ngp eu 8

www.ngpharma.eu.com • Q3 2009

POWER

GROWING UP

Nycomed stands tall amongthe industry’s giants (P36)

SOMETHING FISHY

Why marine-derived omega-3 oil could be Pronova’s next blockbuster (P70)

NEW BEGINNINGS

Chris Viehbacher starts with a clean slate at sanofi -aventis (P74)

How will the competition between generics and branded products

play out? (P32)

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The battle between gener-ics and branded products has been going on for a long time: the claims and counter claims over aspi-rin, for example, started

in the early 20th century. Th e patent system, introduced to help bring order to this chaos, allows drug developers a limited-time patent for each innovative product they develop, so they can recoup their initial investment. Simi-lar, unbranded drugs are introduced into the market aft er the patent expires, bringing lower prices for those not fussy about what it says on the label.

For a while, the system seemed to work, but lately things have changed. Th e pharma-ceutical industry as a whole is facing some tough challenges: blockbusters – on which many big companies depend for the majority of their income – have become harder to fi nd, many major diseases already have multiple treatments, pipelines are drying up. Add the

global recession on top of that, and you can see why many companies are looking to boost their bottom lines in any way they can.

One of those ways is playing tougher with their generics-producing counterparts. In the US, where President Obama is trumpeting greater production of generics as a way of cut-ting healthcare costs, some companies have even taken the step of introducing generic copies of their own drugs, before the patents on the originals have expired. Th is can help coun-ter the tactic used by certain generics produc-ers, who bring out copycat versions of drugs while their patents are still valid, depending on the slowness of the American legal system to allow them ample time to make a profi t.

Here in Europe, it is the developers of branded products who have been accused of not playing fair. Last year, the European Com-mission launched an inquiry into the Euro-pean pharmaceutical sector, citing as one of its reasons a delay in generic medicines reaching the market. According to the Commission’s

FROM THE EDITOR

Tough competition

fi nal report, released in early July, manufactur-ers of branded drugs have been using what it calls ‘delaying strategies’ to block the release of generic products.

Who will come out on top? Globalisation may provide the answer. Th e pharmaceutical industry, whose main source of profi ts has long been North America and Western Europe, is now increasingly venturing into new markets, where patent protection oft en doesn’t exist and all drugs must compete on a level playing fi eld. It could be this, more than anything else, that determines the next stage of the game.

Marie Shields, Editor

The rise of generics could mean a new game plan for big pharma.

5

“When it comes to creativity, I don’t think there is an advantage of scale – it could actually be a disadvantage of scale” Håkan Björklund, CEO, Nycomed (Page 36)

“We’ve been dancing around a number of issues in this industry and haven’t wanted to face up to them” Chris Viehbacher, CEO, sanofi -aventis (4)

“We must have more competition and less red tape in pharmaceuticals” Neelie Kroes, European Commissioner for Competition (Page 32)

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Winner takes allWho will grab the prize as the competition betweengenerics and branded products heats up?

32

36

In with the newSanofi-aventis CEO ChrisViehbacher on mergers, mega trendsand why he’s optimistic about thepharmaceutical industry’s future

74

The small company that grewWhen Håkan Björklund becameCEO of Nycomed in 1999, thecompany was a relatively minorplayer in the industry. Now it ranksamong the top 40 in the world

CONTENTS9

CONTENTS NGP EU8:july09 29/7/09 14:58 Page 9

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MANUFACTURING

42 Joining forcesBayer’s Edgar Sur explains how Lean and SixSigma can work together in pharmaceuticalmanufacturing

56 A limited shelf life?Schering-Plough’s Brent Saunders examinesthe industry’s move toward OTC switch

70 Economies of scalesHow Pronova’s use of omega-3 hastransformed an age-old remedy into apotential blockbuster

RESEARCH & DEVELOPMENT

82 Running the riskGSK’s Ellen Strahlman outlines why a balanceof safety and efficacy is essential in clinical trials

90 Trials and tribulationsThe importance of good decisions for ensuringpatient welfare, according to John Smith

96 Changing timesWyeth’s Thorir Bjornsson on attrition, mergersand what the future holds for the industry

100 Bringing drug discovery intofocusAnne Phillips looks at transparency, patientbenefits and the challenges of global clinical trials

MARKETING

108 Personal bestWhy individual accountability plays a crucialrole in sales force effectiveness

ROUNDTABLE DISCUSSIONS

47 Lean/Six Sigma With Ian Cox ofJMP, Erik Tieleman of R&G GlobalConsultants, Harry Clark of SIAssociates and Steffen Himstedt ofTrebing & Himstedt

59 Drug delivery With John Fraher ofEurand and Gerd Paulus of SwissBioAnalytics AG

113 Marketing With Corbett AccelHealthcare Group’s Scott Cotherman,Grey Healthcare Group’s MichelDubery, IDEA Pharma’s Mike Rea andZaicom International’s GraemeChrystal

123 CRM With Rob Halkes of VanSpaendonck, Vivian Hunt of McKinsey& Company and CDM’s Torben Vogt

93

86

90

Trials and tribulations

Dipti Amin

CONTENTS11

ASK THE EXPERTS

86 Richard Lake, Restek Corporation88 Ayelet Dilion-Mashiah, Do-CoopTechnologies Ltd.93 Dipti Amin, Quintiles106 Michael Butler, Xceleron134 Ethan Smith, Metastorm


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70

104

66

136 Travel 138 Events140 In review142 Profile144 Photo finish

Economies of scales

Photo finish

128 Keeping in touchThe importance of physician-patientrelationships in ensuring adherence to drug

CONTENTS13

IN THE BACK

China

EXECUTIVE INTERVIEWS

94 Ralph McDade, Rules-BasedMedicine120 Amanda Smith, Caudex Medical127 David Swinbanks, NaturePublishing Group

INDUSTRY INSIGHTS

54 Philip Fairhurst, Sodexo66 Martin Svantesson, Geodis Wilson68 Abhijit Mukherjee, Dr. Reddy’s104 François Rechenmann andAdrienne Craig-Kennard, Genostar132 Masao Moriyama, GE Healthcare


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STACEY SHEPPARD, HUW THOMAS

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UPFRONTLEAD FEATURE16

According to the EuropeanCentre for Disease Prevention

and Control, out of the 31EU and EFTA coun-

tries, 30 countrieshave reported atotal of 17,733 con-firmed cases, in-

cluding 33 deaths asof mid-July. Because novel H1N1 is

a new virus, many people mayhave little or no immunity againstit, and illness may be more severe

decision to raise the pandemicalert level to phase 6 is a reflectionof the spread of the virus,not the severity ofthe resulting illness.There is still un-certainty aroundhow many peopleinfected with H1N1will develop seriouscomplications or die, be-cause experience with this virusso far is limited and influenzais unpredictable.

multiple parts of the world.According to the WHO, morethan 81 countries are now report-ing cases of human infection withnovel H1N1 flu, including 40countries in the WHO EuropeanRegion, where the number ofcases had risen 73 percent be-tween 26 June and 2 July. Therewere nearly 18,000 confirmedcases in Europe as of mid-July.

The WHO stressed that its

IN THE MIDST OF A PANDEMICIn June, the World HealthOrganization (WHO) raised itsworldwide pandemic alert level tophase 6 in response to the ongo-ing global spread of the novel in-fluenza A (H1N1) virus (alsoknown as swine flu). Phase 6 in-dicates that a global pandemicis underway.

The pandemic alert reflectsthe fact that there are now ongo-ing community level outbreaks in

There were nearly

confirmed cases in Europe as of

mid-July

18,000

GPO - A - Flu capsules, used to treat theH1N1 virus, at the warehouse of theGovernment PharmaceuticalOrganization in Bangkok, Thailand

UPFRONT NGP EU:25 June 29/7/09 13:48 Page 16

UPFRONTLEAD FEATURE 17

and widespread as a result.There is also currently no vac-cine to protect against it.

In early July, the BritishBroadcasting Corporation (BBC)reported that the first doses of anH1N1 vaccine had been pro-duced in Europe, but that itwould be several months beforeany could be distributed. Thevaccine was produced byNovartis at a plant in Marburg,Germany. According to theBBC, the vaccine was made incell culture, a much fastermethod than the traditional wayof growing it in eggs.Novartis has saidthat although thevaccine is ready,the first batchwill not be used,as it was createdusing the wild typestrain of H1N1.

Also in July, the WHO wasinformed by health authoritiesin Denmark, Japan and HongKong of the appearance ofH1N1 viruses that are resistantto the antiviral drug oseltamivir(known as Tamiflu), based onlaboratory testing. The viruseswere found in three patientswho did not have severe dis-eases and all have recovered.Investigations have not foundthe resistant virus in the closecontacts of these three people.The viruses remain sensitive tothe drug zanamivir (Relenza).

H1N1 is a virus of swineorigin that first caused illness inMexico and the United States inMarch and April, 2009. It is be-lieved to spread through thecoughs and sneezes of affectedpeople. It may also be spread bytouching infected objects andthen touching your nose ormouth. H1N1 infection has beenreported to cause a range ofsymptoms, which include aches,

chills, fever, cough, fatigue andsore throat.

The American Centers forDisease Control and Prevention(CDC) has issued the followingguidelines outlining what to do ifyou should become infected withthe virus. If you are sick, you maybe ill for a week or longer. Youshould stay at home and avoidcontact with other people, exceptto seek medical care, but do notdo so unless you are severly ill.Be aware that you may be conta-gious from one day beforeyou develop symptoms to up

to seven days after youget sick. Children,

especially youngerchildren, might po-tentially be conta-gious for longer

periods.If you are severely

ill or are at high risk for flucomplications, you should contactyour healthcare provider or seekmedical care. Your healthcareprovider will determine whetherflu testing or treatment is needed.Antiviral drugs – prescriptionmedicines (pills, liquid or an in-haler) with activity against influen-za viruses – can be given to thosewho become severely ill. Thesemedications must be prescribed bya healthcare professional.

In order to protect your-selves and your loved ones, it’simportant to stay informed.More information can be foundat www.cdc.gov/h1n1flu/ orwww.who.int/csr/disease/swine-flu/. You should also observe thefollowing precautions. Cover yournose and mouth with a tissue whenyou cough or sneeze, then disposeof the tissue in the trash after youuse it. Wash your hands often withsoap and water, especially after youcough or sneeze, and avoid spread-ing germs by touching your eyes,nose or mouth.

Becausenovel H1N1 is a

many people mayhave little or no

immunity against it

new virus

United Nations Secretary General Ban Ki-moon says developingcountries could need more than US$1 billion by the end of thisyear to fight the H1N1 pandemic

Swiss pharmaceutical group Novartis announced it is to purchasethe Austrian specialty generics business EBEWE Pharma in a bid toimprove the reach of its own generic drug division, Sandoz

NEWS IN PICTURES

Researchers at Harvard Universityhave found that those who travelare three times more likely thanthose who do not to developvenous thromboembolism

Two pharmaceutical companies,Novartis and GSK, beganworking on the production of anH1N1 vaccine at theirlaboratories in Germany


UPFRONTIN MY VIEW18

ALEXANDER KAMB

Executive Directorof Oncology at

Amgen

on the business side, but I thinkmy view and the view of many ofmy colleagues is that if you actu-ally treat an unmet medical need,the commercial success will fol-low. People, societies and indi-viduals will always want to payfor their health.

There’s no ques-tion that the

trends aretoward de-creasing pro-

ductivity andcompanies still

wanting drugs.They still have the re-

sources to test them, but thesupply is diminishing, so thatcreates an opportunity. It’s anopportunity inside the industryto try to address that and an op-portunity for entrepreneurs andother kinds of people who don’tnecessarily have the taste for bigpharmaceutical companies tomake contributions.

tions that it acquires in its natur-al history as it develops, and un-derstanding that complexity isvery challenging. As we moveforward and try to understand itwe will employ a lot of thesetechnologies that are emerging.It’s not magic.

The more things wecan see and moni-tor, generallyspeaking, themore we end updoing and themore it costs, buthopefully the betterthe results will be. As im-portant as the technology is, thekey thing is still the biology.People who can understand thebiology have a vision, have ideas;those are the people that aremuch needed and are arguablyin short supply.

There is obviously a role forbusiness experts and creativity

All the investment in researchover the last 30 years or so isbeginning to pay dividends andwe understand a lot about can-cer, and so now we can be muchmore predictive in what we do.We can predict if we inhibit thistarget and attack this part of thecancer cell, it will die and thepatient will survive.

What has unfolded in the lastfew years is actually not as sim-ple as that and in fact the viewthat cancer might be a simpledisease genetically: in somecases that’s true, but it’s a limit-ed number of cases. For themost widespread cases like col-orectal cancer, prostate, breastand lung, the disease when youlook more closely is actually ge-netically very complex, withminimally dozens and possiblyhundreds of genetic cases.

Cancer, as we’ve learned in thelast few years, has many muta-

As important

as the technology is, the

is still the biology

key thing


In the UK, the National Institutefor Health and Clinical Excellence(NICE) has issued its final tech-nology appraisal for Alzheimer’smedicines. The appraisal was up-dated following the court caseagainst Eisai and Pfizer, manu-facturers and distributors ofAricept (donezepil).

NICE has decided to upholdits original decision to ban the re-imbursement of Aricept, as well asExelon (rivastigmine, Novartis)and Reminyl (galantamine, Shire),for patients with early stageAlzheimer’s. NICE had previouslyrefused to release the model it hadused to make the decision, whichhad raised objections from thecompanies involved.

Although some small changeswere made to the model followinga consultation with stakeholders,NICE’s independent advisorycommittee decided they would notmake enough difference to thecost-effectiveness of the drugs. Theguidance is therefore being left un-changed, and the drugs will beavailable on the National HealthService only to those patients whohave the moderate, rather than themild, form of the disease.

Sanofi-aventis’ atrial fibrilla-tion treatment Multaq(dronedarone) was recentlyapproved by the FDA in theUS. The approval meanssomething of a comeback forthe drug, which was rejectedby the FDA three years agoamid safety concerns. Multaqfailed to benefit patients suf-fering from severe heart fail-ure, and also increasedoverall mortality in one of itsinitial clinical trials.

After this major set-back, sanofi researchersbegan to look at whathad gone wrong.“Based on theAndromedastudy, we wereable to examinethe data and seewhat sort of pa-tients should not getMultaq, and that wasthe basis of starting theAthena trial,” said Paul

Chew, Chief Science Officerand Chief Medical Officer forthe company’s US operations.

Instead of targeting pa-tients experiencing severeheart failure, sanofi decidedto examine atrial fibrillation(AF) – an irregular rhythmin the upper chamber ofthe heart leading to bloodclots and potential strokes.Patients with

the disease have an increasedrisk of hypertension, highblood pressure and an associ-ated risk of heart attack.

The most commonlyused therapy for these patientsup to now has been amio-darone, which is not approvedfor AF, and can have seriouseffects: pulmonary fibrosis,hyperthyroidism, tremors andsevere skin rash.

CASE RESOLVED

FAST FACT Cardiovascular disease causes more than

deaths in Europe each year

4.3 million

POSSIBLE HEART BLOCKBUSTER

UPFRONTCOMPANY NEWS 19

Danish pharmaceutical company NovoNordisk recently launched its brandedTwitter site ‘Race with Insulin’ to keep pa-tients up to date with the life of indieracer and diabetic Charlie Kimball.

In his tweets, Kimball talks aboutliving with type 1 diabetes and about usingNovo Nordisk’s Levemir to treat the disease.

Twitter is a system of ‘mini-blogs’ thatallows users to put up very short posts – or‘tweets’ – that are read by ‘followers’. TheNovo Nordisk account was apparently creat-ed for free just like any other Twitter account,and is updated by Kimball from his iPhone.

Such social media tools are not yet inwide use in the pharmaceutical sector, partlybecause the technology is so new and partly be-

TWITTER ON cause there are as yet no clear guidelines onthe type of information pharma

companies can post onsuch sites.AL

ZHEIM

ER’S

DRUG


UPFRONTINTERNATIONAL NEWS20

JACKSON DEATH

Israeli pharmaceutical compa-ny, Teva, has recalled thousandsof drugs after investigators im-plied a possible relation toMichael Jackson’s recent death.The pop icon was found dead onJune 25 after suffering a cardiacarrest in his Beverly Hills home.The anesthetic was also found inhis home.

Teva decided to pull vials ofthe powerful drug Propofol afterit found over 40 users whobought the drug in May were suf-fering fevers and chills, and it wasdiscovered two lots of the distrib-uted drug were contaminated.

A Teva Pharmaceuticalsspokeswoman, Denise Bradley,told the Associated Press there wasno connection between the conta-minated drug, which promptedthe recall, and Jackson’s death.

MEDICAL TOURISMNot a new phenomenon forSouth Korea, but the popular des-tination for medical care is aboutto get an even greater boost. A re-vised law going into effect in Maywill allow hospitals to hire agen-cies to help lure medical tourists.

Previous to this, advertise-ments to the public were disal-lowed and medical institutionswere unable to hire agencies toseek patients for them or direct-ly target marketing efforts at spe-cific groups.

With the help of the newlaw, South Korea’s HealthMinistry hopes to attract 100,000medical tourists by 2011. SouthKorea is already a popular desti-nation for Asian women seekingcosmetic surgery and the govern-ment now hopes to get patientsfrom all over the world.

BRAZIL’S INNOVATION

A new report released from thePharmaeutical Research andManufacturers of America(PhRMA) has stated that Brazilhas made substantial progress re-garding its drug innovation poli-cy and is now able to compete inmedical innovation.

‘Innovation in Brazil: PublicPolicies and Business Strategies,’ isbased on several seminars and ad-vises that the region can now at-tract innovation investments frominternational players, such asprocesses, products and services.

Patent registration is one ofthe indicators that measure inno-vation. According to the report,the Brazilian companies that haveregistered the most patents arethose that operate in the interna-tional market. It is believed thatuntil now, Brazil has been missingthe opportunity to attract R&Dcentres of foreign companies.


UPFRONTINTERNATIONAL NEWS 21

AIDS RESEARCH

A major AIDS conference cur-rently under way in Cape Townhas announced global spendingon HIV vaccine research is cur-rently in decline, following a fallof 10 percent in 2008, equallingapproximately US$93 million.

The Working Group,which comprises the UnitedNations AIDS agency UNAIDS,the International AIDS VaccineInitiative and other organisa-tions, believe the decline to beattributable to the global eco-nomic crisis as well as disap-pointment at the outcome of themStep and Phamibili trials.

The two international trialsof a vaccine developed by drugcompany Merck were haltedafter results showed they failedto prevent HIV infectionsamong participants.

WORKFORCE CUT

Sun Pharmaceutical’s US sub-sidiary, Caraco Pharma, haspledged to cut its workforce bymore than half after the recentclampdown by the US FDA onthe company’s manufacturingfacilities idled most units.Caraco’s 667 full-time employ-ees are expected to be reducedto approximately 350 person-nel, after the FDA pulled up thecompany for “repeated manu-facturing standards violations”last month.

On June 25, US Marshalsseized drug products manufac-tured at Caraco’s Michigan facil-ities in Detroit, Farmington Hillsand Wixom. The seizure put animmediate stop to the firm dis-tributing drugs, pending an as-surance that it would complywith the FDA’s current manu-facturing practices.

PATENT RESTRAINTSA gathering of 12 states inMorocco in July, is due to addressthe current issue of corporatecompanies producing genericmedicines and the effect this hason developing countries trying toaccess affordable medicines.

The global charity Oxfam hasarranged the meeting to bringabout a new Anti-CounterfeitingTrade Agreement (ACTA) todraw up new regulation of patentsand trademarks. The charity saidgeneric manufacturers could besubject to criminal prosecutionsand have their medicines seizedon orders from big drug compa-nies under new international lawsbeing discussed.

The charity fears the EU ispushing for a deal that will requirecompanies to increase seizures andprosecute companies who producegeneric medicines legally. Oxfamsaid this in turn could lead to bigpharmaceuticals having a monop-oly on medicines.


UPFRONTCOMPANY NEWS22

OLDEST NEW MOTHER DIESThe world’s oldest new motherhas died, aged 69. Spanishwoman Maria del CarmenBousada de Laragave birth at age66 in December2006 thanks toin vitro fertilitytreatment andthe help of donorsperm and eggs.She died in mid-Julyof cancer.

Bousada had said in inter-views that her own mother had

lived to 101, and she hopedshe would also have the ex-

tended life span gene. Inan interview with

Associated Presstelevision news,Bousada said:“I think every-one should be-

come a motherat the right time

for them”. Her deathraises questions about the

safety of in vitro fertilisation inolder women.

In the Q4 2008 issue of NGP, KARE SCHULTZ examines the growingglobal epidemic of diabetes and looks at the exciting new treatmentsnow appearing on the market. Shultz also discusses the ethicaldebate surrounding human stem cell research.

Go to www.ngpharma.eu.com, click on ‘Previous issues’ in the leftcolumn, choose ‘Issue 6, November 2008’ and scroll down to ‘Coverstories’ to read about NOVO NORDISK’s efforts to find newtreatments for Europe’s 48 million diabetes sufferers.

FROM THE VAULT

FLU CASES RISE IN UK

GPs in Britain have experienceda nearly 50 percent increase inpatients fearing that they mighthave contracted swine flu.According to BBC News, in thesecond week of July, 40,000 morepatients contacted their doc-tors to report flu-likesymptoms.

With manyGPs criticisingthe govern-ment over itshandling of thepandemic, it hasemerged that re-ported cases rose by 46percent from the previous week,with those aged between five and14 at the highest rate with 159.57per 100,000 visiting their doctors.The second highest rate was inyoungsters and babies aged up tofour at 114.12 per 100,000.

Central England still had thehighest number of cases with 94per 100,000, with London still re-maining a hot spot for the virus.The north of England, however,has also witnessed a recent in-crease, with cases going up from

6.6 to 37.16 in one week.The swine flu

vaccine is not ex-pected to arrive inthe UK until theend of August,

and will only beadministered to

those on the prioritylist, such as people aged six

months to 65 with a conditionsuch asthma, diabetes, heart, liveror kidney disease, or a suppressedimmune system.

The rest of the UK is due toreceive around 60 million doses ofthe vaccine, enough to cover halfthe population, by the end of

December. The rest will follownext year. Until then, it is

clear that doctor's surg-eries will continue tosee ever increasingnumbers of cases.

“I think

should become amother at the right

time for them”

everyone

In the second week of July

more patients contacted their

doctors to report flu-like symptoms

40,000

FAST FACT

Iceland has thehighest fertility ratein Europe, with

per woman

2.07

children


UPFRONTH1N1 SPECIAL REPORT 23

EU Health Commissioner Androulla Vassiliou haswarned that 60 million people in Europe will need pri-ority vaccination against the H1N1 (or ‘swine flu’) virus,saying that “there won't be vaccinations for everyone.”

Vassiliou was speaking to Lusa, the Portuguesenews agency, after visiting a health centre near thePortuguese town of Estoril. She pointed out that thenumber of people across the EU most at risk fromH1N1 had been estimated at 60 million by expertsin Brussels.

In October, Health Ministers from the 27 memberstates of the EU will meet to decide how a vaccinationprogramme against H1N1 will work. The virus had in-fected nearly 150,000 people worldwide by the end ofJuly, and had resulted in 850 deaths. Most people whocontract the virus suffer less severe symptoms thanthose caused by ordinary seasonal flu.

Four cases of a strain of H1N1 resistant to os-eltamivir (Tamiflu) have been identified. However,because of the large amounts of the drug being usedworldwide, such isolated cases of resistant strainsare expected.

Flu vaccine manufacturers have increasedproduction of seasonal flu vaccines and several

companies are currently working on a vaccine againstthe virus, which it is hoped will be ready before themain flu season begins in Europe in the autumn.Although the virus is currently still relatively mild,medical professionals fear that it could mutate and gainstrength in the next fewmonths. Germany, Franceand the UK have already or-dered billions of euros worth ofvaccine stockpiles.

Source: ECDC situation report

PRIORITY VACCINATIONS NEEDED

Cumulative number of confirmed H1N1cases in EU and EFTA countries as of22 July 2009

TOP 10

32

54

1

87

109

6

UK

Germany

Spain

France

Sweden

Greece

Cyprus

Switzerland

Italy

Netherlands

Source: ECDC situation report

10649

1818

1486

628

326

323

297

272

258

211

FLU OUTLOOK Reported cumulative confirmed cases of H1N1 in EU and EFTA countries as of 22 July

1

10

100

1000

10, 000

Confirmed cases in EU/EFTA countries



HAMILTON UNVEILS BIOLEVITATOR

The BioLevitator is the first benchtop 3D cellculture system on the market, delivering sig-nificant productivity gains to researchers indrug discovery, cell-based therapeutics andregenerative medicine. The BioLevitatorbrings the engineering and automation ex-pertise of Hamilton together with Global CellSolutions’ unique approach to cellculture for a scalable and auto-mated system that reducescosts whilst improving theconsistency and relevance ofcultured cells.

The BioLevitator elimi-nates traditional peripheral cellculture instruments, such as incu-bators and centrifuges, and minimises manu-al handling. Each of the BioLevitator’s fourhydrophobic, PTFE-filtered 50 mL cell cul-ture tubes can produce cell growth equivalentto up to ten T75 flasks, depending on the cellline. The system features a user-friendly touchscreen interface with real-time monitoringand control of environmental temperatureand CO2 levels.

The BioLevitator utilises the GlobalEukaryotic Microcarrier (GEM) technology

from Global Cell Solutions. The GEM providesan optically clear and non-autofluorescentpipettable substrate for adherent cell lines. TheGEMs contains paramagnetic particles that fa-cilitate suspension in the LeviTube and mediachanges. Custom protein coatings are availableto facilitate growth of difficult cell lines and the

GEM’s hydrogel core inhibits ice crys-tals during cryopreservation, en-

suring high survivability andcell function.

Hamilton Company is aleading worldwide supplier

of precise liquid handling de-vices, laboratory automation

and storage systems, serving cus-tomers in academic and private research lab-oratories, pharmaceutical and clinicaldiagnostic companies and governmental in-stitutions. Hamilton maintains headquartersin Reno, Nevada and Bonaduz, Switzerland,both of which house R&D and production fa-cilities. Hamilton has subsidiaries for directsales and service in many countries and workswith a wide distributor network in other re-gions. Hamilton is a privately held company.

TheBioLevitator

traditional perip-heral cell culture

instruments

eliminates

Swiss drug maker Roche has begun cutting staff atGenentech, following its recent US$46.8 billionacquisition of the biotech company. The move isthought to be the first step in a a widely antici-pated integration programme. According to aGenentech spokesperson, less than one per-cent of Genentech’s 8250-person workforcein San Francisco will lose their jobs. No spe-cific figures or timeframe for the cuts wereimmediately available.

The cuts which will be carried outthrough voluntary contract buyouts, could

impact Genentech’s late stage drug develop-ment and administrative sections. It is believed

that few jobs will be lost in the company’s man-ufacturing and production operations. Roche’s

integration efforts up to now have focused on uppermanagement. Genentech’s CEO, Arthur Levinson,

and President of Product Development, Susan Desmond-Hellmann, have both left the company.

UK-based GlaxoSmithKline has signed a collab-oration agreement with three-year-old biotechfirm Concert Pharmaceuticals. Under the termsof the deal – which is worth US$35 million upfront and up to US$1 billion in additional pay-ments – Concert will develop three of its com-pounds through agreed-upon clinical trials, andGSK will have an exclusive option to licensethem worldwide.

Concert will also provide versions of threeGSK pipeline drugs modified using Concert’snew deuterium technology, which replaces ordi-nary hydrogen atoms in some existing drug mol-ecules with deuterium (also known as heavyhydrogen), an isotope of hydrogen with a nucle-us containing one proton and one neutron

Deuterium is easily isolated from seawater,and has twice the atomic mass of ordinary hy-drogen, allowing it to bond differently with otherelements. For example, it forms a much strongerbond with carbon.

Concert has demonstrated that this in-creased bond strength can be used to improveimportant drug properties in certain cases, in-cluding bioavailability and half life. The resultingnovel compound holds the promise of improv-ing tolerability, efficacy and safety.

One of the drugs covered by the agreementis Concert’s CTP 518, a protease inhibitor creat-ed by substituting deuterium for hydrogen incertain key areas in atanazanavir. CTP 518maintained full antiviral potency in preclinicalstudies, with significantly slower metabolism inthe liver. Researchers hope that it will be easierto maintain higher blood levels of CTP 518,meaning the drug could become the first pro-tease inhibitor to be used without the need for abooster drug.

NEW DEAL

For more information, visit www.hamiltoncompany.com

JOB CUTS AT GENENTECH


Hamilton.indd 1Hamilton.indd 1 28/7/09 13:31:1328/7/09 13:31:13

CONFIDENCE IN A CRISIS EMOTION – A PART OF CHANGE“Emotional intelligence is the pri-mary source of human energy,authenticity, aspiration anddrive.” When we do any kind ofchange, whether it be changingthe way we problem solve, im-proving the culture of a company,launching products, improving

customer satisfaction or se-curing monies, we

need to get theemotion runningthrough the or-ganisation andput the fire in

our hearts, toonce again excite

the masses. Coopercontinues, saying, “By devel-

oping the emotional quotient(EQ), we learn to readily ac-knowledge and value core feel-ings in ourselves and others.”

Once emotional change isachieved organisational changeswill take place and the companycan begin the process of movingforward. So maybe it is time forcompanies to consider this kind ofchange, which might start a revo-lution of breakthrough ideas andpossibilities.

It’s often been said you shouldleave your emotions at the doorwhen you go to work. I’m sure wecan all relate to this over our manyyears of working, whether it is for acompany, a charity, or for ourselves.I would like to convey the counterto this old saying by stating that it’sokay to be emotional aboutwork. We have manychallenges in ourwork that pro-vide us withpleasant andunpleasant ex-periences. Weoften shrug off theemotion, saying “It isnot my job to get involved.”We have lost our emotional intelli-gence and purpose for being emo-tional in the work place. Driving theemotional passion into our work isabout driving purpose behind whywe are doing what we do. This kindof emotional change is necessary forgrowth. We need to be emotionalabout what’s happening and be apart of driving the emotion backinto our working lives.

In his book, ‘EmotionalIntelligence,’ Robert Cooper says,

Today’s defining crisis is in con-sumer confidence rather than the fi-nancial markets. The harsh lessonfor businesses is that apparently ro-bust brands become fragile oncereputation is undermined. Sharesrise and fall, but once trust is lost it’sextremely difficult to recover. Whilelow stock market value can be dam-aging, lack of faith can be fatal.

The pharmaceutical industryhas long appreciated the value oftrust, but this should not admitcomplacency. Bad news sells, andwith dwindling advertising rev-enues, some in the media seestorm-chasing as a growth market.Though pharma has emerged rela-tively unscathed from recentevents, the wider message is clear:failing to have a strategy to protectand rebuild trust leaves a compa-ny’s most precious asset danger-ously vulnerable.

Effective crisis communicationis proactive. Risks should be con-stantly identified and mitigated,and all media outlets – includingnew media channels – need to be

monitored to pick up problems be-fore they hit the front page. Even ifthe crisis breaks, companies need tobe ready to influence the right peopleat the right time, using the rightchannel with the right message.

An appropriate response is asimportant as a rapid one: implausi-ble denials later retracted will notbuild trust. Responses should reflectthe source of the threat – a tradition-al press statement will achieve littlewhen the damage is being done onTwitter. Key crisis personnel, includ-ing designated spokespeople, shouldbe identified and regularly briefed sothey can respond with speed and ac-curacy. External PR and legal sup-port, bringing additional expertisewhen needed, should form an inte-gral part of this core crisis team.

An effective crisis communica-tion strategy is good business, dri-ving a company to be alert, agile andresponsive. These are valu-able lessons, because theworst crisis is the onefrom which a busi-ness fails to learn.

FAST FACT

SHIRE’S US BREAK

UK-based specialty drug makerShire Pharmaceuticals may be onthe brink of breaking into aUS$1.2 billion market sooner thanexpected after regulators theregave its drug Velaglucerase-alphaa fast-track designation that couldsee it on the market late next year.

Velaglucerase-alpha is cur-rently in the final stage of clinicaltrials. According to Shire, the orig-inal timetable to file for approval

was the end of this year. Fast track-ing means the US FDA will allowthe company to send informationin on a rolling basis. There is noguarantee the drug will be ap-proved more quickly, but the movedoes suggest the FDA considers ita priority.

Velaglucerase-alpha is beingdeveloped for the treatment ofthe rare genetic conditionGaucher’s disease.


We have lost our

intelligence andpurpose for beingemotional in the

work place

emotional

Nearly

of people of AshkenaziJewish descent maycarry the gene forGaucher’s disease

10%

For more information visit www.3ppartnersdls.com

Jane Brearley is Head of Waggener Edstrom’s EuropeanHealthcare Practice in London


We Know the Tools.

We Have the Strategies.

We Engage People.

www.3ppartnersdls.com

Let 3P Partners Make a Diff erence in Your World

Whether the help you require is to fi ll the gaps in the short-term or to engage and empower all levels of your organizati on, 3P Partners makes a diff erence by…

• Extensive Assessment & Gap Analysis • Working with You the Client to Develop Improvement

Plans and Initi ati ves to Achieve Higher Levels of ROI • Transformati on of Culture • Uti lizati on of Lean Six-Sigma Tools to Achieve

Sustainable Improvement Throughout Your Organizati on

• Assisti ng Your Organizati ons with Restructuring Eff orts • Adaptability of Key Technical Soluti ons

3Ppartners.indd 13Ppartners.indd 1 28/7/09 13:23:1828/7/09 13:23:18


POSITIVE RESULT IN LUPUS TRIAL

Human Genome Sciences andGlaxoSmithKline have announcedthat Benlysta (belimumab, formerlyLymphoStat-B) has met the primaryendpoint in BLISS-52, the first oftwo phase III trials in patients withserologically active systemic lupuserythematosus (SLE). In the placebo-controlled BLISS-52 study, the re-sults showed that belimumab plusstandard of care achieved a clinical-ly and statistically significant im-provement in patient response rateat week 52, compared with standardof care alone.

Study results also showed thatbelimumab was generally well toler-ated, with adverse event rates compa-rable between belimumab andplacebo treatment groups.

“The BLISS-52 results demon-strated that Benlysta has the poten-tial to become the first newapproved drug in decades for peo-ple living with systemic lupus,” saysH. Thomas Watkins, President andChief Executive Officer, HGS.“Given the limited treatment op-tions currently available, patientswould benefit greatly from potentialnew treatments. Benlysta is an out-standing example of the type oftreatment HGS is working to devel-op and bring to patients. Assumingpositive results in November fromour second phase III trial ofBenlysta, we and GSK plan to sub-mit marketing applications in theUnited States, Europe and other re-gions in the first half of 2010.”

Belimumab is an investigation-al drug and the first in a new class ofdrugs called BLyS-specific in-hibitors. No new drug for lupus hasbeen approved by regulatory au-thorities in more than 50 years.Belimumab is being developed byHGS and GSK under a co-develop-ment and commercialisation agree-ment entered into in August 2006.

“Benlysta is the first medicinebeing developed specifically forlupus that has reached this late stageof clinical development with posi-tive results,” says Carlo Russo,Senior Vice President, BiopharmDevelopment, GSK. “We look for-ward to completing the pivotalstudies, with the hope of bringingthis potentially important therapeu-tic advance to patients sufferingfrom SLE.”

WEB-BASED LABELLING SYSTEM A special event launching thenew web-based version ofPRISYM Medica, the world’s onlypurpose designed labelling man-agement software for FDA regu-lated environments is being heldin Munich on 1st October 2009.

PRISYM ID today announcedthe official launch event for a web-based version of PRISYM Medica,a market leading GMP-based la-belling management software forFDA 21 CFR Part 11 regulated en-vironments. Medical device, phar-maceutical manufacturers, clinicaltrials companies and industrypress have been invited to see theproduct demonstrated live.

PRISYM Medica Web is thefirst web-based labelling solutionto include web-accessed label de-sign and approval routing as wellas printing. The web version de-livers significant benefits interms of efficiency, accuracy andcompliance in the design andapproval of labels. PRISYMMedica offers a collaborative la-belling environment with auto-mated processes and prompts forthose involved in label design, ap-proval and production whereeverthey might be located.

Manufacturers using PRISYMMedica Web are also able to givetrusted suppliers, distributors and

partners secure, print-only accessto approved labels in an environ-ment that monitors and recordsevery activity along with electronicsignatures in a time and datestamped audit log maintaining ahigh level of security and FDAcompliance.

This can deliver major oper-ational and production advan-tages as product can more easilybe switched from one productionsite or distribution centre to an-other. This enables manufactur-ers to capitalise on the labour,tax, shipping or production effi-ciencies of using a particular sitefor certain types of products orshipment destinations.

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

VITAL STATISTICS

of adults 65years and over

received an influenza

vaccination during the past

12 months

64%

Between

of the US population get

the flu each year

5-20%

The CDC has antigenically

characterised

seasonal humaninfluenza viruses

since October2008

1567

It has also characterised

novel H1N1viruses

84

Between Octoberand May, the

influenza-associated

hospitalisationrate for children

aged 0-4 was

per 10,000

3.85


Prisym.indd 1Prisym.indd 1 28/7/09 13:32:3028/7/09 13:32:30

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

3P Partners 26, 27ActivX 6Aegis Analytical Corporation 72Alternatives Technologies 45Amphora Research Systems 81Anagnostics IBCAstraZeneca 128Bayer 42Biotechnology Industry Organization 32Boehringer Ingelheim 90Bürkert 15Caudex Medical 10, 120, 121CDM 123, 125Cisbio Bioassays 99Corbett Accel Healthcare Group 8, 113, 114Créapharm 78Do-Coop Technologies Ltd. 88, 89, OBCDr. Reddy’s 4, 68, 69EMD Serono 108Eurand 61, 62European Commission 32Farmak 65Field Fisher Waterhouse 32

Frost & Sullivan 32GE Healthcare 132, 133Genentech 74Genostar 104, 105Geodis Wilson 66, 67Grey Healthcare Group 119GlaxoSmithKline 74, 82, 100Hamilton 24, 25IDEA Pharma Consulting 112, 113Innovex IFCJMP 47,51Johnson & Johnson 130McKinsey & Company 123Merck 74Metastorm 12, 134, 135MPI Research 31Nature Publishing Group 127Nycomed 36Pfizer 74PricewaterhouseCoopers 56PRISYM ID 28, 29Pronova BioPharma 70Quintiles 93

Restek Corporation 86, 87Roche 74R&G Global Consultants 46, 47Rules-Based Medicine 94, 95sanofi-aventis 74Santarus 56Schering-Plough 56, 74Shire Pharmaceuticals 32SI Associates 47, 48Siemens 59Sodexo 54, 55Swiss BioAnalytics AG 60, 61Trebing & Himstedt 47, 53Van Spaendonck Group 122, 123Waggener Edstrom 26, 129Waters 2Wyeth 96Xceleron 106Zaicom International 113, 116

HEALTH TOURISM CRACKDOWN

REGIONAL FOCUS

China’s emergingpharmaceutical market

SWITCHING SIDES

Brent Saunders onwhy OTC makes sense

DON’T MISS...

36

56

136

COMPANY INDEX Q3 2009

UPFRONTCOMPANY INDEX30

BIG PLANS

Håkan Björklund over-sees Nycomed’s growth

The UK government is apparentlyaiming to cut down on so-calledhealth tourism by proposing thatvisitors to the UK from outsideEurope take health insurance, toprevent non-EU nationals fromtrying to use free NHS services towhich they are not entitled.

The Department of Healthand the UK Border Agency willalso examine ways immigrationrules might be changed so that

those with large debts for servicesthat should have been paid for up-front could be expelled from thecountry or refused permission tore-enter.

Conversely, access to freehealthcare for some non-UK resi-dents would be broadened underdifferent measures recommendedby proposals from the Departmentof Health and the Home Office.This group would include unsuc-

cessful asylum seekers who haveofficially recognised difficulties re-turning home, and unaccompa-nied children.

These proposals, which are dueto be published later this year, alsosuggest the possibility of a changein policy for non-UK residents whoare HIV-positive. Currently, suchpeople are offered diagnosis andcounselling free of charge, but haveto pay for treatment.


MPIresearch.indd 1MPIresearch.indd 1 28/7/09 13:32:1928/7/09 13:32:19

32 www.ngpharma.eu.com

COVER STORY

The competition between branded drugs and generic copies has been going on for years, but as generics threaten to take the lead, how will their rivals fi ght back? By Marie Shields

GENERICS ED P32-35.indd 32GENERICS ED P32-35.indd 32 29/7/09 15:05:0229/7/09 15:05:02

www.ngpharma.eu.com 33

“Overall, the idea that profi ts from branded products are needed to invest in new research is tapering off . Having a comprehensive business model that works in the current situation is more important.”

No matter which argument you believe, producers of branded phar-maceuticals are not about to take the onslaught of generics lying down. In the US, ‘copycat’ drugs are oft en launched on the market before the patents on the original drugs expire, with generics companies depending on the slowness of the American legal process to hold up any resulting litigation. Some drug developers have responded by launching generic copies of their own branded products before the patents have expired.

Making inquiriesTh e branded vs generics battle is also hotting up here in Europe.

Late last year, the EC launched a sector inquiry into EU pharma markets under EC competition rules. According to the Commission’s website, the inquiry was launched for two reasons: because of a decline in novel medi-cines reaching the market (average 27 per year in the 2000s compared to 40 per year between 1995 and 1999), and delays in generic market entry,

leading to potential extra costs for consumers.Th e Commission’s preliminary report, released last November, was viewed by many as a full-on attack

on the European pharmaceutical industry. John Cassels, a competition lawyer at Field Fisher Waterhouse, believes that the preliminary report was too harsh, and indicated that the Commission did not truly understand the patent law system and how the pharmaceuti-

cal industry operates. “Part of the Commis-sion’s problem is that it was trying to use the

wrong tool. Th ere are problems in the pharma-ceutical sector, but they’re not necessarily problems

that you can address via the competition rules. It’s widely recognised, for example, that the way patents are registered could be im-proved, but using the competition rules is not the way to get at them.”

Another angle to the situation is provided by what are known as ‘settlement agreements’: agreements between branded pharmaceutical manufacturers and generic manufacturers aimed at ending ongoing liti-gation in a patent dispute. In some cases, a ‘reverse payment’ is agreed, where the generic supplier agrees not to enter the market for a certain number of years in exchange for a sum of money .

Such payments can be regarded as a way for big pharma companies to prevent generic copies of their products from entering the market, thereby keeping the price of drugs unnecessarily high. According to data from the European Commission, more than 10 percent of settlements in pharmaceutical litigation cases were reverse payment settlements, amounting to €200 million.

Just how widespread is the practice of reverse payments? Th e Euro-pean Commission said in its initial report that it had identifi ed 200 cases that it intended to investigate. However, as Cassels points out, unlike their US counterparts, European companies do not have to register settlement agreements, making them extremely hard to track.

Th e Commission’s fi nal report, released in early July, although less aggressive in its condemnation of the industry, still highlighted several

Heavy hitters all over the world are throwing their weight behind the cost-reducing poten-tial of generics. In the US, President Obama has recommended smoothing the pathway to their introduction, as a way of bringing down the cost of treatments for consumers. Govern-

ments of EU countries are also keen to ease the way for generic prod-ucts – understandably, given that in Europe, generic medicines enter the market at a price that is, on average, 25 percent lower than that of their branded equivalents.

What eff ect will this generic focus have on research-based pharma-ceutical companies, which have argued for years that extended patents on their products are necessary in order for them to recoup the mil-lions they invest in research and development?

Add to that the fact that big pharma companies are facing a host of other pressures at the moment: problematic pipelines, a dearth of new blockbusters, patent expiries – not to mention the global fi nancial crisis – and you have a potentially explosive situation for the industry.

According to Barath Shankar, Senior Industry Analyst, Pharmaceu-ticals and Biotechnology, for Frost & Sullivan, big pharma is facing an almost unprecedented amount of competitive pressure. “Th ey’re losing their pipelines and losing out on their big drugs to generic versions that are fl ooding the market, especially in areas like cardiovascular.”

Shankar points out that in many European countries, generics already account for a signifi cant number of the prescriptions being written, whereas in the US, branded drugs still drive price and revenue growth.

Worldwide, the encroachment from generics is forc-ing big pharma companies to change their business models. Rather than focusing on fi nding blockbuster drugs, they are increasingly developing their pipelines for the long term, becoming more fl exible, focusing on core specialties, and even producing their own generics.

Big investmentProducers of branded products point out that they put a lot of

money into developing their drugs, and if the money that comes from patent exclusivity is withdrawn, the development process will come to a halt. For example, Robert Spiegel, Chief Medical Offi cer at Schering-Plough, argues that, “If we say that generics are good enough, that the current medicines you have today in 2009 are probably good enough and we don’t really need any new medicines, 20 years from now we’re going to have major issues with an aging population and many diseases that still have major unmet medical needs.”

Barath Shankar, at least, doesn’t buy it. “I think that argument held true back in the 1990s and probably even the early 2000s,” he stresses. “But if you look at the way innovation is being driven in the current scenario, it’s a global market. Companies need to drive down costs. Th ere’s a lot of outsourcing happening with regard to clinical trials and contract manufacturing, so companies have to re-look at their business models and understand what their core competency is and then look at areas they should invest in.

Th e CNove

on

swr

ceutic

cing an y’re

. are

The total market for medicines in Europe is

worth more than

€214 billion at retail prices



a clear indication that manufacturers of branded products are taking the incursion of generics seriously.

Rather than trying to get rid of generic competition using question-able methods, in times like these, companies need to stick to their core business – designing the product – and ensure they have a solid supply chain. Th ey may also need to look at other areas, such as vaccines and biologics, in order to provide a steady income fl ow.

Some companies have already been smart enough to move in this di-rection – the speciality areas where the returns and reimbursement rates are high. One company that has done this very successfully is UK-based Shire Pharmaceuticals. Its Human Genetic Th erapies division, for exam-ple, focuses exclusively on the rare diseases known as ‘orphan diseases’.

As Sylvie Grégoire, President of the division, explains, “Our port-folio of products focuses on the very rare end of orphan diseases – the populations we treat are between 2000 and 3000 worldwide. We are able to gain suffi cient revenues and profi ts even though there’s a rarity of patients by commanding a high price for these products. If they don’t receive these replacement therapies or the drugs that we develop, their quality of life declines and they suff er from a very high morbidity as well

as oft en early mortality.”It’s certainly been a worthwhile strategy for

Shire, with six product launches in the past three years, and within Human Growth Th erapy, 300 additional staff taken on in 2007, and another 275 in 2008.

In addition to focusing on speciality thera-peutic areas, many big pharma companies are also investigating the potential of biologics. Europe was the fi rst to introduce guidelines for the approval of biosimilars, through the European Medicines Agency in 2005. Since then, the region has emerged as a testing ground for how the process will work in the

rest of the world. In the US, President Obama’s recent budget proposed the development of a faster pathway for generic biologics, and guidelines for their approval have also been issued in Japan. As competi-tion within the industry increases and margins grow smaller, generics producers may also see biologics as their next big opportunity.

Despite understandable opposition from big pharma and biotech companies, it seems likely that the development process for generic bio-logics will be improved. However, there are still hurdles to be overcome. Frost & Sullivan’s Shankar sees the main problem as the lack of a clear idea as to how the regulatory pathway will work. “I believe the FDA will require a stronger proof of bioequivalency and potentially also require some small-scale clinical trials, because the way in which biologics work is completely diff erent to the way small molecules or traditional phar-maceuticals work.

“Th at could create some complications. It could be a situation where companies are following a ‘wait and watch’ policy, but it is defi nitely something that will happen because in the current situation, with the way the pricing of biologics has been moving, this is a way to introduce a competitive marketplace and to encourage companies to compete more and create more opportunities.”

what it called “delaying strategies” used by manufacturers of branded drugs in an attempt to block generics from entering the market.

As a result of its inquiry, the EC says it will apply increased scrutiny to companies under EC Treaty antitrust law, as well as keeping a close eye on the use of specifi c instruments by originator companies to delay ge-neric entry. Defensive patenting strategies that focus on excluding com-petitors without pursuing innovative eff orts will also be discouraged.

Th e Commission recommends that member states be asked to provide an automatic/immediate pricing and reimbursement status for generic medicines that are equal to the original products, and to intro-duce legislation that facilitates generic uptake, such as prescription by substances rather than brands.

“We must have more competition and less red tape in pharmaceu-ticals,” said Neelie Kroes, European Commissioner for Competition, at the time the fi nal report was released. “Th e sector is too important to the health and fi nances of Europe’s citizens and governments to accept anything less than the best. Th e inquiry has told us what is wrong with the sector, and now it is time to act. When it comes to generic entry, every week and month of delay costs money to patients and taxpayers. We will not hesitate to apply the antitrust rules where such delays result from anticompetitive practices. Th e fi rst antitrust investigations are already under way, and regulatory adjust-ments are expected to follow, dealing with a range of problems in the sector.”

Time for changeIf practices such as reverse pay-

ments are indeed taking place, they are

UNFAIR TACTICS?Methods used to block generics from entering the market, according to the European Commission’s inquiry into the pharmaceutical sector:

• Originator companies fi ling so-called ‘patent clusters’ – a large number of EU-wide patents and pending patent applications for a single medicine.

• Unnecessary patent litigation. According to the EC report, there were nearly 700 cases of reported patent litigation with generic companies, which on average lasted three years. The generic companies ultimately won more than 60 percent of these cases.

• ‘Reverse payment’ settlement agreements. The EC report says that originator companies concluded more than 200 settlement agreements with generic companies in the EU. In approximately 50 percent of these, generic entry was restricted.

• Originator companies intervening in national procedures for the approval of generic medicines, which on average led to four months of delay for the generic medicine.



For companies whose major market is in the US, the ge-nerics vs branded products situation could be complicated even further by a bill that would allow US-licensed phar-macies to import cheaper FDA-approved medicines from

outside the country. President Obama himself has proposed allocating US$5 million to the FDA to “develop policies to

allow Americans to buy drugs approved in other countries.”Barath Shankar says that one potential roadblock to these

plans is the issue of oversight. “Th e problem is maintaining oversight over the FDA-approved manufacturing plants where these products come from,” he says. “Th e FDA ran into trouble with some overseas generic manufacturers in the recent past, with safety record and con-tamination issues.

“Th e lobby that is against importing drugs from other countries could then question whether the FDA has the capability to have oversight over these areas. However, I do know the FDA is moving in that direction, because they’ve established offi ces in India, which has the second-largest number of FDA-approved manufacturing locations outside of the US.”

It seems, in the long run, that companies that develop and manufac-ture branded products will need all their resources at the their disposal to fi ght off the generics challenge. Th ey will need to collaborate more, which will enable them to play to their strengths and let their partners take on the work that isn’t essential to their core business.

With generics on the rise and the twin threats of dwindling block-busters and upcoming patent expiries to cope with, the future looks chal-lenging for pharmaceutical and biotech companies. But this is a powerful sector, with a lot of money and experience behind it. Chances are, most will fi nd a way to come through unscathed.

Proof requiredAs Shankar points out, one potential

hurdle in the development of biosimilars may be the US Federal Drug Adminis-tration, and whether it decides to require proof that biosimilars are equivalent to their branded counterparts. Although the FDA’s rulings apply to drugs on the market in the US, it does tend to set the standard for the rest of the world. If the FDA decides to require proof of bioequivalency, it could make things much more complicated for generics manufacturers; and if it doesn’t, it could result in a situation where consumers don’t trust generic biologic drugs to provide the same benefi ts as the original versions.

Shankar explains that the fi rst concern for the FDA is from the bio-tech lobbies. “Th e biotech lobbies are saying this is not going to work because it completely diff ers from traditional generics. When you’re working with proteins, if you make a small change to the process, you’ll end up with a completely diff erent drug. Whereas with small molecules, it doesn’t matter what process you use, the end product will have the same chemical composition. Th at’s their argument. Th en the generic manufacturers are saying that this is not something they can’t do. It’s been done before.”

Both parties have a fairly strong argument, and at some point a decision will need to be made. Th ere is no doubt, however, that the approval timeframe and marketing process for biologics will be dif-ferent. Generic companies could see this as an opportunity to make more money with less competition, by building core competencies in a particular set of biologics.

aall

Bs S, it

Each European citizen spends an average of

€430 on medicines

annually

“We must have more competition and

less red tape in

pharmaceuticals”

- Neelie Kroes, European Commissioner for Competition


FEATURE INTERVIEW

Once a minor force in the world pharmaceutical market,Nycomed became a major player following its acquisitionof Altana Pharma in 2006. CEO Håkan Björklund tellsMarie Shields how the company is positioned to meet thechallenges of its extraordinary growth.

THE SMALL

grewCOMPANY THAT


Bjorklund ed:13July 29/7/09 13:58 Page 36

When Håkan Björklund became CEO of Nycomed in1999, it was still a relatively small company based inDenmark. Then in 2007 Nycomed acquired AltanaPharma, and almost overnight the combined compa-ny was catapulted into the top 40 in the world. What

has it been like to oversee such a huge transformation?“You rapidly forget how it used to be,” Björklund says with a chuckle.

“You think that where you are today is the most natural thing on earth. Butwhen I compare the figures, I realise that we are about 12,000 people now, andwe were fewer than 2000 people in 1999. And of course we have considerablymore subsidiaries as well. What it means is that you need to change your man-agement style from being directly involved in a lot of things to having a moreoverseeing attitude.

“I have many very competent collaborators and experts in every field.There is no need for me to be involved in the details. I look upon myself asmore responsible for strategy and for creating the culture in the company,which is absolutely essential, especially when you’ve been through a mergerlike ours with Altana. You need to create a winning culture where people areproud of being with Nycomed; where they feel empowered and where theyare happy to go to the work every morning, and thereby are contributingmore and having a good time as well.”



You can’t institute a big change like the Altana merger without meetingsome challenges, however. Björklund says the most obvious of these was the factthat Altana was twice the size of Nycomed – like David buying Goliath. In addi-tion to coping with the size issue, Björklund’s other aims for the new companywere to make the culture more open and to change its R&D structure.

“I think a lot of people in the former Altana organisation were question-ing the new strategy,” he says. “They wondered if it would work, and alsowould whether we do what we said we intended to do. It took a lot of effort inthe beginning to convince people that yes, this strategy would work, and thatwe were very committed.

“Our other challenge was that we had to reduce costs significantly, whichinevitably means reducing the number of employees, which is never a fun thingto do. It’s always nicer to open a new plant than to close a plant. However, theAltana organisation was aware of the fact that they would have needed to re-structure even if they had not been acquired, so there were no surprises when wesaid we would reduce the number of employees and thus cut spending.”

Merger trendBjörklund talks about his career path as “a long and winding road from

academia to pharmaceuticals”. He started out as a medical student at theKarolinska Institutet in Stockholm in the mid 1970s. He describes himself atthat time as a basic scientist, and his intention was to remain in academia.But in 1984 he saw a job advertised at Pharmacia for a scientist to lead asmall biology group focusing on ophthalmology, which is how he got intothe pharmaceutical industry.

He moved up the ranks of R&D before switching to the commercial side,running Northern Europe for Astra before it became AstraZeneca. Fromthere is was but a short step up to his current position.

Having gone through the merger experience with Altana has givenBjörklund a unique perspective on the recent trend of mega mergers that haveswept through the global pharmaceutical industry. “There is a difference be-tween these mergers and the previous mega-mergers,” he emphasises. “Thistime around, cost-cutting will be absolutely essential in order to make themsuccessful, whereas previously people always talked about how with a biggerR&D organisation, one plus one would equal three.

“I don’t think the mergers have anything to do with the current financialsituation. They are more about developments in the pharmaceutical industrythat have been going on for a number of years. If you look at the 10 biggestcompanies, they have lost market share as a group over the last five to 10 years.There are exceptions, of course – Roche is one of them. But the idea of ‘thebigger, the better’ no longer applies.

“So cost-cutting is important, and if we look outside in the market, thepressure on our industry is totally different than it used to be, and this will alsomean that we need to be more cost-effective.”


It’s a well-known fact that the global pharmaceutical industry is facingsome serious challenges in the immediate future, including an upcomingwave of patent expiries and a scarcity of new blockbusters. Björklund says thatin order to cope with these issues, the industry needs to shrink.

“The industry needs to be more selective in R&D. It used to be that a lotof money was spent developing follow-up compounds and me-too com-pounds, with a new patent life but with limited medical advantage comparedto what was on the market. But you were still fine – you could get a decentprice for it and you could take market share. That is no longer the case. Themarket will go with the generics as long as you don’t have a significant ad-vantage with a new compound.

“For instance, to launch a new statin today – or maybe even more diffi-cult, to launch an expensive new protein pump inhibitor – when you havegenerics out there at a fraction of the original price is going to be very, verydifficult. That’s going to change the R&D model, and medical utility will beabsolutely essential. If you cannot prove that your new product adds medicalbenefits, and hopefully also reduces costs for society, you will not be able toconvince the payers that they should pay for it. That process has been goingon for quite some time here in Europe, and I’m convinced that it will alsocome to the United States.

“So R&D will need to be more focused, and if anything, theR&D part will be reduced. Sales organisations will alsobe smaller: we’ve seen that happening nowfor a number of years, and there isstill more to come. Accessto doctors is be-coming more diffi-cult, and it does notpay off to have thesehuge armies of sales repsany longer, not in the ma-ture market.”

PartnershipsNycomed’s own pipeline

strategy is somewhat unusual for abig pharma player. Rather than pro-ducing the majority of new compoundsinternally, it has chosen to create four-fifths of Nycomed’s pipeline growththrough in-licensed products. Björklundpoints out that the biotech industry has grownexponentially over the past two decades, with ahuge number of potential new products in differ-ent phases of development.

“Most biotech companies will not have the re-sources to bring these products to the finishing lineon their own; they need a partner at some stage in de-velopment. There is also reason to believe that thebiotech industry – which in most cases is small and en-trepreneurial – has been more effective in developing newdrugs than the big R&D organisations and big pharmacompanies.

“This is not the time to get scared and withdraw; this is the time to

take market share”


an interesting phase III project comes along, the company is able to ramp upclinical trials with the help of external partners. Björklund puts it this way: “Ilike to have the brain power inside the company, whereas the people doingthe clinical trials and monitoring can to a large extent be outsourced.”

Nycomed’s strong emphasis on partnerships and external collaborationextends beyond R&D and into marketing. “In R&D, most of our partnershipsare earlier stage projects from smaller biotech companies,” Björklund says.“But we also pursue collaboration on the marketing side, where we out-licenseproducts. The biggest product we have out-licensed is Pantoprazole to Wyethin the United States. We’ve also recently completed a deal with Baxter aroundTachoSil, which they will launch in the US, and we’ll do some of the develop-ment for the US market together.

“A large part of our product portfolio in Russia is in-licensed. Our biggestpartner there is Merck Serono, where we acquired their portfolio and have beenvery successful in growing it. I always tell my people that partnership, regard-less of whether it’s in-licensing or out-licensing, R&D or marketing, is absolutelyessential. We’re not big enough to do everything on our own, and we shouldonly do the things in which we can add value, and in many cases someone elsecan add more value.

“Partnership is a skill; you needto be good at it, and you need toapproach it with the attitude


“When it comes to creativity, I don’t think there is an advantage of scale– it could actually be a disadvantage of scale. If you put together more peoplein an organisation, they do not necessarily become more creative; maybe it’sthe other way around. Because to be creative you have to think outside of thebox, and it’s probably easier to do this in a small biotech organisation.”

Björklund also explains that when he started at Nycomed in 1999 it wasobvious to him that the company did not have the resources to do its own dis-covery research, which made in-licensing a necessity. After the merger withAltana, Nycomed did gain an R&D organisation, which it intends to main-tain, because early stage in-licensing requires the company to have its ownR&D capabilities in order to evaluate and work on what it’s bringing in.

“When you bring in a pre-clinical project you need to have a lot of thesefunctions yourself,” Björklund says. “And that four-fifths is not written instone. Whether that’s 60 percent, 70 percent or 80 percent, only the future willtell. Of course we hope that our own discovery research will also be produc-tive, but we don’t depend on it. We assume that the majority of the productswill come from the outside,” he continues with a smile, “Although if my ownscientists prove me wrong, I’ll be extremely happy.”

Pursuing an in-licensing strategy naturally meant having to makechanges to Altana’s existing R&D structure. One major impact was the sig-nificant reduction of the pre-clinical unit. Nycomed also outsources a lot ofits clinical work to avoid having a large fixed cost structure internally. When

A PARTNERSHIP APPROACH Rather than developing the majority

of its new compounds internally, four-fifths of Nycomed’s

pipeline growth is generated through in-licensed products


of ‘I need my partners.’ It’s never easy with partnerships, because you don’t al-ways get your way. There is a famous quotation by Winston Churchill that I oftenparaphrase, in which he says that the only thing worse than fighting a war withallies is to fight it without them. Maybe it’s difficult to work with partners, but it’smore difficult to work without them.”

Focus on growthNycomed has had a strong presence in Russia-CIS since the early 1990s,

and even before that under the old Soviet Union. Since 2000, its Russian saleshave grown from US$25 million to US$480 million. As Björklund explains,emerging markets are becoming increasingly important for the pharmaceu-tical industry as a whole. “Growth in the pharma industry is coming from twoplaces: emerging markets and specialist products in the more mature markets.We have been successful in Russia-CIS, and we’ve also got a strong presencein Latin America. We believe in investing in these markets. We’ve also clear-ly stated that we would like to expand in Asia, where we’re not sufficiently strong.

“I always tell people, both internally and externally, that if you’re in theemerging markets you need to be in, you have to be willing to ride the ups anddowns. Now we’re seeing an economic crisis, which of course is hitting theemerging markets a little more than the rest of the world. This is not the time to

get scared and withdraw; this is the time to take market share. For example, inRussia, yes, we have been hit by currencies, but we’re still growing in local cur-rency and we’re taking market share. You have to be resilient and persistent.”

Closer to home, Nycomed has two products that are nearly at the market-ing stage: Instanyl and Daxas. Instanyl is a nasal spray of fentanyl, the short-act-ing opioid that has been on the market for some time. The nasal form is new, andis indicated for the treatment of breakthrough pain in terminal cancer patients.These patients normally have a fentanyl patch, which treats the day-to-day painfrom which they suffer, but many also experience breakthrough pain.

The advantage of fentanyl in a nasal form is that it offers a very quick onsetof action because it’s rapidly taken up into the bloodstream, so pain relief beginswithin five minutes. Fentanyl is also quickly eliminated from the bloodstream.Björklund says Instanyl has seen a lot of interest, both from specialists and fromthe authorities.

Instanyl is a specialist product, to be used primarily in cancer clinics andhospices, and also at home. The second product, Daxas, is a little furtheraway from the market but Björklund says it offers a bigger commercial op-portunity. “Daxas is a possible phosphodiesterase-4 inhibitor , so it acts inthe inflammatory cascade in patients with COPD – smoker’s disease. Thesepatients are suffering from an inflammation, which in many cases leads toexacerbation of the condition. In some cases, people have to be admitted tothe hospital.

“COPD is a huge disease worldwide: it’s the fifth largest killer, with manymillions of patients are affected. Currently we don’t have any good anti-inflam-matory treatment for COPD. Most patients will be treated with inhaled corti-costeroids, which were originally developed for asthma and are very effective incountering the inflammation that asthmatics suffer from. But they are consider-ably less effective in COPD, because the inflammation in COPD is different.Daxas is a once-daily tablet, the first anti-inflammatory that has been specifical-ly designed for COPD.”

According to Björklund, clinical trials have shown that Daxas offers a sig-nificant reduction in exacerbations and a significant improvement in lung func-tion. When Daxas is added on top of the bronchodilators that most COPDpatients are treated with, it gives a further improvement in lung function.

Expiry dateThe good news around Daxas could not come at a better time: Nycomed

desperately needs a new superstar to bolster its product list. The patent onPantoprazole, the company’s biggest product, expired a couple of months agoin most European markets and is due to expire in the US in 2011. This will in-evitably lead to a decline in sales, and Björklund says this was one of the rea-sons why the cost-cutting exercise was necessary after the Altana acquisition.

“We needed to prepare ourselves for a time without patent protection onPantoprazole,” he emphasises. “Although more than 40 percent of ourPantoprazole sales do come from markets where there is no patent protectionor where there has not been a patent protection for a long time, so we’re con-vinced that we’ll be able to maintain a significant portion of our sales. Eventhough we will lose sales with the patent expiry, Pantoprazole will remain thelargest selling product for us for the next few years. But it’s important that newproducts are coming along to compensate for the eventual drop inPantoprazole sales.”

Nycomed has taken the unusual step of launching its own generic versionof Pantoprazole in partnership with Wyeth in the US, even though the drug’spatent has not yet expired there. In the American market, it is not unheard of forgenerics manufacturers to create copycat versions of patented drugs, with the as-sumption that they will be able to invalidate the patent in a court case.

In the case of Pantoprazole, Björklund says that the first generics werelaunched in the US about 18 months ago. Nycomed immediately counteredwith a lawsuit, but because the American legal system moves quite slowly, thelawsuit is still ongoing and the generic versions are still being sold. “We’reconvinced the patent is enforceable and strong,” Björklund underlines, “andthat we will eventually prevail in the courts. But the reason we launched thegeneric was to counteract those that had already been launched, and therebybe able to compete more strongly in the market as it is now.”

In privateIn contrast to many of its big pharma competitors, particularly in the US,

Nycomed is privately owned. Other non-public European based companiestend to be family-controlled, but Nycomed’s main shareholders are two pri-vate equity firms, Nordic Capital and DLJ Merchant Banking.

Given the current state of the global economy, has private ownershiphelped insulate the company from market fluctuations? Björklund says it has.“We’ve been privately owned now for 10 years by various groups, and it hasserved us very well, because it has allowed us to focus on building long-termvalue in the company. We don’t need to focus on the next quarterly result. It

“When it comes to creativity, I don’t think there is an advantage

of scale – it could actually be adisadvantage of scale”



with GDPs in the Baltic countries, for example, decreasing by 15 percentin the first quarter of this year.

“That is also affecting peoples’ ability to buy drugs,” Björklund continues.“But it’s not dramatic, and this industry is relatively resilient to downturns. So I’mnot so worried about the financial crisis – at least not in the mid term or long term.

“On the other hand, within the big five EU countries, I think the pharma-ceutical industry will see very little growth, and it will be primarily in specialistproducts and only certain of them. The growth will come from Eastern Europeand from Russia-CIS: emerging markets.”

In the case of his own company, Björklund’s optimism does not seemmisplaced. Nycomed, the small company that grew, seems to have its placeamong the top 40 pharma players firmly established. And who knows, ifit continues to play its cards right, in a few years it could be knocking onthe door of the top 10. �


has also aligned the interest of the shareholders and man-agement; everyone has the same ambitions to grow thecompany and create value. There are no politics.

“When it comes to the culture, I think it has alsobeen good in the sense that we’ve been able to be con-siderably more open in a private equity-owned com-pany than if we were a publicly owned company,because I don’t need to worry about following therules of the stock exchange in terms of what I can and can’tcommunicate. I can tell my people what we think and how things aregoing, which I could not do in a public company because of the risk of it get-ting into the public domain and having an impact on the stock price. It’s eas-ier to be open in a private company.”

Of course privately owned companies do not have the same requirementsaround transparency as public companies do, but Björklund explains that the in-formation Nycomed publishes doesn’t differ from that of its public rivals. “If youread our annual report, which we publish and which is readily available, you won’tsee any difference in the way we report compared to a public company.

“We’re just as transparent and open with everything. You can even findmy salary in there. We are reporting as a public company, and also preparingfor the possibility that in the future that we may go public, which is not out ofthe question.” Björklund won’t be drawn on when this might happen, sayingonly that the current situation in the financial markets will need to stabilisebefore the idea is given serious consideration.

When asked what the future holds for Nycomed, Björklund’s responseis an optimistic one. He doesn’t foresee any restructuring as a consequenceof the current recession, provided it doesn’t worsen significantly. Hepoints out that the financial crisis has had an impact primarily in emerg-ing markets in Eastern Europe, because of the weakening of currency thathas taken place there. The economic downturn has also had an impact,

Håkan Björklund is Chief Executive Officer of Nycomed. Before joining Nycomed, Björklundwas Regional Director at Astra (now AstraZeneca), and was President of Astra Draco from1991 to 1996. He is a member of the Board of Directors of Atos Medical AB, Coloplast andDanisco A/S and holds a PhD in neuroscience research from Karolinska Institutet, Sweden.

LONG-TERM VALUE The Zurich-headquartered firm believes being

privately owned allows it to focus on building long-term growth rather

than the next quarterly result

Nycomed headquarters building in Zurich, Switzerland


Th e advantage of putting the two together, says Sur, is to prevent people from seeing them as two separate sets of toolboxes, but instead thinking of Lean and Six Sigma as a complement for each other: “In Lean there are a lot of things that you can immediately address and solve. For example, when you’re involved in a project, there may be things that would normally take three to six months. When you go through Lean, you can go to the improve phase in one week, as opposed to in Six Sigma, where you’ll probably get to an improve phase in three months or even less. But certainly, there’s the shorter variation of period in time in ad-dressing these things.”

MANUFACTURING

JOINING FORCES

The terms Lean and Six Sigma have been used in pharmaceutical manufacturing for a number of years. Now there’s a new concept on the block that melds the two. Bayer’s Edgar Sur fi lls us in.

According to Edgar Sur, Head of Bayer’s Operational Ex-cellence for North America, Lean Six Sigma is a com-bination of Lean, which is focused on removing waste, plus the value-added step of Six Sigma, which is all about reducing variation. “Both use the same approach

in solving the problems,” he explains. “In Lean, we use the approach of plan, do, check, act; and in Six Sigma, it’s called DMAIC, which is defi ne, measure, analyse, improve and control. It’s about putting rigour in the approach of problem solving with the fl exibility of using some Lean tools and some Six Sigma tools.”


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Another advantage is increased effi ciency. “You increase the cash fl ow through the reduction of your inventory,” Sur says. “Everything is data driven, so it can be defended when it’s questioned. Th ere is a rigour, again, to the approach of solving the problem, which you don’t get from one phase to the other without completing or having the deliverables on prior phases.

“It also forces people to partner, because you can’t do this in a silo; this is more of a cross-functional group of people that need to make things happen. Another advantage is that you focus on the customers – we always ask what is critical to quality for the customer. It’s not a shotgun approach where you try to hit everything. You go through the data to tell you what to do, and you ask the customers what is critical to them, and you go aft er those things.”

ChallengesTh at doesn’t mean there aren’t challenges involved in implement-

ing Lean Six Sigma in the pharmaceutical sector. “It’s a highly regu-lated environment,” Sur points out. “Th ere is a mindset and a culture that change cannot happen because it is not allowed. You continually want to challenge these things and ask the right questions, while en-suring that you stay in compliance with what the regulatory agency is asking you to do.

“Th e other big thing that I see in a lot of companies is that because the profi t margin is so high, there is really no pain and so there is no mo-tivation to improve until it’s too late. And trying to build a culture that is sustainable is also a challenge. Th e other piece is also allowing time for people to have closure of the old ways of doing things and embrace the change – the new paradigm of how we approach things. Having the sense of urgency as opposed to taking our time as we did in the past.”

Sur says there is also a challenge related to building the credibility and the impact of Lean Six Sigma. In the beginning, he explains, many operational excellence organisations will try to build their credibility by tackling the biggest problem projects that no one has been able to

solve, which can obviously take some time. Th e issue of needing to gain credibility can arise from the fact that

people are not always familiar with the process, and there is a certain amount of learning involved. “In Lean Six Sigma, there are also soft skills that you have to learn. It’s a change management piece where you don’t just drive change and hope that everybody will buy into it. It’s what I normally call the wilderness, where you allow people to just wallow and have closure on how they used to do things, so they can embrace the new things that are about to happen. Until they have had the time to have closure, this new approach can’t be eff ective.”

Th ere are also challenges in implementing Lean Six Sigma across diff erent sites or diff erent business units, as Sur explains. “One of these

Defi nitions of Lean and Six Sigma

LeanLean manufacturing is a production practice that

considers the expenditure of resources for any goal other than the creation of value for the end customer to be wasteful, and thus a target for elimination.

Working from the perspective of the customer who consumes a product or service, ‘value’ is defi ned as any action or process that a customer would be willing to pay for. Lean is centred around creating more value with less work.

Lean manufacturing is a generic process management philosophy derived mostly from the Toyota Production System (TPS). It is renowned for its focus on reduction of the original Toyota seven wastes in order to improve overall customer value.

Lean is a variation on the theme of effi ciency based on optimising fl ow; it is an example of the recurring human tendency towards increasing effi ciency, decreasing waste and using empirical methods to decide what matters, rather than uncritically accepting pre-existing ideas.

Six SigmaSix Sigma is a business management strategy, initially

implemented by Motorola, that today enjoys widespread application in many sectors of industry.

Six Sigma was originally developed as a set of practices designed to improve manufacturing processes and eliminate defects, but its application was subsequently extended to other types of business processes as well. In Six Sigma, a defect is defi ned as anything that could lead to customer dissatisfaction.

It uses a set of quality management methods, including statistical methods, and creates a special infrastructure of people within the organisation who are experts in these methods, using a system of ‘belts’ similar to that employed in martial arts.

Each Six Sigma project carried out within an organisation follows a defi ned sequence of steps and has quantifi ed fi nancial targets (cost reduction or profi t increase).

“Th ere is a mindset and a culture that change cannot happen because it is not allowed”


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if you don’t have the background around healthcare, normally they’ll say, ‘It’s not applicable, what your skill sets are,’ but that’s where the mistake is in sometimes trying to retain these skill sets. When there’s a process that needs to be addressed, OE has a place for it and whether you use Lean or Six Sigma, it’ll get you to the same end result,” he says.

He is also keen to point out that Lean Six Sigma is just not used in operations. “We’ve done this in an HR environment. We’ve done this in global supply chain as well as procurement. I’d like to get the message out to all practitioners that this is applicable to just about anything and everything.”

FutureTh e original concepts of Lean and Six Sigma have been around and

been developing for a while. How does Sur see them continuing to trans-form in the future? “I think they will continue to grow and expand,” he confi rms. “Th ere’s always a need for these types of programmes. Th ere’s a need to stay competitive with other companies cost-wise because, going forward, the need for quality and effi cacy will be a given in our industry. Th e opportunities are the increased speed to market, the response to customer needs, and reducing costs so that we can transfer some of these savings to the patients.”

challenges is creating one voice, one roadmap that everyone can follow and measure themselves against to track progress. When you’re deploy-ing Lean Six Sigma in many diff erent sites, some sites will be in diff erent stages of the process or of the deployment. What you need to do is make sure there’s one roadmap that they can follow. It doesn’t really matter what stage of the process they are at in their implementation, they need to know that in the end it will be a similar approach to what everyone has done, so that you have the consistency. Everything’s standardised and it’s one voice, and everyone can share and benchmark off each other.”

ImplementationSur explains that when you’re implementing something like Lean Six

Sigma, it’s important to integrate that into an overall operational excel-lence rollout, again because of the need for consistency. “It’s important to ensure that you’re talking the same language – not reinventing the wheel – and making sure that your goals and objectives are aligned and not con-fl icting each other. Again, if you don’t have that aligned approach, there is the chance that there may be confl icting goals and objectives that can go against each other, and that would not add any value to the process.”

In operational excellence at Bayer, Sur is working to build a culture that is sustainable. “In a way, I’m trying to work myself out of a job, so that the ownership and accountability transitions from the OE organi-sation to the site because that’s the only way you can have a sustained programme, if the ownership and accountability is back to the site.”

Sur has experience in carrying out similar programs in diff erent industries and sectors, including aerospace and IT in a technology envi-ronment, and he believes a lot of what is done around operational excel-lence is transferable from industry to industry.

“It’s sometimes diffi cult when you go to the healthcare sector where

“It’s important to ensure that you’re talking the same language – not reinventing the wheel

– and making sure that your goals and objectives are aligned”


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What are your defi nitions of Lean and Six Sigma? How do they differ from each other?Ian Cox. Both are examples of leveraging a key idea; namely that any system of production has the potential to generate data that can be used to drive improvements to that system. From this perspective, the diff er-ence between Lean and Six Sigma is just a diff erence between the kind of data on which they tend to focus – Lean deals primarily with transac-tional data (What stuff is where? How long has it been there? Where does it have to go next?), whereas Six Sigma tends to focus on what might be called physical data (What is the stoichiometry? What is the blend time? What is the friability?). Clearly both kinds of data are important.

Erik Tieleman. Businesses should not be interested in questions like these. It is not about the methodologies or their diff erences, but about

ROUNDTABLE

Keeping it LeanNGP talks to four industry experts about the applications of Lean and Six Sigma in pharmaceutical manufacturing.

impactful business applications – how to create sustainable (fi nancial) results with Lean and/or Six Sigma?

Lean and Six Sigma are both great toolkits to pull from when tackling on-time delivery and working capital in supply chain, cycle time reduc-tion and throughput improvement in manufacturing, better milestone attainment in new product introduction, improved quality testing and results in labs, faster process and product validations in engineering.

“An essential element of Lean and Six Sigma is a continuous learning

and improvement process” Steff en Himstedt

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Yield improvement 33% to 93% in five months

On-Time In-Full customer service 36% to 93% in three months

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SiAssociates.indd 1SiAssociates.indd 1 28/7/09 13:33:5328/7/09 13:33:53


sively benefi cial. Traditional CMC approaches do not suffi ciently demon-strate the relationship between product attributes and product quality. Six Sigma approaches will identify, understand, manage and mitigate risk, and ensure the development of product that is genuinely fi t for purpose.

Six Sigma enables quicker time to market. Submissions refl ecting ICH recommendations mean faster NDA approvals. Each increases the com-mercial window for patented products.

Lean improves effi ciency, reduces costs and increases available work-ing capital. Margins can be maintained and research levels sustained whilst increasing the aff ordability/availability of safe and effi cacious drugs for new markets. Th rough, for example, ‘5S’, Lean helps make organisa-tions safer places in which to work and, by unit reduction in energy and material costs, more environmentally friendly.

Th e most meaningful variable in eff ectively implementing Six Sigma and Lean is the extent of senior-level commitment.

IC. Th e word ‘potential’ is important. Th e advantages of using data to manage the risk inherent in all production are well understood (faster, cheaper, higher quality, enhanced predictability, greater agility, to name

Executed correctly, both can be eff ective approaches to productivity and improvement. Th e (over)emphasis on the methodology (doing the things right) should shift to a focus on how to organise for productiv-ity and improvement (doing the right things). Th is has more to do with execution and making things happen, than with a conceptual discussion on methodologies.

Harry Clark. Both prevent waste. Both design customer-centric ‘quality’ into a product/process. Lean prevents waste across the entire operation. ‘Waste’ is defi ned in this context as that portion of any activity that is not intrinsic to adding value to the end customer.

Six Sigma prevents waste, defi ned here as variability in products and processes. Products must be fully understood and characterised. Associ-ated manufacturing processes must be understood, capable and in control. Sources of variability must be anticipated. Such risks to product integrity must be identifi ed and mitigated. Six Sigma is associated intrinsically with product quality.

Lean eliminates waste across execution activities, such as inventory levels, labour utilisation, capacity planning and layouts, which is critical for, but ancillary to, the delivery of a Six Sigma quality product. Lean can be characterised as execution effi ciency.

Manufacture of defective product is a key waste. Preventing such waste is the goal of Six Sigma, and describes where Lean and Six Sigma philosophies merge.

Steffen Himstedt. We mainly see Lean and Six Sigma projects as a focus on added value and quality. Th is generally involves adjustments of organisational structures, as well as reducing the complexity of the decision-making processes. In contrast to a greater number of consultants who primarily focus on such organisational aspects – with minimum IT eff ort – Trebing & Himstedt regard IT as a key enabler for successful proj-ect implementation.

An essential element of Lean and Six Sigma is a continuous learning and improvement process. In order to support this process, direct feedback about variations and disruptions in the production process is necessary. Our experience is that display boards and reports that are not generated in real time slow down the learning process. Modern operator cockpits with real-time information from various sources, which are aggregated and visualised in KPI and displayed on mobile devices, such as Blackberries or on production hall displays, achieve much better results.

What are the potential advantages and challenges involved in imple-menting Lean and Six Sigma in pharmaceutical manufacturing?HC. Implementing Six Sigma around a ‘design space’ philosophy is mas-

Ian Cox works in the JMP Division of SAS as the European Marketing Manager for JMP. He worked for Digital and Motorola in the 1980s and has consulted on how best to use data for more than 20 years. He is co-author of Visual Six Sigma – Making Data Analysis Lean (Wiley, in press).

Harry Clark is the Managing Director of SI Associates. Following his postgraduate degree at Liverpool University, he joined General Motors, spending several years in the automotive and transportation sectors before working with PERA Consulting and subsequently joining SI.

As Founder and Managing Director of Trebing & Himstedt, Steffen Himstedt

is an active member of the OPC Foundation, ISPE and the PROFIBUS Organization. In the business area of manufacturing integration, Trebing & Himstedt is implementation partner for SAP manufacturing solutions and provides best practices based on SAP MII.

R&G Global Consultants’ Erik Tieleman is a seasoned Master Black Belt, and has held operational leadership positions in supply chain, (external) manufacturing and business excellence within General Electric and Johnson & Johnson. Tieleman has made organisations and leaders successful in chemical, pharmaceutical, medical device, healthcare and nutritional businesses.

Ian Cox works in the JMP Division of SAS as the European Marketing Manager for JMP. He worked for Digital and Motorola in the 1980s and hasconsulted on how best to use data formore than 20 years. He is co-author of Visual Six Sigma – Making Data AnalysisLean (Wiley, in press).

Harry Clark is the Managing Directorof SI Associates. Following his postgraduate degree at Liverpool University, he joined GeneralMotors, spending several years in theautomotive and transportation sectors before working with PERA Consulting and subsequently joining SI.

As Founder and Managing Director of Trebing & Himstedt, Steffen Himstedtis an active member of the OPC Foundation, ISPE and the PROFIBUS Organization. In the business area of manufacturing integration, Trebing &Himstedt is implementation partner for SAP manufacturing solutions andprovides best practices based on SAP MII.

R&G Global Consultants’ Erik Tielemanis a seasoned Master Black Belt, and has held operational leadership positions insupply chain, (external) manufacturing and business excellence within General Electric and Johnson & Johnson. Tieleman has made organisationsand leaders successful in chemical, pharmaceutical, medical device,healthcare and nutritional businesses.

PAN

EL

“Lean improves effi ciency, reduces costs and increases available working capital”

Harry Clark

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transparency, focus, priorities, fact-based decision-making, on-time ex-ecution, a clear plan, implementation skills and sustainability of results.

It is the lack of oxygen (O2) that causes current Lean Six Sigma pro-grams to not make traction. O2 is the respirator of improvement: ‘organi-sation’ and ‘operating system’.

Lean and Six Sigma contain ‘know-how’. O2 contains ‘know-what’. True Lean Six Sigma programmes have both in place.

What tools and techniques can pharmaceutical companies use to ensure a smooth roll out of Lean and Six Sigma in their manufactur-ing operations?ET. Successful organisations have clarity on the Big ‘Y’ and the Big ‘WHY’ (subject of change). Successful leaders are personally involved and attach themselves to this change, empowering people, having daily involvement,

setting standards and making people execute against these standards (pre-requisite of change). Successful leaders test their thinking with data and chal-lenge their teams on popular beliefs, untested hypotheses and paradigms, and eff ectively execute on their think-ing (window of change). Successful organisations are building improve-ment capability, the vehicle of change, not only by introducing Lean and Six Sigma, but more importantly by

implementing a clear performance architecture (Organisation*Operating system = O2).

Organisations and leaders that execute these things well are winners; they work on the right things. Lean and Six Sigma are then great execution methodologies to do the things right the fi rst time.

IC. What ends up in manufacturing is, of course, that which development and scale-up can deliver. So the ultimate, but oft en inconvenient, answer is that we need to understand and embrace Quality by Design (QbD) prin-ciples from product conception onwards. Th e two challenges mentioned above remain, and the diffi culty of meeting them rises by at least an order of magnitude for several reasons. Th e pragmatic answer for products al-ready in manufacturing is to invest in systems that can be used to store, structure and analyse data in the most streamlined way, and to promote a culture in which all stakeholders can contribute to making discoveries that have business value.

An obvious requirement is that the value of such discoveries must more than off set the cost and eff ort of making them. Typically, transac-tional systems do not structure data in a way that supports discovery, and users have an understandable resistance to unfriendly or complex analysis soft ware that does not fi t their needs, or that makes too many assumptions about their capabilities given they may well be using data in this way for the fi rst time.

SH. Well-concerted, purposeful application of IT tools can support Lean and Six Sigma projects signifi cantly. We have designed and built such ‘manufacturing cockpits’ in numerous Lean projects. At a global phar-

a few), Th ere are specifi c nuances in pharmaceutical manufacturing de-pending on the therapeutic area, technology base, supply chain, competi-tive situation and so on.

Making this potential real has two key aspects. One is that, for power-ful and relevant data to be available, we need to measure the right things with the right frequency. Th e second is that, like it or not, people are ‘part of the system’. So the challenge lies in leveraging both useful data and the contextual scientifi c, medical and engineering knowledge in people’s heads. Bringing these two ingredients together is the best, even the only, way to promote the data-driven discoveries needed to fuel both Lean and Six Sigma. Overcoming these challenges will be multi-faceted, but an im-portant infl uencing factor is the persistence of the idea that a validated manufacturing process is sacrosanct, and therefore not legitimately the subject of improvement.

SH. In pharmaceutical manufacturing, highly infl exible processes run within regulatory limits. Th is costs a lot of money, creates rigid decision-making processes, and inhibits innovation. Clas-sic Lean subjects are reduction of material stocks, cycle times and waste. Under ever-increasing cost pressure, companies are forced to strike a balance between compliance and fl exibility at a reasonable cost. Lean and Six Sigma, as well as PAT – smartly implemented – can be catalysts for a new structure in pharmaceutical manufac-turing.

Another fi eld for Lean projects is the integration of production and laboratory processes. In most pharmaceutical companies, elementary value potentials, especially in asset utilisation or yield, are underachieved because of the existing organisational separation of production and labo-ratory processes. Th at is why, together with SAP and partners, we started the Perfect Laboratory initiative as part of SAP’s Perfect Plant Initiative, in which we use the optimisation potential of laboratory processes that are highly integrated into the production. Th e goal is to reduce cycle times of laboratory samples, to integrate laboratory personnel directly into the production and to reduce interfaces and paper workfl ow through elec-tronically supported processes.

ET. Th ere are specifi cs in pharmaceutical manufacturing (product or process validation, regulatory approval, quality systems, outsourcing) but let’s face it: the challenge is, as in any industry, to apply it right (selective, tailored to the business context), to get leadership truly involved, to ac-celerate the pace of change.

Many senior executives are frustrated that their (Lean, Six Sigma) im-provement programs do not gain the necessary speed nor the impact they need, nor do they meet the desired return on investment.

Executives face challenges like: how to rally my team around the need for change? (shared view on current reality); are we working on the right things? (focus); how to get there? (roadmap); what organisation do I need? (roles and responsibilities); is my team able to deliver? (execution skills); are we seeing it clearly? (potential) .

Lean Six Sigma programs should support these leaders in getting

“We need to understand and embrace Quality by Design

principles from product conception onwards”

Ian Cox


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HC. Th ere are three compelling reasons why Lean and Six Sigma will pervade the pharmaceutical sector. In the current economic and political climate insurers and public health bodies/agencies are increasingly fo-cused both on reducing the prices paid for drugs and on increasing their availability. For research-led life sciences companies maintaining profi t margins at levels that will sustain their missions to enhance wellbeing and quality of life through innovation, the singular conclusion is an unam-biguous need to exorcise waste and cost from their operations.

Regulatory approaches will evolve further in this direction. With the currently non-binding recommendations and guidance in ICH Q8, ICH Q9 and ICH Q10 prompting the adoption of best practices in R&D, commercialisation and manufacturing, the deployment of Lean and Six Sigma will simply represent a pragmatic response to this regulatory challenge.

Principally, patient safety and wellbeing are paramount. Lean and Six Sigma represent the best available approaches to mitigating product and therefore commercial risk. We live in an increasingly litigious age, with several examples of such failures in our collective memory. A marketed product that cannot be demonstrated to be fully characterised, understood and manufactured to the requisite quality is unacceptable.

IC. Th e application of Lean or Six Sigma (or both) in manufacturing is a necessary and useful band-aid. But as personalised medicine takes root

and the QbD agenda is pursued more aggressively, it will gradually force the convergence of Lean and Six Sigma. Ideas like Design for Six Sigma, Lean Product Introduction and Kansei Engineering will be assimilated within QbD, and the means to effi -ciently explore a complex design space will become even more important and valuable than it is now. Using data this way is a grand challenge to the phar-maceutical industry, and there are many diverse as-pects culturally, organisationally and systemically. But we should draw comfort from the fact that the semiconductor industry has been working this way

for 30 years, and the resulting benefi ts are many and obvious.

ET. With eroding gross profi ts, higher R&D spend to fi nd treatments for untreated disease states, regulatory bodies that drive evidence-based medicine and governments and insurance companies that want to contain healthcare spend and reimbursements, the case for productivity is clear.

It becomes imperative to have a comprehensive and integrated operat-ing system to manage productivity on a structural basis. Th is operating system is about having transparency about performance, being clear about how you manage performance (process), how you evaluate performance (metrics), how you are organised for managing performance (roles and responsibilities), and last but not least, how your people are driving perfor-mance consistently (behaviour).

All work is process and processes are unstable and not well-connect-ed. Leaders need to rethink how to design the operating system, a way of working that makes people more engaged, more eff ective, more productive and happy. Lean and Six Sigma continue to be important toolkits to tailor solutions for pharmaceutical companies.

maceutical company aiming to become the ‘Toyota of the pharmaceuti-cal industry’, signifi cant success could be achieved within the scope of a Lean initiative in the packaging division. Large information displays keep workers constantly informed of quality and performance fi gures. Seamless integration of ERP/MES and LIMS into manufacturing is key.

In order to achieve this aim, a lot of information must be gathered from separate IT systems. In numerous Lean projects, we have built up manufac-turing cockpits that aggregate the relevant information and provide it in an intuitive way. In this case, the Trebing & Himstedt SAP MII Best Practice solution for overall equipment effi ciency (OEE) is also suitable, although many experts do not use OEE as key performance indicators (KPI) for Lean projects in order to avoid an incorrect focus on utilisation optimisation. But more important is the interpretation of the single OEE factors and the analysis of the causes of disruption. Automatically generated KPI can pro-vide full transparency and help to eff ectively and objectively evaluate pos-sible measures and their eff ects. In this way, improvement processes can not only be monitored with minimal eff ort but also implemented much faster, and the respective saving eff ect can be rendered transparent.

HC. Fundamentally, the output of a manufacturing operation is its manufactured product. Th e quality of that output is only as good as the degree of understanding about that product that has been generated, and the uses to which that knowledge have been put.

So, in research-led and technology-led manufacturing companies, the place to begin to apply Six Sigma and Lean is in late discovery/early development – the ‘design’ phase, where design space defi nition is commenced. Th e tools and techniques are typically those found in the Design for Six Sigma (DfSS) toolkit, from practices such as Functional Analysis, Fault Trees, Failure Mode and Eff ects Analysis and Taguchi/Design of Experiments at the front end to the routine ap-plication of process controls such as PAT and Statistical Process Control and the wider Lean toolkit (Kanbans, 5S, SMED and Value Streams) in commercial volume manufacturing.

Neither Six Sigma nor Lean are principally technical challenges. Suc-cessful implementation must understand the nature of the ‘change’ chal-lenge that each represents.

How do you see Lean and Six Sigma developing in the pharmaceutical industry in the future?SH. In today’s situation of the general economic downturn and the pres-sure existing in pharmaceutical manufacturing, Lean and Six Sigma methods must prove that they are suffi ciently fl exible to meet these new requirements. Lean and Six Sigma do carry the stigma of not being fl exible enough. In addition, global collaboration and supply chain processes be-tween pharmaceutical companies and their suppliers need to be mapped. Th is calls for new ways to be established, with the seamless, integrated application of IT tools.

“It becomes imperative to have a comprehensive and

integrated operating system to manage productivity on a

structural basis” Erik Tieleman


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icated health and safety quality teams accreditedto ISO9001:2000 standard to advise on best prac-tice and audit.

Their laboratory service solution is designednot to be a one-off but one that can be built intomanagement processes for the future. R&D labsand manufacturing operations alike are constant-ly being improved and updated to meet rapid ad-vances in technology.

As one client explains, “Knowing that a teamof competent staff who understand our science,equipment and business are at hand and able toreact quickly and appropriately to our issues real-ly helps. This is both in a proactive way forplanned services and a highly reactive way forthose unplanned downtimes, which really helpsus focus on what we do best – the science.”

The new process ensures that the lab userspends less time preparing the systems. An on-site labour and parts cache ensures faster re-sponse to end-user needs, whether this is glasswash, consumable replenishment, sampledespatch, instrument set-up, calibration or re-pair. Each request is attended to by a technicalexpert within two hours. For instrument sup-port typically 80 percent of the average labora-tory equipment is within fours hours by Sodexoself-delivered technical engineers.

Sodexo’s expertise in theconsolidation of laboratory sup-port for its clients comes into playby reducing customers, overallmanagement costs, employing itsintegrated facilities managementtool to streamline administrativeresources. Sodexo can identifyand re-deploy existing surplus as-sets via Sodexo asset managementteams across the client’s business,resulting in reduced capital ex-penditure, sharing capital invest-ment among various labs.

Working with its pharma-ceutical clients has enabledSodexo to develop a laboratoryservice that can be applied to anylab operation where chromatog-raphy, spectroscopy or automa-tion systems are in use. Sodexohas the expertise to provide acomprehensive multi-site labora-

tory service and is keen to continue to identify newclients that will benefit. �

With laboratory equipment andscientific resources ranking asthe highest value asset to thescientific industry, deploying

a responsible and cost-effective managementsystem is proven to deliver significant gains inboth cost efficiencies and improved utilisationof equipment by scientists within the laborato-ry. Traditional solutions tend to be costly, in-hibit efficiency and are inherently servicefragmented.

Seeing the positive benefits in bringing asingle solution to its clients, share best practicesand deliver innovation, Sodexo launched itsPharmaceutical Division – not simply focusedon chromatography repair, it is a solution thathas been supplying a range of scientific supportservices since 2003.

Sodexo has built a strong, dedicated teamof experts focused on delivering laboratory in-strument support and other laboratory serviceactivities. They have applied a fresh approachto a long-term problem. Further innovation ofthese services allows the group to continue itsgrowth into new areas of scientific support,having a proven and positive impact on itsclients’ business.

The results speak for themselves: commercialsavings of 25-40 percent; improved instrumentuptime from two days to withinfour hours (fixed); and a com-plete laboratory solution, fromlab auxiliary through technicianup to competent engineers fixingscientific assets.

Sodexo’s heritage is built onthe staff it attracts and retains. Ithas successfully managed thetransfer of thousands of em-ployees who continue to thriveand develop in their organisa-tion. This brings continued de-velopment for its people, whichconsequently improves clientsoperations.

The laboratory services solu-tion managed by a central teamcomprises dedicated engineersdelivering instrument serviceswithin the labs; an administra-tion team and systems to simpli-fy and challenge the processes;commercial experts to negotiate the best possibleterms and meet regulatory compliance; and ded-

Delivering laboratory servicePhilip Fairhurst explains the importance of a singlesolution for efficient laboratory management.


INDUSTRYINSIGHT

Philip Fairhurst joined Sodexofrom Agilent Technologies inJanuary 2006, as BusinessDevelopment Manager forLaboratory Services. Hisresponsibilities to thePharmaceutical Division focus onthe engagement of lab supportservices to the pharmaceuticalindustry and assisting Sodexo’sclients in achieving their qualityand financial goals.

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MANUFACTURING

Schering-Plough’s Brent Saunders tells Natalie Brandweiner how pharmaceutical companies can combat patent expiries by switching branded products to OTC.

Having begun his career in compliance at Pricewater-houseCoopers, Brent Saunders is a noted speaker on risk management issues in the healthcare industry – a useful tool in his current position as Senior Vice President and President of Consumer Healthcare at

Schering-Plough. Knowing when the time is right to risk the success of an over-the-counter switch requires a certain element of business savvy, and Saunders certainly seems to be the man for the job.

He describes OTC switching as being a very simple process: the switching of an FDA-approved prescription medicine to a non-pre-scription over-the-counter or OTC status medicine. Saunders explains that OTC switch is becoming more and more prevalent as both drug companies and patients themselves are keen to reap the benefi ts of this simplifi ed system.

“If you have a well-established medicine that is safe and eff ective and you believe that consumers can self-diagnose and treat with your medi-cine, then it’s appropriate for OTC or over-the-counter status,” Saunders says. “Th e reason a company may be interested in doing this is that on the prescription side they may either be losing their patent or they may see their market eroding and recognise that a better place for the medicine may be in the OTC status versus the prescription status.”

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But facilitating the decision as to when a prescription medicine should be switched and what sort of process should be involved requires a variety of factors. Saunders advises that generally, those major switches that have occurred over the last two or three years have been due to patent life, each switch requiring a complex process.

“We have to work out with the FDA whereby you need to demon-strate that the drug is fi rst and foremost safe, and then you have to go on to also establish that consumers can self-medicate without harm or concern.

“Th ere are diff erent ways of doing this. One of the primary tools we’ll use is label comprehension studies, and surveys. We’ll spend a lot of time analysing how a consumer views a label and their comprehension and understanding of how to use a medicine, as well as understanding if there is any potential for misuse or misdiagnosis. Th en we work with the FDA to ensure that labeling is clear and appropriate for each medication in its OTC status,” he explains.

More effi cientSaunders believes that the impact of OTC switch on the healthcare

system can benefi t consumers – providing greater time effi ciency. How-ever, he also advises that on the negative side, patients do oft en have to pay for the medicine in its OTC status.

“When people have to pay out-of-pocket for something, they tend to use it only when they need it,” he points out. “As opposed to being completely reimbursed or having the cost passed through, so that it’s in essence free to them. Take a category like upper respiratory infections. A Consumer Healthcare Products of America study (CHPA) showed that moving several treatments to OTC status saved the US healthcare system about US$4.75 billion annually.

“What we are seeing around the world is that a lot of governments are becoming more interested in self-medication or OTC status for drugs because it shift s the burden from the public health system to the individual,” he says.

In the US, President Obama’s healthcare reform plans have pledged to expand healthcare coverage, but will this mean a lesser need for over

the counter, as patients will now be able to receive medication through their insurance? Saunders says that this will depend on the category to which the drug belongs.

“For example the PPI category, or the allergy category, most of the prescription drugs, though not all, are moved to a third tier co-pay. Th e co-pay for some of those medicines can be between US$35 and US$45, so it’s either the same price as the OTC for treatment or it’s more expensive than the OTC treatment itself. In prescription status, that drug may cost US$200 and in an OTC status it may cost US$20, ” he explains.

Patent expiriesOft en the motivating factor behind an OTC switch is an expiring

patent. Governments in many countries are hoping to promote the great-er use of generic drugs and allow them to become more available, which will supposedly make medicines cheaper. It remains to be seen how these two issues, patent expiry and generic usage, will run in tandem.

“In most instances when you go over-the-counter you do face compe-tition from store brands”, Sanders says. “Generally stores will create their own version of your compound, so it then becomes a brand competition. Th ere are certain people who tend to like brands and there are certain people who are more cost-conscious and tend to trust or look to a private label or store brands,” he says, suggesting OTC switches provide competi-tive benefi ts to a drug that is already on the brink of losing its patent.

He provides Schering-Plough’s drug Claritin as an example of this. “When the patent life ended, we could have simply walked away from the category, or we could have switched it. By switching it, we’ve gener-ated well over US$2.5 billion of additional sales since the patent expired. Th at’s a nice lifecycle strategy for a brand. Claritin as a prescription had a fi nite patent life, but now Claritin as a brand should last forever.

“Innovation doesn’t end because the patent has expired and the drug has been switched to OTC status. Innovation in the hands of a good consumer healthcare company continues through the entire life-cycle. Th is year we launched a new formulation of Claritin in a liqui-gel format, which was never part of the prescription life of that product. It was something we innovated. We had to fi le with the FDA for a new drug

application for that formulation. It took us a couple of years to do it, but we now have Claritin Liqui-gel availble for consumers.”

StrategyOTC switching is certainly a determined strategy

for Schering-Plough. Ninety-fi ve percent of the com-pany’s OTC products were once prescription, com-pared to an industry average of 26 percent, making the company an industry leader in OTC switch. “We’ve had a very solid 30 year track record of doing it, and frankly we do it because it’s a strategic priority for our division,” says Saunders.

“We focus on good medicines. We like to say that we provide products that really help consumers with their healthcare. By the time a medicine is a candidate for over the-counter status, you have demonstrated effi cacy because you’ve gone through a new drug

“A lot of governments are becoming more interested in self-medication or OTC status for drugs because it shift s the burden from the public health system to the individual”

Brent Saunders



application, you’ve gone through all the clinical testing required to bring an approved drug to patients, and you know the safety profi le is strong. So it’s a really good basis for a successful product.”

Schering-Plough recently developed a proprietary switch process. Saunders explains that no two switches are ever exactly the same, and the world of switching is becoming ever more complicated. “A lot of the low-hanging fruit has already been switched,” he says. “Switches in the future will require more thought and more expertise than ever before.”

He explains that the company’s tried and tested method to ap-proach a switch is to bring together a small group of experts within Schering-Plough and to leverage outside resources, as appropriate. Th e emphasis is placed on ensuring a dedicated team is attached to each switch so that it can address the specifi c needs and require-ments of each particular switch. Th e team must then manage the switch process through the lifecycle to the launch.

Th e approach used by Schering-Plough diff ers from that of other companies, which oft en have people either in their market research or their R&D groups who are responsible for switches. Th e main diff erence with Schering-Plough is its proven methodology and heavy use of a dedicated and struc-tured team format for switching.

Saunders is reluctant to highlight any of the switches that Schering-Plough currently has in its pipeline; the switching business is a highly competitive game. However, he does men-tion one that is currently in process – Zegerid, a prescription product in the US used for frequent heartburn. “It was fi led by a company called Santarus out of California,” he explains. “Th ey market it as a prescription product today. We have signed a licensing arrangement with them to switch the 20 mg product to OTC status. We are now in the process of working with the FDA to make that happen, and it’s going to be a really

unique entry into that marketplace.”Despite conducting a huge amount of

switches in comparison to other pharma companies, the actual amount of switches carried out by Schering-Plough is around one per year. As Saunders says, “A switch is a big deal. Th ere is not a large pool of drugs that are at the stage of switching.” He notes a successful switch – two and a half years ago Schering-Plough switched a drug called MiraLAX, a medicine used

for constipation – and advised to get to that stage of success took a relatively long period of time.

Th e future for switching as an increasing trend does looks prom-ising, however, “Around the world, we see governments more inter-ested in self-medication, which is a positive for OTC switches,” he predicts. “Public policy is moving in the direction to support OTC switches, and a lot of that is the burden that it relieves from healthcare systems fi nancially.

“But by that same token there’s some counterbalancing in that the interesting switches that are out are for more chronic ailments. And those are more diffi cult switches to do: they require longer and more extensive studies to prove the safety case.

“Policy is moving in that direction, but the work that has to be done is more complex and diffi cult. Th e industry has a bright future, but we need to continue to look at ways to use technology and good marketing prac-tices to help ease some of the concerns of abuses around medicines in the OTC side,” he concludes.

“Innovation doesn’t end simply because the patent has expired and it has been switched to OTC status. Innovation in the hands of a good consumer healthcare company continues through the entire lifecycle”

Brent Saunders is Senior Vice President and President of Consumer Healthcare for Schering-Plough Corporation.


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developments in the formulation can focus on an enhancement of the resorption by using vehicles as PEG400 or using excipients infl uencing the permeability, like ethoxylated fatty acid derivatives, such as Gelucir. A very specifi c approach is the development of liquid dispersions. Secondly, modifi cation of the API could be considered, such as the change of the counter ion or the usage of a polymorphism. For the latter example, the future release specifi cations have to be kept in mind. Finally, the development of a soluble pro-drug would be an option.

The effectiveness of a pharmaceutical product can be adversely impacted by pa-tient non-compliance. How common is this problem? What can be done to help allevi-ate it?GP. It is a common problem that depends on the severity of the illness, the progression of the disease, the dosage form, the subjective impression of the patient and the doctor-pa-tient relationship. An obvious example is non-compliance in antibiotics treatment – taking

tion rate of poorly water-soluble drugs, thereby enhancing the rate and extent of absorption.

Gerd Paulus. Insolubility poses problems in formulation development, and in dissolution and release testing. Insoluble drugs cannot be developed as parenteral drugs. Furthermore, the absolute bioavailability will be low, lead-ing to high dosages and therefore higher cost of goods.

Companies can try to enhance the solu-bility by following three major routes. First,

ROUNDTABLE

Why does drug insolubility poses signifi cant challenges during drug development? What can companies do to counteract this?John Fraher. In order for a drug to be an eff ec-tive oral treatment, it must be able to dissolve and be absorbed by the bloodstream. Perme-able yet poorly soluble class II compounds can present challenges such as lack of or reduced levels of absorption or slow solubilisation ki-netics that cause a delay in a drug’s onset of action and reduced bioavailability. It may be possible to compensate for low solubility by el-evating drug dosage to increase the absorption amount without leading to safety concerns, but in many cases the drug must be developed in an injectible dosage form.

Eurand’s proven Biorise technology ad-dresses poor solubility through a novel propri-etary process. Biorise breaks down a crystalline drug into nanocrystal and/or amorphous (noncrystalline) form of the drug that is then stabilised in a carrier system to maintain the drug in its activated state. Th is approach cre-ates a greater surface area to volume ratio that increases the intrinsic solubility and dissolu-

John Fraher of Eurand and Gerd Paulus of Swiss BioAnalytics talk to NGP about common problems in developing successful pharmaceutical products.

Challenges in drug development and delivery


“Line extensions that hinge on new or unique formulations are a key component of lifecycle management”- John Fraher

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ual drug particles with a polymeric membrane that provides an immediate or customised release profi le with complete taste and odour masking. Used together, AdvaTab and Mi-crocaps create a convenient, patient-friendly orally disintegrating tablet with eff ective taste masking and a pleasant mouth-feel.

Multiple dosing per day can oft en be dealt with through the development of once-a-day dosage forms. Eurand’s customised release platform contains a number of technologies that can provide for the development of cust-omised release multi-particulate or monolithic (tablet) once-a-day dosage forms.

What techniques or tools can pharmaceuti-cal companies use to turn drug candidates into easy to administer, successful pharma-ceutical products?JF. Th e oral route of administration for drugs remains the most popular delivery vehicle for

patients. Techniques aimed at convenient oral dosing and administration, when applied to prescription and over-the-counter (OTC) drug candidates, can pro-duce eff ective products.

Eurand continues to develop a portfolio of suc-cessfully commercialised products with its partners, due in large to the breadth and depth of its technology platforms. Our successes include partnering with Cephalon to develop Amrix (cyclobenzaprine hydro-chloride extended-release capsules) the fi rst and only once-a-day muscle relaxer; partnering with Chattem to commercialise UNISOM

SleepMelts, and our most recent success – the FDA approval of orally disintegrating tab-lets, Lamictal ODT (lamotrigine), soon to be launched by GlaxoSmithKline.

GP. Th e development of an easy to adminis-ter dosage form, such as tablets or capsules, should be the main goal. To avoid surprises, the strict follow up and implementation of ‘developability’ concepts from early develop-

non-compliant. Th ree key drivers of patient non-adherence are poor taste, diffi culty in administration or swallowing, and the incon-venience of multiple doses per day. Th e extent of the problems can be reduced through the ap-plication of sophisticated technologies. Eurand has a range of technologies within its platforms that can be used to address all three issues.

Poor taste and diffi culty in administra-tion and swallowing can be addressed through the application of AdvaTab and Microcaps technologies. AdvaTab is an advanced orally disintegrating tablet technology that enables rapid disintegration in the mouth without water. Microcaps is a versatile and precise mi-croencapsulation technique that coats individ-

the drug less than the prescribed seven days. Due to this non-compliance, a high rate of re-sistant bacterial tribes has emerged. Another experience from the past can be found in the area of oral contraceptives, whereby includ-ing placebo tablets to achieve a daily regimen decreased the rate of non-compliance.

By changing the dosage form or formula-tion, compliance can be enhanced, such as by changing from a three times a day formulation to a once daily modifi ed-release formulation.

JF. Patient compliance is fundamental to the successful medical management of the vast majority of diagnosed disorders. It is esti-mated that 40 percent of patients are considered

John Fraher has been Chief Commercial Offi cer of Eurand since August 2006, President of Eurand Incorporated since April 1999, and was Vice President of Eurand Incorporated from 1995 to April 1999. Previously, Fraher was Production Manager at American Home Products Corporation’s affi liate, Fort Dodge Laboratories, located in Ireland, and has worked at Sterling Drug in Ireland.



portfolio of existing drug candidates may op-timise market share for our pharmaceutical partners, or create an opportunity to expand into emerging geographies.

Innovative and eff ective lifecycle manage-ment strategies need to include core elements such as identifying new clinical indications or creating line extensions that incorporate drug delivery technologies, with the goal of creating additional clinical benefi ts for cur-rent drug candidates or addressing patient groups that are currently not addressed by present therapeutic treatments. Additionally, enhancing the intellectual property around the molecule to defend against generic entry is a key element of lifecycle management. New formulation patents as well as technol-ogy patents may serve to maintain a drug’s share in the marketplace.

Th is situation has been supported by following the patient-centric approach by the introduction of new comfortable formulations, such as granulates, and the creation of combination products.

JF. An interesting industry trend that is de-veloping is the pursuit of the lifecycle man-agement strategies at large pharmaceutical companies, an area once inhabited only by the likes of specialty pharmaceutical com-panies. Line extensions that hinge on new or unique formulations are a key component of lifecycle management. Incorporating custom release profi les, improved solubility or ad-vanced taste-masking techniques within a

ment should be consid-ered. For example, the physico-chemical param-eters of a drug candidate should determine the de-cision for further devel-opment – there could be a caveat to develop a BCS class four compound.

What is the best way to promote innovative and effective life cycle management that can prolong the market life of products?GP. Among multiple options three should be highlighted here: the label extension, a patient -centric approach and a strong brand. Marketed drugs can be explored in neigh-bouring indication fi elds. Th is strategy can be observed in the fi eld of oncology. Generally only effi cacy studies are needed, as all safety data are available.

An example for a strong brand name is As-pirin. Despite heavy competition from generic products, sales fi gures continue to be high.

In June 2005, Gerd Paulus was appointed General Manager of Swiss BioAnalytics AG. He has worked for pharmaceutical companies in quality control at Bristol Myers and R&D at Ciba-Geigy. As the holder of executive positions in business units and country organisations, Paulus gained in-depth expertise of the general management, as well as experience in the global pharmaceutical industry.

“By changing the dosage form or formulation, compliance can be

enhanced” - Gerd Paulus


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Geodis Wilson is continuously devel-oping its scope for the distributionof temperature-controlled ship-ments for airfreight with the ability

of securing the correct temperatures and compli-ance with GDP-approved procedures at all times.This is an ongoing process between pharmaceu-tical companies, manufacturers of materials andlogistics providers when operating a successfulsupply chain.

Pharmaceutical companies require the righttype of transport mode and equipment for a spe-cific product, for a specific market and at the rightprice. Temperature management is a crucial areafor the distribution of pharmaceuticals. It is im-portant to be able to monitor the temperaturethroughout the complete supply chain. Today,the most commonly used solution for ambienttransportation between 2° C and 25° C is the ship-per-purchase insulated pallet box. The disadvan-tage is that this way of transportation can becomeexpensive.

The challengeAs pharmaceuticals are considered high value

goods, they demand a safe, well-monitored andGDP-approved process throughout the completesupply chain. The distribution ofpharmaceutical products with ademand for door-to-door con-sistent 2° C - 25° C ambienttransportation versus a compet-itive price is a huge challenge formany airlines and logisticsproviders.

The solutionThe Geodis Wilson G-Box

was developed to provide stabil-ity and protection for 2° C - 25°C ambient shipments. The G-Box provides the correct insula-tion qualities against varioustemperature variations. The G-Box is strong, flexible and waterrepellent 0.3 percent absorptionby volume, with thermal con-

ductivity properties of 0.030 W/mk. It has a vaporresistivity of 480 MNs/gm.

Due to its enormous flexibility, the G-Box canbe used with AMA (main deck containers), AAP(lower deck containers) or even down to AKEunits. In addition, we have recently developed theG 2 Box, an independent free standing version ofthe G-Box, which allows shippers greater freedomof choice of carrier, as the G 2 Box fits directly onto the airline pallet. (Lower deck and main deckversions available). The shipments are loaded in a

secure and ambient temperatureenvironment and can be mea-sured by the customer’s temper-ature monitor or the GeodisWilson developed temperaturemonitors throughout the wholedoor-to-door transportation.

The benefitsIn developing the G-Box

we are able to offer a price com-petitive solution for ambientcargo. The price competitive-ness is based on lower packag-ing costs on insulated palletboxes through using the GeodisWilson Custom Made G-Boxesor G 2 Boxes to airline specifica-tions; less handling charges forthe shipper; and cargo optimiza-

tion and freedom to choose any airline due to thehigh flexibility of the G-Boxes. Our innovativeproduct has successfully been monitored, testedand used by several customers within the phar-maceutical industry.

Due to strong relationships with our preferredglobal operating airlines and local trucking com-panies, we’re able to utilise direct carriers, reduc-ing trans-shipment points and additional handlingand risk to the product. Geodis Wilson is verymuch focused on clear procedures for changes oftransport mode: a thorough route risk analysis iscompleted to ensure quality compliance, as this hasbeen recognised as one of the challenge areas for atime effective and secured solution.

The customer uses Geodis Wilson’s freightmonitor and a document management system tolocate shipping information, wherever the cargomay be. This doesn’t just provide increased con-trol over the shipping process – it also guaranteesthat the customer knows exactly when their ship-ments are going to arrive. n

An airfreight-focused logistics solutionBy Martin Svantesson


INDUSTRYINSIGHT

Geodis Wilson makes customers more competitive bydelivering its cargo across five continents by sea and airand by making its supply chain transparent and easy tomanage. Geodis Wilson, the freight management divisionof Geodis Group, has more than 5000 employees in morethan 50 countries. The Geodis Group is a global logisticsprovider with 26,000 employees in a network covering120 countries. As part of the French railway companySNCF, Geodis offers a wide range of sustainable,innovative and cost saving multimodal solutions.Formore information about the G-Box, please send an e-mailto: [email protected] or visit Geodis Wilsononline: www.geodiswilson.com.

Martin Svantesson is VerticalMarket Director of GeodisWilson Pharmaceuticals. Hehas 15 years’ experience inglobal distribution and holdsa Master’s degree in SupplyChain Management.Svantesson’s role is todevelop Geodis Wilson’spharmaceutical distributionsolution/proposal forexisting and potentialpharmaceutical customers.

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both low-cost as well as high-cost medicines therefore has advantages. An interesting and unprecedented fallout of the focus on emerging

markets has been the blurring of the traditional roles companies play: customers and suppliers, innovators and followers. For example, there have been several recent acquisitions by large pharmaceutical companies of generic companies, such as sanofi ’s acquisitions of Zentiva in central Europe, Kendrick in Mexico and Medley in Brazil.

But perhaps what is most interesting for us is the development of partnerships and strategic relationships that would have been unthink-able just a year or two ago; partnerships designed to drive innovation, improve costs and to make better medicines more widely available.

Dr. Reddy’s, for example, traditionally would have been seen as a generic pharmaceutical com-pany. Th rough our Custom Pharmaceutical Ser-vices business, however, we are now an established player for providing contract manufacturing and services to innovators, in particular lifecycle management. We actively engage with innova-tor pharmaceutical companies, using our skills, expertise and speed of development in generic API manufacture and formulation to help in the development of the next wave of advantaged and enabling combination therapies. Dr. Reddy’s also has large global manufacturing capabilities, making us one of the largest suppliers of API to the industry. Finally, we have tremendous experi-ence of operating in emerging markets. Th is has most recently culminated in a strategic alliance with GSK for developing and marketing branded generic products and diff erentiated formulations across emerging markets outside India.

So with a changing world we have a changed pharmaceutical industry. Th e norms and conven-tions of past decades have all but gone, replaced with innovative business models and collaborative partnerships focused on the most effi cient means to innovate and manufacture pharmaceuticals.

It is such partnerships that will allow for cost-eff ective innovation to return to the industry and for medication to reach the furthest corners of the globe and usher in a new era of sustainable growth for the phar-maceutical industry.

Towards more affordable and innovative pharmaceuticalsAbhijit Mukherjee explains the current woes facing the pharmaceutical industry.

The last decade of the 20th century could well be termed as the golden decade for the pharmaceutical industry, with mega-blockbuster drug launches, growing pipelines and unmatched profi t margins. With the turn of the clock into the 21st century, this has given way to a decade of

challenges. Th e pharmaceutical industry today fi nds itself in the midst of the perfect storm – R&D productivity is at historic lows, the patent cliff of 2012 looms, and the most profi table market, the US, is due for major healthcare reforms and soaring healthcare costs, resulting in un-precedented price pressure.

To add to these woes, the current global economic turmoil has left its mark on our supposedly recession-proof industry. IMS Health predicts that in 2009 pharmaceutical sales in the US will decline between one and two percent, while the global pharmaceutical market is expected to now grow by only 2.5 - 3.5 percent.

What then are some of the main conse-quences of this new, unfamiliar and changing environment? One of the most immediate conse-quences has been the wide ranging reassessment and restructuring of the extensive manufactur-ing infrastructure within the pharmaceutical industry in a bid to improve utilisation rates and sustainability. Outsourcing will continue to be a critical element of every pharmaceutical com-pany’s business strategy and the extent to which companies outsource key activities will only grow. Th is follows a trend already quite common in many other industries.

Finally, pharmaceutical companies are increasingly looking at emerging markets to sustain growth. A new world order is appar-ent as the IMS-coined ‘pharmerging’ markets of Brazil, Russia, India, China, South Korea, Mexico and Turkey grow collectively at a 13 – 16 percent pace through 2013. However, operating in emerging markets calls for a complete rethink of the existing business models of large pharma companies. Successful strategies in emerging markets need not incorporate the most innova-tive medicines. In these regions, most drug spending is out-of-pocket and there are high levels of income disparity. Th e ability to provide

INDUSTRYINSIGHT

Abhijit Mukherjee is President, Pharma Services and Active Ingredients forDr. Reddy’s Laboratories.

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NEWPRODUCTS

The benefi ts of essential fatty acids have long been established, but introducing them into the pharmaceutical sphere is a relatively recent phenomenon. Hilde Steineger

explains how Pronova’s use of omega-3 has transformed an age-old remedy into a billion-dollar blockbuster.

ECONOMIES OF SCALES

Norway has traditionally used fi sh oil as a natural remedy, most notably cod liver oil, but it wasn’t until the late 1970s that a Danish scientist discov-ered that the large intake of fats by Eskimos did not have the normal correlation of cardiovascular problems that are seen in the Western world. Fur-

ther analysis of the types of fat uncovered large quantities of omega-3, and the understanding of its cardiovascular properties was born.

“Th ere has been a lot of scientifi c research in Norway on lipids and omega-3s since the late 1980s,” explains Hilde Steineger of Norwegian-based Pronova BioPharma. “Between the late 1980s and early 1990s, Norsk Hydro looked into omega-3 to produce it in a very high concen-tration, and this is what makes our product diff erent than the supple-ments from those you can buy in the pharmacy: we have a much higher concentration of omega-3. A normal supplement would be somewhere between 30-50 percent concentration, while our product is above 90 per-cent concentration of omega-3.

“At that time Norsk Hydro, which is a large conglomerate in Norway, fi led patents on this concentration and they started to do clinical trials. When they started they had an open mind about which indication and diseases this could be used towards, and what they ob-served was that it was quite eff ective on lowering triglycerides. So that was one of the indications that we ended up with in the clinical trials going forward.”

Steineger also notes the work of a large cardiologist group in Italy, the GISSI Group, who began work on the eff ects of omega-3 at a similar time. Th ey also began studying the eff ects of omega-6, and whether it would work, as well as if similar results could be produced from Vitamin E.

Clinical trialsFollowing this, the GISSI Group then took the lead with Pronova

and began performing large-scale clinical trials, with over 7000 post-myocardial infarction patients. For instance, patients who had previously experienced heart attacks would receive either a placebo drug, omega-3 or Vitamin E to determine the eff ects. Th e Vitamin E groups proved to

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show no eff ects, whilst the highly concentrated omega-3 groups showed tremendous eff ects on all-cause mortality, new cardio arrests and heart attacks, as well as on sudden deaths.

Most astonishingly, the trials showed a four to fi ve percent relative risk reduction in sudden death groups and a 20 percent reduction in all-cause mortality. Steineger notes that these results were responsible for the formation of the basis of post-myocardial infarction in Europe, the other indication present being a lowering of triglycerides.

She explains the results of omega-3 on cardiac prevention as being due to a regulation of heart rhythms – electrocardiac signals – in the body. “On cardiac prevention, you must remember the human race has eaten fi sh for hundreds of thousands of years, so we have the metabolism

and the system in place, and fi sh oil and omega-3 are involved in an extremely high number of diff erent pathways in the body,” says Steineger.

“Th ere are many modes of action of this drug; we can’t pinpoint one and say, ‘Th is is one of them. Th is is how it works.’ We can pinpoint several, but which of these modes of action is the most impor-tant is diffi cult to say. However, on the prevention of cardiac events, the scientists and we believe that this is a regulation of heart rhythms, electrocardiac signals.

“How would that come to be? Well, it’s believed that every cell membrane of phospholipids has lipids in it, and if you exchange the lipids from saturated or monounsaturated with polyunsaturated, they get more liquid: the membranes get higher fl uid-ity. Because the more saturated fat is, the harder it gets.

“If you then go to the other extreme and have a polyunsaturated fatty acid, like omega-3, and you incorporate this into the phospholipid layers it has been shown that the lipid layer will get a higher fl uidity. Th is fl uidity has an eff ect on the electrocardiac channels, such as the calcium potassium channels conducting the electric signals between the cells. Th at’s one change in the phospholipid layer and how that might change electrocardiac signals.

Omega-3Popularly known as fatty acids, omega-3s are a group of unsaturated acids that have a fi nal carbon-carbon double bond in common. Awareness of their benefi ts to health has grown over the last few decades, and as a result, the number of foods enriched in omega-3 fatty acids has increased – such as milk and eggs that can be naturally enriched. They were deemed ‘essential’ when scientists found that they were indispensable to normal growth in young children and animals.

“Th ere is a lot of research that shows there is potential in

omega-3, but it all depends on the clinical trials that you do to

support your product”

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and also dementia, as well as having shown to have anti-infl ammatory eff ects. Th ere’s a lot of research that shows there’s potential in omega-3, but of course, it all depends on the clinical trials you do to support your product. We have a business model whereby we don’t perform large clinical trials ourselves; it’s our partners that perform the clinical trials,” explains Steineger.

Th e timeframe for looking into such other potential applications is still uncertain. She notes that there is still a lot to do on cardiac preven-tion and on the lowering of triglycerides, in the sense of harvesting all the potential. Th ere is also a large clinical trial, known as ORIGIN and driven by sanofi -aventis, which includes Pronova’s product in two of the arms, and involves 12,000 pre-diabetic patients.

Th e remainder of 2009 looks promising for Pronova, and with March end-user sales hitting US$1.1 billion, the company is aiming for blockbuster status for Omacor/Lovaza, and as Steineger says, “Th ere are not many products that can do that.”

“Aft er the GISSI-Prevenzione study the GISSI Group also performed a study reported in 2008 called the GISSI Heart Failure study. Th ere they showed the reduction in all-cause mortality to be around nine percent this time, however heart failure patients are quite sick and are on a lot of diff erent drugs, so it was an add-on therapy and not a switch. Th is is the mode of action on the cardiac prevention.

“Th e lowering triglycerides is a bit more complicated in the sense that natural or fatty acids are natural ligands for PPARs. When the fatty acids bind to PPARs, the PPARs then regulate quite a lot of diff erent metabolic pathways, stimulat-ing the uptake of triglycerides in the blood and reducing the body’s own production of triglycerides, and also increasing the metabolism of fatty acids and triglycerides. So it has quite a lot of diff erent modes of action, which all together give a reduction in the very high triglyceride group, because there’s diff erentiation on how high levels you have with triglycerides. Th erefore, in the very high triglyceride we see a 45 percent reduction of triglycerides, which is comparable to Niaspan and Tricor, but without having the same side eff ect profi le,” explains Steineger.

Regional attitudesPronova’s omega-3 product, known as Omacor in Europe

and Asia and Lovaza in North America, is the fi rst and only EU- and FDA approved omega-3 derived prescription drug. It is indicated in Europe for lowering all forms of triglycerides, as well as for use in post-myocardial infarction patients; whereas in the US it is indicated only for lowering very high triglycer-ides. However, the US market is expanding, following a recent re-launch. Reliant Pharmaceuticals launched Lovaza in 2005, and when GSK bought Reliant in 2007, a diff erent sales team was put together, the sales force was doubled and the product was re-launched three months later – creating a bigger market. However, Steineger believes the pick-up rate to be the same at home as it is abroad, regardless of the long tradition of omega-3 use in Norway. In fact, the greatest market currently for Pronova is the Mediterranean.

“Th ey already eat a lot of fi sh there, so you would think that they wouldn’t need extra fi sh oil or extra omega-3, but the perception that fi sh oil and omega-3 are good for you is easier to penetrate there than in the more northern European countries,” says Steineger.

Although there is no scientifi c proof, she alludes to the fact that in a region where the intake of fi sh oil is already high, having extra is consid-ered even more benefi cial. It is this approach towards omega-3 that has received tremendous attention within the US, and she explains GSK is promoting the product, “very well and very professionally, it’s one of the growth drivers for GSK for the moment.”

So how is this steering the future of Pronova? Steineger explains that this area is due for even more growth, and there is certain to be a greater market in the future for these marine-derived omega-3 products.

“We have just scratched the surface of the potential, but it will of course be dependent on clinical trials and what we can prove. Omega-3 has been coupled up with CNS diseases, like depression, Alzheimer’s

Hilde Steineger has served as Head of Investor Relations at Pronova BioPharma since 2007. Before that, Steineger was Senior Associate at NeoMed Management from 2006 to 2007, Business Development Consultant at Maxfi eld/Amino from 2003 to 2006 and Senior Financial Analyst at Nordea Securities from 2001 to 2003. She graduated with a PhD in medical biochemistry from the University of Oslo in 2000.

“Th e human race has eaten fi sh for hundreds of thousands of

years, so we have the metabolism in place to process omega-3”

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FEATURE INTERVIEW

Viehbacher ed:13July 29/7/09 14:08 Page 74

You could say Chris Viehbacher has been around. He started hisworking life at PriceWaterhouseCoopers, then in 1988 movedinto the pharmaceutical industry with GlaxoWellcome, whichlater became GSK. He holds both Canadian and German pass-ports, and has lived and worked in the US and Canada, as well

as Germany, France and the UK. But it’s his latest move that is big news. Last December he left his posi-

tion as President of GSK’s Pharmaceutical Operations North America – afterbeing passed over for the top job in favor of Andrew Witty – to become CEOof its French rival, sanofi-aventis. The move caused shock waves throughoutthe industry – the previous CEO, Gerard le Fur, had been in the position foronly 18 months.

Although, with hindsight, the change did not come as a complete sur-prise. Sanofi’s share prices had dropped in 2008, following the rejection in theUS of its Acomplia obesity drug, once the company’s most promising prod-uct. Last July, sanofi and partner Oxford BioMedica said their TroVax medi-cine had failed to meet the target of a kidney cancer study, and developmentof Multaq, a heart drug, was delayed after US regulators rejected it.

When Viehbacher’s appointment was announced, he was seen by manyas being a kind of saviour, brought in to turn around a troubled company.Immediately after the announcement, sanofi’s shares rose by 6.8 percent, theirbiggest gain in more than two years.

While he admits that his new company has suffered from a bit of animage problem, Viehbacher insists he has a strong foundation to build on. “Ihad two months between leaving GSK and starting at sanofi, and as part ofthe analysis I carried out during that period I found a number of strengths thatI would not have know about coming into the company. When we presentedour fourth quarter results, where we talked a bit about the strategy, even peo-ple in France who’ve known the company for a long, long time discoverednew things.

“The first was that we have a leadership position globally. We’re oftenperceived as being a company that is very franco francais, very French, but ac-tually this is the company that’s got the number one position outside the USand Europe. It was one of the first companies into China, it has a major posi-tion in India, big positions in Latin America, and a major position in Africa.


When Chris Viehbacher arrived to take upthe reins as CEO of sanofi-aventis at theend of last year, he found a company withan image problem that had forgotten howto communicate. Now he plans to changeall that, as Marie Shields finds out.

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and organising the structure. He believes in moving money and resourcesacross a range of projects and teams, some of which may be internal and someof which may be external.

Time to collaborateIt’s for this reason that Viehbacher is willing to allocate up to 50 percent

of his research resources to outside collaborations. He gives the following ex-ample: “When we put forward a proposal to build a biotechnology factory inFrance, I said I’d like to make sure that this factory is also available to otherbiotech companies who might want to use the facility. That’s in an interest forus because we might be able to partner with some of those companies.

Another factor in this equation is Viehbacher’s view, based on his 20 yearsof experience in the industry, that you can never have enough pipeline. “Thereisn’t a company in this industry that has enough pipeline,” he emphasises, “andenhancing that and working collaboratively outside has got to be a way of life –and a constant way of life, not just something you do on an ad hoc basis to sup-plement your own. The model we must move away from is this notion of ‘We’regoing to keep throwing money at a black box’ – which is the way I often perceivedresearch and development in the past– and hope that we can do everything fromA to Z, from discovery through to commercialisation.”

With external collaboration, there’s obviously a process of competition thatdoesn’t occur with internal projects. It’s through this competitive process thatsome of the best ideas emerge, and weaker projects often get weeded out.Companies don’t always put the same level of due diligence behind the choice ofinternal projects, because they’re committed to sites and committed to teams.

“This might mean we need to bring a lot more rigour in deciding which arethe best ideas to invest in,” Viehbacher says. “Then we need to get behind them,make sure the teams have passion and conviction, and give them the latitude todecide. The construct of a team may differ from one therapeutic area to anoth-er, but at the end of the day we are betting on teams and their ideas. It’s a ques-tion of how do you identify those, encourage them and put some stress on thetesting of those ideas?

“You have to let them run and try to keep as little process and bureaucracyas you can from impeding those efforts. Then after three or four years, you seewhat results they have come up with. That’s also something that in our industrywe haven’t been good enough at – looking for the results early on. As an indus-try, we do development pretty well; it’s the discovery research piece that we’vegot to go back and look at from a people point of view.

“You’ve got to be able to voice a problem before you can solve it. To a de-gree, we’ve been dancing around a number of issues in this industry and haven’t

“When you think that in the future more than 50 percent of a globalpharmaceutical market growth is going to come from outside of tradition-al markets, sanofi is positioned with not just the market share, but also withthe people, resources, local market knowledge, government contacts to ben-efit from this period of growth.

“We’re also a lot more diversified than people realise. We’ve obviously gota leadership position in vaccines, and a position in OTC that I don’t think any-body realised we had, either inside or outside the company. It provides a basis onwhich one can build. We have fledgling operations in generics, which we havesince reinforced, and we have quite a significant older product range that con-tinues to grow, and that really supports the business globally.”

Let’s talkWhat then, was the problem? Viehbacher feels that one of sanofi’s mis-

takes in the past has been the lack of effort put into communicating with in-vestors and the general public. “Sanofi is a company that experiencedsignificant success for many years, and didn’t pay attention to the need tocommunicate. It’s when you run into difficulty that you suddenly realiseyou’ve got to explain where your strategy is and where the strengths of thecompany are,” he says.

“Management didn’t focus enough attention on it, and we never ex-pressed a vision about where we wanted to go. We had the building blockslying on the ground, but there was no plan to make the house and no realexplanation of what house we were going to build. There’s been some workneeded on architecture and construction. But at least the fundamentals werethere; it’s just a question of now building upon those and turning them intosomething.”

There also needs to be increased emphasis on external growth,Viehbacher explains. He would like to see the company open up more to theoutside world. “We were a company that was focused internally; a compa-ny that lived within its own walls. We were looking principally inside in ourown research for new product opportunities, and we weren’t spending a lotof time communicating with the outside world.

“One aspect of my plan is to bring the outside world into the companyand open it up to what’s out there. We have just carried out a pipeline re-view within our research and development organisation, and we examinedit not just from the traditional point of view of safety and efficacy, but wealso looked at the value to customers. Cutting 14 out of our 65 projects wasa strong signal that we’re only going to progress those medicines that arenot only safe and efficacious, but also add value to patients. So there is aneed to change the culture.”

Viehbacher has also been looking at R&D structure. He says it’s im-portant to keep in mind that there is a lot of fantastic science going on out-side the company. “The model – if there is such a thing – is to say you’regoing to be doing some research inside, but you’re also going to be doing alot of research through collaboration. To a degree, outside research is stillseen as adding to internal efforts, and to that I say, ‘There are plenty of com-panies outside and they’re doing plenty of things. Why replicate that?’”

Companies still need to do enough of their own research to be able tounderstand the research being carried out externally, and big pharma willalways have some depth of expertise that smaller companies don’t.Viehbacher stresses, however, that for him, the discovery research model isvery much one of osmosis, and not so much about creating smaller units


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Diversify and multiplySince becoming CEO, one of Viehbacher’s constant refrains has been

that he aims to turn sanofi-aventis into a diversified healthcare companywith a more global reach. What exactly does this mean?

“If you think about strategy you essentially start off with a certainnumber of things,” he says. The first is: where is there an attractive mar-ket, and you come down to that by looking at what are some of the megatrends amongst consumers? What are some of the disease areas of unmetneed? What’s the evolution in the marketplace in terms of payers and in-surance companies and regulations? And you try to then marry that withwhere you’ve got some sort of capability, presence or experience, and tryto focus in on those market areas that are the most attractive.

“On the pharma side, we’ve gone too long where we start with a medicineand go look for a customer. If you look at the fundamentals of the healthcaremarket, it’s huge. There is going to be economic growth at some point. Evenwith the economic crisis, quite a number of markets are still growing; for ex-ample, countries like China that suddenly decide they need to significantly in-crease the level of investment they have behind healthcare.

“If you look at the ageing population as a mega trend, if you’re looking atobesity, you’re looking at a trend for wellbeing, you’re looking at time compres-sion, you’re looking at urbanisation of populations. You’re suddenly seeing thatthere is going to be a focus on healthcare, but on a certain type of healthcare, andthat our style of living is creating new healthcare issues. To me, healthcare – es-pecially if you don’t define it too narrowly – is fundamentally a strong area. Andyou’ve also got major diseases that still are not well treated, such as diabetes, on-cology and Alzheimer’s disease.

wanted to face up to them. We do need to acknowledge, for example, that wedon’t have enough new products to replace the ones we’re going to lose. And wehave not been realising an appropriate return on the money we’ve been spend-ing on research and development.”

Diagnosis mergerThe pharmaceutical industry has recently seen a spate of mega mergers –

Pfizer/Wyeth, Roche/Genentech, Merck/Schering-Plough. What doesViehbacher think of this trend, and is it one he’s considering buying into himself?

“One way or another, we all have to think about where we’re going to getsustainable growth from, and everybody starts off with a different set of cards.”he explains. “You have some companies that have become almost purely smallmolecule-based in Europe and the US, and when you’re facing a patent cliff andyou don’t have an awful lot of other things in your hand, you pretty much haveto do something to continue to survive. Pfizer has said, ‘We need to be more di-versified. We need more biologicals and vaccines, for example, and OTCs,’ whichthey didn’t have, and so it was a way of getting that.

“Everybody starts with a different position. We’ve got a lot of ele-ments upon which we can grow; I don’t necessarily need to do a big dealto seek that out. If you’re trying to get away from dependence on block-busters, you want to focus on those businesses that have different com-petitive profiles and different barriers to entry. And they’re not necessarilygoing to be easy businesses either, but they’re going to have a differentlongevity and a different perspective in terms of growth.

“My first objective is to continue to build on this notion of a globalhealthcare company as opposed to a pharmaceutical company based in theUS and Europe, and therefore have an acquisition strategy that buildsupon those things where we already have a strong presence. Like vaccines,like emerging markets, like OTCs and generics, where we’ve been weakbut where we can strengthen ourselves. I don’t think the size of the acqui-sition necessarily matters. It’s a question of we are all looking to strength-en our companies as we face patent expiries, and some of us, like sanofi,have things upon which we can build internally; some of us have to seekmore externally.”

Viehbacher says that the big question, whether you’re buying big, medi-um or small, is still going to be around innovation. He believes most compa-nies are struggling with the question of how to come up with an innovationmodel that is sustainable. He doesn’t think anyone has found the solution, buthe stresses that innovation is something that needs to worked hard at, and thatyou can’t let merger and acquisition activity completely dominate that.

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“Therapeutically you’ve got some very interesting areas, but then of coursenot everybody can afford the same level of healthcare. We’re seeing an increasedpresence of government regulation trying to go after some of the private sectorin terms of over-the-counter, or in countries where there’s no real social securi-ty or health insurance today – which is true of most countries in Asia – and youhave to ask, can you get into more services, OTCs, generics and some devices?There are all kinds of growth opportunities out there, and our strategy is to goafter those, versus just saying well, we’re a pharmaceutical company.”

One constant lament within the industry is the lack of new blockbusters. butViehbacher points out that blockbusters are unlikely to disappear completely.“The model that didn’t work was betting on the blockbusters; relying upon themfor your success. There’s no better business in terms of profitability, with low lev-els of resources needed, than when you’ve got a blockbuster. If you’ve got oneyou’re in a great place, but you can’t always count on them in terms of timing.”

Increasing productivityAnother area that Viehbacher feels the industry should be looking at is

the strength of its R&D. With this in mind, sanofi recently carried out a port-folio review. “Our intention was to do what a lot of other companies had al-ready recognised, and that is that you can’t develop a new medicine unless itadds value to patients,” he explains. “In so doing we’ve established newprocesses where the market is represented at the decision table as to when weadvance a product – nothing revolutionary there. The next step is to ask fivequestions of R&D. The first two we’ve already answered: do our products addvalue, and who needs to be at the table when we make decisions?

“The third, fourth and fifth questions are: how do we restore creativityand productivity back into our organisations? How do we make sure our or-ganisation is as interested in seeking science outside the company as inside?And, what are the new technologies and areas for investment that we want tobe in? Science is moving on – where do we want to place our bets?

“I’m not going to define all those; we do know we have some issues. I’mmeeting with some of our scientists right at the bottom of the company: we haveanywhere from nine to 10 hierarchical levels between the head of R&D and thescientist. That means a lot of our best people have become managers, and youget a promotion in the company by becoming a manager, not by being a greatscientist. We’re not doing enough to recognise innovation. We’ve got some greatpeople, but it’s very hard sometimes to get a project advanced if you really be-lieve in something, because you’ve got to go through so many steps.

“We’re trying to go back and have a very basic look from a human pointof view at who are the people who can succeed, how do we test whether they’regoing to succeed, and how do we give them a chance in our organisation andgive them enough latitude? We’ve become quite risk-averse as companies.

“One of the reasons we’re having difficulty in discovery is that we’re stillpursuing a lot of the same targets, and at some point you have to branch outand go after some non-validated targets, some new frontiers of science. Wehaven’t allowed enough of a risk profile at that level of the organisation tobranch out into new areas. If you look at the targets in oncology, in metabol-ic disease and in CNS, and you compare how many companies are going afterthe same target, it’s incredible.”

Recession-proof?It is unlikely that any industry will emerge completely unscathed from

the current recession, and recent rounds of job cuts among pharmaceutical

companies are an indication that they too are feeling its effects. ThePfizer/Wyeth merger resulted in the loss of nearly 20,000 jobs. GSK elimi-nated 800 research positions late last year, and recently announced it couldshed up to 6000 more jobs across its global operations. AstraZeneca alsosaid in February that it would cut its workforce by about 6000 positions. Inlate 2008 Sanofi-aventis cut nearly 1000 sales jobs in France and severalhundred more in the US, and at the end of June the company announcedan overhaul of its R&D operations, but said this would be accomplishedthrough what it called “voluntary staff departures.”

When asked about the possibility of further job reductions as part ofcost-cutting measures under his leadership, Viehbacher refuses to be drawn.“We will certainly go through a process of looking at how we can reallocateand reorient our resources, and that may end up in fewer resources. But no-body’s going to invest in this company because we cut costs. One of thelessons I’ve learned in the last 20 years is if you want to provide sharehold-er return you have to present a company that’s got a sustainable growthprospect. If you go through endless rounds of cost cutting you end up withan organisation that becomes very distracted and demotivated.

“We’re becoming more of a global company. We’re going to focus a lotmore of our growth into emerging markets and places like vaccines andOTC. Those all have ripple effects within a company; if you’re suddenly ingenerics, the manufacturing organisation has got to be able to support 100launches a year versus 15 – a launch being the launch of an SKU, not a newmolecule. And so you’re going to have to have a different organisationalmodel.

“We’ve got the lowest SG&A ratio in the pharmaceutical industry.Sanofi has never stood up and beat its chest and said, ‘We’re going to elim-inate all these jobs.’ It has just quietly and effectively managed its costs. Tome, cost management is just part of good management. We’ll continue todo that, and there are certainly opportunities to take some costs out of thebusiness.

“An endless round of cost cutting is not necessarily helpful, and it does-n’t create value in the longer term. It has to be to get the company growing onits feet again.”

Optimistic outlookDespite the challenges his company and the entire industry are facing,

Viehbacher is optimistic about the future. In his opinion, there is too muchfocus on the patent cliff, when the future is in healthcare. “In our companywe’ve got a lot of talented people and we’ve got a lot of financial resources.There are a lot of patients out there, and we’ve got the medicines and vaccinesto help them.

“We’re going to be a company that grows well on into the next decade.We need to get past the blockbuster phase, but the base business that wehave and our ability to partner and do acquisitions gives me an awful lot ofexcitement for the future.

“Healthcare is still something that matters more than anything else – thereis huge unmet need out there. It’s a massive marketplace, and if we’re a little bitcreative and a little bit flexible in how we go after it there are big opportunities.”

Despite the initial controversy surrounding his appointment, Viehbacherseems to be settling nicely into his new role. As he looks forward to the rest ofhis family joining him in Paris later this summer, perhaps this ‘man on themove’ will decide to stay put for a while. �



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route was not only a very fascinating and complicated process, but also a way to change the lives of millions of patients at a time,” she explains.

“For me to see that GSK considers safety and potential risks, even in the design of the molecules and the drugs at the front end is an important statement about the values that the company has. Th en wanting to use all the data at our disposal and inventing technology to do that, whilst being willing to share it, displays this even more.”

Safety and effi cacyIn a recent presentation to the Harvard Medical School, Strahlman

notes the impossibility of separating safety from effi cacy in clinical trials

As CMO for GlaxoSmithKline (GSK), Ellen Strahlman is primarily responsible for ensuring the safety of medicines and patient care. It may be a tough job, but Strahlman is certainly not lacking in passion. As a physician, her medi-

cal training began in general surgery and ophthalmology, which she admits to have initially given her that “fl avour of things,” and the desire to infl uence patients’ lives through the pharmaceutical sphere.

She explains her time spent in epidemiology and public health as that which prompted her to the move into the pharma industry. “I was pretty uncertain at fi rst; the fi rst part of my career was at Merck, and I found that actually inventing a drug and bringing medicines to patients through that

CLINICALSAFETY

Ellen Strahlman, Chief Medical Offi cer for GlaxoSmithKline, explains why a balance of safety and effi cacy is essential in clinical trials.

RUNNING THE RISK

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“So society indirectly made a decision that a very extensive screen-ing programme would be tremendously benefi cial for their pediatric and their newborn population. What was realised is that there was a tremendous benefi t to doing something in this situation, and then the cost decisions were made by the values of this to society aft erwards. One of the things that is important to us is that the medical benefi ts, in comparisons of treatment, be front and centre and that doctors make those decisions for their patients.

“However, an emphasis on costs, as we have seen in other parts of the world, we don’t think will be as productive. We want to bring medicines to patients to improve their health and wellbeing, to treat diseases and meet unmet medical needs. We believe this is of tremendous value to society, so if cost becomes the front and centre issue there’s defi nitely a feeling that we might lose some of the important benefi t and value to society conversations.”

Strahlman explains that the elements important to compara-tive eff ective research propos-als should therefore include an understanding of benefi ts and risk, as well as an understanding

of populations that respond diff erently. She describes that some of the ways that comparative eff ectiveness research can be conducted may be through randomised trials or observational data within the context of the real world, both elements being applicable to CER.

Real world data“You need both types of information to understand the benefi ts

and the risks of a medicine. Randomised trials are the ultimate experi-ment – the testing conditions are right, you actually test the benefi t and the safety versus either the standard of care or sometimes the placebo, and in the purest sense, it gives you the most unbiased view of the ef-fectiveness and the safety of a treatment.

“Th e downside of randomised trials is that because the populations are selected, and everything is very well-controlled, sometimes when things happen in the real world they don’t exactly go according to those criteria. For example, our population of diabetics would be in a clinical trial, a uniform population, to ensure that the experiment works well. But in fact, diabetics have a wide range of medical conditions. So in the real world, that may be diff erent.

“Th erefore, clinical trials can’t always answer the questions about what happens to an entire range of people in the population. Th at’s the fi rst thing. Th e second thing is, because of their usually limited size, if you have between 3000 to 5000 patients who have been in randomised trials, and an adverse event happens one in 100,000 or one in 500,000, you may not be able to detect that. So, there are size limitations based on the rarity of events that may occur.

in determining whether a drug is benefi cial or not for patients. Th e two cannot be separated, as a decision such as this is a benefi t/risk decision, which is made between a patient and a physician. Strahlman argues that from a scientifi c point of view, effi cacy endpoints are established and safety parameters are prescribed, and the interpretation of the two must always be placed into consideration together, which forms the founda-tions of a benefi t/risk assessment.

“For example, an adverse event in this situation where a patient has a life-threatening illness is taken in a diff erent consideration than if it’s a medicine people would take every single day for the rest of their lives. So, if you’re an oncology patient and you take a medication and you have a severe stomach upset, but it’s part of your chemotherapy or part of your regimen to save your life, you may tolerate that. If you have to take a medicine every day for arthritis and you constantly have a stomach upset, that would be a very diff erent situation,” Strahlman explains.

She also notes comparative eff ectiveness research within the presentation as being a major part of how GSK operates – from the test tube to the clinical trial, the com-pany retains its emphasis on discerning how a medicine compares to other medicines that are currently available for patients. As she puts it: “Quite simply, comparative eff ectiveness of treatment means comparing two or more treatments for a given condition.

“In our view we do this all the time, even in the daily work of bringing medicines to patients and devel-oping drugs. Of course, comparative eff ectiveness research now has a larger context, especially in the current debate, in the US and all over the world. We support this when its intent and focus is to improve the health of patients. We believe these comparisons should mainly be medical, assessing the benefi ts of a medicine versus the safety risks it may have, and then comparing among two or more treatments to determine which one is best for the individual patient.

“Central to this is the health and wellbeing of the patient and the input of his or her healthcare provider. People want to know if their medicines work, and how well they work compared to others, and that’s really where we think comparative eff ectiveness research has its greatest value,” she explains.

Th e intent and focus on improving the health of patients is very much at the forefront of current debate, but there are oft en other focuses that are placed on comparative eff ectiveness research. Strahlman ex-plains how GSK implements this in regard to the medical and clinical aspects of comparing treatments for patients. Th ere is also comparative eff ectiveness research that examines cost – it being a major part of the analysis aft er the medical benefi t is determined.

Strahlman once again provides an example, this time focusing on Phenylketonuria, a condition oft en referred to as PKU and an enzyme defi ciency. “In the US all babies are screened for this,” she says. “It’s a very rare condition, but if you have it the babies universally die; it’s fatal. It happens very rarely, so it’s not an inexpensive thing to do this for the entire population. But if it’s caught within the fi rst few days of birth, it can be treated and the babies grow up to have completely normal lives.

“People want to know if their medicines work, and how well they work compared to other things, and that’s where comparative eff ectiveness research has its greatest value”



“So randomised clinical trials are absolutely essential to establishing the foundation of the science for the benefi t and the safety of a medicine. What it doesn’t address is the generalisation to the population and it doesn’t provide the capture for even more rare safety events. And that’s where real world data comes in. Th e observational data that companies and regulators use have to do with the adverse events reporting systems, capturing that information. So you do need both,” she explains.

Th is is certainly the case within the US. Insurers there now have access to patient data through electronic databases, allowing them to view information in regard to safety – a tool valued as extremely benefi -cial. It is the usage of these tools by pharma companies that contributes to the industry as a whole; drug fi rms have the expertise to analyse the information and make it available to others, not just for themselves.

Strahlman notes the tools GSK has developed specifi cally to en-hance the pharmacovigilance process: “Th e regulations require that we analyse information, and I’m very proud of the fact that GSK goes beyond what’s required and in terms of what the regulations say, be-cause we’re very interested in understanding the full range of benefi t and risk for our medicines,” she says.

Innovation“One way we look at things is something called

the online signal management, or the OSM tools. Th is is spontaneous data, adverse events reports that doctors and healthcare providers supply to regula-tory agencies in general for all medicines. In the past, this was done more on an ad-hoc basis, and collected into a large, stacked database by the FDA. GSK devel-oped an online signal management tool to proactively identify, capture and make connections in a more streamlined fashion, and integrate the information back into where it needed to belong in terms of which drugs were being accounted for.

“Th e system is so good that the FDA and the European Medicines Agency (EMEA) use it: the regulators now use the technology that GSK invented. As we were developing it, we brought them into the discussion so they had some input – it was a real partnership in terms of making that development – and then the company made the investment in the soft ware and the tool, which it now makes available to regulatory agen-cies all over the world that want to use it. We’re extremely proud of that, and that’s our most salient example.”

Strahlman explains GSK’s focus on CER as being “from test tube to the patient,” and what the benefi t and risk could be for the company’s medicines. In addition, online signal management is used to evaluate adverse events for drugs that are currently on the market. GSK has an innovative tool to support this called Safety Works – she notes its recent win at the 2009 Bio-IT Innovation Prize.

“Th is technology actually looks for benefi t and safety informa-tion mining electronic claims health records, and we’re piloting it in a number of dimensions,” she says. “We are working with a third-party vendor called ProSanos. GSK has invented this technology and devel-oped it along with ProSanos, and we’re making the licenses available to anyone who would like to use it – regulators, payers, academic institu-tions and so on. Th ere’s no profi t for GSK involved; it’s a break-even

Ellen Strahlman is Chief Medical Offi cer at GlaxoSmithKline. She joined GSK from Pfi zer Inc. where she was Vice President of Licensing and Worldwide Business Development.



organisations; the Innovative Medicines Inititative (IMI) sponsors the initiative. In Europe, GSK participates in various programs for its Innovative Medicines Initative, which it co-chairs with the EMEA, strengthening the monitoring of benefi t/risk medicines in the region. Th is is reliant on the range of technologies and innovative methods that enhance early detection and assessments of adverse reactions.

As a pharmacovigilance project, GSK will be partnering with the EMEA and other academic institutions that are interested in under-standing proactively the early detection of safety information in the company’s medicines. Th e IMI’s role is to provide the grant money: several billion euros have been set aside to create these public/private partnerships for the advancements of science and technology. Th e regulatory agencies will also be providing expertise at the initiative, whilst the academic centres and patient organisations will be providing staff and questions to advance the project.

GSK’s commitment to fi nding ways to solve the problems of unmet medical needs is the reason that attracted Strahlman to the company. Th e responsibility is not viewed as a chore but as an opportunity to ensure the safety of patients, as well as ensuring compliance is met within the various regulatory, medical and safety groups within the company. “What better way as a physician with all this experience to be able to contribute to a company, to try to be the medical voice, the voice of science for the patients, and also for their care, safety and wellbeing,” she says.

Swine fl uAlthough her tenure at the company has been for under a year,

Strahlman has certainly experienced the ups with the downs, as US healthcare policy becomes repeatedly under strain and attracts global attention. She explains the weeks so far of the H1N1 crisis have been tu-multuous, since the disease has reached a level 6 pandemic status from the World Health Organisation, but asserts that working for an organi-sation with the ability to provide a solution brings an overwhelming sense of satisfaction.

“GSK is a company that has medicines for fl u and also makes vac-cines. Th e response of the company to the WHO, to the CDC and to government is remarkable; we may be able to provide medications and services that would save millions of lives. It’s just a tremendous thing to be able to be a part of,” she concludes.

endeavor for us. But we think this is going to be a very valuable tool to further leverage observational data, by being able to look at claims data and electronic health records. It’s a very new invention.”

GSK also has another program molecular clinical safety intelli-gence system (MCSI), which is responsible for taking safety informa-tion for compounds that are already in development or on the market. It is then fed back to the company’s discovery organisation so they can choose which chemical entity to pursue. Th e process integrates toxicol-ogy as well as clinical data into that decision, which helps determine which molecules they will then pursue once the target is understood.

“We’re integrating safety information into the decision for making a drug – we’re very proud of this tool as well, we also share this with our academic partners in particular, and also anybody who wants to use it,” she says.

CollaborationGSK’s commitment to immersing itself in partnerships is demon-

strated through Project Protect, an initiative that shares technology for both public and private partnerships. It is made up of 12 phar-maceutical companies, four academic centres and also certain patent

“What better way as a physician with all this experience to be able to contribute to a company, to try to be the medical voice, the voice of science for the patients, and also for their care, safety and well being”



(UHPLC). UHPLC, due to greater efficiency and linear velocity, can reduce analysis time by as much as 5-10 fold. UHPLC is a viable short-term solution for labs that have already adopted this technology. However, UHPLC equipment can require a substantial capital expenditure, and labs that have not invested in these systems yet may be reluctant to do so in the current economic climate. Labs interested in the benefits and practical ap-plications of UHPLC can find more infor-mation at www.restek.com/uhplc.

While there are several short-term so-lutions available, these techniques are not always optimal over the long term. In order to reduce dependence on acetonitrile over the long term, labs must focus on develop-ing methods on columns that perform better with other solvents. While C18 columns are the most commonly used phase in drug de-velopment, other phases can give better per-formance with alternate mobile phases. For example, phenyl columns are more retentive and provide alternate selectivity when using methanol instead of acetonitrile. Restek has developed a Biphenyl phase, which is com-parable to C18 and other phenyl columns when used with acetonitrile, but provides much greater retention and selectivity than other phases when used with methanol. This versatility makes them ideal for method development with either solvent. For more information on the practical use of Biphenyl columns, visit www.restek.com/biphenyl.

Over the long term, method development strategies that optimise chromatographic column properties can make laboratories less vulnerable to solvent supply f luctua-tions. While short-term solutions can solve immediate needs, long-term strategies that invest in versatile column chemistries will be necessary in order to maintain develop-ment timelines and overall laboratory pro-ductivity.

Restek is committed to helping chro-matographers through trustworthy and sound technical advice. For help selecting and implementing a solvent-reducing strat-egy, contact us at 800-356-1688 ext. 4 or at [email protected].

formance and method parameters). Larger di-ameter columns require higher fl ow rates, and thus larger volumes of mobile phase, to reach the desired linear velocity. Reducing column inner diameter is a simple way to decrease the volume of acetonitrile used, while maintain-ing equivalent method performance.

Switching to an alter-nate solvent system is also often cited as a short-term solution. While viable, this fix is not as simple as it may appear. With alternate solvent systems, the chemical properties often differ and prior to implementation several points must be considered, including: mode of separa-tion, detector issues (such as UV cutoff) and analyte compatibility. Revalida-tion is usually necessary when an alternate solvent is used, thus, using smaller diameter columns is gen-erally the easiest, most immediate way to reduce acetonitrile use. Details on

implementing both strategies are available at www.restek.com/acetonitrile.

Another way to reduce solvent consump-tion is by implementing fast LC through ultra high-pressure liquid chromatography

In today’s economic climate, labora-tory productivity is an increasingly important key to bringing new drugs to market efficiently, and the current

acetonitrile shortage has created a significant challenge to productivity for many labs.

Acetonitrile is the most widely used organic solvent in the pharmaceutical industry, and suppliers have indi-cated that rationing and/or cost increases should be expected until at least the end of the year. While the duration of this shortage is unknown, it presents an opportunity to review labo-ratory practices and make strategic changes. This article presents both short-term solutions for reducing costs by cutting current consumption levels and long-term method develop-ment tactics for reducing overall dependence.

Using smaller columns is one of the most com-monly recommended ways to reduce acetonitrile consumption over the short term. By decreasing the internal diam-eter of the analytical column, a 52-80 percent reduction in solvent consumption can easily be achieved (values vary based on system per-

References1 M. Yang, S. Fazio, D. Munch, P. Drumm, J. Chromatogr. A. 1097 (2005) 124.

ASK THEEXPERT

Strategic choices to reduce acetonitrile dependence

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

By Richard Lake

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Bringing a new drug to market is one ofthe most expensive procedures in thebusiness world. As the costs of newdrug development currently weigh in

at approximately $500 million, late-stage failureis a disaster for the company’s finances.

Traditionally, the early-stage focus has beenon toxicity, with the question of efficacy relegat-ed to the later stages of the drug trials. This oldparadigm – toxicity first, formulation later – hasproven to be an enormous boondoggle, wastingthe time and money of companies that utilise it.Studying dose response translation only in thelate stages of phase III opens the door to disaster,as it is impossible to predict how a compoundmay impact the disease entity.

As a result, efficacy has finally become an in-tegral part of early-stage drug development.However, it is still the standard operating proce-dure to use different vehicles at different stages ofthe research process. This can lead to unpre-dictable dose responses in human subjects, some-times leading to catastrophic late-stage failures –precisely what the change in paradigm was de-signed to avoid.

The industry therefore needs to recognisethat an early-stage focus on the delivery system isnot only fiscally responsible, but experimentallyprudent. DMSO has long been the vehicle ofchoice for solubilising hydrophobic and hy-drophilic compounds. However, the use of DMSO

and the sole focus on solubility has led us downthe path of false assumption, leading to an in-creased potential for the dreaded late-stage failure.

Although it is possible to formulate virtuallyany drug into solubility in vitro; the focus mustshift to bioavailability in vivo. This requires theidentification of a medium ideal for both solubil-ity and delivery, ensuring that it can both be de-livered to the desired site and extracted to reachthe targeted points on the cells.

The key issue regarding drug vehicles is hy-drophilic versus hydrophobic properties. Deliveryvia bodily fluids demands that compounds be ini-tially hydrophilic, and this becomes a problem atthe cell membrane site, which is composed of hy-drophobic lipids.

A great deal of attentionhas therefore been focused onusing lipids to deliver drugs,such as liposomal vesicles.One key pitfall of these sys-tems is that they are not inert,and contain other materialsfor the upload and release ofthe payload drug.

A safer, natural and morecost-effective solution hasbeen found in Neowater. Aunique form of water struc-tured similarly to intracellularwater, Neowater is composed

of two hydrogen atoms and one oxygen atom –the same basic chemistry as bulk water. The keydifference is that the water molecules are organ-ised in clusters and therefore feature differentproperties. Its key feature is the clusters’ very largesurface area; this enhanced surface area isachieved by introducing nanoparticles to thewater via a proprietary process.

Neowater’s post-production composition isdistinct from regular water in that the CO2 con-centration is 10- to 100-fold higher, and the en-larged surface area, due to the nanoparticles,provides structure in the liquid phase. Thesecharacteristics result in an enhanced ability to dis-perse hydrophobic and hydrophilic compoundswhilst simultaneously heightening bioavailabili-ty and stability.

The Neowater vehicle facilitates delivery ofdrugs by leveraging the surface effect. This differ-entiates the Neowater system from any other de-livery system. However, as Neowater is a natural,general solution, it provides the same vehicle

structure for many drug compounds, and re-quires only minimal customisation.

Now that there is a shift toward examiningboth toxicity and efficacy during the first stage ofdrug development in order to avoid the lack ofpredictability in later stages, use of standardisedaqua-vehicle systems must be considered as thelogical next stage in the process.

By leveraging Neowater,companies can now streamlinethe drug development process,moving from in vitro develop-ment to in vivo delivery, andfrom early laboratory experi-ments to late-stage studies inhumans, with the same vehiclesystem. This eliminates the riskof needing to change the vehi-cle after all results are in, pre-venting the widely varyingreliability that can result inlate-stage failure, and the lossof significant capital. n

Utilising cutting-edgewater-based nanotechnology

By Ayelet Dilion-Mashiah


ASK THEEXPERT

“The industry needs torecognise that an early-stagefocus on the delivery systemis experimentally prudent”

Ayelet Dilion-Mashiah is the VP ofBusiness Development and CFO ofDo-Coop Technologies Ltd.

DO-COOP:13July 29/07/2009 14:41 Page 88

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CLINICALTRIALS

Boehringer Ingelheim’s John Smith tells NGP about the importance of accountability in the pharmaceutical industry and the responsibilities

for behaviour when a trial doesn’t go exactly to plan.

Clinical research has now standardised as a macro operation.Globalisation’s emergence since the breakdown of internationalborders in the 1950s has steadily increased, making it mandate forresearch to be conducted from various centres. However, this does

not come without its challenges. John Smith, VP of Clinical Research atBoehringer Ingelheim, explains the approach his company has used to combatthe challenges found in multi-centre trials.

“We have a structure of international research where our different operat-ing units have ownership of a particular trial allocated from our central clinicalresearch in Ingelheim – the corporate clinical research centre,” he explains. “Byan operating unit taking ownership, they are responsible for coordinating theoperations and allocation of the trial throughout the world. It is a challenge.

“Many trials, particularly in some of the larger indications – for example,cardiovascular and diabetes – you need to do over 30 or 40 operating units, eachwith slightly different regulatory requirements, and standard of care may be a lit-tle bit different in each of the countries.

“We want to be sure that we have a product that is investigated under abroad range of conditions, but that we can actually pool that data into a regis-tration file that can be used throughout the world. We do it in a different waythan other companies, and where most of the research is centralised out of a sin-gle unit we do this in a more decentralised approach, and it has worked for us.”

Emerging marketsAs Western Europe and North America continue to increase the regula-

tions surrounding clinical trials, Boehringer is approaching the emerging mar-kets, seizing upon the opportunity to gain clinical experience in countries thatwere not previously used for clinical research. However, Smith is aware of theneed for caution with such an approach.

He explains that in order to do so, Boehringer has set up regional centresin Eastern Europe for South America, Latin America and the Far East, and thoseregional centres then are responsible for coordinating the clinical trials in thoseareas. Through knowledge of local regulations and an understanding of quali-

Trials and tribulations

Smith ED:13July 29/7/09 14:05 Page 90

ty and monitoring, Smith explains that these centres are becoming increasing-ly important to the contribution of Boehringer’s clinical trials.

Boehringer is essentially a science-based company with a long-termR&D focus, ensuring a constant chain of products in the pipeline and imple-menting complete sustainability. But Smith expounds that the company isnot completely internally focused, ensuring that snap decisions cannotalter the overall company goal.

“We have made some selected partnerships with companies along thepath, and we continue to look for things that would complement the port-folio. We’re active in looking at licensing and co-development opportu-nities in most of our therapeutic areas, so it’s not that we have totallyclosed our eyes to outside opportunities, but clearly we’ve been success-ful with organic development internally,” says Smith.

“A good company should constantly reassess what their strategy isand make sure that it makes sense for the current strategic period. Clearly,there’s some great innovation going on in some smaller companies, biotechsfor instance, and we would be unwise to not keep our eyes open to those op-portunities as well, but it’s important to remember how we got to where weare now and making sure that we continue to make good decisions.”

AttritionBut despite carefully selected ‘good decisions’, there are still big chal-

lenges currently within clinical development. There is always a concernof the high attrition rate of compounds from development,which impacts all companies. Smith advises that as an in-dustry, pharma companies need to make better decisions ininvestments earlier.

“Our ability to absorb late-stage failures is past. As anindustry, we really need to be leaner and making better de-cisions. The trials are getting larger and larger, as well as ourability to get approvals – for example, traditionally, in car-diovascular disease you could get approvals for surrogateendpoints, but the tough job ahead of us is keeping the trialsize appropriate so that we can still continue to do work insome of the big areas like diabetes mellitus and cardiovas-cular disease.

“We’re still involved in fairly large programs in that re-gard with one of our compounds; so that is a concern andutilises resources that we could use in other therapeuticareas. We continue to be vigilant in drug safety for our com-pounds, both in development and post-marketing, and thatis an area where the industry has really come a long way inthe past decade. Just being able to service the portfolio of thecompany and try to make the best of what’s coming out ofour research pipeline. Obviously, we’ll have to make somechoices as to what will be developed, and if we can be moreefficient we’ll be able to develop more with the resourcesthat we have,” he says.

RiskTo combat attrition, it is not uncommon for drug firms to

severely focus on translational medicine, and the same is truefor Boehringer Ingelheim – it being selectively done in several

of the company’s therapeutic areas, specifically on the inflammatory diseasesside. Smith believes this to be one opportunity to try to mitigate some of theearly risk by translational or experimental medical approaches.

However, some risks cannot be mitigated. Boehringer recently sponsoredresearch into Profess, the prevention regimen for effectively avoiding secondstrokes. Designed to examine the effects of different prevention regimens on re-current stroke, including the Boehringer’s product Aggrenox versus clopidogreland Micardis versus placebo, the results were not brilliant in the company’sfavour. Yet despite this, Boehringer was able to use the strategic processes with-in the company to cope with the negative publicity, even transforming it andturning the criticism around.

“We do have responsibility to fully develop our products and we need to becareful about the choices that we make, but to realise the full potential ofthe products in the portfolio, sometimes it requires us to take a chance,”replies Smith. “This is particularly so if the prescribers see that there is anopportunity for the compound to potentially be useful for more patients,and that we have clinical proof of that efficacy. So as a result we have em-

barked on a fairly large clinical trial program in the past six to seven years.Unfortunately, in the case of Profess it didn’t quite work out as well as wewould have liked it to.

“But a trial that delivers a clear result shouldn’t be considered a negative trial.It informes the prescribers. It informs the medical community. In that regard, itis successful. We’ve learned a lot about our compounds in that exercise. Certainlyit would have been better if it had turned out the way that we had anticipated, butthat’s part of our responsibility as an industry – to continue investigating andmonitoring our products,” he says.

The products involved in that trial are still of clinical benefit to the patients,which they’re indicated, and will continue to be available. Smith explains that forthose teams involved in the trial, they are still in the process of understanding theresults and producing further analyses and publications, which are widely antic-ipated. A clinical trial of that size, incorporating a rich database, takes great mea-sures to understand the disease, specifically if they don’t turn out as they wereoriginally predicted to do so.

“The model of disease is not quite what we thought it was, and that gives usan opportunity to explore new hypotheses. So there’s still a lot of work to be doneon those datasets. They’re large and robust, and we still have more to learn,” ex-plains Smith.

At the other end of the scale, Boehringer’s BIBW2992 product recently re-ceived fast-tracked status by the US Food and Drug Administration, but Smithdoesn’t believe this to have impacted the company’s other programs. “Obviously,we’re happy that the FDA has given it that designation. Clearly, we now need to


“You learn when you graduate frommedical school that being a physician

and relieving suffering is one of the highest callings there is”


TrustSmith believes this to be not the only area in which clinical research can

build trust with the consumer. He advises that as a healthcare consumer and aprescribing physician himself, there can be no way that the American public canbe happy with the current treatment options. “For the past 50 years it was the

pharmaceutical industry that really bridged that gap be-tween where we are now and where we really need to bein treatment options for the patients in the future,whether that be in chronic diseases, malignancy, or invirtually any condition that we have under study. Sowhat we need to do is make sure that the public under-stands that we really are working with their best inter-ests in mind.

“You learn when you graduate from medicalschool that being a physician and relieving suffering isone of the highest callings there is, and the industryis part of that. The physicians get the tools for reliev-ing that suffering predominantly from the industry,and it’s unfortunate that that message really has notgotten across. But certainly we want to make surethat we are fully transparent in our clinical research,that we do ethical clinical research; I think that we do

that and that we get definitive answers to the clinical problems, and get theminto the public domain as quickly as we can.”

Smith concludes by looking to the future. President Obama’s healthcare re-form agenda has unveiled a determination to offer easier access to generics, ahuge part of pharmaceutical’s business. Boehringer – like other pharma compa-nies, being intrinsically linked to the industry in terms of intellectual property pro-tection – has a destined future, which to a certain extent is uncontrollable. But, asSmith has explained, the current portfolio of medicine does not meet the con-sumer’s need, and so there has to be a balance between access to affordable med-icines and intellectual property that allows the innovation to move forward.

“Hopefully, we don’t undo a system that has really produced a significantnumber of medical advances over the past few decades. We’ve stumbled a lit-tle bit as an industry – we’ve not had as many innovative approvals, and that’swith a footnote. There have been some really remarkable medications thathave come out in the last five to ten years. Given the amount of effort andspend by the industry we certainly could be doing better – making better de-cisions earlier in development and being more efficient so that we can bringmore innovative compounds forward.” �

do the work and deliver the data on a similarly accelerated timeframe. It’s veryexciting for us to really be branching into this therapeutic area. It’s an area whereBoehringer has been active on a research side for a while, but we reallyhaven’t realised success in the clinic. There is hope that this will reallylaunch our oncology portfolio, and clearly there’s a lot of competition foroncology in the US.

“We’ll have a big hill to climb to get that recognition of Boehringer as anoncology company, much like we have for respiratory or cardiovascular dis-eases outside the states. But hopefully if we execute well, we’ll be successfuland be able to take advantage of that designation by the FDA,” he says.

MergersIn light of recent partnerships, Boehringer’s former Chief Executive,

Alessandro Banchi, told Reuters that a merger and acquisition strategy is,“Not the way forward,” citing Pfizer as an example of this. But BoehringerIngelheim recently acquired Actimus Pharmaceuticals, taking a U-turn in pre-vious company activity.

“Not speaking necessarily for the company, but clearly the mega-mergermodel has run into some rocky ground in the US as wellas globally, and Boehringer has generally grown with or-ganic growth by doing a good part of our research anddevelopment internally, making selective partnershipswith companies for promising products that comple-ment our pipeline. But my sense is that we watch whatgoes on elsewhere in the industry, and Dr. Banchi wasquite wise in avoiding getting caught in those traps thatmaybe other companies have fallen into – that you cangrow by combination.

“Well, we’ve been able to successfully grow organi-cally. And while I don’t make those judgments going for-ward for the company, presumably our new leadership isalso looking externally and carefully watching the indus-try, making good decisions for the company in the longrun,” explains Smith.

Pharma companies have previously always been thefirst to be cast in a negative light by the public, but Smith believes this phase to bediminishing and communication to be increasing: “We are moving into an erawhere there is going to be more public availability of data, and that’s going to help.

“There is obviously going to be more transparency in the industry broadly,mostly in terms of clinical trial disclosure, and we’ve made some very good stridesin that regard. Results are now starting to be posted on websites such asClinicalTrials.gov. There will always be a difference between an academic re-sponse and a corporate response in terms of the timing and we’re going to bestudying the issue carefully – we need to meet our regulatory reporting require-ments, and that’s very important from a compliance standpoint.

“But academics will be free to review our data and offer their opinionon this. So we are moving into an era of more transparency and broader dis-cussion of the information; academics may in fact do combinations of clin-ical trial data from different sponsors, and that’s something that maybe wewouldn’t necessarily do, combine our data with that from another company.But that might happen with academics, and we will have to be proactive in try-ing to understand the findings, where they may differ from our conclusions, andhave a healthy debate in public,” he explains.


John Smith is VP ofClinical Research atBoehringer IngelheimPharmaceuticals, Inc. Hewas formerly theExecutive Director of theCardiovascular andMetabolic ClinicalOperations group at BIPI.Prior to moving to BI,Smith was Director ofCardiovascular Diseasesat Centocor, Inc.

“Given the amount of effortand spend by the

industry wecertainly could

be doing better – making better

decisions earlier”



ASK THEEXPERT

for changes in the research methodology and the use of certain proce-dures and tools, such as central monitoring and controlled sampling of source data (both authorised by the ICH E6 GCP Guideline, Section 5.18.3). Central monitoring – monitoring techniques from a remote monitoring resource – can be done successfully, especially when there is a solid understanding of the effi cacy and risks of a product. Con-trolled sampling of source data using statistical sampling methodology can be used for certain criteria and risk-based studies.

Th e introduction of risk identifi cation and triggered monitoring techniques are used to measure risk to subjects or risk to data, such as sampling methods, source data, query rates or even such qualita-tive risks as site communications. Triggered monitoring is a planned methodology for timing onsite monitoring and source data selection based on on-site workloads or other quality triggers.

Greater incorporation and/or access to electronic health record information – the use of EHR would help identify subjects qualifi ed for trials in any phase, abbreviate the process of moving data or complete entire studies using only electronic health records, such as a retrospec-tive examination of a control element of a previous study.

With existing large-scale phase IV studies, we can step away from a single use approach to study design and use the existing infrastructure or portions of it for additional, specifi c research. As such, the infra-structure is available not only for basic safety and exposure data, but also for focused investigations to meet either regulatory demand or strategic, post-marketing needs.

We believe this new model produces both the service delivery ef-fi ciency and cost advantages to do all.

The FDA, through the FDA Amendments Act of 2007, has new authority to require post-marketing studies, and the EMEA in 2005 made the submission of risk management plans manda-tory in the European Union.

New regulatory requirements mean that pharmaceutical compa-nies must allocate additional resources for large-scale patient safety studies that assess adverse events in real-world patient use. Getting a drug to registration, therefore, is becoming just a step along a long and winding road.

Meanwhile, payers are also demanding more health econom-ics and comparative outcomes data – the layer behind the safety and effi cacy data – to determine if one drug is better than others for a particular indication. Th e growing signifi cance of comparative eff ec-tiveness research opens the door to new types of phase IV trials and to a reconsideration of how clinical research is conducted to maximise service delivery.

At Quintiles, we believe in starting the conversation about late-phase study design during phase II. What will it take to get the work done eff ectively? What have we seen with other drugs in this class? What are the data requirements? With a choice of possible study de-signs, we can decide what truly distinguishes the evolution of phase IV, with a consideration of everything from global lifecycle benefi t-risk management to prospective and retrospective epidemiology studies. Th ese opportunities introduce a new view of large-scale phase IV stud-ies that can make the entire research eff ort more effi cient.

Th e thinking goes like this: if large-scale phase IV studies are going to be built, they also can be used cost-eff ectively as the backbone for any subset studies, since shared systems, sites, trained personnel, data management platforms and contracts are already in place. Such sub-studies could include comparative, side-by-side studies, treatment satisfaction studies, target biomarker investigations, burden of illness assessments, randomised clinical trials, patient-reported outcome studies, observational/non-interventional studies and registries and new indication studies.

Th is use of an existing phase IV research infrastructure also calls

Dipti Amin is the Senior Vice President and Global Head of Quintiles, Late Phase and Safety Services unit. Educated in the United Kingdom, Amin earned professional degrees through GKT Medical School of the University of London. She earned graduate degrees or certifi cates in medicine, surgery, family planning, obstetrics and gynecology, child health and clinical pharmacology. She is licensed to practice medicine in the US as well as the UK.

Sound responses to the changing late-phase gameSafety concerns in drug development, both from the public and regulators, have clearly intensifi ed – and there will be no let up. By Dipti Amin

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EXECUTIVEINTERVIEW

are processed in RBM’s CLIA-certifi ed lab using proprietary reagents and soft ware to give the most accurate and reproducible pro-tein measurements.

Second, multiplexing allows all of these assays to be processed from a 500 microlitre sample of serum or plasma, compared with single-plex platforms, such as ELISA, which would require 10 to 15 millilitres of sample. And fi nally, all samples are processed on an in-dustrialised, automated platform that enables the discovery of biomarker patterns made up of multiple proteins, many with small, yet re-producibly detected, changes.

Once a customer receives his or her initial data, is that the end?RM. No, and that’s another reason Discovery-MAP is so unique. While being a cost-eff ective way to measure 189 analytes, it’s also the fi rst step of a process that can yield a new custom panel tailored for each customer’s needs. Dis-coveryMAP includes biomarkers known to be important in the major disease indications for drug development. Once a pattern is discov-ered, we can convert those biomarkers into a new custom panel for high-throughput sample processing in clinical trials as a service from RBM or supplied to the customer as an opti-mised kit. And since all of our work is done on a clinically validated platform, our biomarker pattern discoveries are more easily applied throughout remaining clinical trials.

Are there any noteworthy success stories to date?RM. In fact, DiscoveryMAP has already been successfully used in the discovery of new diagnostic biomarker panels. RBM’s partnerships with Psynova Neurotech, Sato-ris, Inc., and leading academic researchers have yielded diagnostic biomarker patterns that have been validated with multi-site sample collections for applications such as neuropsychiatry, neurodegenerative disease,

nephrology, immunology and cardiology. RBM is also partnering with several phar-maceutical companies to develop companion diagnostic products. Looking forward, RBM is seeking additional collaborations to de-velop diagnostic and companion diagnostic applications based on patterns detected with DiscoveryMAP.

You mentioned the ‘RBM approach’ earlier. Can you tell us more about that?RM. Let’s use an example to illustrate the RBM approach. Th irty years ago, researchers found that blood cholesterol was a good marker for cardiovascular risk. Unfortunately, elevated cholesterol only identifi ed roughly 50 percent of the at-risk population. Eventually, research uncovered the role of lipoproteins (HDL and LDL), which showed better predictive value than cholesterol alone. Today, research has identifi ed 25-30 blood-based markers that pro-vide even better predictive value in assessing cardiovascular risk.

Th e problem is that measuring all of these markers has been prohibitively expensive and unreliable. Applying multiplexing technology, the RBM approach provides drug developers and researchers with a cost-eff ective and re-producible way to measure dozens of relevant clinical markers and pinpoint the biomarker patterns that are either directly involved in the disease process or are useful surrogate markers. When those patterns can be reliably measured, the effi ciency of drug development is accelerated while achieving greater effi cacy and safety.

What is DiscoveryMAP?Ralph McDade. DiscoveryMAP v 1.0 is Rules-Based Medicine’s (RBM) newest and most comprehensive biomarker assay, measuring 189 clinically relevant proteins from a single 500 microlitre sample of serum or plasma. Th e service off ers drug developers broad coverage of the most physiologically relevant pathways, providing key biological information, leads for further study and support for go/no-go decisions. Th e sheer number of important analytes in a single test increases the odds of identifying new protein biomarker patterns in almost any drug development or diagnostic discovery project.

What prompted the development of the service?RM. When it comes to identifying meaningful biomarker patterns, more data is better. Discov-eryMAP was designed in response to requests from our biopharma customers who recognised the value of combining our various human MAP services into a single comprehensive assay.

How does RBM’s DiscoveryMAP service compare to alternatives?RM. First, DiscoveryMAP utilises RBM’s pro-prietary multi-analyte profi ling (MAP) plat-form to quantify key blood-based biomarkers representing dozens of important biological pathways. With this platform, customers receive the most robust, quantitative data compared to any other available proteomic service or platform technology. All samples

Ralph McDade is Strategic Development Offi cer for Rules-Based Medicine and has held this post since the company’s inception in 2002. He was formerly Chief Scientifi c Offi cer for Luminex Corporation from 1996-2002, where he was closely involved with the development of xMAP technology. He received his PhD in Microbiology from the University of Texas Southwestern Medical School in 1980.

The future of biomarker assaysRalph McDade tells NGP why more is better when it comes to data used to identify meaningful biomaker patterns.

Ralph McDade

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The targets have been set. By refi ning the number of potential therapeutic targets analysed and de-creasing development times, R&D expenditures are expected to drop substantially. But how can the industry achieve this? Bjornsson advises that a number of industry challenges must fi rst be ad-dressed, from decreasing productivity to increas-

ing guarantee costs. “Th e most important issue aff ecting the industry, certainly from my

perspective, is attrition. Attrition is very high and varies from company to company, from therapeutic area to therapeutic area, but by and large it’s about 90 to 95 percent. What this means is that the likelihood for suc-

cess for any given new compound that comes into development is around fi ve to 10 percent, which is terrifi cally important to keep in mind.

“Th at’s the baseline where we are today. Anything we try to do to in-crease productivity means we are up against this, so the question is how can we become more productive? Productivity overall is the underlying solution to the challenges that we have today, and so the fundamental solution has to focus on a better understanding of compounds, a better understanding of the likelihood of success and how likely is it that that will become a positive outcome. We also need to ensure that safety issues are not going to become safety problems with our compounds.

“Similarly, it’s important to understand how the body handles the compounds, and when we do, then we can add up these diff erent char-

Wyeth’s Thorir Bjornsson talks to NGP about dealing with attrition, the fallout from the merger with Pfi zer, and what the future holds for the industry.

Changing times


RESEARCH

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“Th e merger will create an extremely

strong company capable of doing

things even Pfi zer wouldn’t necessarily have been able to do

on its own”

acteristics and if they all line up then our likelihood of success and thus productiv-ity will increase drastically. So productiv-ity is key: predicting the likelihood of what will happen and getting the desired outcome,” says Bjornsson.

Th e subject of increasing productiv-ity has always been high on the industry agenda. Historically, the approach to at-trition within the pharmaceutical indus-try has varied from company to company. Wyeth’s approach is steered by the recent works with metrics instituted by former President of Research, Robert Ruff alo, when he joined the company in 2002.

“We set productivity metrics, meaning you get so many compounds per year that are put on the development track and so many R&Ds per year,” he explains. “Wyeth very recently tuned down the number of compounds going into development to a lower number. For us, the issue is always quality, and the ability to have compounds better characterised and therefore likely to succeed.”

Global challengesWyeth’s R&D centres are situated across the globe, and despite

the obvious benefi ts of multinational operations, the challenges these centres face is increasing. Bjornsson notes the latest big trials and the problem of conducting them with the US and Western Europe, due to bigger regulatory requirements. Most major pharmaceutical companies now conduct many of their biggest trials in the emerging markets of China, India and the Far East, as well as in Eastern Europe where the number of hospitals is increasing.

“It brings increased challenges in terms of the monitoring of sites, due to some of their practices not being perhaps exactly the same as we are used to. Similarly, there are regulatory agencies in those countries that we have to work very closely with, and they become more cumbersome in a way. Th ere are now more regulatory agencies involved, rather than the FDA or the indi-vidual regulatory agencies previously used in individual European countries.

“Also, the number required for such trials to get to a statistical out-come has led to an increased number of patients. With diseases also ever-changing, the process becomes more complicated, and again requires a higher number of patients than before.”

When asked if the days of so-called ‘easy wins’ for the big drug com-panies have come to an end, Bjornsson agrees. “I’ve been in this industry for a while and looking back, I’m not sure I would call it the good old

days, but it is true, certainly for those where disease cases were easier to investigate. Studies were shorter; it would take a shorter time to see whether you had clinical eff ect or effi cacy, and you would see the results much sooner.

“Nowadays, studies are much more complicated, and chronic dis-eases, such as Alzheimer’s, are now of key interest to the major drug com-panies. Some of the immunological diseases – arthritis, lupus and so on – only require a year maximum to see a meaningful clinical outcome.”

MergersTh e recent pharma buyouts are sure to

only increase these challenges, as the bigger the operations, the bigger the challenges. Th e mergers – Pfi zer/Wyeth, Roche/Genentech, Merck/Schering-Plough – met with a mixed reaction within the industry. For example, John Lechleiter, CEO of Eli Lilly, was dismis-sive: “I think we’re seeing deals that are really driven more by weakness than what I would describe as strong strategic combinations. Th ey are predicated on synergies and mas-sive cost cutting that will improve short-term problems but fail to answer the long-term question of research productivity.” So how is the focus on R&D retained during the

merger and acquisition process to ensure Wyeth continues to combat these problems?

Bjornsson is quick to note that staff at Wyeth “are all extremely excited” about the planned acquisition. “It will create the world’s big-gest pharmaceutical company and will build on the strengths of both companies. When you add those together you have a hugely diverse pharmaceutical company that crosses all platforms: small molecules,

Thorir Bjornsson



“Th ere is one thing we should never lose sight of. If you look back over the history of drug development, many of the big successes – such

as cholesterol lowering and the oncology diseases, like the Philadelphia chromosome that led to Gleevec – in both

instances the scientifi c basis that led to those very successful therapies was due to medical knowl-

edge that had been accumulating over fi ve de-cades. So even though things are challenging

and diffi cult, things usually become better and better. We also have to be patient; it takes time for science to move on and become evidence-based.”

One of the more infamous challenges within the pharmaceutical industry was

the recent health scare regarding GSK’s Avandia. Bjornsson says that the pressure on

the pharmaceutical industry is too much, and that responsibility should be placed on the na-

tional agencies rather than leaving it to the drug fi rms to fi nd every disease cure.

“We are all in this together. We all die at some time. We all have diseases. It is too much to expect that only the pharmaceutical industry will identify the challenges in the societies we have. Th e pharmaceutical industry certainly will do its part and has done so in the past, but phar-maceutical development is an extremely costly endeavour, and we need to have the room to be able to identify the future breakthrough drugs that will eventually come.

“Most of us in the pharmaceutical industry feel that some of the criticism that has been leveled against the industry is just not well-found-ed. Th e industry, through its various organisations, has tried to make its case, but it takes a lot of eff ort and some other mechanisms might be utilised to explain the value that the pharmaceutical industry has to society,” he adds.

But times are changing. Th e Obama government in the US has un-veiled the preliminary details of its healthcare reform plan and is dis-playing a commitment to provide wider access to generics, which is sure to have an impact on the pharmaceutical industry.

“We’ve only seen the broad strokes of what the new administration is thinking about so far, and in many respects it isn’t that diff erent from what we saw in an administration one or two removed.

“From my own department we’re dealing with the earliest part of ge-neric development, and I don’t see it impacting on that a whole lot, except we all have to be doing better and applying greater science to identify the best possible way the drugs can benefi t those who need them and fi nd-ing value-added medicines through better tests. Personally, it challenges us to do better from a pharmaceutical perspective. I’m not quite certain how that will all play out.

“I fi rmly believe that when there are challenges we need to rise to them. With the challenges come new solutions and we will typically do better at the end of the day.”

biopharmaceuticals, vaccines and then subsequently also the new av-enues for development like nucleotides.

“Th at’s the view we have taken and we fully embrace the future as a part of Pfi zer. Th e merger will create an ex-tremely strong company capable of doing things even Pfi zer wouldn’t necessarily have been able to do on its own.

“Granted, over the years there have been various criticisms, questions or people rais-ing doubts about mergers and acquisitions in the pharmaceutical industry, and cer-tainly, if you go back 20 years, you see how many companies have just disappeared. Prediction is always on a case-by-case basis, but as for this particular one that is facing us, we’re extremely positive and focused on the future, and will be sure to make certain that people remain optimistic and focusing on the proj-ects they have to work on today, because that will only make the future better for the combined company.”

To combat any disruption that the merger may cause, Bjornsson notes Wyeth’s strategy of focusing at local levels. He advises that by keeping individuals focused on their individual projects, the amount of disruption will be kept to a minimum. Simultaneously on a higher level, plans are being formulated as to how the combined company will work.

Disease therapyBjornsson says it’s impossible to predict how the industry will de-

velop in the future. “I wish I had the answer to that. Th ere has been a lot of interest in bioinformatics to better understand biological pathways, to understand what pathways fi t best with a given disease or a given indica-tion. Similarly there has been a lot of interest both in the lay press and the scientifi c press about topics like personalised medicine.

“Th ose two are related. Our understanding of what causes a disease in one person or another may not be exactly the same on disease expres-sion, but it looks very, very similar. So looking to the future, probably more than two decades, one does fully anticipate and hope that with increased scientifi c understanding, better biology systems and increased user technology, we will eventually progress to be able to address the most signifi cant diseases,” he says.

Thorir Bjornsson is Vice President of Early Development and Clinical Pharmacology at Wyeth. He joined Wyeth in 2001 from Bristol-Myers Squibb, where he was Vice President of Clinical Pharmacology and Experimental Medicine.

“We are all in this together. It is too much to expect that only the pharmaceutical industry will identify the challenges in the societies we have”


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BRINGING DRUG DISCOVERY INTO FOCUS

RESEARCH

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It is Anne Phillips’s background as a physician that led her to a patient orientated area of pharmaceuticals. As Medicine De-velopment Leader at GlaxoSmithKline, Phillips works at the oncology group within Research and Development, overseeing the development of any one particular asset from the earlier

preclinical development to managing it in diff erent markets around the world.

“I am fortunate enough to oversee the aspects of the development of Eltrombopag, which is a drug that works to increase platelet count in patients who have low platelets and are predisposed to bleeding as a result of that. We currently are indicated for ITP in the US, and the job is really fantastic because it brings together all of the experience that I’ve had in pharma to date,” she explains.

So how has the transition from doctor to her recent appointment at GSK aff ected her management approach? Phillips advises that her role involves a multitude of management and leadership aspects, as she over-sees a huge number of individual projects.

“As a physician I have this very strong desire to add value to the lives of patients. It doesn’t really matter what role I’ve had, that’s always been core to what’s important to me. Th is role is fantastic because the drug is very eff ective at increasing platelet count, and the patients are really at risk of serious bleeding, so there’s a huge impact,” she continues. “In my

view, ultimately, it all moves towards making a very important drug of great value, and available to patients who need it.”

Clinical challengesPhillips entry into the pharma industry,

specifi cally drug discovery, has come at a time of challenges. Modern drug delivery is now very diff erent to the way it once was. She notes that even when proof of concept has been shown within a drug, conducting clini-cal trials themselves is a huge challenge to undertake in a global environment. “You have to make sure that you conduct the study in the

right patients at the right dose and design the correct study. Sometimes the logistics in the global environment of getting subjects enrolled in the study can, in and of itself, be a big challenge.

“Th ere are clear regulatory challenges; diff erences across the globe, once again, in regulatory requirements and what is needed there. Th e safety hurdle that we’re seeing for drug development is now unprece-dented globally. Th at is a huge challenge – it’s a very risk-averse environ-ment. You have to anticipate those potential challenges to any drug, and then once you do get approval, what the label looks like and how you can get that drug to the patients themselves. Th ere’s the payer component:

GSK’s Anne Phillips offers a clearer picture on transparency, creating value for patients, and the challenges of conducting clinical trials in a global marketplace.

“As a physician I have this very strong desire to add

value to the lives of patients. It doesn’t really matter

what role I’ve had, that’s always been core to what’s

important to me”



“So this Centre of Excel-lence for External Drug Discovery is a very small group of individuals that has gone out over the past number of years to work with biotechs around the world, creat-ing alliances with them to allow the biotechs who really have that very strong expertise in certain areas to develop their own pipelines in alliance with GSK.

“Th e idea is that we don’t get in and interfere and take over their assets they develop in a biotech way with their ex-pertise to a proof of concept point, and at that junc-ture GSK can option that molecule. It’s a risk-sharing model, and it’s one where the biotech is incentivised by milestone payments along the way. So it’s a diff erent kind of externalisation of drug discovery, and it’s a way to supplement what is going on internally. Now what we’re seeing is more and more of this activity – in the diff erent centres of excellence for drug discovery they have an increasing proportion of their work – they’re con-tinuing those programs that they’re excellent at internally.

“However, they’re also looking outside for individual assets that they might bring into GSK; in a bigger sense GSK is looking for smaller companies that we might want to acquire. Sirtris was an excellent ex-ample of a small biotech company that GSK recently purchased. Th ere are a number of diff erent innovative business models that we’re using and looking at around the globe to really supplement the core R&D work that’s ongoing. Importantly, there’s a diversifi cation of the way that we are going to feed that R&D pipeline.”

Personalised goalPhillips’ own ultimate goal is not self-serving; her vision is to bring

medicines of value to patients, and for her, 2009 is a year to be look-

you can get a drug approved, but if you can’t get the payers to pay for it, the patients can’t get the drug.

“So that, again, is a huge challenge, and there is such a diversity of payers and requirements and what they need and don’t need from any particular drug. Th at’s a new and more important challenge than ever right now. And you need to be able to solve that in order to get the drug available for patients who need it,” explains Phillips.

As Medicine Development Leader, Phillips has a small core team that works alongside her on an ongoing basis, with a number of broader teams that work to deliver the diff erent aspects that feed into the core team. She has no direct reports and no direct managerial control over individuals, but does have control and input into annual bonuses. GSK’s structure ensures that its individuals report up through their lines, determining ef-fi ciency within the diff erent processes of the drug’s development.

“I can choose the individuals to work on a particular project. You have to have an incredible team spirit and an incredible commitment to development of an asset to run this kind of structure well,” she says.

Global challengesGSK’s R&D centres are located around the globe, and so multi-site

operations bring an even bigger possibility of challenges. “To have that available is fantastic,” says Phillips. “You can get diversity of subjects enrolled in the clinical trial. Diversity in terms of input and expertise into how you develop an asset the best way can be incredibly benefi cial. Th ere are many of patients around the world that you can access and get the drug to, so there are a lot of advantages. Time zones are oft en a problem – working on the east coast of the US and working with Japan and Australia makes both timing and language an issue.

“Very oft en in clinical trials some of the scales that we use may be validated in one language, but may be interpreted quite diff erently in another. As we have to have more and more health outcome measures, you have to make sure that what is important to somebody in the US is important to somebody in the country in which you’re conducting the clinical trial. Standards of medical care can be very diff erent in diff erent countries. Certain procedures may be routine in one country and not acceptable in another country.

“So there are a multitude of diff erences involved during regulatory approvals – you can get a trial up and running quite quickly in certain countries; it can take 10 months to get a study started in other countries. Th ere are a lot of huge diff erences, but in the end to get the diversity of subjects into a clinical trial outweighs those challenges.”

Being part of a successful global brand does bring innate weight and advantages, however. Th e size of the company, number of contacts and knowing individuals in diff erent parts of the world are just some of the benefi ts that Phillips points out. She notes the way in which other global companies operate, working through CROs to enjoy similar benefi ts.

How has the current pharma climate of major drug mergers and buyouts has aff ected GSK and does it add to their list of challenges? GSK’s long-term strategy has been to install a very strong R&D group. Over a number of years, the company has been supplementing very strong scientifi c internal discovery engines with more externalisation, which has been conducted many ways. Phillips notes CEEDD as an ex-ample of this.

“With Avandia and with any

drug, the key was and is to be transparent. If you have

data, get it out there, let people know it, understand it, query

it, and that is what we had done”



ous in continuously improving and becoming leaner and focused. “Ever since I’ve been in the industry I have seen that very clear drive

towards becoming very lean, very eff ective and maintaining the highest possible standards.”

Safety scareTh e recent safety scare surrounding Avandia produced quite a wide

impact throughout the industry. From Phillips’ perspective, the han-dling of the situation was nothing other than successful. She remarks on the transparency: “Th e meta-analyses that GSK had done had been given to the regulatory authorities many months before this became a big media issue, so there was certainly transparency there. Th e data had also been in the public domain on the clinical trials register, so it also had been available for a long period of time. What happened around Avandia became larger than life.

“It became a very big media issue, and patients reading the newspa-pers, listening to the television or listening to the radio became fright-ened, and it was a diffi cult situation. I’m not sure that there could have been any more transparency because science was out there, but the all-important relationship between a physician and their patient is where we had some diffi culty here.

“Th at relationship between physician and patient, for all medicines, is pivotal. It is unfortunate when any situation becomes a big media issue and people watching the media make their own personal decisions based on what they’re seeing rather than making sure they get the advice from their healthcare provider.”

Phillips explains how GSK worked hard to place the science in the public domain at that time, and published all of the data, but the dif-fi culty remained with the attractiveness of a sound bite, which can be digested and incorporated. Th e scientifi c explanation isn’t as attractive to the media, and is therefore a diffi cult message to get across. Th e key, for Phillips, is to, “Continuously make sure that the science is in the public domain, is available to those who can understand it, digest it and then transmit it to patients and to the public in an appropriate way.

“With Avandia and with any drug, the key was and is to be transpar-ent. If you have data, get it out there, let people know it, understand it,

query it, and that is what we had done. We had done that with the regulators. We had been in constant communication.

“It’s what is expected. As with Avandia, pub-lication is critically important, not just to try to generate information, but it has to get into the public domain. Th at can be done by registers, publishing in journals, presenting at scientifi c conferences – there are diff erent venues for doing this. But the key is to be very open and transpar-ent about the scientifi c data.

“Th e lessons learned was around the impact of a sound bite or what an interpretation of data can mean. You have to be rigorous about the science, you have to be rigorous about the safety profi le of every drug, and you have to be always transparent about it.”

ing backwards, not forwards, in terms of revolutionary therapies.

“Th ere’s a change in the focus now, and we are beginning to take a look backwards, in a sense: we work from the patient to what we’re actually developing. It’s the end-user who will be changing the focus as to how drugs are going to be developed.

“What are the unmet medical needs? What is of real

value to patients, to payers? What is that need, and then how

do we develop molecules that will go there? Whereas previously we

would focus a lot on developing as many molecules as we could. Th ere was

also a lot of ‘me toos’. Th e fast followers didn’t have to be terribly diff erentiated.

“It’s not going to be acceptable going forward. Each new medicine is going to have to demonstrate clear

value before it will be reimbursed and before patients will be able to get access to them. So we’re going to have to start thinking very early on, ‘What are the characteristics that are going to make this medicine

add that incremental value?’ Just being a diff erent new chemical entity doesn’t necessarily translate to value for the patient,” says Phillips.

She explains that forcing these changes also bring challenges, such as the death of blockbuster drugs and technological advances, as well as being able to meet individual needs of particular patients. She also notes the importance of generic competition: “If you have a patient with a medical condition, and you have three to fi ve genericised medicines; in order to rationalise paying for a new drug, you have to have value over the generic medicines in order to justify paying a premium price for new entry into a particular therapeutic market.”

Th e pharmaceutical industry’s recent race towards a super-fi t manufacturing and supply chain was something blueprinted by the auto-motive and aerospace industry around 25 years ago, so why has it taken so long to get to this method? Phillips is quick to add that developing a drug has always been expensive – one out of 10 molecules successfully becomes a drug – and the process has always been diffi cult.

“It’s even more diffi cult now,” she says. “My background isn’t in manufacturing, so I can’t speak specifi cs about what has happened in the past, what’s happening in the current environment or what is happening going forward, but certainly our manufacturing processes at GSK have always been extremely rigorous. Not only because they have to be when creating medicines, but very rigor- Anne Phillips



understanding the complexity of living systems and designing biological systems to meet healthcare and environmental needs.

Exploration, querying and visualisation of interacting entities are necessary steps in designing biological systems. Th e next step is to un-derstand and predict their dynamics through mathematical modelling and simulation. Genostar’s Genetic Network Analyzer (GNA) soft ware was designed to build, simulate and validate molecular regulatory net-work models. It relies on qualitative modeling technology developed by the INRIA and off ers an excellent balance between data requirements and predictive capabilities. A GNA model can be used to predict the con-centration of gene products such as mRNA and thus predict the level of gene expression, which can then be compared with experimental results for validation or refi nement.

GNA has been validated in numerous modelling projects. D. Ropers et al. describe and simulate the interaction network involved in the carbon starvation stress of E. coli (2006, BioSystems, 84(2):124-152). GNA has been used by many research laboratories worldwide for modelling and understanding phenomena and systems, including the biochemical network underlying quorum sensing in human-pathogenic Pseudomonas aeruginosa (A. Usseglio Viretta, M. Fussenegger, 2004, Biotechnology Progress, 20(3):670-678).

Genostar provides bioinformatics tools for genomic and proteic analysis, and for modelling and simulation of molecular interaction net-works. We participate in COBIOS, a European-funded project that aims to develop well-characterised, engineered, synthetic biology devices for therapeutic use, in particular for timely insulin delivery. Th e COBIOS project brings together biologists, mathematicians and bioinformati-cians from academic institutions and private industry in four European countries and the United States to meet the goal of designing, verifying and validating synthetic genetic networks. Future breakthroughs in syn-thetic biology will come from such multidisciplinary associations.

The engineering challenge of synthetic biologyBioinformatics and computational modelling are essential to meeting the challenges and potential of synthetic biology. A new generation of computer-aided design tools for validation of synthetic networks is rapidly emerging. By François Rechenmann and Adrienne Craig-Kennard

Synthetic biology brings the life sciences together with engi-neering to design and optimise cellular behavior. By building biological systems from component parts, synthetic biology is expected to produce proteins and molecules with specifi cally engineered functions by designing or reprogramming genetic

circuits and metabolic networks. Th e market potential for products result-ing from synthetic biology technology is high and the impact on healthcare will be signifi cant. Simpler, lower-cost production of biopharmaceuticals, novel drug delivery systems and eff ective therapies for chronic illnesses are examples. Synthetic biology also provides promising solutions to environ-mental problems such as sustainable, economical production of chemicals and biofuels, and bioremediation using engineered micro-organisms.

Th e engineering challenge of synthetic biology lies in the design of genetic networks that will rewire cells to produce the expected molecules in a timely way. Modelling and simulating the synthetic network prior to its implementation is a critical step made possible by bioinformatics, which has become the indispensable computer-aided design tool of synthetic biol-ogy. In order to perform meaningful systems level analyses, it is necessary to access and connect diverse data on the networks of interacting entities involved. Data integration becomes essential for dealing with the complex-ity of these networks and extracting useful knowledge quickly. Integrated soft ware and databases that connect and structure information on the links between genes, proteins and biochemical data – compounds, reactions and pathways – enable researchers to productively analyse their data.

Genostar’s MicroB database and Metabolic Pathway Builder (MPB) soft ware integrate powerful, user-friendly methods for eff ective navi-gation, querying and analysis of genomic, proteic and metabolic data. With these tools, researchers can also easily visualise their experimen-tal data. Visual representation off ers a real advantage to the biologist: for example, gene expression data sets may be readily mapped onto the metabolic pathways, allowing for quick and effi cient diff erential analysis. Collaboration and partnerships are vital to progress in this fi eld. MicroB was developed in partnership with the Swiss Institute of Bioinformatics (SIB) and the French National Institute for Research in Computer Sci-ence and Control (INRIA). Partnerships between industry and academia as well as between industries will continue to drive progress towards

François Rechenmann is Scientifi c Advisor and co-founder of Genostar. Rechenmann has 30 years of experience in the design of knowledge-based software and databases for the understanding of biological systems and led Genostar’s technology platform development. A Senior Research Director with the INRIA, he holds a doctorate from the Institut National Polytechnique de Grenoble.

Adrienne Craig-Kennard is Chief Operating Offi cer of Genostar. She has over 10 years of experience in the agrochemical and pharmaceutical industries, as well as in international consulting. She holds a Bachelor of Science degree in chemistry from the University of California at Berkeley and an MBA from the Grenoble Ecole de Management in France.

INDUSTRYINSIGHT

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EXECUTIVEINTERVIEW

Starting at

tive dose. This issue has been the subject ofconsiderable debate over the past 10 years.

Pharmaceutical companies have collabo-rated twice to investigate the representativenessof a microdose to a pharmacologic dose. Theseare the so-called CREAM and EUMAPP stud-ies (www.eumappp.com). At Xceleron, we alsobenefit from our experience from proprietaryclient investigations.

Of the results in the public domain, the mi-crodose intravenous pharmacokinetics is al-most 100 percent representative of that seen ata therapeutic dose. For orally administereddrugs, the PK of about 79 percent of the drugsgiven as a microdose are within a factor of ±2of the therapeutic dose (a widely accepted cri-terion used in allometric scaling).

Why is microdose data for a minority of com-pounds not representative of the pharmaco-logically active dose?

approach that could allow pharmaceutical re-searchers to study sub-therapeutic doses of adrug in humans.

The EMEA in Europe and the FDA in the USboth define a microdose as 100th of the predictedpharmacologic dose or 100 μg, whichever is small-er. These small doses are considered inherently saferthan pharmacologically active doses. Therefore, theregulatory authorities are comfortable with a muchreduced safety toxicology package. This allows thedrug candidate to be administered to human volun-teers earlier, faster and with less expenditure com-pared to a phase I clinical study.

In order for a microdose approach to be useful,the results from such studies must be repre-sentative of the situation under pharmaco-logically active doses. Can you comment? MB. Microdose studies must yield results thatcan be relied upon to represent a similar inves-tigation conducted at a pharmacologically ac-

What is a microdose study?Michael Butler. A microdose study is a human clin-ical study that is typically conducted very early in thedevelopment of a new drug and which is definedby the dose administered. Microdose studies areideally conducted just before or in parallel withpreclinical and CMC development. A well-de-signed microdose study will yield PK and ADMEdata on a promising drug lead or candidate series.Because of their role in very early clinical devel-opment, microdose studies are also known asphase 0 clinical studies.

What is the regulatory environment for mi-crodose studies?MB. As part of the FDA’s Critical Path Initiativeto streamline drug development and improvethe understanding of drugs early in the clinicalprocess, the Agency has produced guidance on‘Exploratory Investigational New DrugStudies’. Microdose studies are included as one

Michael Butler looks at the value a microdose study adds to a drugdevelopment programme.

phase zero

Xceleron ED:13July 29/7/09 14:11 Page 106

MB. One reason we see isthat certain enzyme systems

might be saturated at higherdoses, thus leading to differ-

ences between a microdose and apharmacologically active dose.

How are the low levels of drug in microdosestudies measured? MB. The bioanalytical technologies most oftenused to measure such low doses of drug are accel-erator mass spectrometry (AMS) and LC-MS/MS. The choice of instrumentation isdetermined by the need for sensitivity to ensurethat the drug is measured over a suitably long pe-riod of time in all of the tissues and compart-ments of interest.

Xceleron provides its customers with themore sensitive AMS option. Under the right cir-cumstances, we can quantify in the femto to at-togram range (10-15 to 10-18 g) or typically three tofour orders of magnitude more sensitive than LC-MS/MS. It’s important to use a fit-for-purposeapproach. If a microdose study is deemed appro-priate, then the next question to be asked is whichbioanalytical approach is better.

How does a microdose study add value to adrug development programme?MB. There are situations in which such studiesmake perfect sense and situations in which theyadd no value. We have observed changes overtime in the way that pharmaceutical companiesuse microdose studies and differences betweenlarge and small companies.

We have conducted microdosing studies fordrug candidate selection, on drugs which haveconflicting animal ADME/PK data, on drugs witha novel mechanism of action for which there maybe no human precedent, to investigate drug/druginteractions and to enrich PET imaging studies.

Smaller companies often use microdosing toinvestigate individual compounds for better deci-sion making and to add value for potential fi-

nancing opportunities. Larger companies tend tostudy multiple compounds concurrently. Whenthe ADME/PK of multiple compounds is studiedit is often for two reasons: as a screen of multiplepre-clinical candidates; and to expedite the devel-opment of back-up compounds where the leadhas performed poorly in phase I.

We can also gather much more than simplePK/ADME data from a microdose study. In oneXceleron study, a respiratory anti-infective wasadministered orally and intravenously. Blood andexcreta were collected, lung biopsies were takenand a bronchoalveolar lavage (BAL) was per-formed. We demonstrated that the IV pharma-cokinetics were very favorable. Conversely, the oralkinetics showed that the drug was poorly absorbedand underwent extensive first pass metabolism. Wealso demonstrated that the drug accumulated in

the lung tissue plus the alveolar macrophages.Therefore, once in circulation, this drug candi-date was likely to provide very effective exposure.Since an oral formulation was less likely to be ef-fective, the inhalation route was prioritised. Themicrodose data provided invaluable insight to en-able informed choices to be made early. You mayhear others refer to this as de-risking downstreamdrug development.

What do you see in the future of microdosing?MB. In addition to the applications I’ve alreadymentioned, I’d expect to see more studies in sen-sitive populations such as pediatrics, more stud-ies looking beyond the systemic circulation as wedid with BAL, and more imaging.

You mentioned that you use a 14C microtracerto measure drug levels from microdose stud-ies. What are its other uses?MB. There is still confusion around the terms mi-

crotracer and microdose. Microtracer in ourworld is a small amount of 14C labelled drug andit’s used it in all of the studies in which AMS is thebioanalytical method of choice. A microdosestudy is just one of many that can use a 14C mi-crotracer.

Just as we’ve seen the utility of microdosestudies grow with time, we’ve witnessed growthin the use of the 14C microtracer generally. Wehave used a 14C microtracer in microdosing,IV/PK absolute bioavailability, MIST solution,drug/drug interactions, regulatory ADME,straight bioanalytical and investigations of pro-teins. Our microtracer regulatory ADME studieshave been submitted in the filings of six market-ed drugs. That aside, phase I is probably the areaof greatest interest for us because of the opportu-nity to gain vital information within existing safe-

ty studies at small incremental expense. This isespecially the case for absolute bioavailability andMIST elucidation. In the case of the former, com-plexity warrants additional internal standard ap-proaches to ensure that the quantitativebioanalytical data is representative

I’d like to finish on a point that is importantto me and others at Xceleron. We recognise that14C AMS studies and microdose studies in partic-ular may not always be the answer. We must takea fit-for-purpose approach in offering our clientsa drug development solution. However, under theright circumstances, a microdose study can pro-vide quite unique clinical insight at an early stage.The cost-effectiveness of this approach should notbe underestimated. �


Michael Butler is CEO of Xceleron. He has 20 years ofexperience in science-driven businesses in Europe, USand Asia. Butler has been President, Scientific Operationsand Chief Scientific Officer with Aptuit, Group VicePresident at MDS-PS, and Group Director, BusinessDevelopment for Huntingdon Life Sciences.

“A well-designed microdose study will yield PK and ADME

data on a promising drug lead or candidate series”

MICHAEL BUTLER

Xceleron ED:13July 29/7/09 15:35 Page 107

As the Chief Commercial Of-fi cer, Hoyes faces the everyday responsibilities for sales and marketing within the US man-

aged organisation. Included within this is also EMD Serono’s commercial excellence group, which incorporates sales training, market-ing excellence and sales excellence, as well as the various support functions for those three

commercial pillars, such as market research, analytics and business intelligence.

But the arena of sales and marketing has not always been such a structured business. Hoyes explains that in recent years there has been a tremendous change in the pharmaceu-tical sales model, mostly due to the industry shift from an emphasis in primary care to speciality.

MARKETING

Sales model“Th at shift has occurred for two reasons,”

he explains. “Th e fi rst being very pragmatic, there’s been a lot of the large primary care blockbuster-type brands going off patent and on the fl ipside, a lot of the new innovation that’s been in pharmaceuticals has come into speciality space, such as in oncology and neu-rology, for instance. Because of that, there’s

Central to the success of global drug fi rms is the need for transparency and individual accountability. EMD Serono’s Jim Hoyes explains why these

characteristics play a crucial role in sales force effectiveness.

PERSONAL BESTPERSONAL BEST


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provide support for our patients to make sure they get the best outcome from the therapies that they’re on,” he explains.

As trends are changing, the sale forces must adapt quickly, which is not necessar-ily straightforward or an easy task. Hoyes explains a main shift in recent trends to have been the integration of EMD Serono’s care ac-count managers into the sales and marketing mix. “Th ey need to work as a team to provide the best solutions to large clinics and physician practices,” he says.

“One of the main drivers that physicians look at aft er they make the right diagnosis and as they look for the right therapeutic agent is the managed care coverage. Th ey don’t want to write endless prescriptions that then end up getting called back or any other form of a hassle factor about coverage. We focus very much on driving high access levels for our pharmaceu-ticals and then making sure that as we execute that at the physician offi ce level, our sales, our marketing and our managed care teams are all seamlessly working together.”

FutureHoyes believes there is a promising future

for sales force eff ectiveness, both within the industry and EMD Serono itself. Th e result of the rising trend of individual account-ability and transparency to create a more tar-geted form of sales force will create motivation amidst those individuals who understand the need for such a change. “Th ey like to see the cause and eff ect of their work, and in the older models where there are four and fi ve reps call-

ing on a specifi c physician, again it was hard to see who was doing what. So accountability will be increasing.

“Th e quality of the call will need to go up, and we’ll need to fi nd ways to measure that beyond just tracking prescription data. Th ere’s potential ways. Do we need to be

explains, and ensuring patients have the sup-port they need to navigate what can be a com-plicated reimbursement journey.

“We really need to understand the entire patient spectrum. What’s the role of managed care in a patient’s treatment paradigm? How can we help ensure that patients get reim-bursed, or make sure that if there’s a device as-sociated with a product that the two get linked together?

“And so that’s where we have a very close interface in all of our therapeutic areas that we sell in with patient call centres, so we can help offi ces align those activities and make

sure that if a prescription is written that it gets reimbursed and that there’s nursing support provided, whether that’s on simple things like injection training, as well as reconstituting the product if they have questions about contin-ued therapy. So none of this gets in the way of the physician-patient relationship, but it helps

been a move away from the mega sales forces where you had layered or mirror images of sales forces on top of each other driving call frequency, now to a shift towards call quality and driving value for the patient.

“For us at EMD Serono, that is the model we’ve had historically because we’ve always been in the speciality space, so we spend a lot of resources on training. Th at’s becoming more important – not just product knowledge training, but training to uncover customer needs. Our concern is to really understand how physicians interact with their patients in their practice. What’s the patient fl ow? What’s on the patient minds? What are the physicians really trying to accomplish in their prescribing decisions? Th at adds a lot of value to the innovative pharmaceuticals that we bring to the market as well.

“Th e other change is that there has been a move to more compliance training for sales forces in the industry, both from the chang-ing landscape of the Research and Manufac-turers of America Pharmaceutical guidelines (PhRMA) that our sales forces in the industry follow, as well as internal company policies regarding higher levels of compliance. So that’s an integral part of companies’ sales training programs, and in speciality spaces and for companies like us. You’re getting a higher level of sales reps certifi ed through a formalised training process that leads to a certifi cation that allows you to move from a Level 1 to a Level 2, and you see that play out with legislation at the state level.”

Th e District of Columbia now enforces a law that demands sales professionals to be cer-tifi ed before calling on healthcare profession-als in Washington, DC. A number of states, including Massachusetts most recently, also have legislation pending requiring sales reps to be certifi ed to sell in their fi eld. Th e result of this has produced focused, smaller sales forces with a clear direction, and a movement away from mirrored sales forces. Th is also creates better accountability, as it demands less reps calling on a certain physician and there is greater awareness of who’s driving the prescription activity.

Customer careAnother new signifi cant focus for the

industry today is on the payer system, Hoyes

“To sell eff ectively with innovative products, especially considering what’s going on in overall healthcare reform, is going to heighten the value

of a well-trained sales rep to a company”

Jim Hoyes



Conclusion“Th e key of the speciality space is growing

in importance, and that’s where the innovation is going to lie in the future from a healthcare perspective,” says Hoyes. “To sell eff ectively with innovative products, especially consider-ing what’s going on in the overall healthcare reform, is going to heighten the value of a well-trained sales rep to a company. It’s going to be critical that you have a strong sales force to be successful, and that doesn’t mean the old days of having a countless number of reps.

“It’s an individual basis, and you’re going to have to have stars in your sales organisation – they’re going to have to be performers and they’re going to be held accountable for suc-cess in a very challenging environment. But sales forces enjoy that challenge and therefore they’ll continue to thrive.”

which has proved critical in drawing together the various means of sales, marketing and managed care, and bringing in the results.

“We have to align patients, prescribers and payers into the story, so that’s something we’re focused on, and the other is really making sure and measuring that our sales forces are improving year over year and are ranked one or two in their therapeutic classes in terms of eff ectiveness. We have a scorecard whereby we use a number of metrics to track that – we want to look at it longitudinally, so again we can see the continued progress upwards and a number one or number two ranking due to the work in pursing leader-ship in our therapeutic areas, and not just the brand. Th at includes the people that we have in the direct face of the customer and that’s usually our sales force.

doing, for instance, 360º reviews with key prescribers to see what the reputation of the company is, how high the service level is, and then how useful our products are for them?

“Another future trend will be the rise of companies assessing their core competencies, for instance the ability to launch products eff ectively. If the window of exclusivity that you have is shrinking for a variety of factors, you’re going to need to get out of the gates very quickly, so launch experience is going to be very important. On the other hand, you may see companies start to use external sales forces – contract-selling organisations – as products hit the more mature parts of their lifecycle. So greater fl exibility, and a real evaluation of what is the critical success factor for your own company and your own product portfolio that you need to maximise sales, will become more signifi cant than a one-size-fi ts-all approach that was used in the past,” says Hoyes.

He attributes the success of EMD Se-rono’s sales teams to its teamwork approach,

James Hoyes is the Chief Commercial Offi cer at EMD Serono, Inc., responsible for business operations in the company’s key therapeutic areas of neurology and endocrinology, as well as managed care and sales and marketing operations.

“Th ere has certainly been a move to more compliance training for sales forces in the industry, both from the changing landscape of the pharma guidelines that our sales forces in the industry follow, as well as internal company policies”


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Mike Rea. Branding isn’t optional – there are only two alternatives. Branding will happen, either passively when the audience makes up their own minds about the brand (or are led to do so by your competitor), or actively when you get to shape what they believe. So, a quali-fi ed ‘it’s essential’.

Th e qualifi cation is that we need to be clear about what we mean – too oft en in pharma, people hear the word branding and think logos and colours, maybe even a tagline, but in this industry, those have been proven to be among the least important parts of a brand. Brand communication is actually non-visual – it happens peer to peer, or in the literature, and our buyers are all informed buyers. Th at is where ‘bad’ brands get built passively – oft en by companies that believe the product’s benefi t is self-evident from the data collected, or that ads and logos are more important. Brands that outperform their market have always actively built their whole idea, and those that haven’t

communication become ever more complex, the existence of a strong brand acts as an anchor for customers, a short cut that sim-

plifi es choice in a world where choice multiplies faster than ever before. In pharma 20 years ago, the fi rst brand in a new class could have three to fi ve years of exclusivity before being followed by a com-petitor. Today that can be as little as three to fi ve months, with another fi ve competitors following in that previously exclusive three-to fi ve-year period.

In the absence of strong brands that stand for something, payer pressure can rapidly turn innovation into a price-led commodity market, particularly if the fi nal users are in-diff erent to the choices they are off ered.

What is the importance of branding for a successful marketing strategy?Scott Cotherman. In this globally driven, regulatory-focused marketplace, more reliance than ever is being placed on the scientifi c in-tegrity of a brand, leading the industry to com-municate more credibility at every front. From developing a unique nomenclature and lexicon to position the brand in clinical communica-tions, to establishing visionary campaignability with long-term application, some agencies are taking advantage of this shift in grounding professional value propositions by developing innovative ways of approaching branding.

A focus on core values is a primary req-uisite for the opportunity to create uniquely ownable and motivating language and visuals. Th ese branding hallmarks are the most perma-nent public expressions of the brand’s character or personality – how it looks and feels, as well as its tone of voice. Th ey are important contribu-tors to overall brand equity that are inextricably linked to the brand for its lifetime. While they are certainly a signifi cant component of adver-tising and promotion, they also live in venues

where advertising and promotion do not – such as scientifi c conferences, packaging and so on.

Michel Dubery. Branding still remains core to any marketing strategy. As channels of

ROUNDTABLE

Four experts give NGP the inside scoop on the latest techniques for establishing and promoting brand awareness.

Strategies for successful marketing

Michel Dubery is Managing Director of GHG London. He is a leader in strategic healthcare communications with extensive experience in healthcare professional marketing, together with deep understanding of patient communication. Dubery has 28 years’ experience in healthcare, including seven years as a nurse and 15 years in sales and marketing for AstraZeneca and Novartis in the UK and global positions, before joining the agency side seven years ago.

“Branding still remains core to any marketing strategy” - Michel Dubery

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need to be researched and understood to best utilise new marketing channels.

MD. Th e use of the web has, or should have, been established for years as core in any company’s marketing strategy. Th e way this technology is applied, though, has changed and will continue to change. Th e old model in which people sat at their computers and consumed content provided for them is as out of date as watching black-and-white soap powder ads on one of two TV channels. Th e growth of mobile browsing, user-generated content and social networking has encour-aged an environment in which customers talk to each other about anything that pleases them, including the brands of which we are so proud.

Research shows that customers are far more trusting of information provided to them by their peers about products than that from any commercial organisation. Th is is far more pervasive than the growth in review sites that was seen a few years ago. If people have a disappointing experience with a brand, it’s on Twitter two seconds later and at the same time their Facebook and other social network pages have been updated with the same content. If you think that this doesn’t apply to pharma, try going to Facebook and searching for a medical condition. As for how user-generated content may aff ect marketing, take a look on YouTube and see what individuals with a little time on their hands have done to well-known brands’ ad campaigns. Many of these new ver-sions are more interesting and engaging than the originals.

SC. Successful customer relationship mar-keting (CRM) depends on multi-channel communications that let companies reach cus-tomers any time, anywhere, and in whatever way they prefer. Our defi nition of closed loop marketing (CLM) is the ability to optimise communication by capturing brand message interactions, measuring them for marketing

For strategic marketing, anything that can help understand the unmet need and benefi t headroom in the market – from better data mining and gaining insight from broader groups of customers, to ways to prototype and test new ideas with those customers – will be immensely valuable. Th ink for example of the lost internal time and cost to get advisory meetings together now, and even more of just how inconclusive they usually are.

GC. New technologies open up exciting oppor-tunities for reaching the target audience, and in particular the emergence of online communities is facilitating a more rapid spread of communica-tions messages. We must remember though that however exciting a new technology may be, it is only a marketing chan-nel and the technology is just that – a technology – a tool, system, tech-nique. New marketing channels facilitate the delivery of messages but don’t guarantee the ef-fectiveness of our com-munications.

As marketing pro-fessionals we need to really understand how

individuals interact with these new technolo-gies, and how this cyberpsychology impacts on how messages are received. When we in-teract with technology, our minds will work diff erently, and it is not enough to simply communicate through technology, we need to ensure that the message is received in the way it was intended. Cognition of the technology linked with the emotional experience and the culture it is being used in are all elements that

have underperformed. Th ere have been oc-casional exceptions, but they were truly that – unexpected. You’d hope that unexpected success wouldn’t be part of companies’ ambi-tions for their pipelines. Graeme Chrystal. If the goal of a marketing strategy is to optimise profi tability by identi-fying, anticipating and satisfying customer requirements, then the importance of brand-ing in successful marketing is much the same as the importance of having wings if you are a bird and want to fl y.

At the absolute core of marketing suc-cess lies the ability to understand and com-municate consistently and succinctly what a brand stands for, and what rationally and emotionally makes it unique, versus its com-petitors, when meeting or resonating with an important need in a de-fi ned target customer’s mind. Th at distilled comprehension of the brand should permeate all internal and external communications and provide the basis for the marketing strategy.

It is imperative that the brand is marketed in such a way that at all its touch points the words and actions of the brand are cogent and consistent. Th e only way to achieve this is to have a single-minded view and application of the brand throughout the marketing process.

As communications evolve, what new tech-nologies can companies use to enhance marketing?MR. It depends whether the marketing is tactical or strategic. For tactical marketing, the goal of connecting a message to its audi-ence would suggest that new technologies that make a message more tailored to people’s wants and needs, and where they’re receptive to hearing it, will succeed.

Mike Rea is CEO of IDEA Pharma, a leading global consultancy in pharmaceutical strategic marketing. Rea has worked in international healthcare communications for over 20 years, and has developed global marketing solutions for most of the world’s top 10 pharmaceutical companies. His principal point of interest is the incorporation of best practice into pharmaceutical marketing strategy, and he has helped lead the strategic direction of over 50 pharmaceutical brands.

“Brands that outperform their market have always actively built their whole ‘idea’, and those who haven’t have underperformed” - Mike Rea


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to spend a whole lot less eff ort aft erwards to persuade them they want it. In the former case, we tend to use techniques like prototyp-ing to help prescribers and payers understand what might be possible – aft er all, unmet need isn’t always apparent to people who, day in and day out, are doing their best with what they have. Many companies end up relying on ‘research’ that tends to state the obvi-ous – we’d all like what we have, but a little bit better: more effi cacy, more safety, better tolerability, less cost. Henry Ford made that point a century ago when he said that, had he asked, people would have said they wanted a faster horse. Th e work of uncovering what might be wanted, via ideation, has to happen really early – discovery people are great at it – before it gets channelled into a more ‘paint by numbers’ development and marketing programme.

MD. Th ere are formal research tools available to research the marketing needs of clients, but as an agency, the most eff ective methods oft en do not use formal tools. Staying close to the cli-ent’s business and spotting trends in their, and other, sectors that may be applicable, can allow smart agencies to anticipate or even create new marketing requirements.

More formal approaches, such as the use of the discussion tools on business network-ing sites such as LinkedIn, can also generate useful insights into the evolving requirements of marketing clients. Half-yearly review meet-ings with senior clients that involve general discussions around major trends in their mar-kets as well changes in their own commercial objectives are also invaluable in ensuring that your client off er stays current.

Th e other key change is a move towards deeper understanding of the emotional and psychological needs of customer groups. Ap-proaches used to access this information go beyond the more standard left -brain and tra-ditional question and answer that has been the mainstay of healthcare research. Th ey involve advanced projective and elicitation techniques – such as role play, drawing and gestalts to name a few; skilled, executive level interview-ing; as well as advanced methodologies such as psychographics, ethnography and semiotics to provide deeper contextual information and advanced analysis based on grounded theory, neuro-linguistic programming (NLP), trans-actional analysis and linguistics.

SC. Established research techniques, such as industry analysis of trends and prescribing patterns, as well as one-on-one and group responses to product activities, remain im-portant components to understanding and supporting the marketing needs of clients. Many of these response activities can be con-ducted online, to broaden the number of re-sponses and reach a larger geographical area. However, in crowded markets, where there is little clinical diff erentiation in products, more sophisticated techniques can tease out a dif-ferent kind of information.

Th ere is an increas-ing awareness of the value in understanding the non-clinical needs and perceptions of customers. Cultural anthropologists and psychologists are using a variety of tools, such as semiotics and psy-chographic analysis, and interactive activities such as a visual collage stimulus, to gain customised insights that enhance established research techniques. Segmentation is a research tool designed to identify a communication bullseye within spe-cifi c audiences and leads to the prospect, who may be a subset of the total market.

MR. Again, I’d clarify what we’re covering: strategic marketing or tactical marketing strategy. If we can understand what people really want, and then give it to them, we need

eff ectiveness, and refi ning the experience for future interactions. CLM is the process of information exchange; CRM is the process of developing relationships using technology to facilitate deeper and more meaningful inter-actions with our target audiences to help in both personal and non-personal selling.

Content management solutions output information by specifi c need, including audi-ence and timing of distribution. Campaign management solutions construct and distrib-ute customised content through a variety of

media channels and measure the output of the content to segmenting audiences. Sales force automation systems provide two-way dialogue that addresses physician expecta-tions of what they consider valuable, and help build a foundation for future interactions. Th ere is also a rich opportunity to integrate CLM technology with handheld, wireless technology. Mobile healthcare applications and text support are growing exponentially through mobile phones, gaining permission-based status with customers while managing one-way and two-way messaging with both patients and healthcare professionals.

What research techniques are used to un-derstand the marketing needs of clients?GC. Many healthcare companies have moved towards a much more customer-centric at-titude and thinking in terms of understand-ing and reacting to needs. In some pharma companies, precedence is now given to un-derstanding patients’ and payers’ needs over those of healthcare professionals. So voice of customer research is a key technique.

Scott Cotherman is CEO of Corbett Accel Healthcare Group. Cotherman shapes the strategic direction of the company, leads its growth and diversifi cation initiatives, manages its reputation and corporate image, and develops leadership talent. His integrity and high performance standards earned him recognition as a top 100 inspirational industry leader. Cotherman is Chairperson-elect of the Medical Advertising Hall of Fame.

“Th ere is an increasing awareness of the value in understanding the non-clinical needs and perceptions of customers” - Scott Cotherman



Secondly, the deeper the strategic market-ing mindset goes into an organisation, the closer it fi ts with R&D – the two have to be iterative and highly aligned. In fact, the best performers in the past 20 years have been those brands whose strategic marketing infl uenced the course of their R&D, regulatory approach and indication roadmap. Diff erentiation and the value proposition needs to begin early, during phases I or II, so that companies that continue to try to stick on some positioning and health economic arguments in phase III will really struggle.

Hopefully the future of tactical marketing will be a more targeted, higher ROI one, which is better because the strategic gearing will be higher, and also because it is one area where the industry’s image continues to falter.

GC. Th e biggest shift will be that pharma-ceutical companies will move from illness management solutions to providing wellness management with their drugs/devices spe-

cifi c or bundled into wellness programmes. Th e impact on marketing will be signifi cant, requiring a more consensual and integrated approach based on co-creation or co-devel-opment with key stakeholders, such as less telling people why they should want a brand and more understanding of how a brand fi ts into an holistic wellness system, and working within a fl ow of communication rather than trying to control the communication.

Th e drivers for this shift will be that pharma companies and patients will play a greater role in responsibility and payment for welfare man-agement regardless of payer system. Payers are likely to start to incentivise consumers/patients for healthy habits and to disincentivise for un-healthy habits. Also, it has been suggested that regulatory bodies will come to expect such pro-grammes as part of the cost of getting product and price approval and to help optimise drug use or need and develop better adherence.

one say something nasty about your brand on your site where you know about it, than somewhere you may never see it.

SC. Th e industry’s progression towards more eff ective and effi cient approaches to the cre-ation and execution of global communications is infl uencing the convergence of new technol-ogies, globalisation and enhanced marketing disciplines.

Personalised healthcare and genomic-based therapies are slowly disintegrating broad-based marketing approaches that seek to reach large groups with a general message. Th e move towards CRM will meet the individual needs – clinical, product, psychological and emotional – of customer targets with tailored messaging. Social media will help deliver the message any time, anywhere and in whatever platform customers prefer.

Global marketing will become increas-ingly effi cient, leveraging technology for the application of brand messages throughout all

markets through the fl exibility of customi-sation for individual markets. Given the need for increasing accountability, marketing will become even more cost-eff ective for pharma clients, because there will be the need for fewer local agencies.

MR. First of all there needs to be a recogni-tion across the industry that marketing isn’t a single discipline. It has been treated as one for too long, and fails to refl ect that there is strategic marketing – trying to decide what a market wants or might want and will pay for – and there is tactical marketing, the business of persuasion, which overlaps with sales. Compa-nies that don’t recognise the skills and exper-tise diff erence presented by that very simple separation will always come second. Th at isn’t a simple solution – most marketers (and fewer management consultancies, it seems) don’t recognise that split either.

How do you see the future of marketing developing in the next few years?MD. Marketing will continue to evolve away from the one-way, one-to-many communica-tions of the past. Smart marketers will realise that, at any one time, there may be thousands of conversations going on that involve their brand, and the only way to have any infl u-ence is to get involved in the more important conversations out there. Th is may involve set-ting aside the disdain that some feel for the humble blogger, but that should be measured against the infl uence that some of them wield. It may be far more than that treasured inside front cover spot on your favoured medical

publication or even, heaven forbid, your own carefully constructed website.

More and more companies need to invite customers to talk to them. Th e easiest way to do this is of course to use their own websites, although this oft en causes terror from a legal and regulatory perspective. What if someone posts an adverse event? Th ere are of course ways to handle this and many companies are doing so already. Free text entry on a site may look terrifying from a medical perspec-tive but in terms of insight generation it is an invaluable resource. It’s better to have some-

Graeme Chrystal, Founder of the Zaicom International group of companies, has 30 years’ experience in pharmaceuticals and marcomms, developing and implementing prelaunch communications programmes. Passionate about behavioural change, he is a qualifi ed practitioner in NLP and hypnotherapy, a member of the International Association of Business Communicators and a student of the psychology of communication.

“Th e biggest shift will be that pharmaceutical companies will move from illness management to wellness management” - Graeme Chrystal


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Over the next three to five years, what willdrive medical communication programmes?Amanda Smith. The world of medical marketingand communications is changing fast. In this en-vironment medical communications agencies willneed to understand how to help the pharmaceu-tical industry achieve clinical positioning that isnot only credible and well-founded, but impact-ful. I see increasing demand for medical commu-nications coming from the push to improvetransparency and reputation. The continuedmove towards evidence-based health will need in-creased leverage of evidence-based informationand assets, including expert opinion. At the sametime, the ongoing expansion of the stakeholderbase influencing treatment decisions will drive agreater need for educational support, especially inthe area of disease prevention. This broader andmore heterogeneous mix will include not onlyhealthcare professionals at all levels but also pa-tients and carers, all needing the evidence base tobe interpreted and communicated in ways thatare meaningful for them.

Will this affect the range of products and ser-vices on offer?AS. Increasingly complex targeted therapiesneed educational support to help healthcare pro-fessionals and others to understand their placein clinical practice. The need for high-level sci-entific communications at international con-gresses and in peer-reviewed journals willtherefore continue. Taking the messages to locallevels, however, will require a different ap-proach. There will be growing demand for inte-grated programmes that provide a consistentthread from global to local level, while also en-suring that key messages are appropriate for themarkets in which they are delivered.

Examples of such programmes include inte-grated payer programmes to reflect increasingpayer power, as well as the need for payer insightand engagement, and activation of evidence pro-grammes that connect evidence, education and

behavioural change. We are already seeing a needfor validated decision-making tools to supportpersonalised healthcare, and I foresee increaseduse of education programmes targeted at im-proving adherence to treatment, optimising boththe clinical and economic value of a given thera-py. Reflecting these changes, there will be in-creased emphasis on educational initiativesdesigned specifically for nurses and pharmacists,to reflect their growing role in patient manage-ment. We may also see a need for medical com-munications for non-prescription drugs.

Do you see an impact in Europe from the ongo-ing legal investigations involving pharmaceu-tical and medical communication companies inthe US? AS. The retrospective nature of these casesdemonstrates the need to think ahead of regula-tory requirements to ensure that we are operatingin a transparent and ethical manner now. The up-

dated guidelines for Good Publication Practice(GPP2), due to be published in late 2009, havebeen designed to establish high levels of integrityfor all those involved with communicating clini-cal trial data, and I expect that they will rapidly beaccepted as the ‘gold standard’. Before long, fail-ure to comply with GPP2 will be assumed to meanunethical practice. Agencies and their clientstherefore need to start working to these standardsas soon as possible.

Do you think that there will be further regu-latory changes affecting medical communica-tions programmes?AS. It is clear that regulatory bodies want to en-sure that scientific publications remain free frommarketing influence. This will also be driven bythe need for greater transparency, such as theconflict of interest disclosures mandated byGPP2. In practice, this will lead to increasing sep-aration of relationships with external experts.Experts who work on clinical trial programmeswill author the scientific publications and work

with clinical or medical departments, while themarketing department will work with a separategroup of experts, at company-sponsored meet-ings and elsewhere, to explain the relevance of thedata for clinical practice. Pharmaceutical compa-nies will have to expand their network of externalexperts beyond clinical trial investigators and en-sure that they invest additional time and energyworking with professionals whose endorsementwill be influential with their peers. n

Medical communications in a changing world

Amanda Smith explains the effects of the movementtowards evidence-based medicine.


EXECUTIVEINTERVIEW

For more information please [email protected]

Amanda Smith is Global Head of Caudex Medical.She has a background in nursing and has over 20years of industry and agency experience in a varietyof commercial roles, encompassing sales, marketingand communications. Moving to medicalcommunications in 1990, Smith has worked withEuropean and globally based pharmaceuticalclients, including GlaxoSmithKline, Roche, Novartis,Merck Serono and Johnson & Johnson.

“I see increasing demand for medical

communications coming fromthe push to improve

transparency and reputation”

CAUDEX EXEC:13July 29/07/2009 14:43 Page 120

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Van Spaendonck’s BU “Value Innovation in Medical and life Sciences”is a focused consultancy fi rm on strategic change.

Van Spaendonck management consultancy supports and directs parties and professionals involved to proper choices and processes to create and develop their USP, a better market position and performance. In the dynamics of health care systems, pharmaceutical industry, health care insurers, social parties, and health care professionals will be challenged more and more to their added value.

Expertise and experience to initiate and develop processes for the practice of health care, marketing, sales and management systems, professional development, and strategic organisational change. More than 20 years of consultancy expertise to pharmaceutical and medical industry, life sciences and health care. Actual research and publications in health care and marketing developments.

Rob Halkes | T +31 418 578000 | www.medicalandpharmamarketing.com [email protected] | the Netherlands

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What is your definition of customer relationship management?Rob Halkes. CRM is the company’s attempt to make the most of its relation-ship with buyers. It relates to the company’s value orientation on customersthroughout the company with an accent on its business model. However,CRM systems in pharma are predominantly used as a sales reporting systemand for the segmentation of target groups to be visited by the reps of the com-pany. To create sustainable and profiting relationships with customers, itneeds to see the individual customer in its personal context of influences fromother stakeholders. If the proposition of pharma turns into a commodity, itsrelation with stakeholders turns into a commodity.

Torben Vogt. CRM is a way to organise your business. Embracing all aspectsof the relationship between the customer and the supplier, CRM is a struc-tured process with which a company can maximise the efficiency of all cus-tomer-related activities, ultimately increasing revenues.

For pharmaceutical companies, CRM is a tool for organising a dialoguewith the healthcare environment, strengthening the perception of the com-pany among doctors, healthcare personnel and other stakeholders, thus en-

hancing reputation and brand value. The customer-oriented processes ofCRM are typically supported and automated by an IT application known asthe CRM system.

Vivian Hunt. We think of CRM as a collaboration between marketing, sales,customer service and IT to re-evaluate and optimise how a company most ef-fectively interacts with its customers. It should be much more than a tech-nology tool and requires a clear viewpoint on value creation. Our experiencesuggests that those organisations that excel at CRM share a number of char-

acteristics. They invest in superior insights, taking asegmented view of customers, and have a deep under-standing of the value drivers; they use CRM as the basisof focused sales and marketing activity, aligning mar-keting and sales resource with opportunities, and un-derstanding which vehicles and channels should beoptimised to capture those opportunities; they tailorcustomer service to the needs and value of segments;and they link CRM to overall business unit strategiesand continually measure impact.

Why should a pharmaceutical company considerimplementing a CRM system? What are the ad-vantages?TV. The main benefit of a CRM system is that it enablespharmaceutical companies to increase the efficiency ofall customer-related activities, enabling them to growtheir revenues without expanding their resourcespending. For example, a well-updated CRM systemallows the company to see if its sales efforts are work-ing effectively by measuring both the influence onhealthcare contacts as well as hard sales facts.

Implementing the right kind of CRM helps coor-dinate collaboration between sales, marketing and reg-ulatory and customer service departments, presenting

The importance of CRMNGP talks to Rob Halkes of Van Spaendonck, Vivian Hunt of McKinsey & Companyand CDM’s Torben Vogt about optimising relationships with customers.

ROUNDTABLE

“CRM should cover relationshipswith all stakeholders and specifically

with their decision-making units”Rob Halkes

CRM RT:13July 29/07/2009 14:42 Page 123


one face to the customer. This ensures that sales representatives and market-ing keep the pharmaceutical company in the top of mind of doctors and otherkey stakeholders.

A CRM system is pivotal in maintaining the greatest asset of a pharma-ceutical company – its good reputation. In the close-knit world of healthcare,the negative experience of one doctor who has an interaction with the com-pany may ruin the hard-earned reputation of the company for years to come.Having a CRM system that is used optimally will counteract this.

To sum up, CRM is extremely important for the professionalism of phar-maceutical communications and a cornerstone in maintaining the companyimage and brand.

VH. Successful CRM organisations view every customer interaction as an op-portunity to create value: offering the right product or service to the right per-son at the right time. Equally important is to focus on the activities that offerthe highest return on investment by taking a holistic view of the value poten-tial of a customer, and the costs to serve them. We would argue that bothshould matter as much to a pharmaceutical company as to any other com-mercial organisation.

Typically the distribution of value from customer accounts is very wideand the 80/20 rule applies: a relatively small group of customers often accountfor a disproportionately large amount of value. Understanding which cus-tomers generate most value, and why, can have a significant impact on thebottom line, directly impacting the selling process in three areas. The firstbeing coverage and contact strategy: focusing sales resources on the currentcustomer accounts that offer the highest potential value, by virtue of their ab-solute size, cost to serve and propensity to work with your organisation. This

isn’t just about having the right reps in place: youneed to make sure you cover the touch points thatmatter most to you customers, providing the com-bination of channels they need. Equally important-ly, helping identify higher potential new accounts.

The second is opportunity spotting and bidmanagement: identifying opportunities to increaseshare with the customers that count and defendingagainst potential competitor attack; and the thirdis pricing. Effectively using the pricing and dis-counting opportunities available to set your over-all pricing strategy, optimise tactical pricing, andto tailor commercial propositions to customersneeds and value.

RH. The effectiveness of pharmaceutical promotionto individual prescribers is quickly diminishing.Market conditions change and networks aroundthe prescriber get more influence. CRM shouldcover relationships with all stakeholders and specif-ically with their decision-making units. This is con-ditional for effective promotion in advancedmarkets, but probably not sufficient for keeping upsustainable performance. When decision-makingin therapy and drug selection gets more complicat-ed, pharma needs to follow up on that.

These advantages of a CRM system are both in coordination of relation-ships with stakeholders, and in the generation of relevant stakeholder infor-mation. Used adequately, CRM renders information that indicates wherepreferences, concerns, interests and needs of stakeholders are heading. Newsegmentations may be done for specific campaigns, and one could find dis-tinct new trends that could be relevant for one’s business.

What tools and solutions would you recommend to ensure a companygets maximum benefit from a CRM system?RH. Maximum benefit will lie in sound alignment of the CRM system withthe specific business approach that accommodates with specific market char-acteristics. If the influence of networks around the prescriber on drug selec-tion is raised, stock taking of these networks and their decision-making unitsis needed. If done right, this segmentation will lead straight to a target hierar-chy of DMUs of networks with which quick wins are possible, down to thosethat need longer lead times. Hence, a system of focused account managementwill be more effective to cover relationships with these networks than just a

Rob Halkes has been a consultant to the market ofpharmaceutical and life sciences for 20 years. He worksat strategic change, innovation and professionaldevelopment with executive, marketing, sales andmedical management. In the pharmaceutical industry,he is currently developing value innovation as a newbusiness model.

Torben Vogt has more than 20 year’s experience in thelife science sector, with various leading positions insales, marketing, finance, IT, logistics and planning. Thisincludes three years with Novozymes in Brazil,managing the planning and logistics for Latin America.At CDM A/S, he is VP of Sales and Marketing.

Vivian Hunt is a Director at McKinsey & Company,based in London. She is the Head of McKinsey’s UKPharmaceutical and Medical Products Practice andleads its Medical Technology Practice for Europe. Shehad a 15-year career serving a variety of healthcareclients across the full value chain.

“Addressing the challengesassociated with launching a CRM

initiative is critical to overallsuccess” Vivian Hunt

THE PANEL

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promotion effort by reps only. The question of who in the company will dowhat, with whom of the targeted account, will quickly be made possible. Onewould also need to install real account managers that who account for the de-velopment of the network and will be the spokespeople and coordinators tothe relevant people of the network for the company.

TV. Start with a business process review and improve/redesign it with in-dustry best practices. Identify the three to five technical and/or economicalkey success factors for CRM in your company. In our experience, high useradoption is probably the most important in ensuring maximum ROI onyour CRM investment.

The sales and marketing tool moving ahead of all today is MicrosoftDynamics CRM. The key to its success is that it is seamlessly integrated withMS Outlook, the IT system in which sales people typically spend more than80 percent of their IT time.

CRM should not be a data island in itself and it is thus important to getthe CRM platform integrated well with other systems – and Microsoft meetsthis challenge with Dynamics CRM. This platform offers the lowest TCOof any solution in the market. It is the fastest growing CRM platform glob-ally, with more partners, solutions and technical resources available thanany other.

VH. CRM tools do not always have to be sophisticated, and there is real meritin considering what fits best within your existing sales and marketing culture.At one end of the spectrum are dynamic tools that automatically generate rec-ommendations. They tend to have high compliance rates but their obviousdrawback is the upfront investment cost. The lower tech solution of statichandheld PDAs (the modern equivalent of handouts) can work well for reps,giving them fast access and the ability to record information real time.

Regardless of the system adopted, addressing the challenges associatedwith launching a CRM initiative is critical to overall success. For example,companies that reported successful CRM implementation in a recent studywe conducted were almost twice as likely to report that implementationspecifically addressed the cultural shift required to adopt the new system. Evenmore claimed that modules were launched at intervals to prompt adoption.

How do you see CRM developing in the future?VH. We believe that CRM and the importance of understanding your cus-tomer may actually be becoming more critical in pharma as healthcareproviders struggle to control the growth of their budgets and demonstratethey are achieving value. This puts increased pressure on pharma to ensurethey understand, anticipate and meet the needs of their core customers nowand into the future. Added to this is the mounting pressure to create value asthe commercial model undergoes radical change in many markets.

TV. Briefly put, CRM will move back to basics. Pharmaceutical companies –in particular big pharma – have a long experience with CRM. This is oftenan expensive and unsuccessful implementation projects, as pharmaceuticalIT and sales directors have seen large systems featuring loads of functionali-ty go virtually unused by the sales and marketing staff, due to high complex-ity and unclear processes. Thus we see a growing focus on quickerimplementations of smaller, more user-friendly and cost-effective CRM so-lutions, which will surely help increase the success rate of CRM projects.

An emergence of new communication channels will significantly broad-en the concept of CRM in the coming years. CRM systems need to coordi-nate these, keeping communication with healthcare contacts uniform.Examples of emerging new channels include Web 2.0 and the newest com-munication tools like web meetings, e-learning, one to one videoconferenc-ing, and e-detailing. Only CRM systems with flexible integration points willbe able to handle this.

Finally, we see a huge increase in CRM deployed as hosted or Softwareas a Service implementations. However, the hosted CRM systems with thegreatest success will be those built on familiar and widespread technologysuch as .NET and that are tightly interwoven with mail programs such asMicrosoft Outlook.

RH. In several countries, the future is here already. We have seen develop-ments in which variables for target group segmentation are augmented withmethods of profiling. This profiling is aimed at further behavioural segmen-tation of prescribers – one expects that specific personal and psychologicalvariables will further differentiate between targeted persons in terms of drug,therapy preferences and/or attitudes. This detailed segmentation will also di-rect the process, substance and communication style of rep calls. Advocates

of this profiling hope that this will generate more effectiveness of calls. Butthis stays within the framework of the traditional promotion to individual pre-scribers and will get obsolete with the further development of a more com-plex structure of drug decisions.

Therefore, the pharma company needs to reconsider added value tostakeholders. On the basis of the company’s own detailed information aboutthe drug and its administering characteristics, effectiveness, side effects, ad-verse reactions and the like, one is able to develop added value propositionsrelevant to the quality of healthcare itself. Support and information to pre-scribers and users of the drugs to enhance compliance, reduce feelings of un-certainty and raise experience of satisfaction with the treatment opens the wayto co-create the healthcare experience.

This is already being done. But the difference in using these services lies inthe market approach with these propositions. Companies will need to think ofspecific kinds of services marketing and concepts: experience marketing, expe-rience co-creation and the like. Differentiation between accounts will make thedifference in effectiveness and efficiency. New segmentation methods and ac-count management will show a tremendous change in how pharma companieswill set up their market approaches and consequent CRM systems.

CRM innovation will go together with value innovation. When phar-ma companies do not do so in a coherent way of rethinking and redesign-ing their business model, both will be too costly and insufficient to renderbusiness results. n

“A CRM system is pivotal inmaintaining the greatest asset of a

pharmaceutical company – its goodreputation” Torben Vogt

CRM RT:13July 29/07/2009 14:42 Page 126


Apart from Japan, what other markets is MMC operating in? DS. Based on our success in Japan, we set up a new company in Madrid, NPG Iberoamerica, in 2007, with an MMC unit to handle medical com-

munications in Spanish, Portuguese, French and Italian in the markets of southern Europe and Latin America. Like its Japanese counterpart, it has quickly gone into profi t. And this year we have set up an MMC unit in India using the infra-structure of Macmillan India, a large Macmillan company that has been operating in India for over a century.

Do you have plans for medical communications in the West?DS. We already have a presence in pharma-related content sales in our NPG offi ce in Boston, and we are investigating the potential for us to establish a larger foothold in medical communications in the West. In this regard, we would very interested to hear the views of your readers on how medical communications is evolving in the West, particu-larly with the advent of online publishing. If you are a reader working in medical communications and/or pharma sales we would be delighted if you would fi ll in our short online survey at www.natureasia.com/en/pharma_survey/. You will re-ceive a free copy of the results of the survey and

10 participants in the survey will be awarded on a lottery basis a one-year free subscription to the Nature journal of their choice.

MOVING AHEAD IN MEDICAL COMMUNICATIONSDavid Swinbanks tells NGP about Nature Publishing Group’s recent move into medical communications with its new division, Macmillan Medical Communications.

Could you please explain why has Nature Publishing Group has moved into medical communications?David Swinbanks. Nature Publishing Group, alongside Nature, publish-es over 30 Nature-branded research and review titles in the life sciences, physical and chemical sciences, and clinical medicine. We also publish nearly 50 life science and clinical medical titles, such as Kidney International, the American Jour-nal of Gastroenterology, the American Journal of Hypertension, and the British Journal of Cancer. Our portfolio of journals in clinical medicine has grown substantially in recent years and we have also launched a whole series of Nature-branded review journals in clinical medicine.

Th is wealth of high quality clinical medi-cal content has opened up an opportunity for us to move into medical communications, based both on our content and our expertise in medical publishing.

A second factor behind our decision to move into this area is our very strong and growing pres-ence in Asia, where there are some of the largest pharmaceutical markets in the world.

Nature has had a presence in Japan for over a quarter of a century, and in the past four years we have rapidly built our publishing capabilities in the Asia-Pacifi c region.

Why was Macmillan Medical Communications (MMC) fi rst set up in Japan?DS. Japan is the world’s second largest pharmaceutical market, and neighbouring China is growing rapidly. Our fi rst venture into content-based medical communications began in 2006 with our publication of Kidney International: Selections, a quarterly digest edition of Kidney In-ternational translated into Japanese and distributed to Japan’s nephrol-ogy community supported by an educational grant from Kyowa Kirin.

However, we quickly learned that the biggest slice of medical communications business lies outside of peer-reviewed content in bespoke publishing, medical writing and editorial services, and, most importantly, the handling of all aspects of drug launch campaigns. So, based on our reputation for high quality medical publishing, we embarked on a strategy to win bids against other large players in medical communications to handle some drug launches. I am pleased to say that in the space of less than three years we have won bids to handle the launch campaigns for two drugs that will go on the Japa-nese market in 2010.

EXECUTIVEINTERVIEW

David Swinbanks is Publishing Director of Nature Publishing Group (NPG), publisher of Nature, the international science weekly, and is responsible for all of the group’s publishing activities in the Asia Pacifi c region, with headquarters in Tokyo and offi ces in Hong Kong, Seoul, Melbourne and Delhi. He is also the Publishing Director responsible for overseeing the group’s global physical sciences publishing.

Nature, the international weekly journal of science, is one of the world’s most revered scientifi c journals. The publisher of Nature, Nature Publishing Group (NPG), has recently

moved into the business of medical communications to support the pharmaceutical industry by setting up a new division, Macmillan Medical Communications (MMC), named after Macmillan, the parent company of NPG. MMC recently won bids to handle the launches of two drugs in Japan. David Swinbanks, Publishing Director of NPG, explains this success and seeks your feedback on how medical communications is developing in the West, at www.natureasia.com/en/pharma_survey

MORE ABOUT NATURE

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vide physicians with resources to help foster more open, frequent discus-sions with their patients about how their medicines are working andwhether they have affordability concerns,” she says.

Smith notes that in addition to online and offline marketing chan-nels, case management approaches also involve multiple care providers,such as physicians, nurses, pharmacists and so on, who have been recog-

nised as being effective in ensuring pa-tients take their medicines as prescribed.

“Innovative approaches using pa-tients who successfully manage their con-ditions as ‘peer-coaches’ to other patientshave also been investigated. Health tech-nology companies can help patients taketheir medicines as prescribed by provid-ing one-on-one, electronic patient sup-port programs that reinforce theinformation patients receive from theirphysicians. For example, AstraZenecapartners with one company that uses textmessaging to remind asthma patients totake their medication or schedule a fol-low-up doctor’s appointment.

“E-prescribing systems can make itmore convenient for patients to fill theirprescriptions by allowing prescriptiontransmissions and approvals to takeplace electronically, minimising patientwait time and inconvenience. This sametechnology can enable doctors to send anautomatic reminder to a patient who hasnot filled his or her prescription in a spe-cific time period,” says Smith.

She describes the adherence effortsbeing made by AstraZeneca, in additionto those already mentioned, as being pa-tient-focused. For the past 30 years,

AstraZeneca has offered prescription savings programs for patients whomay have difficulty affording their medicines, and the company also aimsto ensure that physicians’ offices can share information on these pro-grammes with their patients. �

As VP of External Medical Relations, Karen Smith fully en-dorses the building of relationships between physicianand patient to ensure adherence. “The physician-patientencounter during the time in which a disease is diagnosedis considered a ‘teachable moment’,” she explains. “It is

vital to adherence because patients learn about the impact of a disease,how it can be treated and how to avoidthe risks and consequences of ineffectivemanagement.”

In a study conducted by theStanford University School of Medicine,185 patient-physician interactions wereanalysed to understand more of how theinformation was relayed. The resultsconcluded that simple conversationswere insufficient to promote long-termadherence to treatment, and instead newprograms were needed to convey themessage to patients.

“Providing research data regardingwhat works to improve adherence is aneffective way to support physicians inthe important role they play in demon-strating the value of adherence to their pa-tients,” explains Smith.

Following a 12-month survey con-ducted by AstraZeneca of more than 200office-based physicians, two out of threephysicians noted that they believe theyhave considerable infuence overwhether or not their patients followtheir instructions. The final third be-lieved a patient’s caregiver, health in-surance company, nurse or pharmacisthad more influence than the physician.An additional study funded byAstraZeneca evaluated prescription data and found that longer days ofsupply and lower out-of-pocket cost of medicines also positively impact-ed patient adherence.

“Effective messages should explain that it is important for people totake their medicines as prescribed if they want to experience the full ben-efit of the medicine and avoid future health issues. It is also critical to pro-

Keeping in touch


Karen Smith explains the importance of physician-patient relationships in ensuring adherence.

MARKETING

Karen Smith is Vice President of External Medical Relations (EMR) at AstraZeneca PLC.

“AstraZeneca provides a number of resources

to help physicians have more open,

frequent discussions with their patients about

how their medicines are working”

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“With the next generation sequencing technology, each technol-ogy could generate hundreds of millions of sequence reads in a single sequencing reaction. Th is poses a big computational challenge for us. In order for us to address this challenge, we set up a cluster computing en-vironment so that we can divide the computational jobs into chunks. For example, for the human genome, we could divide them by the number of chromosomes so that we could send out the computational jobs to diff er-ent computing nodes simultaneously. And then once the jobs are done, we could assemble everything back into a coherent result.

“Anybody who is working with next generation sequencing data would need to have some sort of infrastructure like this. Th is was not as much of an issue before we got into the next generation sequencing technology, since the traditional server was suffi cient to deal with the computational load. But as soon as we did get into the next generation sequencing technology, we realised we would not be effi cient if we did not have the cluster computing type of environment.”

One of the primary goals of bioinformatics is to increase our understanding of biological processes by developing and applying computationally intensive techniques. Qingqin Li, informaticist and Senior Project Lead in the Depart-

ment of Pharmacogenomics at Johnson & Johnson, uses an example in next generation sequencing to illustrate how this works: “Th is is perhaps more focused on the computational loads than the computation tech-niques, even though the techniques in the sequence area have been in use for more than 10 years. Th ose techniques are primarily focused on long reach, and next generation sequencing is more short-reach technology.

“Th is technology allows us to identify normal polymorphisms and mutations within the whole genome or a predefi ned specifi c genetic region. Imagine if we have two related biological conditions, and we could use this type of approach to identify the underlying molecular diff erence that might explain the relevant biological process driving the phenotype diff erence.

BIOINFORMATICS

Johnson & Johnson’s Qingqin Li tells NGP how bioinformatics helps us to understand biological processes.

A flash of insight

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Li and her colleagues also work on discovering the biomarker im-pacting effi cacy and adverse events using clinical samples. Th e team col-lects DNA samples from clinical trials, and through collaboration with the clinical team and statistics, they also have access to the clinical data. Th ey then perform experiments to genotype individuals by looking at a set of predefi ned genetic variants using either a candidate gene approach or a genome-wide association study approach.

“Both approaches allow us to look at the genetic sequence variation in a predefi ned set of loci,” Li points out. “Typically they are the ones that are common in the study population; common being greater than fi ve percent of frequency in the population.

“By combining the genotype data derived from these loci and com-paring that to the clinical information using statistical models, we are able to identify markers that impact effi cacy or side eff ects. Because of the nature of this type of marker, we typically call this a common disease/common variant approach in identifying the biomarker.

“Another area is next generation sequencing. Th e next gen sequencing approach allows us to look at the rare variants within the human genome so that we can sequence a pre-selected panel of individuals and identify the rare variants, which include those not captured in the public variation databases. With the rare variant discovered, we are then in a position to do the association studies again, but now looking at the rare variants.”

DevelopmentHow then is the information that comes from these activities used in

the drug development process? “Imagine we have a biomarker that could be validated in diff erent clinical populations and have a good enough clinical eff ect size,” Li says. “Meaning that the subjects carrying the biomarker, for example, have a much better response than the overall population or have a less adverse event. So if we have a marker like that, we could potentially use it to stratify the clinical population and use it in the subset of the population that has a better benefi t/risk ratio.

“In addition, we could use the information derived from this type of study to better understand the relevant pathway and the relevant target for a given therapeutic area and feedback into discovery as a next genera-tion of drug targets.”

Th e fi eld of bioinformatics is in a constant state of development, and Li believes it will evolve in line with improvements in technology, and will address the additional computational challenges posed by this new technology. “Th is has been my experience in the sequencing fi eld, in the gene expression and now in the genetic area. For example, in the genetic fi eld in the past 10 years, people were still using the microsatellite mark-ers. But with the International HapMap Project taking place and also the advancement of chip technology, new chip platforms have come on board, allowing scientists to look at 10,000 markers at a time and then hundreds of thousands of markers and now millions of markers at a time.

“Th e new methodology needed to address this type of data would direct the bioinformatics fi eld to advance and address the question posed by the new technology.

“Bioinformatics is an interdisciplinary fi eld. It will continue to involve people from diff erent fi elds such as molecular biology, statistics, computer science and mathematics, working together to come up with new analytic methods and information platforms to address the biological question.”

Genetic varationsAt Johnson & Johnson, the type of bioinformatics activities Li is in-

volved in are related to pharmacogenomics activities. “Th ey are all tied to the fact that there are genetic variations within the human genome,” she explains. “While a few are critical to the biological function, the majority of them may not be.

“Our job is to try to fi nd the few ones that have phenotypic con-sequence, being either as disease risk, diff erential therapeutic effi cacy or adverse events upon therapeutic intervention. People sometimes de-scribe this as trying to fi nd the needle in the haystack.

“Th e fi rst activity is focused on drug targets. You can imagine that if there are sequence variations in the drug targets some of them might interfere with the binding of the therapeutic agent; if there’s inadequate binding, you might expect insuffi cient effi cacy.

“What we do is to systematically provide the target variability infor-mation so that this type of information can be taken into consideration during screening assay design and during high throughput screening. Aft er all, that's the fi rst step in identifying the lead compound for thera-peutic intervention.”

“We could use the information derived from this type of study to better understand the relevant pathway and the relevant target”

Qingqin Li

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Procurement offi cers, as well as facility and lab managers, have traditionally had no option other than to work directly with original equipment manu-

facturers (OEMs) to manage their company’s assets, each with diff erent service level agree-ments and requirements. When we take into account that most companies have multiple laboratories and multiple sites, this can add up to thousands of diff erent suppliers and a cor-respondingly large number of contracts.

Working directly with OEMs in this way carries a massive administrative burden and can divert thousands of dollars worth of time away from core scientifi c projects to deal with equipment contracts, troubleshooting and service calls. With the pressure mounting on R&D departments to deliver more with less resources, employing a company that can provide detailed data and insight on all assets off ers a massive advantage.

Consolidating contracts through bring-ing in an asset management service provider, such as GE Healthcare’s Scientifi c Asset Ser-vices (SAS), is one solution that companies are increasingly turning to in order to improve effi ciency and drive down costs. Th e unique combination of services off ered by SAS can be adapted to suit the needs of each individual company, with the ability to support the entire lifecycle of their assets from equipment fi -nance, maintenance and validation, to site moves and disposal.

Asset management service providers take control of equipment inventories, categorise and barcode each item to enable easier track-ing, review existing contracts to help customers choose the best service model, and implement preventative maintenance plans designed to

fi t around research schedules. Validation pro-tocols can be customised and standardised, off ering a combined solution with signifi cant time and fi nancial savings, and simplifying the FDA auditing process. Th e benefi ts of em-ploying an asset management service provider include cost reduction.

A detailed review of existing contracts is carried out, which can be used to advise on the best type of cover to suit individual needs and to re-negotiate more cost-eff ective contracts from individual suppliers. Th ousands of R&D dollars can be saved, as scientists’ time can be redirected away from repairs to allow them to focus on key research projects. Purchasing agents can save vast amounts of time that would have been spent negotiating contracts and managing invoices. Enhanced service levels is another benefi t, as onsite engineers drastically reduce response times, ensuring that repairs are dealt with quickly and effi ciently. If OEM

Laboratory asset management strategiesMasao Moriyama explains how using a single provider for the management of laboratory equipment throughout its entire lifecycle reduces administration, improves effi ciency and provides critical data to help optimise resources.

Masao Moriyama is Service Director, GE Healthcare (Japan).

Moriyama has years of experience in engineering and

service logistics, and in-depth knowledge

of healthcare and Six Sigma methodology.

engineers are required, the process is managed by the GE Healthcare team, reducing adminis-tration and ensuring that quality of service is monitored and not compromised.

Powerful data and analysis are also ben-efi ts. Data such as contract spend, service and maintenance history, preventative mainte-nance completion, and current asset market value, are collected for each instrument and service event and held in a single, secure database, AssetPlus. Th ese data can help to understand asset utilisation and minimise under-use. Combined with an understanding of current market value, companies are able to make informed decisions about their surplus or unused equipment. Options could include transparent storage or disposal, with any pro-ceeds fed back into the business.

Th is leads to the advantage of increased staff retention. As equipment downtime is re-duced to hours instead of days, there is greater freedom to focus R&D resources on science. Th is has a positive eff ect on motivation and job satisfaction, resulting in improved staff reten-tion rates.

SummaryIn the current climate of increased M&A

activity and decreasing budgets, pharmaceuti-cal and biotech companies are under increas-ing pressure to enhance productivity whilst at the same time driving down costs. In a recent survey, Accenture found that executives at top pharma companies rate analytics/data-driven insights as one of the top factors critical to out-performing their competitors. However, few companies collect all data potentially available to drive their asset management programs. Partnering with a global company that can adapt and grow to meet a company’s needs and deliver a total solution for asset management throughout its lifecycle presents an ideal long-term solution.

INDUSTRYINSIGHT

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ASK THEEXPERT

Ethan Smith outlines a successful approach to the drug development process. the underlying process models. Otherwise, team members will suff er a great deal of frustration in having to manually maintain and connect stand-alone models – so simple drawing and diagramming tools will not suffi ce. Ideally the modelling tool selected should also serve as an educa-tional tool, allowing the models to be reviewed, annotated and published to the entire enterprise for consumption.

Publication of the models enables process owners and end-users to better understand how key elements and various roles fi t into the overall process. Th ese models also serve as a basis for training, communication and compliance. Organisations that successfully model and publish their R&D processes may also use the online models as the source for linking standard operating procedures (SOP), work instructions and forms, thus providing end-users one source of truth for how a particular process is to be executed and what associated documentation is to be used.

SuccessEarly adopters have already made great strides in process improve-

ment and the adoption of enterprise modelling and business process management soft ware tools. Now that R&D conferences and association meetings are preaching the value of having well-documented, widely communicated processes, it is only a matter of time before business pro-cess improvement as a strategic initiative becomes a competitive neces-sity within the life sciences industry. Implementing a formal enterprise modelling program and the right technology will enable the agility required to bring products to market faster, more safely and more cost eff ectively – so take action now while you still have the opportunity to gain a strategic advantage.

In today’s economic environment, research and development func-tions are under signifi cant pressure to bring products to market more quickly, and reduce costs. Regulatory authorities are approv-ing fewer applications, driving costs to nearly US$1 billion dollars

to bring a new pharmaceutical product to market in 10 years. While drug discovery can be diffi cult to manage and standardise, the product develop-ment processes can be defi ned, standardised and optimised in ways that signifi cantly reduce costs, lower risk and accelerate time to market. In fact, some large pharmaceutical, biotech and medical device fi rms are already tackling this challenge with a great deal of success.

Modelling the drug development process with all its intricacies, dependencies and overall complexity is oft en seen as a Herculean task. Success requires sound planning and a focused, segmented approach – fundamentally breaking down the drug development lifecycle into a series of smaller processes that can be defi ned and standardised in phases, incrementally contributing to overall results. To support and enable this approach, senior clinical leadership must develop a taxonomy of business domains and their interrelationships.

Th ese domains may be based on functional areas, organisational entities or a combination of the two, but the important thing is that they are enterprise-level and can be enforced globally. From the enterprise taxonomy, the various functional areas and underlying processes can be modelled by separate teams in parallel or done by a central team seri-ally. Either way, the business taxonomy enables the modelling team(s) to focus on discrete process initiatives with clear understanding of how each process fi ts into the overall enterprise to ultimately deliver an end-to-end product development process.

ComplexitiesYou can see how this eff ort could become very complex, very quickly.

Even following a methodical approach and employing a variety of re-sources to accomplish the goal, there is a defi nite need for technology to help manage such a critical initiative. Enterprise modelling soft ware suites – such as Metastorm ProVision – provide a repository-based mod-elling environment to enable reuse of common elements (organisations, roles, activities and so on) and serve as a central point for collabora-tion and big-picture understanding. Any tool selected must automati-cally maintain the linkages between the business taxonomy and all of

Ethan Smith has extensive experience in business process consulting in life sciences. He has driven process initiatives across research and development, sales operations, incentive compensation, physician spend management, and compliance. He has delivered well over a dozen BPMS implementations in the industry, and developed enterprise BPM strategies and centres of excellence. Smith currently serves as the Director of Life Sciences Solutions for Metastorm.

Clinical process modelling – taking control now

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Terracotta Warriors

Beijing Olympics 2008 opening ceremony

IN THE BACK136 REGIONAL FOCUS: CHINA

An already established manufacturing epi-centre and emerging R&D market, China is receiving investment into its pharma-ceutical industry, both at home and abroad.

With a region that encompasses almost a fi ft h of the world’s population and an area of 9.6 million square kilometres, it is the world’s second largest country by land area.

Shanghai is the country’s largest city in terms of population, housing over 20 million people. It is the largest centre of commerce and fi nance in mainland China.

China’s second largest city, Beijing, is a metropolis in northern China, and a major transportation hub. Th e city is recognised as being the cultural centre of the People’s Republic of China and played host to the Olympic Games in 2008. Th e city is renowned for its opulent palaces, temples and huge stonewalls and gates. Its emphasis on art has long re-mained integral to its title as the city of culture.

tht et it it i

136

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IN THE BACK137REGIONAL FOCUS: CHINA

China’s pharmaceutical marketChina accounts for 20 percent of the world’s population, and as

its healthcare environment continues to change and expand so does its pharmaceutical industry. Th e healthcare sector within the region is evolving – a target has been set to extend basic heath insurance to a wider section of the population, and as a result, the operations of the pharma industry are set to expand dramatically to cope with the change.

Th e industry itself is highly fragmented, and it is the fragmenta-tion that has brought the greatest problems. As the number of pharma companies continues to grow, the government is recognising the problem with compliance. Th ere are almost 6000 pharma manufac-turers and around 14,000 distributors operating within the country; there are around 3500 drug companies competing within the €7 bil-lion market, but without any of them carving up enough of a slice to become a leader.

During the last few years, China has put together several regula-tions and reform measures within the State Drug Administration – the organisation is now responsible for all drug trading, manufacturing and registration. Since 2004, the SDA has been sanctioning and clos-ing down manufacturers that do not meet the Good Manufacturing Practice (GMP).

China’s over-the-counter market is simultaneously growing just as fast, becoming the fourth largest OTC market in the world. Foreign pharma giants have been noting the trends in the Far East and have begun expansion plans, targeting China as an emerging market. Merck announced the launch of its OTC program in September 2003; Roche has listed China as one of its 10 core markets, aiming to expand its OTC sales by 50 percent in the next fi ve years; and both Novartis and Wyeth are setting their sights on the region for expansion purposes.

Pharma companies of ChinaIt is only in recent years that the chinese government

has begun to invest time and money into pharmaceutical R&D, in its aim to boost further expansion.

Shijiazhuang Pharma Group is based in Shijiazhuang, the capital city of Hebei Province in northeast China. It is one of the largest drug fi rms and typical of China’s emerging pharma companies with an interest in research. It works very closely with universities and research groups to develop its research, as well as applying for generic drugs rights before drug patents expire, and has also modernised the traditional Chinese medicines (TCM) to a quantifi able method.

Wuxi Pharmatech operates as a pharma and biotechnology R&D outsourcing company, providing laboratory and manufacturing services in the process to pharma companies. Its operations include process development and manufacturing of advanced intermediates. One of the more major and successful companies, Wuxi Pharmatech is listed on the New York stock exchange.

Harbin Pharmaceutical Group Co. is currently planning a €175 million capital infusion from two foreign investors, Warburg Pincus of New York and Citic Capital of Hong Kong, with the aim of expanding its R&D operations. As the industry continues to grow, chinese pharma companies are clearly becoming more competitive.

Shanghai

Great Wall of China


IN THE BACK138 INTERNATIONAL EVENTS

Drug Delivery Summit

London, England

2 Sep - 4 Sep 09

Tel: +44 1787 315120

[email protected]

www.selectbiosciences.com/conferences/DD2009/

18th International Mass Spectrometry Conference

Bremen, Germany

30 Aug - 4 Sep 09

Tel: +49 30 2093 6985

[email protected]

www.imsc-bremen-2009.de/

AestheticMed St Petersburg

Exhibition Centre Lenexpo, Saint Petersburg, Russia

7 Oct - 9 Oct 09

Tel: +44 207 596 5221

[email protected]

www.primexpo.ru/aesthetic/eng/

Biotechnology for the Non Biotechnologist

Radisson SAS Hotel, Basel, Switzerland

23 Sep - 25 Sep 09

Tel: +44 1483 730071

[email protected]

www.management-forum.co.uk/gxp/eventid/1127

ICSE International Contract Services Expo

IFEMA, Feria de Madrid, Spain

13 Oct - 15 Oct 09

Tel: +31 346 559 489

[email protected]

www.icsexpo.com

7th International Bottom of the Barrel Tech-

nology Conference & Exhibition

Athens, Greece

8 Oct - 9 Oct 09

Tel: +44 207 357 8394

[email protected]

www.europetro.com/epc/

Upcoming conferences and events across the globe.


IN THE BACK139INTERNATIONAL EVENTS

Drug Discovery & Development Week

Boston, MA, USA

3 Aug - 6 Aug 09

Tel: +1 800 390 4078

[email protected]

www.drugdisc.com

Next Generation Pharmaceutical Summit

Ritz Carlton, Amelia Island, FL, USA

28 Oct - 30 Oct 09

Tel: +44 117 921 4000

www.ngpsummit.comAnalytica - Anacon India

Nehru Centre, Mumbai, India

23 Sep - 25 Sep 09

Tel: +49 89 949 22 121

www.imag.de

AnalyticaChina 2010

Shanghai, China

21 Sep - 23 Sep 10

Tel: +49 89 949 22 119

nicole.klammer(at)imag.de

www.analyticachina.com

CPhI SA

Transamerica Expo Center, Sao Paulo, Brazil

26 Aug - 28 Aug 09

Tel: +31 346 559 444

[email protected]

www.cphi-sa.com

Microarray World Congress

South San Francisco, CA, USA

6 Aug - 7 Aug 09

Tel: +44 1787 315110

[email protected]

www.selectbiosciences.com/conferences/MWC2009/


IN THE BACK140 IN REVIEW

The Cure: How Capitalism Can Save American Health CareBy David Gratzer

Drawing upon his experience as a physician in both Canada and the US, Gratzer discredits the in-volvement of legislative bodies within the healthcare system, believing it to lead to a multitude of ineffi ciencies and eventually punishing patients. Th e Cure focuses on reforming the structure to make the individual responsible via a detailed and practical approach.

EHM says: an informative account and required reading for anyone wanting to know what went wrong with the US healthcare system. In going against the current prevailing move towards a cen-tralised system, Gratzer makes a strong case for greater deregulation and freedom. May not be to all tastes, but certainly an interesting read.

On the shelfNGP rounds up the latest books in the healthcare and pharmaceutical sectors.

Pharmaceutical Sales for Phools: The Beginners Guide for Medical Sales Representatives By Sahil Syed

With testimonials from Gary Fagg, Principle Sales Representative at Novartis, and Charles Marshall, Director of Axis Development, Pharmaceutical Sales for Phools has received outstanding reviews from all aspects of the industry. Clearly written and with precise and well-established principles, Syed has created a fi rst-hand account of the pharmaceutical selling market.

EHM says: a well-written and concise conveying of both the industry itself and how to achieve suc-cessful sales.

Leading Pharmaceutical Innovation: Trends and Drivers for Growth in the Pharmaceutical Industry By Oliver Gassmann, Gerrit Reepmeyer and Maximilian von Zedtwitz

Examining the ever-emerging technologies in the R&D sector, this group of authors uses empiri-cal fi ndings, as well as an analytical roundup of research technologies, to produce a well-informed and in-depth review of proactive strategies for value-generating business strategies. As well as new technologies, Leading Pharmaceutical Innovation also focuses on new forms of cooperation and in-ternalisations as other ways of creating a competitive advantage.

EHM says: a well summarised account of strategies, as well as examples from Europe, the US and Asia, for the pharmaceutical executive with a desire to better ROI.

Book review NGP.indd 140Book review NGP.indd 140 29/7/09 15:38:2129/7/09 15:38:21

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IN THE BACK142 PROFILE

As the merger between major drug fi rms Pfi zer and Wyeth becomes reality, what will this mean for the pharmaceutical companies’ heads? Will the union between Jeffrey

Kindler and Bernard Poussot result in a compatible partnership, or will it be a struggle for power with only one winner?

JEFFREY KINDLER, CEO, PFIZER

Prior to his entry into the corporate domain, Kindler’s back-ground was based in law – he clerked for Supreme Court Justice William Brennan and worked at the law fi rm Wil-liams & Connolly – and it was because of this that he was

specifi cally chosen to be Chief Executive. Rather than choose from a pool of 30-something-year experienced

directors, the Pfi zer board selected Kindler, showing a dynamic and fast-paced lawyer to be what is now needed for leadership in an indus-try where legal issues are growing dominant.

On his appointment to the position, Pfi zer’s previous Chairman, Henry McKinnell, described Kindler as a “gift ed natural leader [who] inspires confi dence, and off ers visions and a fresh perspective.”

His leadership is very much infl uenced by the style of both Bren-nan and Jack Welch, former Chairman of General Electric. A belief in creating an entrepreneurial environment for scientifi c leaders to fl our-ish is the way in which he manages a creative business. Rather than a set model, he advocates that diff erent people need diff erent approaches, but at the same time, accountability dependent on results is essential.

Kindler is also a supporter of the freedom of open and robust debate, bring fresh perspective through rethinking and challenging traditional ideas.

BERNARD POUSSOT, CEO, WYETH

A lifer at Wyeth, Poussot has risen to power in a diff erent way to Kindler. He began at the drug fi rm in 1986 as Deputy General Manager of Wyeth France and rose up the ranks to become CEO in January 2008. However, although his

tenure as executive leader has been relatively short in comparison to Kindler, Poussot is not new to leadership roles, previously ranking as President of Wyeth Pharmaceuticals.

In the announcement of the merger, Kindler described Poussot’s leadership as “strong and steady”, and stated him to be an “instrumental part of our integration eff orts [who] will continue to provide us with critical counsel and support until the close of the acquisition.”

Th e relationship between Poussot and Kindler was tumultuous, involving eight months of negotiations. Th e courtship began in June 2008, aft er Kindler contacted Poussot proposing a buy-out. Following a number of stops and starts, and problems with fi nances due to the eco-nomic conditions, a mutual share price was made of $50.19 per share and the sale agreed.

It is thought that Poussot will receive US$53 million if his position is terminated following the sell-out to Wyeth, but until the acquisition is closed and the organisational structure revealed, it is unknown what position, if any, Poussot will take in the combined company.

Profile.indd 142Profile.indd 142 30/7/09 11:38:5530/7/09 11:38:55

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Next Generation PharmaceuticalApproximately 50% of new drugdevelopment fails in the late stages ofphase 3 – while the cost of getting a drugto market continues to rise.

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CATALOGUE PAGE NGPEU:july09 29/07/2009 14:44 Page 143

Cruise ship ‘Ocean Dream’operated by Spanish companyPullmantur carrying 1159people on board off MargaritaIsland, Venezuela, in June. Theship was put in quarantineafter three members of itscrew were found to havesymptoms of H1N1, with afurther 11 people alsosuspected to have the disease.

INTHE BACKPHOTO FINISH144

PHOTO FINISH:13 July 29/07/2009 14:39 Page 144

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