Clinical rd presentation 10 jan2012_sharma

Clinical R&D: Challenges & OpportunitiesAmarnath Sharma MPharm PhD

2nd Annual State of Clinical Development Cost Conference

This document provides an outline of a presentation and is incomplete without the accompanying oral commentary and discussion. Conclusions and/ or potential strategies contained herein are NOT necessarily endorsed by Pfizer management. Any implied strategy herein would be subject to management, regulatory and legal review and approval before implementation.

Amarnath Sharma, MPharm, PhDVice President, Clinical Research & Precision MedicineWorldwide Development OperationsJanuary 10, 2012

Outline

ChallengesLow R&D ProductivityLoss of product exclusivity

OpportunitiesBuild strategic partnership

For External Presentation Purposes; Not for Distribution.

Build strategic partnershipGlobalization of clinical trials

Transformation of Dev Ops at PfizerKey elements of the new model

1

Current R&D Model is Not Sustainable

Low R&D Productivity & Increasing Costs

$1,200

$1,500

R & D Costs to Bring a NME to Market

What will the future be?

For External Presentation Purposes; Not for Distribution. 2

$0

$300

$600

$900

1970 1980 1990 2000 2010

Cos

t ($

Mill

ion)

s la

unch

ed

02-2

008

5

4

3

Successful Launches vs. R&D Spend

Individual R&D Productivity:A Snapshot

For External Presentation Purposes; Not for Distribution.Note: "Successful" NMEs are those that achieve >$600M/yr WW peak sales Source: EvaluatePharma, BCG analysis

0 10 20 30 40 50

Succ

essf

ul N

MEs

betw

een

200

2

1

0

R&D spend in $B 1998-2004

Each dot representsa biopharma company

3

Loss of Exclusivity for Major Products & Patent Erosion

Potential Loss of Significant Revenue


Multiple Reasons For Low R&D Productivity

Compound and / or target related issuesInadequate therapeutic indexThe drug target is not well understoodThe target is valid only in sub-group of patients

Clinical trial design issues


Efficacy observed in the early clinical trials (phase II) have been relatively poor predictors of phase III success Appropriate patient population is not well defined

Clinical trial operations issuesCostQualitySpeed Qualified investigators and sites

Current Industry Trends

• More outsourcing to reduce fixed development costs

• Increased globalization of clinical trialsContinued advancement in execute studies with quality and cost-effectiveness in emerging markets and around the world

• Intensified regulatory focus on GCP compliance & quality


“Quality by Design” in every step of the clinical trial process, from study concept, through protocol development, execution, and reporting

• Amplified clinical trial complexity & “Precision Medicine” approachIncreased complexity of clinical trial design, partnerships and reliance on third parties for trial conduct is likely to result in an increasing shift for sponsors to prove the integrity of their clinical trial dataNeed to prospectively identify patient cohorts of potential “responders” will require the use of biomarkers and alternate trial designs

Cost• The cost of clinical trials continues to increase by more than 20% per

year in developed markets• Conducting trials in developing countries can reduce costs by > 50%

Speed

What is Driving the Globalization of Clinical Trials?


Speed• Patient recruitment in developing markets can more than 100% faster

compared to the U.S. and Western Europe

Availability of large, treatment naïve patient populations

Potential new biopharmaceutical markets for growth

Increased Globalization of Clinical TrialsA Shift to the East

For External Presentation Purposes; Not for Distribution.For External Presentation Purposes; Not for Distribution. 8

Sources: http://www.clinicaltrials.gov/ct2/search/map, date accessed: 16 January 2011.

Karlberg JPE. Responding to Emerging Queries on the Legitimacy and Validity of Globalization of Clinical Trials. Clinical Trial Magnifier. March 2009.

Tufts Center for the Study of Drug Development, Outlook 2008.

R&D centers are looking for opportunities in the emerging markets.

Overall level of comfort with the quality of deliverables/services provided by clinical service providers (including your own company) in each regions.

Providers: Quality by Region Results from 2011 Avoca CRO Oversight Survey

82%

77%

54%

43%

15%

21%

43%

52%

3%

2%

2%

5%

North America

Western/Central Europe

Australia/New Zealand

Eastern Europe

N

102

103

81

99


34%

27%

15%

12%

11%

8%

48%

54%

51%

50%

36%

43%

19%

19%

34%

38%

53%

48%

0% 20% 40% 60% 80% 100%

Japan

Latin/South America

India

Asia, other than India/China/Japan

Africa

China

Very comfortable Somewhat comfortable Not very comfortable

80

89

94

78

73

83

Need for Qualified InvestigatorsA Supply and Demand Imbalance

More Investigators, Lots More Studies Non-US Investigators

8,373

11,22310,735

11,914

8 000

10,000

12,000New Studies New Investigators


2,859 2,676

5,157

7,641

6,226 6,324

1,697 1,518

3,063

4,4613,526

3,038

4,0694,941

4,477 4,482

0

2,000

4,000

6,000

8,000

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

Source: CenterWatch Analysis, FDA, 2008. Published in “State of the Clinical Trials Industry” CenterWatch, 2008

Perceptions & Misperceptions Abound

Misperceptions regarding the globalization of clinical trials include:• Exploitation of vulnerable

clinical subjects• Purposefully seeking loose

regulatory frameworks in which


regulatory frameworks in which to conduct trials

• Ignoring safety concerns• Exploiting loophole in FDA regs:

if studies in U.S. suggest a drug has no benefit, trials from abroad may be used in lieu to secure FDA approval

Increasing Oversight & Regulation

“FDA should expand its oversight of foreign

clinical trials.”

For External Presentation Purposes; Not for Distribution.12

FDA increased its number of inspections from 2007-2009, but still conducts relatively

fewer foreign inspections than domestic inspections - 11% of foreign establishments

inspected in 2009

Recent Trends in Regulatory Inspections

• Both FDA and PMDA have increased the number of inspectors and inspections

• Findings at the site level are increasing and resulting in more findings


The CenterWatch Monthly, Vol 18, Issue 8, August 2010

resulting in more findings of GCP Violations and Warning Letters

Protocol Violations

Inadequate IC Process

Inadequate IRB Review

Requirement of IRB

Deviation

GCP Warning Letter Breakdown(FDA WLs Issued in 2009-10)


http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/EnforcementActivitiesbyFDA/WarningLettersandNo iceofViolationLetterstoPharmaceuticalCompanies/default.htm

0 1 2 3 4 5 6 7 8 9 10

Inadequate Monitoring

Inadequate PI Oversight

Annual IRB Approval Missed

Inadequate Documentation

IRB Deviations PI Deviations Monitor Deviations(3)(18)(5)

How Does Industry Approachthese Issues?

• Ensure compliance with the applicable laws and regulationsNeed to consider all relevant laws in addition to specific medicines laws concerning the conduct of trials, e.g., Privacy laws

• Comply with internationally recognized guidelines and ethical principles

Examples: ICH, GCP, CIOMS and Declaration of Helsinki


• Require a universal position to be adopted for all clinical research activities -- this is ideal

Example: Pfizer’s “Global Clinical Trials Standards” Policy• Support global programs designed to enhance infrastructure for

study conduct and oversightEthics committees, qualified investigators & investigator training

• Seek certification of Research Programse.g., AAHRPP

Site Training & Certification

AAHRPP certification Goal

• All Pfizer CRUs certified (a first for Industry)

• Core Research Sites in progress: Canada, USA, India


India, Hong Kong

• Additional sites progressing towards certification in:

China Russia Brazil

• Global Health Fellows worked with AAHRPP to improve ethical research standards in China

Collaborative Training Workshops:E.g., Clinical R&D in Korea

• 5 Training Sessions on R&D with 550 University Graduate Students; Certificates IssuedCo-hosted with a local CRO (DreamCIS) and co-sponsored with KoNECT (Korea National Enterprise for Clinical Trial), Catholic University of Daegu, Korea University Anam Hospital Clinical Trial Center, Catholic Medical Center Clinical Research Coordinating Center, Inje University Pusan Paik Hospital Clinical Trial Center

• R&D Workshop for 200 physiciansSponsored with Hospitals in Daegu, Severance Hospital. Catholic Medical Center, Korea University Medical Center, Asan Medical Center, Seoul National University H it l B P ik H it l

For External Presentation Purposes; Not for Distribution.–1

Hospital, Busan Paik Hospital.

• Research Operations Training for 40 Coordinators from CRS consortium (Asian Medical Center, Samsung Medical Center, Yeonsei University Severance Hospital, Seoul National University Hospital).

• Pfizer KOREA KoNECT: Expert Course for Clinical Research CoordinatorsSponsored by the Ministry of Health, Welfare, Family Affairs, KONECT, Daejeon City. Hosted with Chungnam National University Hospital CTC, Kyunghee University School of Nursing.

Focus on Quality, Compliance and Performance

% Non Performing Sites

13

23

0

5

10

15

20

25

Emerging Markets Developed Markets–213% –82%


Emerging Markets Developed Markets

0%

20%

40%

60%

80%

100%

Emerging Markets

Developed Markets (ex US)

FDA Inspection results Sep-08 to Apr-10

Official Actions

Voluntary Actions

No actions

–100% –100%

Summary

• Significant trend towards more outsourcing to reduce fixed development costs

• Globalization of the clinical trials is creating “supply/demand” pressures on regulators, sponsors and clinical investigators in emerging marketsThe ind str m st in est reso rces to ens re q alit and


• The industry must invest resources to ensure quality and compliance in the conduct of global clinical trials including a risk based approaches to quality management

• GCP training of investigators and clinical staff is essential• Ultimately, well conducted global clinical trials will improve the

R&D productivity and also increase patient access to medicines

19

Transformation of the Dev Ops Model at Pfizer


at Pfizer

Simple with Clear Accountability

17+ FSPs ICON & Parexel


Key Elements of New Dev Ops Model

From Pfizer's previoussourcing model...

...to innovative, value-creatingstrategic partnerships

17+ Functional Service Providers for individual studies resulting in diffuse accountability & limited transparency

Full service model with alliance partners supporting entire assets with increased visibility and accountability

Quality = imposed Pfizer processes

Quality = AP responsibility for robust process with Pfizer accountable for oversight

Selection of best indi id al Collaboration for best o erall clinical de elopment q alit &


Selection of best individual functional expertise

Collaboration for best overall clinical development quality & performance

Prescriptive specifications on clinical studies

Incentives towards innovative approaches from APs In the clinical development plan, on resourcing, site selection and timeline

Suppliers' competition on unit costs

Partners' competition on overall performance and joint value creation

With focus on speed & qualityImpact on NPV of assets

Transactional relationships Trusting environment / platforms in which innovative ideas can flourish

This is an industry-leading change

Extensive Due Diligence:Evaluation of Leading1 Global Clinical CROs

Quality was a primary driver of selection of the partners:Overall quality approaches/philosophy, quality quantification, learnings from past experienceTechnical capability to execute on plan, including IT support of tracking of qualityWillingness to be transparent and to work with us collaboratively on addressing challenges

Evidence-based process was followedDiscussions with senior management of each companyDeep technical discussions between Pfizer subject matter experts (SMEs) and partner SMEs


on process and cultureOn-site audits by team of internal and external experts covering following areas:

1. Top 4 of 5 by revenue in the clinical development space

Regulatory Inspection ManagementCorrective action and remedial plansQC and QA activitySOP development and managementRecords managementStaff trainingSubcontracting and vendor oversightFacilities

Clinical trial related activitiesInvestigator recruitment and trainingStudy start up and close outProject managementMonitoringTrial Master FileSafety management and reconciliation Medical writing

Key document development (e.g. protocol, ICF)Information TechnologyValidation of computerized systemsClinical data management/clinical programmingData retention, security and recovery

Overarching Quality & Risk Mitigation Strategies

Quality & risk mitigation built into the agreement & operating plansBalanced Scorecard with metrics used as indicators of performance, includes specific quality metricsMetrics are used to assess performance and determine rewards/penalties Service Agreements contain requirements on specific quality/compliance Standards

Support for voluntary certification of Pfizer research programs


Support for voluntary certification of Pfizer research programs Proposal to seek full certification by AAHRPP which is considered “Gold Standard” for independent accreditation of research programs

Regulatory agency considerationPosition of regulatory agencies (FDA, MHRA, EMA) was considered in advance of executing

Organizational model was “built for purpose” over the last 24 months

24

Key Features of the New Model

• Partners input in operational plan and investigator selection to optimize quality, cost and execution timelines

• Partners commit to maintain/develop capabilities in all TAs where Pfizer needs support

• Post-PoC asset allocation to one AP with expectation that they will follow


p ythrough the entire development / life cycle

• Expectation that all studies will be managed by one of the two APs

• Unconstraining the APs by having them use their systems and procedures to deliver value to Pfizer

With overall quality standards defining the “what” set by and actively monitored by Pfizer

25

Clinical rd presentation 10 jan2012_sharma

Business

external presentation

dev ops model

clinical trials

emerging markets

model

trials

pfizer

quality