Safety Risk ManagementC P tiCompany Perspective

Akihisa Harada, MD, Ph.DVP, Development JapanPfizer Japan IncPfizer Japan Inc.

R&D Head Club

AgendaAgenda

• REMS in FDAAA• Safety Risk Management throughout aSafety Risk Management throughout a

Drug’s LifecycleRi k C i ti• Risk Communications

• Conclusions Co c us o s

What is ‘Risk Management’

Comprehensive and proactive science based methodologies•• Identify safety risk earlierIdentify safety risk earlierIdentify safety risk earlierIdentify safety risk earlier•• Assess appropriatelyAssess appropriately•• CommunicationCommunication

Mi i i i kMi i i i k•• Minimize riskMinimize riskEstablish benefit risk profilep

Risk Evaluation and Mitigation

• PDUFA IV FDA Safety Five year plan (draft Mar 2008 )

Strategies (REMS) in US• PDUFA IV FDA Safety Five-year plan (draft Mar. 2008,)• Required Based on FDA Benefit-Risk Assessment with

$250 K - $10 MM REMS violation penalties$250 K - $10 MM REMS violation penalties • REMS Elements:

• Medication Guide• Medication Guide • Risk Communication Plan• Elements to Assure Safe Use• Implementation System

• Assessment of REMAS:• Timetable of Assessments• Information needed for Assessment

Safety Risk ManagementSafety Risk Management throughout a Drug’s Lifecycleg g y

Risk management across the product lifecycleproduct lifecycle

Product Life Cycle

FIM Ph I Ph II Ph III Ph IVAnimal studies

Drug Discovery/PreclinicalDrug Discovery/Preclinical Clinical DevelopmentClinical Development Post Approval Pharmacovigilance

Post Approval Pharmacovigilance

Approval

Estimate potentialbenefit

Understand the

Studies to better understand population, risks, etc

Address anynew emergingsafety issuesUnderstand the

disease

Predict potentialcandidates

ID potential signals

Promote betterapproval analysis

Post-approval studies and epidemiology

Signal detectionDisease Mechanism of Action Studies

Achieve appropriate label

Signal detection

Product defense

risk management planning

Understanding Risk and Accumulation of K l d f S f t P filKnowledge of Safety Profile

Earlier Risk Management Planning is key for successfulEarlier Risk Management Planning is key for successful

Background Spontaneous Observational OtherClinical

product life cycle managementproduct life cycle management

BackgroundEpidemiology

SpontaneousReports

ObservationalStudies

OtherActivities

ClinicalStudies

INCIDENCE OF COMMONLY

OCCURRING EVENT FROM CLINICAL

INCIDENCE OF EVENTIN GENERAL POPULATION

IDENTIFICATION OF

POTENTIAL SIGNALS OF RARE EVENTS

1/100,000

HYPOTHESIS TESTING1/1,000,000

1/500 000

POTENTIAL RISKIDENTIFIED

FROMNON CLINICAL FROM CLINICAL

TRIALS RISK FACTORS

1/1,0001/500

1/10,000

1/5,000

,

1/50,000

1/10,000

1/500,000

1/100,000,

NON-CLINICALSTUDIES

Risk Management/Assessment StrategyRisk Management/Assessment Strategy

1/100,

1/1,000

Risk Management/Assessment StrategyRisk Management/Assessment Strategy

Risk Management Committee (RMC)

• Sub-team of Development Team: formed at Phase IIBCli i l & li i l f t• Clinical & nonclinical safety stakeholders

• Risk Log: documents both• Risk Log: documents both observed and hypothetical risks

• Plans for signal detection• Plans for signal detection, assessment, and mitigation

• Forum for discussion of safetyA forum to formalize the Safety Risk Management program for a compoundForum for discussion of safety

issues throughout a product life cycle

program for a compound

RMC ActivitiesRMC ActivitiesStep 1:

Identify and AssessIdentify and Assess a product’s benefit-risk

balance

RMC

Step 2: Develop and

implement toolsminimize risks

Step 4: Modify risk

minimization tools to further improve

- preserve benefits

Step 3: Evaluate tool ff ti

benefit-risk balance

effectiveness and reassess the

benefit-risk balance

Communication of Risk Internally and Externally

Implementation of RMP in JapanImplementation of RMP in JapanS f t Global-RMPSafety

Specifications

Pharmacovigilance Plan

Japan Appendix (J-RMP)

Basic Plan for Post Marketing Surveillance

C T h i l D t

Basic Plan for Post Marketing Surveillance

Common Technical DocumentJ-CTD module 1

How effectively implement RMP in Japan?

• Basic PMS Plan at J-NDA effective enough?• Should we wait the discussion until later• Should we wait the discussion until later

stage of J-NDA review?I iti ti f di i RMP h ld b• Initiation of discussions on RMP should be more earlier development stage

• Should we have new category of PMDA consultation, Risk Management Plan consultation?

Risk Communications

E t l Ri k C i tiExternal Risk CommunicationRegulatorsRegulators Physicians/Investigators/PatientsPhysicians/Investigators/Patients

Web Site/ Telecons &

F2F meetings

License Applications

Safety Investigator

Reports

Reports to External

Data Safety Monitoring

Boards

DTC (US)

Pre-ClinicalStudy

ReportsRegulatory

Reports

InvestigatorBrochures

Expert Panels/

Dear HCP Letters

ClinicalStudy

ReportsRisk

Management Plans

InformedConsent

Panels/Scientific Advisory Boards

RegulatoryBriefing

Documents Ethics Committees

ProductLabels

Publications

Chantix: Medication Guide (US)

What do you need to know? y• The most important information that patients

should know

• Immediate action that patient should take if that hhappens

N t ti th t ti t h ld t k ft• Next action that patient should take after immediate action

• Common side effect

• Other precautions

Medicine Safety Web Sitey-Direct communication to patients and healthcare providers-

• In Industry First, the Web site is launched to improve understanding of how risks and benefits of medicine

d t i d it d d i t dare determined, monitored and communicated. • A clear need to increase awareness of medicine

safety among patients healthcare providers andsafety among patients, healthcare providers and professionals

• This site delineates the role of• This site delineates the role of – Pharmaceutical companies– The regulatory officeg y– Healthcare provider

http://www.pfizer.com/responsibility/medicine_safety/medicine_safety.jsp

Sutent: Company Web information (Japan)

Risk CommunicationHealth CareHealth Care

Risk CommunicationHealth Care

ProfessionalsHealth Care

Professionals

PatientPatient

CompanyCompanyRegulator p yp y

Patient’s Safety First

ConclusionsConclusions• Increased focus on Safety and Risk Management is

a global issue with diminishing boundariesg g• Focus is representative of the entire lifecycle of a

drug as knowledge and experience further develops and expands with drug useand expands with drug use.

• Development of Global Risk Management Planrather than individual region or country Risk M t Pl ld b i t t tManagement Plans would be an important step forward to more effectively and accurately assess the safety of pharmaceutical drug products.

• Earlier Risk Management Planning b/w Company, Regulator and Healthcare Professionals is key for successful product life cycle managementsuccess u p oduct e cyc e a age e t

• Risk Communication Plan b/w Company, Regulator, Healthcare Professionals and Patients is getting more importantmore important