO of SherTrack,provider of innovative, predictive analytic solutions forsynchronizing supply with demand. He is a past memberof the Technical Advisory Board for Michigan StateUniversity’s Graduate School of Business and is a limitedpartner in North Coast Technology Investors LP.

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Today’s life science researchers utilize technologies from many disciplines. Purchasing then mastering varied instruments

and technologies devours time and monetary resources. Oft en a technique may be needed in only a single experimental phase, leading to infrequently used instruments clutter-ing valuable bench space. Th e ideal solution is an instrument that can perform a myriad of multi-parametric applications. A fl ow cytometer fi ts that description but, to date, fl ow cytometry has not enjoyed mainstream acceptance primarily due to the cost, size and complexity of existing instruments. As with so many technologies, manufacturers have added a seemingly endless series of bells and whistles to mature platforms over time, ren-dering them increasingly unwieldy. Conven-tional fl ow cytometers are expensive, large, high-maintenance instruments that require extensive training to use correctly.

Th e Accuri C6 Flow Cytometer System breaks the fl ow cytometry paradigm. With a footprint, weight and price similar to a real-time qPCR system or microplate reader, the C6 puts an essential cell analysis tool into the hands of more biologists than ever before. Th e instrument off ers all the performance features of larger, complex fl ow cytometers and does not require expert operators or dedicated staff , making fl ow cytometry equally avail-able to both novices and experts.

Researchers have used fl ow cytometry for an expanding application set for decades. Th is quantitative, analytical technology is oft en used to study cellular phenomena that might also be investigated by microscopy, microplate reading, qPCR or Western blots. Beyond classical immunophenotyping, such experiments include cell cycle analysis, apoptosis, cell proliferation and viability as

well as assessment of transfection effi ciency and molecular-level changes in phosphory-lation and methylation states, cellular and molecular profi ling and rare cell screening. Current choices in kits, buff ers, antibody-fl uorochrome conjugates and protocols make designing and implementing multicolor assays easier than ever. Th e proliferation of multiplex bead-based assays has allowed fl ow cytometers to replace time-consuming, com-monplace assays such as ELISAs, and opened the door for fl ow cytometry to be used much more widely in the fi elds of gene and protein microarray analysis.

Due to the wide variations in fl uores-cence and light scatter sig-nals produced by diff erent types of cells and particles, fl ow cytometrists oft en spend signifi cant time and valuable sample, optimiz-ing amplifi er gains and/or PMT voltage settings. Th ese settings cannot be changed post-analysis if signals were improperly amplifi ed, re-sulting in the irretrievable loss of data.

Th e Accuri C6 Flow Cytometer is equipped with pre-optimized detectors, calibrated to operate within their linear range, so it can be used to analyze a wide variety of samples, ranging from dim, barely-fl uores-cent, micron-sized platelets through large, >30 micron, highly-fl uorescent cell lines. Th e combination of high-resolution digital-signal processing (24-bit DSP), resulting in an ex-pansive dynamic range on all detectors, and the CFlow soft ware capability to ‘zoom’ in on

INDUSTRYINSIGHT

Breaking fl ow cytometric paradigms

Grant Howes explains why a multi-faceted single instrument is most effi cient for researchers.

very small areas of data display make the C6 easy to use for both novices and experienced users. Th e C6 allows the separation of data acquisition and data analysis by obviating the need for setting voltages. Th is advance allows novices to be able to collect high-quality data with minimal direction or supervision and to set gating strategies and fl uorescence com-pensation values during, or aft er, data collec-tion. Data collected on a C6 is always retained and can be re-analyzed, at any time, if gating or compensation errors are discovered, or in light of new research fi ndings.

Th e Accuri C6 Flow Cytometer off ers unique advantages over more traditional

methods by enabling multi-parametric, individual cell analysis. With a linear dynamic range over six de-cades, the C6 quantitatively captures the entire scope of biological variations in a single run without the need for data acquisition optimi-zation or tuning. Th e C6 can also quantitatively measure the concentration of cells or particles in samples and correlate this with the spe-cifi c known volumes being sampled. Multi-parametric fl ow cytometric analysis can now replace other less accurate techniques and be accomplished as needs dictate. By designing a two-

laser, six-detector, aff ordable fl ow cytometer, Accuri has successfully addressed the main-stream cell biology applications with a single platform and freed up valuable resources.

For more information please visit www.accuricytometers.com

Grant Howes is Marketing Director at Accuri Cytometers, Inc. An industry veteran, Howes has worked in cell analysis for over 30 years and has close to 25 years of fl ow cytometry experience in both the research and clinical marketplaces.

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LEANSIX SIGMALEANSIX SIGMA

THE LEAN SOLUTIONFollowing in the footsteps of many other industries, in the past few years the pharmaceutical

industry has begun to embrace the concepts of Lean and Six Sigma in its manufacturing operations. Here, Carmen Doran, Global Operational Excellence Champion, and Domingo

Traver, Head of Supply Chain Excellence and IQP for Novartis Pharma Technical Operations, tell us about their company’s progress in implementing these processes.

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ologies and philosophies in the manufacturing area fi rst, and now the ideas are spreading to the rest of the business. In manufacturing it’s very easy to see the processes and to work on the processes because that’s what is right in front of your eyes. In other business areas, some of the work we do focuses on simply making the process transparent,” explains Doran.

As a Global IQP Champion at Novartis, Doran explains that she has a number of requests to provide Lean support; these come from people who have heard about Lean through their colleagues or through seeing the benefi ts themselves. In order to accommodate what Doran explains as a “pull system” for IQP support, Novartis has its IQP Champions across the world, operating diff erent skills in diff erent areas and match-ing the business needs with the company’s resources.

“We oft en use an external pair of eyes on a process. Th at external view may come from another internal function, another manufacturing site or a global function. Novartis has a strong network of people across the globe, all with diff erent backgrounds, but all working on Lean and Six Sigma in a rather unifi ed manner. Th ey are capable of implement-ing various problem-solving tools and methodologies in projects and of linking them together to create a culture leading towards operational excellence,” she explains.

As Global Operational Excellence Champion, Carmen Doran supports all 23 sites for Novartis Pharma’s Technical Op-erations, as well as the global support functions, by provid-ing a systematic training and certifi cation program across

the organization. Th is aims to foster a culture of operational excellence (internally referred to as IQP: Innovation, Quality and Productivity). She comments that operational excellence in Novartis Pharma covers a wide range of topics, tools and techniques, which allow fl exibility in identify-ing the best approach for a specifi c problem or opportunity.

“Th e philosophies of Lean and Six Sigma represent a way of think-ing and looking at a problem, in order to understand the root cause(s) and then solve the problem in a sustainable manner,” she explains. “Th is approach is diff erent to the traditional management styles focusing on short-term ‘quick fi x’ solutions rather than on identifying the problem correctly and ensuring the solution is eff ective and sustainable long-term. We try to use this approach across all areas of the business.”

Initially set out as two diff erent methods, Lean and Six Sigma are very much interlinked and constantly evolving, a development that Doran notes to be present in Novartis Pharma Technical Operations. She explains how previously, projects would solely use Lean and focus on reducing waste, or would apply a Six Sigma approach to reducing vari-ability. “Th e Lean philosophy is to have fl ow through the process and to do this, you need to have processes you can rely on. A stable and reliable process is then the foundation for continuous improvement. So Lean and Six Sigma go hand in hand to achieve operational excellence.

“We look at the fl ow of value all the way through our processes down to the customer, whoever the customer may be; in our case, this is ultimately the patient. If we look at some of the supporting functions like Human Resources, we’ve been applying the Lean and Six Sigma way of thinking to these processes, going through the steps of identifying

the problem, understanding the customer needs and root causes of the problem and then fi nding the solution that matches to those. By doing so, we are for instance ensuring the improvement and sustainability for recruitment processes where the benefi ting customers are actually both the employee and the business.

“We apply the same approach in non-manufacturing environments as we do in production. It’s a natural progression that we need support functions aligned to the new way of working and thinking in manufac-turing. Like a lot of companies, Novartis started to apply these method-

Carmen Doran of Novartis Pharma Technical Operations explains how the unique combination of Lean and Six Sigma is bringing about signifi cant performance improvements through the work of the company’s global and local IQP Champions.

“We have a very clear strategic direction for operational excellence, which allows all of the sites to move in the same direction”

Carmen Doran is Global Operational Excellence Champion for Novartis Pharma Technical Operations.


Healthcare markets around the world are rapidly evolving and pharmaceutical companies need to be prepared to address these changes; for example, reg-ulators and payers are becoming more challenging

while patients are taking a more active role in their disease man-agement. All of this aff ects the pharmaceuti-cal business, where increasing effi ciencies can support future growth.

As Domingo Traver explains that rather than reinventing the wheel, it makes sense for pharmaceutical companies to draw lessons from what their counterparts in other indus-tries have already done. He describes how the processes of Lean and Six Sigma – pioneered by Toyota and Motorola respectively – have taken hold within the Technical Operations organization at Novartis Pharma, where he is Head of Supply Chain Excellence and IQP.

“Th e idea was fi rst that we implement Lean to reduce waste in our processes, and then apply Six Sigma to reduce variability; it’s a two-step process,” he explains. “We have implemented the Lean phase, and in certain areas, such as quality assurance, we have also begun to apply Six Sigma. For example, Lean has been implemented in the diff erent operational units; it is now time to link all of these

units together. IQP is the internal name: innovation, quality and produc-tivity for the operational excellence or continuous processing program.”

In his role at Novartis Pharma, Traver looks aft er logistics and IQP, as well as leading the multimarket network for supply chain. He points to the fact that the current level of regulation and quality control within the pharmaceutical industry has a direct impact on the development and implementation of new effi ciency processes. While regulation is neces-sary to ensure the safety of the end products, Lean and Six Sigma can additionally help to support the overall processes.

“For example,” Traver points out, “existing procedures may show that a particular process takes eight hours. By understanding your internal processes and applying Lean techniques, you will be able to demonstrate improvements and hence reduce the time required. Lean,

therefore, challenges your current processes and technologies while at the same time making them more effi cient.”

Another challenge can lie in implementing such changes across an entire organization, which is why the Technical Operations unit at Novartis Pharma started with several pilot programs. Aft er the suc-cessful implementation of these pilots, the initiative has now been rolled out across global functions, such as supply chain.

Creating changePrior to taking up his current position, Traver

was Functional Champion IQP for Novartis Phar-mOps Spain, where he was principally in charge of deploying IQP and aligning IQP eff orts with the

global Technical Operations vision and strategy. He was leader of the Lean – POO (Process Oriented Organization) project that ended with the implementation of the new organizational structure in Barbera in May, 2007.

Domingo Traver of Novartis Pharma Technical Operations talks about the satisfaction he derives from the successful implementation of Lean and Six Sigma in the pharmaceutical supply chain.

Domingo Traver is Head of Supply Chain Excellence and IQP for Technical Operations at Novartis Pharma AG.

years where you have people with a lot of history at that site, then it takes a diff erent approach for them to change their way of thinking than if you have a brand new site like Singapore. For them, everything is new.

“We can show them results from other sites, and there isn’t that resistance to change because they understand how it works together in the overall business model. So rather than people’s cultural diff erences, adoption depends on the life cycle of the site,” says Doran.

In order to meet the challenges that oft en accompany such implemen-tations, she calls upon the company’s network of IQP Champions: each site has a single point of contact for all best practice sharing. “If I have a site in China that needs some input from a site in the US, they can directly contact the local IQP Champion and ask about the results and learnings.”

Communication between the multiple sites is essential. Doran places most emphasis on the power of speech and interactions between people, and explains that although Novartis publishes its IQP project results on the internal website and in newsletters, most results are seen from the eff ects of a strong network. Monthly teleconferences with IQP

Pharma Technical Operations has successfully handled some natu-ral resistance to change and to the use of these new processes thanks to strong leadership endorsement, although Doran admits that there are still some people who are coming round to the idea. Enthusiasm for a new project, she points out, is oft en created upon seeing the results. If a person working on a project has enjoyed it and demonstrated good results, then others can judge for themselves.

ExpansionAs a global company, Novartis Pharma Technical Operations has

sites located across the US, Europe, the Middle East, Latin America and Asia. Prior to taking up her current role, Doran worked in the company’s recently opened Pharmaceutical Operations site in Singapore. She ex-plains that there are variarions in the take-up of Lean Six Sigma across diff erent locations, but not always in the way you might think. “Th e dif-ference for us in terms of adoption is not necessarily the culture but the maturity of the site. When you have a site that has been around for 50




“It was a very interesting project, because it included two elements,” he recalls. “One was the pure implementation of Lean Six Sigma – hence, applying the techniques and helping the teams understand what these techniques mean and how to use them. Th e other element was about POO, which was aimed at changing the organization’s culture and mindset in regard to how people approach business operations. Among others, this included a change in management tools as well as business understanding.

“We used the Kotter model, starting with the ‘burning platform’. Th is allowed us to see how people behaved diff erently aft er POO had been initiated a number of weeks previously. Th is was really exciting to me, as you could see how the organization as a whole had improved.

“You have diff erent people behaving in diff erent ways; for example, some may be afraid of change. Generally, there will always be 10 percent of people who are quite change resistant. However, you can manage these 10 percent by demonstrating how the other 90 percent benefi ted from

new processes and a new culture. I was very happy that despite the challenges we managed the turnaround.”

Traver feels that Lean and Six Sigma have a strong future within the pharmaceutical industry, as well as in other industries. He points out that there are many areas in which these concepts are yet to be introduced.

“Lean Six Sigma helps us to improve our processes and to reduce variability. It is really helpful in many industries, and yet there are parts of the world that still have not taken advantage of it. So I would say overall that there is a lot of future in this yet.”

In 1995, Harvard Business School professor and change management guru John Kotter published a book entitled Leading Change, within which he outlined his now well-known eight-step change process:

1. Create a sense of urgencyOpen an honest dialogue about what’s happening in the marketplace

2. Form a guiding coalitionSet up strong leadership by gaining support from key people

3. Create a visionHelp people see for themselves what you’re trying to achieve

4. Communicate the visionTalk often about and apply your vision as much as possible

5. Remove obstaclesCheck continually for barriers to change

6. Create short-term winsGive your people an early taste of victory

7. Build on changeKeep looking for improvements

8. Anchor change in your cultureMake sure change is embedded in every aspect of your organization

The Kotter model

“I was very happy that despite the challenges we managed the turnaround”

can be improved, and maybe we haven’t had the challenge that some of the faster-moving consumer industries have had in terms of reaction to market requirements. Th ose companies who can respond quickly to the market needs by being fl exible and reducing their cycle times, both in manufacturing and in development, will be the ones who can overcome these challenges.”

Added pressures come from the highly regulated nature of the industry. “None of us would want to take medicine if it wasn't highly regulated,” says Doran. However, she notes that the pharma industry must also recognize that it is not alone in terms of the level of regula-tion it must undergo, pointing to the aerospace industry as facing similar challenges.

“At the end of the day, what I feel has made the Lean and Six Sigma thinking successful for us is the combination of the technical process improvements, cultural aspects and a clear strategic direction that fos-ters, for all involved, a passion to strive for operational excellence,” she concludes. n

Champion networks, ad hoc teleconferences and regular meetings focus on the challenges facing the site, the successes, their goals and what’s in store for the future.

“Although the sites are on the same journey, they’re all at diff erent stages, but they’re all looking for alignment through our Operational Excellence Scorecard. We have a very clear strategic direction for op-erational excellence in Novartis Pharma Technical Operations, which allows all of the sites to move in the same direction. Th at's one of the reasons we’ve been successfully able to turn those challenges along the journey at a site into something that has been enjoyable and rewarding.”

Novartis Pharma is certainly not alone in facing these challenges. Th e pharmaceutical industry has been dogged by pressures to reduce costs in light of the recent economic crisis. “We could focus on cost, but the better way is to focus on the speed and the agility of the processes,” explains Doran.

“One of the biggest concerns for all pharmaceutical companies is the speed at which they are able to adapt to change. A lot of our processes


INDUSTRYINSIGHT

Pharmaceutical secondary manufactur-ing has long stood in stark contrast tothe drug discovery end of the business,as well as to other sectors, when it

comes to innovation such as continuous manu-facturing. Is that about to change? Siemens’Rebecca Vangenechten and Ivo Backx argue thatthe coming decade could see secondary manufac-turing not just catch up but leapfrog other sectorsand that mindset will be a crucial factor.

Some of the reasons that explain the relative-ly slow pace of secondary manufacturing changealso explain why the sector is likely to see a trans-formation. Few other industries would survive ifthey presided over utilization rates around 30 or40 percent and took as long as a month or eventwo months to manufacture a product that couldbe made in two days. Large inefficient batch man-ufacturing would have been consigned to thedustbin. In pharma, however, the profits thathave come from the traditional blockbuster drugdiscovery model have masked manufacturing in-efficiency and regulation has inhibited change.

Now, however, the traditional businessmodel is breaking down with consequent pres-sures on all parts of the pharma value chain.Manufacturing’s contribution to improving yield,reducing time, cost and waste is increasingly crit-ical. Regulation that previously had insisted on

batch testing is now moving to be much moresupportive of real-time product release andprocess analysis, heralding a future where the val-idation and establishment of continuous manu-facturing will be easier.

A small number of companies are taking ex-tremely innovative steps. At Siemens we areworking with leading players to develop a contin-uous secondary manufacturing process. Such amove seeks to achieve significant business bene-fits. Even a one percent yield improvement trans-lates into hundreds of millions of savings. Small,fully enclosed processes, with a high level of au-tomation and reduced manual intervention, willenable companies to reduce variability, deliverhigh yields, increase profitability and lower oper-ating, inventory and capital costs.

It is an attractive future but the barriers re-main significant. However, achievability is notone of them. Continuous processing with real-time release and full understanding and controlof each step of the process is well established inother sectors, such as chemicals and food andbeverages. What has been different in pharma isthe regulatory context but, with this changing, thebigger barriers are inside companies and, in somerespects, inside mindsets.

Integration of each process stage is crucial forcontinuous manufacturing. However, pharma

companies tend to work with ‘islands of automa-tion’ where every unit of operation is more or lessindependent from an integration point of view.Changing to an integrated approach, which isstandard in many other industries, is a big step forpharma companies. At Siemens, we have wide ex-perience of continuous manufacturing, as well asan understanding of pharma’s needs, and canpartner companies to make it a reality. We findthat companies are excited once they succeedwith integration but find it difficult to be con-vinced beforehand simply because it is outside oftheir experience.

Another key barrier is that these changes re-quire companies to work in a more multi-disci-plinary way, crossing system worlds. For the firsttime, if you are in analytics you have to speak topeople in process control and so on. Multi-disci-plinary teams are an absolute must but not every-one is ready for that. The relatively slow uptake ofprocess analytical technology (PAT), crucial forcontinuous manufacturing, following the FDA’s2004 PAT initiative, highlights the challenge fac-ing companies.

Mindset changes and internal culturechanges will be key to the successful introductionof PAT as a first step towards continuous manu-facturing. The companies that are first to over-come the barriers will not just reap the reward ofincreased competitiveness. Because of the stage ofits introduction, they have the opportunity to im-plement the technology to a higher level than inindustries where it is already established. Frombeing a laggard, secondary manufacturing has thepotential to become a trendsetter. n


The potential of continuous processing in secondarymanufacturing.

LEAPFROGTIME?

Ivo Backx is working atpresent as SeniorConsultant for drugmanufacturing at theVertical MarketManagement Pharmadepartment forIndustrial Automationand Drives Technologyat Siemens.

Rebecca Vangenechtenis a Life SciencesIndustry Consultantwith Siemens. She isresponsible forbusiness developmentlife sciences US andfocuses on innovativetechnologies, includingprocess analytictechnology (PAT).

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nutraceutical and pharmaceutical industries, apivotal step in the decision to enter the consumerhealthcare market is the creation of a strategy foroutsourcing the manufacturing and packaging ofthese sensitive products.

Since 2004, Ropack has worked with bio-pharmaceutical and world-class probiotic organi-zations. Our low relative humidity packaging isbetween 20 percent and 50 percent RH year-round, and the excursion period out of cold stor-age is tracked in the batch dossier. Once packaged,products are returned to the cold chamber untilthey are released and shipments are prepared.Cold room temperatures are maintained at 4-5° Cand are temperature mapped and under alarm inthe unlikely event that the temperature shoulddrop below 1.5° C or rise above 8.5° C.

Our common current probiotics packagingincludes sachets, Alu tubes, CSP flip-top vials,cold form blister and blister with individual des-iccant. At Ropack, we use our expertise and expe-rience to meet your needs with creativity andagility. It is our dedication to client satisfactionthat is your best guarantee of a lasting and trust-worthy relationship. We welcome your nextpackaging challenge.

Ropack offers turnkey primary and sec-ondary pharmaceutical packaging services of solidoral dosages, tablets, powder and encapsulationinto blisters, pouches, bottles and carded blistersin facilities that are cGMP compliant and FDAcertified. We are competitive, flexible and agile,supporting clinical trials, short-run startups, com-mercial production and warehousing and distrib-ution services for more than 90 US, Canadian andEuropean pharmaceutical and nutraceutical cus-tomers. Our proven track record in new productlaunches will help support and accelerate your go-to-market timeline.

At Ropack, we value our culture of innova-tion and continuous improvement and areuniquely qualified to support and fast track prod-uct launches of consumer health, OT and Rxproducts for global pharmaceutical companies. n

While originally regarded strictlyas a specialty market, probioticsupplements are now main-stream. According to

LexisNexis, 231 probiotic products were launchedin 2008, compared with 34 just three years prior;75 percent of women report being interested in adigestive system ‘makeover’. Distinguished med-ical journals confirm the industry’s credibility bypublishing an increasing number of clinical trialswith the popularity of probiotics being measuredby the $43 million drugstore sales in 2008.Notably, probiotics are characterized as “the vitalhealthcare concept of the 21st century,” inProbiotics – A Global Update of Market Trends &Opportunities.

Reputation and R&D are key to the compet-itive advantage. The elements that bring success toleading nutraceutical and pharmaceutical compa-nies – global reputations, sophisticated researchand development, and savvy marketing – positionthem to excel in the consumer healthcare industryand awareness of probiotics has grown exponen-tially in the past decade. Some estimates indicate,for example, that nearly half of Americans know

of probiotics. Yet a significantly smaller percent-age understands their benefits. This disparity be-tween awareness and understanding gives the topnutraceutical and pharmaceutical companies anadvantage – consumers associate perceived bene-fits with the companies whose name they recog-nize and reputation they trust.

Users of probiotics demand the proven clin-ical research that an established nutraceutical orpharmaceutical company can provide. This clin-ical substantiation influences their purchase pref-erence and in the process creates a valuedcustomer because probiotics consumers are loyalbrand users. According to the Natural MarketingInstitute, nearly half of probiotics users reportthat even in a sluggish economy they will pay apremium for what they perceive to be high-qual-ity supplements.

The pharmaceutical and nutraceutical indus-tries’s well-established research and developmentoperations position them to identify and intro-duce new consumer healthcare products beyonddigestive health predominantly addressed by theprobiotics market. Ropack is uniquely positionedto manufacture and package probiotics. For the

The rise ofprobiotics

Paul Dupont

explains how growingtrends in the consumer

healthcare industry signalpromising market

opportunities for leadingnutraceutical and

pharmaceutical companies.

PROJECTFOCUS

Paul Dupont is Director ofBusiness Development North

America for Ropack. He hasover 20 years of experience

launching new businessdevelopment initiatives in

the food, pharmaceuticaland nutraceutical industries,

and expanding marketpresence to new geographic

territories.

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Because regulatory agencies make decisions, recommendations and, ultimately, grant approvals based on the content of regulatory sub-

mission documents, the submission document process is one of the most – if not the most – critical documentation process for every life sciences organization. While this point is widely accepted, the processes by which these documents are produced, reviewed and ap-proved before submission are oft en not well un-derstood or documented and frequently depend on heavy manual intervention and heroics to meet submission deadlines, despite the fact that these deadlines are typically planned for many months – sometimes years – in advance.

Automating submission document pro-cesses with business process management (BPM) soft ware can alleviate these burdens by signifi cantly reducing end-to-end process cycle times and enforcing adherence to submission deadlines. Th e key business processes required for success are the planning, writing, scientifi c review, quality assurance, approval and issuing processes for all submission documents, includ-ing the clinical study report.

With BPM, life sciences organizations can web-enable process work-steps, capture critical content and process data, and create useful in-formation for resource planning, performance metrics, and, ultimately, process improvement. Other strategic benefi ts include rapid access to and incorporation of clinical data, short-ened review cycles, improved global resource management and productivity, and signifi cant transaction cost savings – all of which drive competitive advantage.

Working togetherA common misconception among life sci-

ences organizations is that BPM and content management are competing disciplines, which is absolutely false. Content management is a competency and set of technologies that are complemented and extended through the em-ployment of a BPM solution. With respect to

submission document processes, the content management solution remains the secure, vali-dated repository for controlled documents and associated content. Th e business processes for creating and processing said content and docu-ments are what BPM handles – essentially pro-viding a process wrapper around the validated content management repository.

Furthermore, extracting the business processes from the actual content artifacts increases process agility, and also provides the business greater control without the risks and costs associated with custom changes to validated enterprise content management ap-plications. Once the business processes have been defi ned, the BPM application can access controlled documents via hyperlinks to the content management repository – ensuring the version control features are maintained while seamlessly providing business users immediate access to the working documents associated with a specifi c pro-cess. Taking advantage of the strengths of both technologies, this approach empowers the business to better manage and control its business processes and activities, and also simpli-fi es the maintenance and man-agement of the validated content management system for IT.

Increasing productivityWith growing disease in-

cidence globally and increased access to care in emerging markets, globalization repre-sents a key growth segment for life sciences companies. At the same, rising cost pressures are forcing life sciences companies to look for ways to globalize their operations for sustainable operational cost savings. Another advantage to automating submission document processes through BPM is that it off ers a unique approach to utilizing lower off shore resources,

ASK THEEXPERT

Streamlining regulatory submissionsEthan smith explains how life sciences organizations can automate regulatory submission

processes to gain strategic advantage.

while simultaneously improving turnaround times for submission documents.

Th e automated processes are accessible online and work items can be handled by any resource from any location – and management is still provided with complete visibility into every transaction. Not only does this allow companies to more eff ectively leverage off -shore resources, but it also enables work items

to ‘follow the sun’ and be worked on across multiple time zones – maximiz-ing the available working hours in a 24-hour period. Delivering the means to ef-fectively create more hours in the work day is a dream come true for managers when regulatory submis-sion deadlines are rapidly approaching.

Th ese and other advan-tages provided by a BPM solution make processes both faster and cheaper, while at the same time pro-viding management with complete transparency into where each document

resides at any point in time, and giving them the ability to reprioritize and reassign work with ease. BPM makes all of this possible, while still maintaining the content in the same validated repository where it has always been.

Ethan Smith leads the life sciences industry vertical for Metastorm globally. He has over 10 years of experience consulting to the industry and solving process-related problems to create tangible business value for life sciences organizations.

“A common misconception is that

BPM and content management are

competing disciplines, which is absolutely

false”

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In 2007, the then relatively small Nycomed acquired the muchlarger Altana Pharma, causing some challenges in integration thatwere not always easy to handle for its HR team. Charles Depasse,Nycomed’s Executive Vice President of Human Resources, talksof the uncertainty that a merger creates and the importance ofcommunication in asserting Nycomed’s company values and insupporting both those employees who left and those who stayed.

“It’s not easy to stay in a company when you see some of your colleaguesleave, and also when you get more work and maybe more expectations thanyou had before. And those were the key challenges that we had to work with,”says Depasse.

“We tried to overcome those by sharing our values and our approach,trying to be as open as we could about the changes and keeping our employ-ees aware at least of the timelines. We identified what we thought would be afair way to treat those who had to leave with the necessary support and show-ing that it would be a fair process in the selection, as well as to create a newcompany culture from the two companies.”

Depasse is used to dealing with challenges, many of which result from thepharmaceutical industry’s specific recruitment needs. He points to special-ized areas such as market access or R&D, for which it can often be hard to findthe best candidates. He adds that this situation could be ameliorated by thefact that in recent years large pharma companies have been cutting back ontheir R&D departments – both AstraZeneca and GlaxoSmithKline have re-cently announced reductions in the thousands.

“I expect we’ll see a lot of very good people on the market as a result,”Depasse says. “It will help alleviate the skill shortage, but we need to look inmore detail to see if it will resolve the entire problem. We are also seeing someof those who have left large companies looking forward to working for a mid-size company, where their breadth of responsibility can be increased – wherethey get to understand the whole picture and have more room for maneuverthan they would have in a very large corporation.


RECRUITMENTTRAINING

“That’s at least how we see it. And Nycomed being based in Switzerland,we have people coming from the large companies in Switzerland who arehappy to join us. In a mid-size company like ours, you have more of an op-portunity to have an influence, your individualism can be recognized and ap-preciated more, and that certainly is something that we also try to stress. Theculture of the company is something that we like to cherish. Having an inter-national approach and giving everyone the impression of working in a smallcompany, even though we’re growing to become a bigger one, is part of whatwe keep close to our hearts.”

People developmentEnsuring new graduates are also able to enter the industry and fill the

need for certain skills is important. Depasse cites the benefits of the compa-

PUTTINGPEOPLE

FIRSTNycomed’s Charles Depasse tells NGPabout the challenges of recruiting in

the pharmaceutical industry and whytraining is important for personal and

career development.

Depasse ed_4August 18/02/2010 13:28 Page 138


ny’s R&D centre in Constance, Germany, to the city’s university: “Buildinglinks with universities by participating in common R&D projects, and in gen-eral being seen as a participant in the scientific community, is very important.”

Establishing links with young graduates in order to bring them into thecompany as trainees and participate in training programs is also part ofNycomed’s approach. Depasse adds that being known as a company that haslinks with academia is also good for the commercial side.

The trend towards developing employees to take on new roles rather thanhiring externally is one that is being see in many different industries, in-cluding the pharmaceutical sector. Nycomed has embraced this approach,taking the view that people development is key to keeping people motivat-ed and allowing everyone in the company to develop as individuals, asDepasse explains.

“Motivating, training and developing our people is important for us onall levels, and we focus on internal programs where possible. This is valuablefor our culture, and the professional networking and synergetic sharing of bestpractices. We like to give everyone the option and the opportunity to devel-op in an area that’s appropriate for them. Our internal development center,the Nycomed Academy, offers a broad range of workshops, classroom train-ing and online learning, covering the key areas for Nycomed’s future.

“We have also developed an internal program for young leaders wherewe ask our top executives to present the company and themselves, and haveour employees work on business-relevant projects, where they can see thebenefit of the application. Not all of the projects, of course, will materialize,but quite a few will. We believe that creates as good a dynamic as an externalprogram”, says Depasse.


He describes the challenges as no longer being sodistinct between the two regions; instead, he believesthe biggest challenge facing pharmaceutical recruit-ment lies in the developing world. “The challenge is indeveloping countries, whether it’s China, Mexico,Saudi Arabia or Russia/CIS. Finding the best talentthere is certainly an even greater challenge than in theUS or Europe, because the war for talent is more ag-gressive there.

“We also see that attracting talent from Europeto those countries using generous expat packages hasbecome a thing of the past. We have budget restric-tions, and also the expectation is that you will be ableto hire locally. On the other hand, the good thing isthat we also see a number of people from developingcountries who are highly qualified, highly trained,and more flexible about going abroad, and some-times returning to their home country in a more se-nior position as a result. So that’s been a very positivedevelopment.”

When asked what the future holds for the pharmaceutical industry,Depasse reiterates that the industry as a whole is maturing, and HR depart-ments will find themselves having to adapt to the new challenges and oppor-tunities that this brings. He cites the recent mergers among the industry’s topplayers as one example: “These mergers will result in a number of highly qual-ified professionals being made available on the market, and so perhaps theclassic model of having difficulties in finding R&D or sales and marketing ex-ecutives will be eased somewhat.

“Otherwise, the difficulty of bringing new products to the market is con-tinuing. It’s relentless; it’s even maybe tougher than before. So specializedfields, in particular market access, will remain an area where the whole in-dustry is looking for the best talent. Those are the trends that I see going for-ward,” he concludes. n

Charles Depasse is Executive Vice President of Human Resources at Nycomed.

Nycomed is currently focusing on the sales and marketing area within itsinternal training, developed in conjunction with regional managers, and mar-ket access is one topic that the company has developed. Depasse explains thatthis involves training on key account management, as well as general trainingin project management and value training, whereby the focus is on ensuringthat every new employee understands clearly Nycomed’s values in an attemptto build empathy and trust.

“We want to be sure that everyone understands what’s behind thosewords,” he says. “What does it mean in the day-to-day behavior, what do weexpect from our leaders, and what can employees expect from their leaders,so that we align expectations on both sides.”

World viewWith most large and mid-sized pharmaceutical companies operating in-

ternationally, they are bound to face unique challenges in various parts of theworld. Depasse says that in recruitment at least, areas such as Europe andNorth America are not as different as they once were. One of the main diffi-culties in recruiting across Europe has historically been language, with the USobviously having the advantage of a common mother tongue. Depasse pointsout that this problem is gradually being eroded due to the dramatic improve-ment of the level of English in Europe.

“The situation has reversed itself somewhat,” he says. “Now the fact that inEurope you bring in people from different backgrounds and cultures can be anadvantage because it adds diversity.” He adds that Americans were once morewilling than Europeans to relocate to take up a new job, but now there is moremobility within Europe, with the added bonus of the distances being shorter.


“Building links with universities by participating in common R&Dprojects is very important”

Commitment to professional educationThe Nycomed Academy, a combination of online learningand classroom instruction, offers a range of courses: fromdeveloping leadership and improving team dynamics toglobal marketing courses and building relations with keycustomers. Local and regional courses complement theoffering at the global level.

Personal development tools are being designed toidentify key competencies for motivational leadershipbased on the company’s values, results from surveys andcompetency models. The Nycomed Academy’s motto‘Educate, Motivate, Achieve’ underscores the company’scommitment to becoming a learning organization.

Charles Depasse


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142 www.busmanagement.com

It’s great that this company is working so hard to create a culture that builds loyalty and empowers employees. Em-powering employees is a key lesson in

‘Disney’s Approach to Leadership Excellence’ – one of fi ve core programs we off er at Disney Institute. Th e opportunity for this company and its managers is to examine how to truly empower employees for long-term eff ective-ness. Th e answer may surprise them, as it lies in their hands.

Disney has always trained well and, as recently as the 1990s, many leaders thought that hiring great people and training them was suffi cient. Employees would do as they were told and guest service would be seam-less. Disney employees, or cast members, as we call them, take great pride in their work and want to do more, but we had created an environment where the expectation was to simply collect a paycheck. We were not effec-tive at connecting the cast with their jobs and the guests they were serving, and we were missing a vast opportunity.

child a new one at no cost to the parent. The cast member can do this without checking with his or her leader, as long as he or she records the transaction. This record creates opportuni-ties for coaching and ongoing collaboration between cast members and leaders.

These efforts unleashed the hidden value from within the organization and have al-lowed Disney to become world-renowned for employee engagement and loyalty. And it doesn’t have anything to do with castles and princesses (well, maybe a little bit). Work-ing in the happiest place on earth certainly has its benefi ts, but I doubt we would be the happiest place on earth if we didn’t treat our cast members with respect. Guests come back to our parks again and again because our cast members listen and act when they

make suggestions on ways to improve the experience. The thousands of positive letters, emails and phone calls we receive from guests every year almost always have one thing in common – they rave about our cast members.

The biggest challenge for any company wishing to implement changes, ones that will result in increased employee engagement and loyalty, is to develop a cul-ture of trust. If employees feel they are heard, and that their ideas and suggestions are taken seriously, they’ll respond in a positive way. A company that is successful in introducing this type of

culture will see a positive impact that goes beyond employee satisfaction, all the way to the bottom line.

Bruce Jones is Programming Director for Disney Institute. In this role, Jones oversees the team that develops engaging content built around the fi ve topics that Disney is best known for – leadership excellence, people management, quality service, brand loyalty and inspiring creativity. He also ensures the content is suitable for presentation across a variety of formats, including webcasts, keynote presentations and multi-day courses.

Empowering the workforceNGP asked Bruce Jones to answer one company’s questions about developing a

leadership culture.

It would have been easy to dismiss this as a cast member problem and send them to another round of training. But astute senior leaders saw an opportunity to make bigger changes that would positively infl uence our company for years to come. They started by asking cast members what would help them feel connected to their jobs. The answers were startlingly simple. For example, cast members wanted the freedom to help guests immediately when problems occurred, and they wanted to do so without fear of retribution. In other words, they wanted

to be treated with the same respect we give our guests.

As a result, Disney embarked on a journey focused on developing a cul-

ture of great leadership rather than top-down management. Leaders now must demonstrate effective empowerment, along with coaching and cast member development, to be suc-cessful in their jobs; in fact, leaders’ annual reviews are tied directly to the cast members they oversee. If a cast member is not achiev-ing his or her goals, then neither is the leader. This re-quires leaders to constantly interact with and seek input from cast members, which in turn fosters better service at all levels of our company (fellow cast members can be guests, too).

Tools have been devel-oped as part of this process to empower immediate service recovery. If a child drops her ice cream cone for example, the cast member is empowered to offer the

TROUBLESHOOTER

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Last November’s FDA public hearings on pro-motional use of the internet and social media in Washington, DC, was quite an event. Al-though the FDA allowed 350 attendees, the

60 plus speakers stole the show over the two long days. Speakers presented a variety of issues and concerns focused around questions posed by the FDA. Many of the speakers were very credible and, at the hearings’ conclusion, one could be considered conversant on issues surrounding the use of the internet and social media for healthcare purposes.

Th e FDA called the hearing to address a number of pertinent communication challenges and gain industry insights from a variety of audience participants. Th e key area of focus for the hearing revolved around the accountability of pharmaceutical and medical device manufacturers in providing adequate disclosure for fair balance in limited online formats, such as paid search ads and tweets, and other online formats that healthcare companies use across the web.

What are the responsibilities for follow-up and post-ing of corrective information on sites controlled by third parties? Th ese hearings, presentations and brief discus-sions represent only the beginning of the debate of what should be acceptable use of social media. Unfortunately, this debate could drag on for some time; from these hearings, it was obvious we must move on these issues now. Social media is a two-way communication process supporting industry needs to safely utilize the media for communications while the public engages the industry in an eff ort to get the support and information they seek.

Adverse reporting and the posting of side eff ect information were the two hottest issues presented. It was clear that guidelines do need to be established, and many speakers detailed reasons why they were looking to the FDA to lead this action and demonstrate a true understanding of the issues. Also driving the hearings was the recent FDA action in sending warning letters to pharmaceutical companies regarding the use of internet promotion that resulted in a dramatic reduction in the use of online channels by the industry. Combined with the lack of guidelines, this action has reduced the vital connection between the industry and the general public, thus increasing the chances that patients and their fami-lies will seek information from sources that are oft en unregulated and do not preserve the integrity of the information exchanged.

By defi ning guidelines the FDA will instantly estab-lish the validity of social media as a viable communication channel, reinforcing patient beliefs that communication standards must be met by the industry. Th ese standards must be created to protect the public interest and instill the confi dence to freely exchange information with the health-care industry. Over the past few years, pharmaceutical and medical device companies have experienced unprecedent-ed negative public perception, and these guidelines could help the industry engage both its customers and its critics.

A major part of the industry – healthcare provid-ers – was noticeably missing at the meeting. Where were the voices of physicians and nurses? Th ere were a few exceptions, includ-ing representatives from Sermo, a physician social website who discussed online social media that serves the physicians’ need for peer-to-peer interac-tions. Besides the FDA, providers had the most to learn from these hearings, considering their relationship and regular dialogue with patients. Th is venue could have reinforced their concerns for patient safety and established a perspective for how patients will seek future health information.

Also missing was the American Medical Associa-tion, which could have taken a leadership position and expressed a strong point of view on behalf of its physi-cian members and the managed care organizations that play a critical role in patient/physician communication and management. With the growth of social media and the increased use of the internet, all representatives of the healthcare industry will need to collectively strike a harmonious balance. Th e growth of social media is not slowing down and will continue to impact how patients, families, industry and healthcare providers will interact with each other.

ASK THEEXPERT

Utilizing social mediaChuck Russo examines the FDA’s online balancing act between consumers and the healthcare industry.

Chuck Russo is EVP, Chief Innovation and Customer Experience Offi cer of Corbett Accel Healthcare Group (CAHG). Russo leads and oversees the advancement of CAHG’s interactive and technology based businesses and functional departments, including Kinect Interactive Digital Communications, a full-service strategic interactive agency and LinQ, a studio-inspired technology services company.

“Unfortunately, this debate could drag on for some time; from these hearings, it was obvious we must move on these issues now”

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Feel the forceWith patent expiries and generic competition on the rise, the pharmaceutical industry is being scrutinized like never before. As a result, sales force effectiveness is taking top priority. By Matt Buttell

“Th ere is no such thing as a no-sale call. A sale is made on every call you make. Either you sell the client some stock or he sells you a reason he can’t buy. Either way, a sale is made; the only question

is: Who is going to close? You or him?” Th ese are the words of Ben Affl eck’s character Jim Young in the 2000 movie Boiler Room

– a dark and intense drama depicting the perils of working on a highly pressured, highly-paid sales fl oor at a suburban investment fi rm. While the movie is a dramatization of what

life is like as a cold-call salesman, the ‘boiler room’ concept that goes hand-in-hand with sales is nothing new to the pitching fl oor: especially as far as Hollywood is concerned. Th ink

Oliver Stone’s 1987 classic Wall Street, where Michael Douglas’ depiction of ruthless stockbroker Gordon Gekko earned him an Oscar win: “Greed is good”, Gekko warned us some 13 years ago. Or Alec Baldwin’s Blake in the 1992 movie Glengarry Glen Ross, where he defi nes the ABC of sales as “Always Be Closing.”

Of course, outside the realms of the movies, while the reality for the sales force may not be half as ruthless, it is just as dramatic. And not least for the pharmaceutical industry. Th at’s because the industry is currently at a crossroads, facing the very real problem of patent ex-piries and the rise of generic substitutions – and the pharmaceutical sales force is top of the critical agenda.

Th e challenges facing the pharmaceutical industry in 2010 are multi-faceted and have already been well publicized. For one, a slowdown of growth levels within mature markets is leading to a refocusing for the industry – in particular, Big Pharma – that sees future profi ts lying in emerging markets such as China and India: markets that have been dubbed by the media as ‘pharmerging’.

MARKETING

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As such, the pressures on the sales forces’ of pharmaceutical com-panies are great, not least as many of pharma’s biggest markets are now saturated with sales representatives. A direct result of this sees the indus-try’s selling techniques becoming increasingly ineff ective and the indus-try is now being forced to embrace the reality that this model guarantees neither growth nor future profi tability.

Instead is the argument that there is a new opportunity presenting itself to the industry: the realization of moving beyond sales force growth and mass promotion and into a new era of sales force eff ectiveness.

Denied accessAccording to the Pharmaceutical

Sales Force Eff ectiveness Strategies report published by Business Insights last year, the social, demographic and economic context in which the pharmaceutical in-dustry operates is changing dramatically, with huge implications for the industry as a whole. Dr. Ksenija Jakovcic, a Busi-ness Development Manager at SanMed and author of the report, notes how these challenges will have major ramifi cations for the way in which pharmaceutical companies market and sell the medicines they develop over the coming years.

Th e study aims to highlight how the pressures associated with these challenges impact market effi ciencies and discusses the idea that, currently, no aspect of pharma operations is under as much scrutiny as the sales and marketing function.

It is an interesting point, given how pharmaceutical sales representa-tives are currently facing tight restrictions regarding access to physicians, not to mention – highlighted by President Obama’s ongoing healthcare reform debate – something of a negative public opinion right now. In fact, in reference to a lack of access, Jakovcic writes that about “one in four US physicians work in practices that refuses to see pharma reps.

“And of the doctors who do see reps, about 40 percent will meet with them only with scheduled appointments,” she adds. What’s more, fi ndings reveal that the ‘by-appointment-only’ fi gure jumped by 23 percent during the last six months of 2008, a year before the report was published.

Arms raceOne of the biggest issues facing the pharmaceutical sales force is

the fact that while the perceived benefi ts of high return on investment have, in the past, been a key driver for companies to increase numbers, the reality has meant a surplus in the number of reps. Th at, alongside a raft of new pressures – including busier physicians, the proliferation of new drugs, greater competition among companies that produce and market drugs and evolving customer dynamics – has seen the ROI on detailing decline.

What’s more, the pharmaceutical industry remains somewhat cau-tious about the concept of change, a fact underlined by Dorman Follow-will, Vice President of Healthcare EIA at Frost & Sullivan. In an interview

given at the Next Generation Pharmaceutical summit last year, Follow-will commented, “I began my career in the Silicon Valley, the center of change and speed, so I was very much used to things happening quickly, Th is is a vastly diff erent world from the pharmaceutical industry, where things move much more slowly.”

Followwill went on to use the analogy that, over the last 30 or 40 years, the pharmaceutical industry has operated more like the automo-tive industry, something he defi ned as an “interesting cross-industry comparison”, given the signifi cant meltdown the US automotive indus-try experienced last year.

“Obviously the pharmaceutical industry doesn’t want to see itself at that point, so there is a lot of angst and worry currently circulating in the pharmaceutical world,” he added. “Nonetheless, the industry remains incredibly slow to change.”

In fact, warns Followwill, until pharma-ceutical companies shift their focus, change for the industry is unlikely to happen at all. “Th e industry is largely geared ruthlessly toward Wall Street and shareholder values, which have to be driven on a quarterly basis, Meeting analyst expectations on Wall Street remains the number one metric for a pharma CEO, and as long as that remains the case, there won’t be a gigantic amount of change. Th e pharma industry is probably not going to look that diff erent in 10 years’ time.”

New ideasJakovcic, meanwhile, only echoes Followwill’s thoughts, explaining

that while caution certainly does remain, the industry is slowly begin-ning to explore new ideas and innovative sales models. “Although only seven percent of surveyed respondents believe that new sales models will be rolled out in the next two years, the majority of interviewees expect that focused pilot projects will indeed gradually pave the way to new business models,” she writes.

She believes that the most successful future pharmaceutical sales organizations will include a signifi cant variable component and will be engineered for agility and for greater cost eff ectiveness. “A solution for the future is to establish a smaller internal sales organization com-posed of the highest performing sales reps. To build in fl exibility, this fi xed resource would be supplemented by variable resources provided by controlled sales organizations (CSOs), whose expertise is in the rapid deployment and redeployment of custom profi le sales teams.”

What’s more, the pharmaceutical industry, which has long been de-scribed as counter-recessionary – a fact largely based on the assumption that people will always need drugs regardless of the state of the economy – has shown signs of being far from invincible. According to analysts, whilst the recession-proof theory might be true at a surface level, a more granular analysis reveals dissimilarities between diff erent segments of the industry.

For instance, the providers of branded drugs, blockbusters and the newest treatments tend to make long-term investments in R&D, and have

“Meeting analyst expectations on Wall Street

remains the number one metric for a pharma CEO,

and as long as that remains the case, there won’t be a

gigantic amount of change”Dorman Followwill

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and analysts say that Emotional Intelligence – which includes attributes such as listening skills and dressing and behaving in a professional manner – are required just as much as Consultative Selling Skills (CSS), which include knowledge about the product, the medical condition it treats, and – in the end – the skill to close the deal.

So, maybe Ben Affl eck’s speech as Jim Young in Boiler Room shows some truth aft er all, but for Blake’s “Always Be Closing” mantra of years gone by, it seems the number’s up. And in its place, perhaps the usually static pharmaceutical industry will adopt a new ABC of sales: “Always Be Changing”. n

high sales and marketing costs as a result, while those manufacturers of off -patent, older drugs – usual-ly manufactured at a much lower cost than the branded molecular

rivals – typically operate off a lower R&D cost base, with smaller

sales, marketing and budgets in tow.Th is issue has only been exacer-

bated by the ongoing recession and global economic crisis. As such, companies are asking

themselves if this is the time to be investing in pharma sales or not as the industry refocuses its ideas on the way to approach the sales fl oor. How-ever, the industry’s bottom line (profi t) remains the bottom line, and it is clear that Big Pharma is going to have to change its sales model – though whether this will come about as a want or a desire to change, rather than a necessity, remains to be seen. In the end, the pressures the industry is facing – such as saturated markets, declining margins, increased pres-sure from generic competition and fewer blockbusters – mean that cost cuts are inevitable, and eventually that has to include cuts within the sales force.

Th ankfully though, as change does slowly begin to envelop the pharma industry, the Hollywood mentality of sales force eff ectiveness, at least, seems to be disappearing. As such, Michael Douglas’ egotistical Gekko, or even Alec Baldwin’s belligerent Blake, seemingly no longer have a home in pharmaceutical sales. Instead, the general consensus is that success lies in striking a balance between soft skills and hard skills

Side effectsResearched and organized by eyeforpharma, a division of a private company headquartered in London, UK, the Sales Force Effectiveness Summits for 2010 go a long way to highlight the importance this topic is bringing to the industry.

The fi rst summit will be held in Barcelona in April and aims to give attendees a real insight into how change is impacting the industry. Keynote speakers will share knowledge designed to transform the pharmaceutical business model from product focused to customer-facing.

A second summit will be held in New Jersey in May, tackling similar issues for the US market.

About 40% of doctors will meet reps only with an

appointment

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What new factors are affecting prescrib-ers’ medication choices? Tom Haskell. The list is growing exponential-ly, but we can classify them into three general categories: those that are managed-care driven, patient-driven and technology-driven.

The infl uence of managed care extends beyond the use of generics to include the impact of tier position in drug choice and of noncompliance caused by prior authoriza-tion requirements. A more educated patient population has a strong voice in therapy and medication decisions. And physicians are relying more heavily on the internet through electronic medical journals, e-detailing and physician networking sites. These new infl u-ences will differ in the degree and duration of their impact and sorting the high-value activi-ties from the ‘trendy’ ideas is the challenge.

How have these new channels complicated things for manufacturers? John Moran. Companies are increasingly moving to regional commercial models and fi guring out how best to use traditional chan-nels differentially across regions, which is complex enough. If not done well, adding new channels to the mix could make the process unmanageable for a regional business unit. Also, these various infl uences do not impact healthcare practitioners uniformly. Figuring out the rate and pace of impact regionally and by specialty poses an opportunity to maximize brand performance in the near and long term.

What is the role of headquarters versus each region in adopting these channels? TH. It is up to the headquarters’ commercial analytics and market research functions to vet

EXECUTIVEINTERVIEW

new infl uence sources, qualitatively and quan-titatively, and then to give specifi c deployment recommendations to regional units – and even the national franchise. Of course, recommenda-tions should be made in conjunction with the regional business unit’s strategy and operating approach. For example, a region focused on ob-taining preferred status for second-line therapy will benefi t most from deploying channels that educate healthcare practitioners and payers on patient fl ows and treatment patterns.

Determining how much to invest in which channels involves asking, ‘Which infl uences act where, what level of support should be reallocated from traditional channel and how should investment performance be measured’? These types of questions are strategic, rather than quantitative, and can only be answered with customer insights.

Understanding the new prescribing infl uences Tom Haskell and John Moran of IMS’ Innovation Lab discuss how to evaluate new factors

driving prescribing decisions.

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TH. Often models produce results that aren’t intuitive. In one study of coupon usage among patients in a specialty-focused disease area, IMS found that certain coupon types and offers signifi cantly infl uenced the follow-on adherence of patients. It was reasonable to assume that couponing would have an impact on new patient share, but an impact on patient adherence was a surprise. This fi nding has signifi cant by accounting for the ‘lifetime value’ of the patient brought into the franchise.

What must companies do to adopt appro-priate, new performance metrics? TH. First and foremost, they need to develop a richer dialog with their customers through a combination of primary research and rep interactions. Fortunately, they can fund such research by migrating other, more traditional primary research activities, such as aware-ness, trial and usage studies, to secondary data sources. A good starting point for using new metrics is to apply them initially only to new infl uences. Eventually, they can then be extended to traditional promotion and educa-tion activities.

What other tips do you have for companies as they focus on new infl uence factors?JM. The fi rst step is to expand or redeploy re-search activities so that companies can mea-

sure the extent of practitioners’ exposure to new infl uences and the resulting behavioral change. Brand managers should then look for gaps between the re-search fi ndings and their brand plan. Each year, they should incorporate a few promotional ‘R&D’ elements into the brand plan so that they can keep on top of new channels. Once infl u-ences are identifi ed, prioritized and included in the brand plan, tracking and assessment can begin. The organization will have to add a few key perfor-mance indicators, such as brand penetration, productivity and adherence, to the brand dash-board to monitor the spread of an infl uence and to track how the brand is responding.

Do these new channels represent any op-portunity for manufacturers? TH. Most defi nitely. To the extent that com-panies can select and deploy local activities in these channels, they can drive stronger customer relationships, optimize their P&L through more effi cient brand spending and im-prove brand usage. Companies that understand the rate and pace of a channel’s impact region-ally and by specialty can maximize brand performance in the near and long term.

How can companies assess the impact of these new channels? JM. In general, there are three types of measurement methods that can be used, although there isn’t one right way to assess the impact of an infl uence channel. Often, multiple models are required to best explain the impact on prescribing. First, there are analyses at the healthcare practitioner level that compare the prescribing behavior of test and control groups. This is only possible, of course, if you can identify through second-ary or primary research which practitioners have been exposed to the new infl uence.

The second type is regional-level mod-eling, which includes a strategic framework for understanding the future impact of infl uences that are working together. This entails modeling the infl uence’s contribution to sales, gathering sentiments from participants, obtaining a perspective from the fi eld, and then deploying the activ-ity selectively and tracking its actual impact. The third type is channel-level assessment. With this, primary research is integrated with new-to-brand prescribing metrics and value assessments to identify how the infl uence affects HCP satisfac-tion, loyalty and prescribing. The results are used to prioritize program efforts or to implement region-specifi c programs that increase customer value in lag-ging geographies.

What specifi c metrics can be derived from these research methods?

JM. Traditional metrics such as brand share and volume can be applied to some, but not all, new infl uences. Others require new per-formance metrics such as penetration, treat-ment rates, disease intervention rates and patient compliance/adherence. We’re testing research questions now, but have identifi ed some ‘givens’, such as brands operating under new commercial models must have a way to regularly assess the strength of the prescriber’s relationship to the brand and the corresponding value it delivers.

Also, the believability of the brand’s message should be measured in light of other infl uences that either support or contradict the brand’s value proposition. Particularly in today’s highly connected environment, companies must be attuned to how an infl uence supports or undermines corporate communication and education efforts. Finally, measures should address the dual drivers of cost containment and comparative effectiveness. While measur-ing the impact of a pharmaceutical brand on patient outcomes and cost is still in its in-fancy as a commercial business practice, new metrics of cost and value are taking shape.

Can you give an example of a measure-ment of a new infl uence that produced surprising results?

Tom Haskell is Director, US Innovation Labs for IMS Health. In this role, he directs the development of new, creative solutions for pharmaceutical and biotechnology clients in the R&D, clinical and commercial spaces. Haskell is a graduate of Harvard University, majoring in Applied Mathematics and Computer Science.

John Moran leads the US Innovation Labs for IMS. He serves as an advisor to pharmaceutical clients across a range of commercial disciplines, designing and structuring solutions to meet clients’ key commercial challenges. He holds a BS in Chemistry from Carnegie-Mellon University and an MBA from the University of Pittsburgh.

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NEXT BIGTHING

Choosing a hi-tech venueEric Opron explains what businesses should expect from their communications technology when planning their next off-site event.

“Many hotels and conference centers are ill prepared when it comes to large-scale data delivery”

As technology continues to develop and the need for data to be shared quickly and securely grows, it has become essential for businesses to be able to seamlessly transi-

tion from inside the offi ce to outside of it. Off -site confer-ences and meetings are vital events that bring people and ideas together. Today, present day cutting-edge network technology makes it not only possible, but expected that your convention space will be able to function as offi ce space as well.

Th e primary focus of any meeting should be the successful dissemination of information. Th e most state-of-the-art conferences need to stream live video, share Hi-defi nition images and support thousands of users (both wired and wirelessly) simultaneously. Whether it is for an interactive visual presentation or to provide attendees the ability to conduct business away from the offi ce, the network demands for an off -site conference are great.

Too oft en, organisers take for granted the stress these demands can place upon a venue’s network. Th ere are three primary areas you should concern yourself with when evaluating a venue’s communication tech-nology – scalability, security and prioritization.

Many hotels and conference centers are ill prepared when it comes to large-scale data delivery. In today’s world, you must ensure your venue has a suitable data pipe to the internet, as well as the ability to transmit your data to any and all locations you desire, whether wired or wireless. While you may have months to rehearse and fi ne-tune your message within the comfortable confi nes of your corporate offi ces, any multi-media technology you require within a meeting space must be built in days, not months. Understanding a venue’s network capabili-ties can ensure your message delivery goes smoothly.

Th e oft en sensitive nature of the information being shared at these conferences makes security paramount. When delivering essential content to your staff and at-tendees in a time-sensitive and mission-critical environ-ment, one must ensure the local network is capable of segmenting your data (and message) so that it reaches the intended audience exclusively. Th e greatest risk for any company within a meeting space is the loss of confi den-tial and possibly proprietary information.

In addition to delivering the data to where it needs to go securely and quickly, determining who needs it fi rst, especially at large conferences and meetings, is an important consideration. Communications have many layers when it comes to essential delivery. Th ose who need it fi rst, should get it fi rst. Most venues typically op-erate their networks as one fl at LAN, thereby losing the ability to provide preference. If a certain segment of your meeting needs content fi rst, make sure your venue has the ability to provide it in the timely manner required.

To determine if your conference venue is able to meet the communica-tion technology needs and expectations required for your next off -site event, I recommend you ask three questions that will reveal key insights about your potential partner. Do you have a full-time communications staff on property? A network problem does not occur on a schedule, you need to have on-site access to a qualifi ed technician that can be available when issues arise. Can we test drive before we buy? Hold a pre-event planning and consultation meeting with the communications staff at the venue in advance of your meeting date. By working with the communications staff ahead of time you will be comfortable with their capabilities and confi dent that your event will go smoothly. Have you done this before? If the staff has successfully met the needs of similar hi-tech meetings there is little reason to doubt they will be able to do the same for you. Ask for real world case studies to determine if their capabilities match your needs.

Eric Opron is the Director of Sales and Marketing for the 2265-room Walt Disney World Swan and Dolphin Resort. With more than 20 years in the hospitality industry, he is responsible for the numerous groups that host events in the resort’s 329,000 sq. ft of meeting space.

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HealthcareTh e public system, the National Health Service (NHS), is one of the largest cohesive organizations in the world, employing over 1.3 million people. Th e government’s budget portioned the Department of Health £98.6 billion ($154 billion) for the fi scal year 2008-09, with the major-ity of that being spent on the NHS. Private healthcare operates on a parallel level to the NHS and is paid for by private insurance, which currently is used by less than eight percent of the population.

Pharmaceutical companiesGlaxoSmithKline: a pharmaceutical, biological and healthcare company, GSK is the world’s second largest pharmaceutical company. It is research-based with a wide portfolio of pharmaceutical products covering anti-infectives, central nervous system, respiratory, gastro-intestinal/metabolic, oncology and vaccine products.

REGIONAL FOCUS154

With pharmaceuticals being a huge share of the country’s exports, the UK is a major industry player.

The chemical and pharmaceutical industry is strong in the UK, with two of the world’s largest pharmaceutical fi rms, GlaxoSmith-Kline and AstraZeneca, being based there. Along with other key technical industries, the UK is a world leader in the industry, with pharmaceuticals dominating the export part of the country’s economy. UK companies account for 40 percent of biotechnology products in the pipeline by European public companies and with R&D investment of over £3.3 billion ($5.2 billion) in 2005, it

ranks with the US and Japan as one of the top three centers for pharmaceutical research. Moreover, 45 percent of new biotechnology drugs in late-stage clinical trials (phase III) in Europe are from the UK.

Angel of the North

With h ti l b i h

United Kingdom

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AstraZeneca: a British-Swedish company that was formed in 1999 as the result of a merger between Astra AS and Zeneca Group plc. AstraZeneca develops, manufactures and sells pharmaceuticals to treat disorders in the gastrointestinal, cardiac and vascular, neurological and psychiatric, infection, respiratory, pathological infl ammation and oncology areas.

Astex Therapeutics: a biotechnology company focused on the discovery and development of drugs in oncology and other areas. Th e company’s research eff orts focus on utilization of a proprietary ‘drug discovery engine’ dubbed Pyramid.

155

REGIONAL FOCUS

2012 London Olymic Stadium

Travel focusTh e city of London attracts millions of tourists into its metropolis each year. It is due to host the Summer Olympics in 2012 and the capital is gearing up to accommodate the many more millions of tourists the event will bring. With its own mayor and assembly, London is a prominent city and one of the world’s largest fi nancial districts; central London incorporates more than half of the UK’s top 100 grossing UK com-panies. It also holds Europe’s longest shopping street, Oxford Street, which stretches a mile long.Queen Elizabeth’s home, Buckingham Palace, is situated in central London. Th e city is teeming with historical buildings. Westminster Abbey, the Tower of London and the Palace of Westminster were all built to accom-modate the Royal Family.

Edinburgh military tattoo

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The American PharmacistsAssociation Annual Meeting andExposition (APhA2010)March 12 – 15, 2010The Walter E. Washington ConventionCenterWashington, DCwww.aphameeting.org

Future Directions in PharmacyEducationMarch 24, 2010University of ReadingReading, UK http://beta.pharmacyplb.com/development/events-and-courses.asp

Next Generation PharmaceuticalSummit EuropeMarch 29 – 31, 2010Hotel CampoReal Golf Resort and SpaOeste Region, Portugalwww.ngpsummit.eu.com

Sixth Health Asia 2010International Exhibition andConferenceApril 2 – 4, 2020Karachi Expo CenterKarachi, Pakistanwww.health-asia.com/

11th European Symposium onControlled Drug DeliveryApril 7 – 9, 2010Hotel ZuiderduinEgmond aan Zee, The Netherlandswww.escdd.eu

ADMET Europe April 8 – 9, 2010 Holiday Inn, Munich City Centre Munich, Germanyhttp://www.selectbiosciences.com/conferences/ADMET2010

INTERNATIONAL EVENTS156

A roundup of upcoming conferences and events across the globe.

Munich Seoul

Karachi

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Global Healthcare & MedicalTourism Conference 2010April 13 – 16, 2010Coex Intercontinental SeoulSeoul, South Korea www.asiamedicaltourismcongress.com/index.php

Next Generation PharmaceuticalSummitThe Boulders ResortScottsdale, ArizonaApril 26 – 28, 2010www.ngpsummit.com

Strategies Against CounterfeitMedicinesApril 26 – 28, 2010Maritim Hotel WurzburgWurzburg, Germanywww.counterfeit-conference.org

Armada Speciality PharmacySummitMay 4 – 7, 2010The Wynn HotelLas Vegas, NVwww.armadasummit.com

RNAi & miRNA World Congress May 5 – 7, 2010, Boston Park Plaza Hotel and TowersBoston, MAwww.selectbiosciences.com/conferences/RNAiWC2010

Russian Pharmaceutical Forum May 19 – 21, 2010Corinthian Nevsky PalaceSt. Petersburg, Russiawww.adamsmithconferences.com

INTERNATIONAL EVENTS157

St. Petersberg Oeste

Las Vegas

Washington

EVENTS_FEB10 18/02/2010 14:21 Page 157

SNAPSHOT158

Emergency workers evacuate an unconscious girl in Port-au-Prince, Haiti, following the magnitude 7.0 earthquake that hit the country.

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Market trends and ABC Laboratories’ current expe-rience indicate a healthy and sustainable growth in the outsourcing of major portions of protein pharmaceutical product development. According to a recent industry report, more than 75 percent

of analytical development and testing for large molecules is outsourced, a fi gure that is expected to grow with the number of new large molecule candidates. What are the factors behind these decisions to outsource more and how does the contract pharmaceutical provider assure meeting client expectations?

Time is money. Reduction in time to market is paramount in the pharmaceutical industry and is a universal consideration for all companies regardless of size and number of products in the pipeline. Large companies can leverage the contract laboratory in support of both primary and secondary drug candidates. Smaller R&D focused developers can utilize the contract laboratory now instead of waiting until their internal laboratories can eventually support their sample loads. Extending product lifecycle because of patent protection, generic or biosimilars and intense competition cannot generally reverse any loss of sales resulting from delay in development and licensure. Th erefore, contract development organizations provide a mechanism to extend and enhance internal capacity as a means for meeting commer-cialization targets sooner rather than later.

As a heavily regulated industry, pharmaceutical development and testing is governed by current good manufacturing practices (cGMP) that dictate extensive, highly structured quality systems. Setting up these systems and operating under them is expensive, requires substantial ded-icated senior management oversight, and is training and documentation intense. Th e cost of providing such fully compliant cGMP organizations is many fold that of working in a typical R&D organization. Th erefore, R&D focused companies choose to outsource work that is destined for regulatory agency scrutiny to avoid the cost and personnel required for these operations.

SpecializationMuch of the chemical and biological characterization of new phar-

maceutical entities, especially macromolecules such as protein products, requires highly specialized instruments and expertise to operate them. Unless a company has an extensive pipeline of drug candidates to sup-port, purchase of such equipment and expertise is not cost-eff ective.

Contract laboratory personnel, rather than spending an entire career on a single or a few drug candidates, are constantly working with a chal-lenging array of molecules and thus have vast experience in technical problem solving. Most pharmaceutical companies recognize this experi-ence as another valuable extension of internal assets.

Th e contract developer has the benefi t of exposure to many clients, their interaction with regulatory agencies, and direct contact with regulators at a much higher frequency than typically experienced by a single company with a few products. As such, the contract organization typically has a broad base for identifying trends in regulatory agency ex-

pectations. Advice provided to the client based on these recent regulatory encounters reduces the risk of regulatory rejection of development strategy, providing a benefi t recognized and sought aft er by drug developers.

Th e typical pharmaceutical contract de-velopment organization is subject to constant inspections/audits by government agencies and by its clients. Major contract laboratories, for example, host several formal audits per week and constantly improve their quality systems and operations as a result of critical evaluation. In our experience, the standard for contract lab compliance is oft en much higher than the auditor imposes on his own quality

organization. Th is benefi ts the pharmaceutical industry in assuring that work performed and destined for regulatory submission will be able to withstand agency scrutiny.

In summary, contract pharmaceutical development organizations are cost-eff ective, highly skilled resources that operate under strict compliance to regulations. Th e ability to reduce risk and reach market sooner builds on and extends existing internal resources. Th ese factors, as expressed by our current client base, are the underpinning of ABC Laboratories’ recent expansion of our pharmaceutical macromolecule services, staff and facilities. n

What’s behind the trend in increased outsourcing of biopharmaceutical development? By Byron Hill

The benefi ts of going outside

FINALWORD

Byron Hill is President and CEO of ABC Laboratories and has 40 years of experience

in fi nance and general management, with an emphasis on technology-related

industries. His expertise includes mergers and acquisitions, managing fi nancial turnarounds,

SEC reporting, ERP system implementations, management reporting, treasury and risk

management. Hill earned his undergraduate degree from Southern Illinois University and is

a certifi ed public accountant.

“Reduction in time to market is paramount in the pharmaceutical

industry”

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