New EU Pharmacovigilance New EU Pharmacovigilance Legislation Legislation ggA Company perspectiveA Company perspective

Willemijn van der SpuijWillemijn van der Spuijj p jj p jBristol Myers SquibbBristol Myers SquibbGlobal Pharmacovigilance Global Pharmacovigilance andand EpidemiologyEpidemiologygg p gyp gyInternational Head International Head ofof OperationsOperations & PV & PV IntelligenceIntelligence

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DisclaimerDisclaimerDisclaimerDisclaimer

The views and opinions expressed in the followingThe views and opinions expressed in the followingThe views and opinions expressed in the following The views and opinions expressed in the following presentation are those of the individual presenter. presentation are those of the individual presenter. These views should not be attributed to any organization,These views should not be attributed to any organization,These views should not be attributed to any organization, These views should not be attributed to any organization, group or society.group or society.

AgendaAgendaAgendaAgenda

LegislationLegislation

Objective of legislationObjective of legislation

Top Level ChangesTop Level Changes

New Modules & Impact on MAHsNew Modules & Impact on MAHs

Implementation RequirementsImplementation Requirements

LegislationLegislationLegislationLegislation

Reg 1235/2010Dir 2010/84/EC

Published: 31st December 2010

Reg 726/2004Dir 2001/83/EC Published: 31 December 2010

Regulation will apply from: 2nd July 2012Directive will apply from: 21st July 2012

-“The legislation aims to save lives by strengthening the European-wide system g y g g p yfor monitoring the safety of medicines”

-It is the biggest change for human medicines since the establishment of the EMA in 1995

-16 Modules will replace Volume 9A

LegislationLegislationLegislationLegislation

Reality check…………..Reality check…………..

Good Vigilance Practices (Wave 1)Good Vigilance Practices (Wave 1)–– Released for public consultation on February 21st, 2012Released for public consultation on February 21st, 2012–– Companies’/EFPIA comments releasedCompanies’/EFPIA comments released–– Final Final documentsdocuments in June 2012in June 2012

EU Commission Questions & EU Commission Questions & Answers (February Answers (February 2012)2012)

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http://www.youtube.com/watch?v=IWwhttp://www.youtube.com/watch?v=IWwCjCj--GPel0GPel0

Objective of new legislationObjective of new legislationObjective of new legislationObjective of new legislation

For all parties, the legislation aims to:For all parties, the legislation aims to:

Provide clarity on roles and responsibilitiesProvide clarity on roles and responsibilities Minimise duplication of effort and increase efficiencyMinimise duplication of effort and increase efficiency Minimise duplication of effort and increase efficiencyMinimise duplication of effort and increase efficiency Provide a clear legal framework for postProvide a clear legal framework for post--authorisation authorisation

monitoringmonitoringmonitoringmonitoring RiskRisk--based approach and probased approach and pro--active pharmacovigilanceactive pharmacovigilance Increase transparencyIncrease transparency Increase transparencyIncrease transparency Engaging patients and healthcare professionalsEngaging patients and healthcare professionals

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Top level changesTop level changesTop level changes Top level changes

Legal requirement to have a quality system to support Legal requirement to have a quality system to support PV activitiesPV activities

Introduction of the Pharmacovigilance System Master Introduction of the Pharmacovigilance System Master File (all products)File (all products)

RMP including risk minimisation strategy is required for RMP including risk minimisation strategy is required for all new MA applications from July 2012 all new MA applications from July 2012

Reporting of nonReporting of non--serious cases within 90 daysserious cases within 90 days

Additional monitoring will be brought inAdditional monitoring will be brought in Additional monitoring will be brought in Additional monitoring will be brought in Will replace UK Black TriangleWill replace UK Black Triangle

Product authorisations may be granted with conditions Product authorisations may be granted with conditions

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Module I: Pharmacovigilance systems and Module I: Pharmacovigilance systems and their quality systems their quality systems

Documentation to demonstrate Documentation to demonstrate –– Resource Resource –– Business Continuity PlanBusiness Continuity Plan–– Job Descriptions and training recordsJob Descriptions and training records

Show hierarchical relationshipsShow hierarchical relationships–– Show hierarchical relationshipsShow hierarchical relationships

Compliance ManagementCompliance Management–– Effective communication with HCPs, patients, EMA and NCAsEffective communication with HCPs, patients, EMA and NCAsEffective communication with HCPs, patients, EMA and NCAsEffective communication with HCPs, patients, EMA and NCAs–– Evidence of how scientific evaluation of risk is performedEvidence of how scientific evaluation of risk is performed–– Evidence of timeliness of ADR reportingEvidence of timeliness of ADR reporting

AuditsAudits–– Independent auditsIndependent audits–– Document corrective action plans and followDocument corrective action plans and follow--up measuresup measuresDocument corrective action plans and followDocument corrective action plans and follow up measuresup measures

Module II: Pharmacovigilance system Module II: Pharmacovigilance system master file (PSMF)master file (PSMF)

PSMF is a legal requirementPSMF is a legal requirement–– applies to applicants of traditional herbal or homeopathicapplies to applicants of traditional herbal or homeopathicapplies to applicants of traditional herbal or homeopathic applies to applicants of traditional herbal or homeopathic

productsproducts

Must be in place upon renewal or July 2015 at theMust be in place upon renewal or July 2015 at the Must be in place upon renewal or July 2015 at the Must be in place upon renewal or July 2015 at the latest latest

Must be available 7 days following a requestMust be available 7 days following a request

Master File must include all significant corrective Master File must include all significant corrective action and preventative actions (CAPAs) impactingaction and preventative actions (CAPAs) impactingaction and preventative actions (CAPAs) impacting action and preventative actions (CAPAs) impacting the PV systemthe PV system

PSMFPSMF Modular ContentModular ContentPSMFPSMF Modular ContentModular Content

Qualified Person for PV detailsQualified Person for PV details Organisational structure Organisational structure

(Mergers/Acquisitions)(Mergers/Acquisitions) ProductsProducts Sources of safety data (all studies)Sources of safety data (all studies) Computerised systems and databasesComputerised systems and databases PV process & written proceduresPV process & written procedures PV System performancePV System performance Quality SystemQuality System Document and Record ControlDocument and Record Control LogbookLogbook

Module V: Risk Management SystemsModule V: Risk Management SystemsModule V: Risk Management SystemsModule V: Risk Management Systems

Focus on risks in the context of benefit (not just Focus on risks in the context of benefit (not just managing risks)managing risks)managing risks)managing risks)

Additional Risk Minimisation MeasuresAdditional Risk Minimisation Measures Additional Risk Minimisation MeasuresAdditional Risk Minimisation Measures–– Country specific or global (medical context)Country specific or global (medical context)

T i i f t ffT i i f t ff i tii ti–– Training of staff Training of staff -- communicationcommunication–– Measure effectiveness Measure effectiveness -- howhow

EUEU EUEU–– EU EU vsvs exex--EUEU–– Define roles and responsibilities company staffDefine roles and responsibilities company staff

Module VI: Management and reporting Module VI: Management and reporting of adverse reactions to medicinal of adverse reactions to medicinal products products pp New definition of ADR New definition of ADR

N I t ti l R hN I t ti l R h AE R ti (AE R ti ( Non Interventional Research Non Interventional Research –– AE Reporting (nonAE Reporting (non--serious)serious)–– CU/Named Patient UseCU/Named Patient Use–– CU/Named Patient Use CU/Named Patient Use –– Patient Support ProgramsPatient Support Programs

SolicitedSolicited vsvs SpontaneousSpontaneous Solicited Solicited vsvs SpontaneousSpontaneous Events not associated with AEs (Off label, misuse, Events not associated with AEs (Off label, misuse,

overdose, etc)overdose, etc), ), ) Consumer Reports (Non HCP)Consumer Reports (Non HCP) Literature ReviewLiterature Review Emerging Safety IssuesEmerging Safety Issues

Expedited reporting requirementsExpedited reporting requirements

Serious HCP Serious Consumer Non-Serious HCP Non-Serious Consumer

EU/Non-EU EU/Non-EU EU only EU only

Pre-July 2012 Y N N N

Post-July 2012 Y Y Y YPost-July 2012 Y Y Y Y

Serious HCP Serious Consumer Non-Serious HCP Non-Serious Consumer

Timelines for expedited reporting (calendar days)

EU/Non-EU EU/Non-EU EU only EU only

Pre-July 2012 15 days N/A N/A N/A

Post-July 2012 15 days 15 days 90 days 90 days

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Serious HCP Serious Consumer Non-Serious HCP Non-Serious Consumer

Pre-July 2012 Serious t d

N/A N/A N/Aexpected or unexpected

Post-July 2012 Serious expected AND unexpected if

Serious expected AND unexpected if occurred anywhere in the world

Non-serious expected AND unexpected if occurred in the EU

Non-serious expected ANDunexpected if occurred in the EUunexpected if

occurred anywhere in the world

anywhere in the world occurred in the EU EU

What does this mean for the MAH?What does this mean for the MAH?What does this mean for the MAH?What does this mean for the MAH?The number of reports that need to be submitted to the Regulatory The number of reports that need to be submitted to the Regulatory Authorities in the EU after 2Authorities in the EU after 2ndnd July 2012 will increase dramatically, July 2012 will increase dramatically,

along with the quantity of reporting from pharmaceutical companiesalong with the quantity of reporting from pharmaceutical companiesalong with the quantity of reporting from pharmaceutical companiesalong with the quantity of reporting from pharmaceutical companies

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Module VIII: PostModule VIII: Post--authorisation safety authorisation safety studies studies

Can be voluntary or imposed by CACan be voluntary or imposed by CAStudies may be imposed as a condition of licensingStudies may be imposed as a condition of licensing Studies may be imposed as a condition of licensing Studies may be imposed as a condition of licensing

PASS should not be promotionalPASS should not be promotionalMA sho ld egiste PASS on EU PASS RegisteMA sho ld egiste PASS on EU PASS Registe MA should register PASS on EU PASS RegisterMA should register PASS on EU PASS Register

Progress reports may be requested at any time by HAs Progress reports may be requested at any time by HAs AE d t h ld b ll t d M d l VIAE d t h ld b ll t d M d l VI AE data should be collected as per Module VIAE data should be collected as per Module VI

Reports & results can be publishedReports & results can be publishedi l h ld b b i d i hi 12 h fi l h ld b b i d i hi 12 h f Final report should be submitted within 12 months of Final report should be submitted within 12 months of

completioncompletion

Module IX: Signal ManagementModule IX: Signal ManagementModule IX: Signal ManagementModule IX: Signal Management

Monitor monthlyMonitor monthly

Monitor all available data and perform signal Monitor all available data and perform signal detection activities including the validation ofdetection activities including the validation ofdetection activities including the validation of detection activities including the validation of signals and communication to the EMA & CAs signals and communication to the EMA & CAs

Apply the appropriate method of detection e.g. stat Apply the appropriate method of detection e.g. stat analysis, review of ICSRs or bothanalysis, review of ICSRs or both

Audit trials for signal detection activitiesAudit trials for signal detection activities

Mod le X Additional Monito ingMod le X Additional Monito ingModule X: Additional MonitoringModule X: Additional Monitoring

EMA to provide list of substances for additional EMA to provide list of substances for additional monitoringmonitoringgg–– NA can request for another substance to be addedNA can request for another substance to be added

Stay on the list for 5 years and a removal is tied to a Stay on the list for 5 years and a removal is tied to a y yy yrenewalrenewal–– Reviews are linked to fulfilment of obligations e.g. PASSReviews are linked to fulfilment of obligations e.g. PASS

Extensions to monitoringExtensions to monitoring Products can be added to the list a second timeProducts can be added to the list a second time Black symbolBlack symbol SmPCsSmPCs shall be updated by way of variation to shall be updated by way of variation to

include/remove the symbol and associated statementinclude/remove the symbol and associated statement

Implementation RequirementsImplementation RequirementsImplementation RequirementsImplementation Requirements

Review, update or write new processes, training, Review, update or write new processes, training, d t tid t tidocumentationdocumentation

Assess resourcingAssess resourcingh l d dh l d d–– more emphasis on evaluation, detection and responsemore emphasis on evaluation, detection and response

Engage with multidisciplinary stakeholdersEngage with multidisciplinary stakeholders–– Regulatory, Clinical development, Medical affairs, IT, Regulatory, Clinical development, Medical affairs, IT,

QM & internal audit groupsQM & internal audit groupsD t thiD t thi Document everythingDocument everything–– Impact assessmentImpact assessment

I l t ti lI l t ti l–– Implementation planImplementation plan

RealityRealityRealityReality

Challenging time for MAHs to understand what is Challenging time for MAHs to understand what is changingchangingchangingchanging–– ImportantImportant to continually assess the landscape to to continually assess the landscape to

amend processes and maintain complianceamend processes and maintain complianceamend processes and maintain complianceamend processes and maintain compliance Key is:Key is:

–– Complete and continually revise impact analysisComplete and continually revise impact analysisComplete and continually revise impact analysisComplete and continually revise impact analysis–– Have a well documented but fluid action plan for Have a well documented but fluid action plan for

implementation implementation pp

QUESTIONS?

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