Optimizing Pfizer Inc’s Optimizing Pfizer Inc’s New Product Development ProcessNew Product Development Process
Transforming Molecules to Transforming Molecules to MedicinesMedicines
AMAMX50.9252: Mastering New Product & Service X50.9252: Mastering New Product & Service DevelopmentDevelopmentSunday, November 19, 2006Sunday, November 19, 2006
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Key QuestionsKey Questions
WHOWHO Pfizer IncPfizer Inc
WHATWHAT In Dire Need of a New Product Development ProcessIn Dire Need of a New Product Development Process
WHEREWHERE Throughout the Entire Organization Throughout the Entire Organization
WHENWHEN Within the Next 5 YearsWithin the Next 5 Years
WHYWHYIndustry Challenges / Pipeline Concerns: PFE is struggling Industry Challenges / Pipeline Concerns: PFE is struggling to maintain its growth in the face of increased to maintain its growth in the face of increased competition and the expiration of key patents. competition and the expiration of key patents.
HOWHOWBy Leveraging Internal Insights & Implementing a New By Leveraging Internal Insights & Implementing a New Product Development Process Incorporating the Product Development Process Incorporating the Stage-Stage-Gate™Gate™ Process Process
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An Introduction to PfizerAn Introduction to Pfizer
OUR OUR MISSIONMISSION
We will become the world's most valued company to We will become the world's most valued company to patients, customers, colleagues, investors, business patients, customers, colleagues, investors, business partners, and the communities where we work and live.partners, and the communities where we work and live.
OUR OUR PURPOSPURPOS
EE
We dedicate ourselves to humanity's quest for longer, We dedicate ourselves to humanity's quest for longer, healthier, happier lives through innovation in healthier, happier lives through innovation in pharmaceutical, consumer, and animal health products.pharmaceutical, consumer, and animal health products.
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Pfizer Research and Development: CommitmentPfizer Research and Development: Commitment
DID YOU KNOW ?DID YOU KNOW ?
Pfizer invests more in Pfizer invests more in pharmaceutical research than any pharmaceutical research than any
other private institution in the other private institution in the world. world. 1 1
This research is aimed at a single This research is aimed at a single goal: to develop new medicines that goal: to develop new medicines that will enable people to lead healthier, will enable people to lead healthier, longer and more productive lives.longer and more productive lives.
1 The Department of Trade and Industry (U.K.) The 2005 R&D Scoreboard. Page 96. Available at: http://www.innovation.gov.uk/rd_scoreboard/. Accessed on Oct. 26, 2005.
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Pfizer Research and Development: Key PointsPfizer Research and Development: Key Points
The discovery of new drugs The discovery of new drugs and their development into and their development into useful pharmaceuticals is useful pharmaceuticals is central to the concept of central to the concept of medical progress. medical progress.
The U.S. pharmaceutical and The U.S. pharmaceutical and biotech industries invested biotech industries invested nearly $39 billion in nearly $39 billion in research and developmentresearch and development in in 2004, with 2004, with Pfizer leading the Pfizer leading the way with $7.7 billion and way with $7.7 billion and 12,500 scientists12,500 scientists. . 2,32,3
2 PhRMA. Press Release. Feb. 18, 2005. Available at: http://www.phrma.org/mediaroom/press/releases/18.02.2005.1128.cfm. Accessed on Oct. 26, 2005.3 Pfizer 2004 Annual Report. Available at: /pfizer/annualreport/2004/financial/p2004fin08.jsp. Accessed on Oct. 26, 2005. Also see Pfizer.com Research and Development website, available at: /pfizer/help/index.jsp.
Years to create aYears to create anew drug: new drug: 12-15 years 12-15 years
Probability of Success: Probability of Success: <1% <1%
Costs to create aCosts to create anew drug: new drug: Between $800 Between $800 million and $1.7 billionmillion and $1.7 billion
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Pfizer Research and Development: Risky Pfizer Research and Development: Risky BusinessBusiness Only Only one in fiveone in five medicines that enter clinical trials testing in humans medicines that enter clinical trials testing in humans
is is eventually approvedeventually approved for patient use by the U.S Food and Drug for patient use by the U.S Food and Drug Administration (FDA). Administration (FDA). 6 6 That's part of the risk involved in Pfizer's That's part of the risk involved in Pfizer's business of seeking out new and innovative health solutions. business of seeking out new and innovative health solutions.
6 Stanford Medical School's Academic Consortium for Clinical Excellence in Scientific Studies. Clinical Trials FAQ. Available at: http://clinicaltrials.stanford.edu/patients/ctfaq.html. Accessed on Oct. 26, 2005.
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Seven Goals of a New Product ProcessSeven Goals of a New Product Process
Goal #1: Quality of ExecutionGoal #1: Quality of Execution
Goal #2: Sharper Focus, Better PrioritizationGoal #2: Sharper Focus, Better Prioritization
Goal #3: Fast-Paced Parallel ProcessingGoal #3: Fast-Paced Parallel Processing
Goal #4: A True Cross-Functional Team ApproachGoal #4: A True Cross-Functional Team Approach
Goal #5: A Strong Market Orientation with the Voice of the Goal #5: A Strong Market Orientation with the Voice of the Customer Built InCustomer Built In
Goal #6: Better Homework Up-FrontGoal #6: Better Homework Up-Front
Goal #7: Products with Competitive AdvantageGoal #7: Products with Competitive Advantage
Source: Winning at New Products by Robert G. Cooper, p.115
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With Such High Risks and the Vital Importance of New With Such High Risks and the Vital Importance of New Medicines - New Product Development Systems Must Be Medicines - New Product Development Systems Must Be OptimizedOptimized
Research and Technical Research and Technical DevelopmentDevelopment Gate 1: Idea ScreenGate 1: Idea Screen Stage 1: Technical Stage 1: Technical
AssessmentAssessment Gate 2: Second ScreenGate 2: Second Screen Stage 2: Detailed Stage 2: Detailed
InvestigationInvestigation Gate 3: Application Path Gate 3: Application Path
GateGate
New Product DevelopmentNew Product Development Gate 1: Idea ScreenGate 1: Idea Screen Stage 1: ScopingStage 1: Scoping
Gate 2: Second ScreenGate 2: Second Screen Stage 2: Building Business Stage 2: Building Business
CaseCase Gate 3: Go to DevelopmentGate 3: Go to Development Stage 3: DevelopmentStage 3: Development Gate 4: Go to TestingGate 4: Go to Testing Stage 4: Testing and ValidationStage 4: Testing and Validation Gate 5: Go to LaunchGate 5: Go to Launch Stage 5: LaunchStage 5: Launch Post-Launch ReviewPost-Launch Review
Robert G. Cooper’s Robert G. Cooper’s Two-Stage ModelTwo-Stage Model
Project enters the NP Process at Gates 1, 2, or 3
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Robert G. Cooper’s Robert G. Cooper’s Two-Stage ModelTwo-Stage Model
STAGE 1STAGE 1
STAGE 2STAGE 2
STAGE 3STAGE 3
STAGE 5STAGE 5
STAGE 4STAGE 4GATE 3GATE 3 GATE 4GATE 4GATE 2GATE 2 GATE 5GATE 5
LAUNCHLAUNCH
Scoping Build Business Case Development Testing &
Validation
Decision to spendConfirm case
Review probable execution
Revised financialsQuality = original def.
Work reviewedGo to test
Review costsReview profits
Review strengthsReview weaknessesReview what learned
STAGE 1STAGE 1 GATE 2GATE 2
STAGE 2STAGE 2
GATE 3GATE 3GATE 1GATE 1
TechnicalAssessment
DetailedInvestigation
Research and Technical DevelopmentResearch and Technical Development
GATE 1GATE 1
Legal Technical
Sales InvolvedMarketing Involved
Payback period POST POST LAUNCHLAUNCHREVIEWREVIEW
New Product DevelopmentNew Product Development
Project enters the NP Process at Gates 1, 2, or 3
Application Path Gate
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Transforming Molecules to MedicineTransforming Molecules to Medicine
Phase I Phase II Phase IIIn = 10 - 30 n = 20 - 200 n = 500 - 10,000
ClinicalClinicalClinicalClinical
CH3
C1
R1-10
CH3
C1
R4
DiscoveryResearch Team
Many Compounds
In vitro & in vivo Screening
Drug Candidate Selection
Scale Up & Animal Tox
File IND
PreclinicalPreclinicalPreclinicalPreclinical
++
Regulatory ReviewPhase IV
File NDA
Regulatory Review & CommercializationRegulatory Review & CommercializationRegulatory Review & CommercializationRegulatory Review & Commercialization
RegulatoryApproval & Launch
RegulatoryApproval & Launch
Testing the Experimental Drug in Testing the Experimental Drug in PeoplePeople
Finding the Right Lead MoleculeFinding the Right Lead Molecule
From Laboratory to the DoctorFrom Laboratory to the Doctor
EstablishinEstablishing the g the
Safety and Safety and Efficacy of Efficacy of
a New a New Medicine Medicine
for for PatientsPatients
EstablishiEstablishing the ng the Safety of a Safety of a New New Molecule Molecule for for Human Human TestingTesting
Research and Technical Development Research and Technical Development New Product New Product DevelopmentDevelopment
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Transforming Molecules to MedicineTransforming Molecules to Medicine
DiscoveryDiscovery
0
2
4
6
8
10
12
14
16
0
2
4
6
8
10
12
14
16
Average YearsAverage YearsAverage YearsAverage Years
Phase IPhase I
Phase IIIPhase III
PostmarketinPostmarketingg
Phase IIPhase II
PreclinicalPreclinical
RegistratioRegistrationn
Compound SuccessCompound SuccessCompound SuccessCompound Success
Rates by StageRates by Stage
5,000 – 10,000Screened
5,000 – 10,000Screened
250Enter Preclinical
250Enter Preclinical
5Enter
Clinical
5Enter
Clinical
1 Approved 1 Approved MedicineMedicine
Research and Technical Development Research and Technical Development New Product New Product DevelopmentDevelopment
12
Reasons Why Medicine Candidates FailReasons Why Medicine Candidates Fail
0
2
4
6
8
10
12
No.
can
did
ate
s
0 1 2 3 4 5 6 7 8 9YearsPreclin. Phase I Phase II Phase III Registration
animal toxicity, PKanimal toxicity, PKchemical stability,chemical stability,superior compoundsuperior compound
animal toxicity, PKanimal toxicity, PKchemical stability,chemical stability,superior compoundsuperior compound
efficacy/safety,efficacy/safety,differentiation,differentiation,
dose/cost of goodsdose/cost of goods
efficacy/safety,efficacy/safety,differentiation,differentiation,
dose/cost of goodsdose/cost of goods
human PK,human PK,safety/toleration,safety/toleration,
formulationformulation
human PK,human PK,safety/toleration,safety/toleration,
formulationformulation
efficacy, long-term safetyefficacy, long-term safetyefficacy, long-term safetyefficacy, long-term safety non-approvalnon-approvalnon-approvalnon-approval
It takes 12 CANs to yield 1 marketed drug It takes 12 CANs to yield 1 marketed drug on averageon average
It takes 12 CANs to yield 1 marketed drug It takes 12 CANs to yield 1 marketed drug on averageon average
Research and Technical Development Research and Technical Development New Product New Product DevelopmentDevelopment
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The Drug Discovery and Development ProcessThe Drug Discovery and Development Process
DiscoveryDiscovery
Exploratory DevelopmentExploratory Development
Full Full DevelopmentDevelopment
RegistrationRegistration
Research and Technical Development Research and Technical Development New Product New Product DevelopmentDevelopment
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Drug Discovery: The Overarching QuestionsDrug Discovery: The Overarching Questions
Is there a medical need?Is there a medical need?
What is prevalence of the disease?What is prevalence of the disease?
What is the market potential?What is the market potential?
Do we have a biochemical target?Do we have a biochemical target?
Can we synthesis compounds that are Can we synthesis compounds that are target selective, potent target selective, potent in vivoin vivo, and bioavailable?, and bioavailable?
Are the compounds efficacious in disease Are the compounds efficacious in disease models, show dose models, show dose response, and are not toxic?response, and are not toxic?
Voice of Voice of CustomeCustome
r r ResearchResearchBuilding Building Business Business
Case Case
Technical Technical Assessment Assessment
Detailed Detailed Investigation Investigation
Research and Technical Development Research and Technical Development New Product New Product DevelopmentDevelopment
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Where Do Potential Leads Come From?Where Do Potential Leads Come From?
LEADLEADLEADLEAD
Acquisition CompoundsAcquisition CompoundsAcquisition CompoundsAcquisition Compounds Natural SourcesNatural SourcesNatural SourcesNatural Sources
Endogenous LigandEndogenous LigandEndogenous LigandEndogenous Ligand Newly SynthesizedNewly SynthesizedNewly SynthesizedNewly Synthesized
Random Screening Random Screening of Existing Compoundsof Existing Compounds
Random Screening Random Screening of Existing Compoundsof Existing Compounds
GlaxoWellcomeGlaxoWellcome
AstraZenecaAstraZeneca
MerckMerck
e.g. Natural e.g. Natural peptide, hormone, peptide, hormone, etc.etc.
Combinatorial ChemistryCombinatorial ChemistryLibrariesLibraries
Combinatorial ChemistryCombinatorial ChemistryLibrariesLibraries
Research and Technical DevelopmentResearch and Technical Development
IdeationIdeation
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Discovery (3–4 Years)Discovery (3–4 Years)
BasicScienceBasic
Science
MedicalLiteratureMedical
Literature
MedicalNeed
MedicalNeed
Disease Disease InterventioInterventio
n n HypothesisHypothesis
TargetTargetCharacterizatioCharacterizatio
nn
Synthesis of Synthesis of MoleculesMolecules
ScreeninScreeningg
ActivityActivity
ImprovedActivity
ImprovedActivity
RefinemeRefinementnt
Initial Initial Safety Safety
Testing of Testing of Lead Lead
MoleculeMolecule
Nomination Nomination of Lead of Lead
Molecule for Molecule for Additional Additional InvestmentInvestment
NNoo
YeYess
++ ++
Research and Technical DevelopmentResearch and Technical Development
Ideation, Gate 1, Stage 1Ideation, Gate 1, Stage 1
Go / KillGo / Kill
Voice of Voice of CustomeCustome
r r ResearchResearch
Gate 2Gate 2
Detailed Detailed Investigation: Investigation:
Stage 2Stage 2
17
Discovery (3–4 Years)Discovery (3–4 Years)
Disease Interventi
on Hypothesi
s
TargetCharacterizati
on
Synthesis of
Molecules
Screening
++
Thousands of Potential Disease Targets to Consider
Define Target and Structure at Molecular Level
Synthesis and Testing of Molecules to Bind to Target
Testing Against Target for Biological Effect
Identify and Refine a Portfolio of Identify and Refine a Portfolio of Promising Molecules (“Candidates”)Promising Molecules (“Candidates”)
Identify and Refine a Portfolio of Identify and Refine a Portfolio of Promising Molecules (“Candidates”)Promising Molecules (“Candidates”)
1111
2222
3333
4444
++
Ideation, Gate 1, Stage 1, and Ideation, Gate 1, Stage 1, and Gate 2Gate 2
Go / KillGo / Kill
Research and Technical DevelopmentResearch and Technical Development
IdeationIdeation Gate 1Gate 1
Technical Technical AssessmenAssessment: Stage 1t: Stage 1
Gate 2Gate 2
18
Early Development (3–5 Years)Early Development (3–5 Years)
Lead Lead Molecule Molecule Endorsed Endorsed
for for Additional Additional InvestmenInvestmen
tt
ManufacturManufacture Suppliese Supplies
Required Required Animal Animal TestingTesting
FormulatFormulate Doses e Doses
for for HumansHumans
INDApplicatio
n
INDApplicatio
n
YES!(Proof ofConcept)
YES!(Proof ofConcept)
MetaboliMetabolism Datasm Data
Phase I:Phase I:Human Human Testing Testing
in in Healthy Healthy
VolunteerVolunteerss
Phase II:Phase II:Human Human Testing Testing
in in PatientsPatients
Phase II:Phase II:Human Human Testing Testing
in in PatientsPatients
Is it Is it safe?safe?
How How does it does it behave behave in the in the body?body?
Is it Is it safe?safe?
Does Does the the
drug drug provide provide benefit?benefit?
Is it Is it safe?safe?
What is What is the the
optimal optimal dose?dose?
Safety Safety DataData
Research and Technical Development Research and Technical Development New Product New Product DevelopmentDevelopment
Technical Assessment:Technical Assessment:Ideation, Gate 1, Stage 1, Ideation, Gate 1, Stage 1,
Gate 2Gate 2
Detailed Investigation: Detailed Investigation: Stage 2Stage 2
Application Path GateApplication Path Gate
Building Building Business Business
Case: Case: Stage 2Stage 2
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Early Development (3–5 Years)Early Development (3–5 Years)
Required Animal Testing
Formulate Doses for Humans
Phase I
Phase II
Preclinical Research Requires Testing Candidates in Animals
Determine Dosage Based on Safety and Metabolism Data
Dose Healthy Volunteers (Absorption, Distribution, Metabolization, and Elimination)
Dose Patients (Efficacy)
Test Safety and Efficacy of “Candidates”Test Safety and Efficacy of “Candidates”Under Controlled ConditionsUnder Controlled Conditions
Test Safety and Efficacy of “Candidates”Test Safety and Efficacy of “Candidates”Under Controlled ConditionsUnder Controlled Conditions
1111
2222
3333
4444
Research and Technical DevelopmentResearch and Technical Development
Detailed Investigation: Stage 2Detailed Investigation: Stage 2
Go / KillGo / Kill
Gate 2Gate 2
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Disciplines Involved in Drug Development Disciplines Involved in Drug Development ResearchResearch
Product DevelopmentProduct Development
PharmacologyPharmacology
SafetySafety
Clinical SciencesClinical Sciences
Clinical DevelopmentClinical Development
Development OperationsDevelopment Operations
BiostatisticsBiostatistics
MedicalMedical
Clinical Pharmacy OperationsClinical Pharmacy Operations
Library Sciences Library Sciences
Chemical ManufacturingChemical Manufacturing
Regulatory AffairsRegulatory Affairs
Project ManagementProject Management
MarketingMarketing
BiomarkersBiomarkers
InformaticsInformatics
Etc …Etc …
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Full Development (3–5 Years)Full Development (3–5 Years)
Collect, Collect, Verify, & Verify, &
Analyze DataAnalyze Data
Recruit Recruit 1000s of 1000s of PatientsPatients
File NDAFile NDA
Conduct Conduct Phase III Phase III TestingTesting
RecruitInvestigators
RecruitInvestigators
ManufactureDrug SupplyManufactureDrug Supply
Formulate,Label, &
Ship
Formulate,Label, &
Ship
Design Phase IIIStudies
Design Phase IIIStudies
ConsultFDA
ConsultFDA
StabilityStudiesStabilityStudies
Carcino-genicityStudies
Carcino-genicityStudies
Full Development
Planning
Full Development
Planning
Building Business Case: Building Business Case: Stage 2Stage 2
Research and Technical Development Research and Technical Development New Product New Product DevelopmentDevelopment
Detailed Detailed InvestigatioInvestigatio
n: n: Stage 2Stage 2
DevelopmeDevelopment: nt:
Stage 3Stage 3
Testing & Testing & ValidatioValidatio
n: n: Stage 4Stage 4
Gate 5Gate 5
Full Team Full Team InvolvementInvolvement
22
Full Development (3–5 Years)Full Development (3–5 Years)
Plan Full Development Program
Phase III
Collect, Verify,
& Analyze
Data
File New Drug
Application
Plan Phase III Studies, Supply, as well as Investigator Recruitment and Education
Extensive Safety and Efficacy Testing with Patients under Real World Conditions
Ensure Benefit of Candidate is Clearly Demonstrated in Patient Population
Documented Evidence Concerning the Safety and Efficacy of the new Molecule
Full Developme
nt Planning
Full Developme
nt Planning
File NDAFile NDA
11
22
33
44
Demonstrate Efficacy and Safety of a Candidate in PatientsDemonstrate Efficacy and Safety of a Candidate in PatientsDemonstrate Efficacy and Safety of a Candidate in PatientsDemonstrate Efficacy and Safety of a Candidate in Patients
1111
2222
3333
4444
Research and Technical Development Research and Technical Development New Product New Product DevelopmentDevelopment
Gate 5Gate 5Gate 4Gate 4
Gate 2Gate 2Testing & Testing &
Validation: Validation: Stage 4Stage 4
23
Registration (1–2 Years)Registration (1–2 Years)
Respond Respond to to
QuestionsQuestions
Approved New
Medicine
Approved New
Medicine
Present to Present to Advisory Advisory
CommitteeCommitteess
Other Regulator
yFilings
Other Regulator
yFilings
File NDAFile NDA
RegulatoryRegulatoryApprovalsApprovals
Label Label NegotiatioNegotiatio
nsns
New Product DevelopmentNew Product Development
Launch: Stage 5Launch: Stage 5
Gate 5Gate 5
POST POST LAUNCHLAUNCHREVIEWREVIEW
•Review costs•Review profits•Review strengths•Review weaknesses•Review what learned
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Leverage Internal Resources and Leverage Internal Resources and Stage-Gate™Stage-Gate™ Process to Process to Increase R&D Productivity and Maximize Commercial SuccessIncrease R&D Productivity and Maximize Commercial Success
Leverage Internal Resources and Leverage Internal Resources and Stage-Gate™Stage-Gate™ Process to Process to Increase R&D Productivity and Maximize Commercial SuccessIncrease R&D Productivity and Maximize Commercial Success
Molecules to Medicine: Room for ImprovementMolecules to Medicine: Room for Improvement
CAN CAN
NDA/ NDA/ MAA MAA
ApprovalApprovalKey Commercial Key Commercial Decision Points:Decision Points:Key Commercial Key Commercial Decision Points:Decision Points:
Stage:Stage:Stage:Stage:
Type of Testing:Type of Testing:Type of Testing:Type of Testing:
NDA/ NDA/ IRD IRD
FilingFiling
LaboratoryLaboratory AnimalsAnimalsPhasePhase
I IIA IIBI IIA IIBPhase IIIPhase IIIPhase IIIBPhase IIIB Phase IVPhase IV
POC/POC/R2D2-R2D2-
11R2D2-R2D2-
22DIC-IIDIC-II
PostPostLaunchLaunch
Late Late ClinicalClinicalClinicalClinicalEarly Clinical Early Clinical Pre-Pre-
ClinicalClinicalDiscoveryDiscovery
IdeaIdea
Accelerate candidate identification and screeningAccelerate candidate identification and screening Accelerate development timeAccelerate development time Improve labels and market accessImprove labels and market access Leverage depth of knowledge from exploratory through loss Leverage depth of knowledge from exploratory through loss
of exclusivityof exclusivity Ensure global knowledge sharing and collaborationEnsure global knowledge sharing and collaboration