The diversity of safety reporting requirements and Systems in Asia

2010.05.17 Beijing China

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Presenter

Jean-Christophe DELUMEAU MD PhD

Head of Pharmacovigilance Asia-PacificBayer HealthcareGlobal R&D Center Asia, Beijing

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+86 10 6536 0829 office phone+86 13910420935 Blackberry phone

http://www.linkedin.com/in/delumeau

delumeau.phv@me.com

Disclaimer; The views and opinions expressed in the following slides are those of the individual presenter and should not be attributed to DIA or Bayer Healthcare.

Harmonization in Pharmacovigilance

ICSR submission requirements

Electronic submission (E2B standards)

Aggregate reports submission requirements

Coding dictionary

Risk Management Plan and Risk mitigation requirements

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Risk Management Plan and Risk mitigation requirements

Harmonization in PharmacovigilanceICH countries and beyond

ICH Guidelines and MEDDRA dictionary implemented in USA, EU and Japan and more or less followed by other countries

Specific Risk Management requirementsEuropeUSA

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Specific ICSR submission requirements e.g.France-specific causality assessment (imputabilite)Spain: Mandatory reporting in Spanish

E2B submission of ICSRs from Global pharma databasesUSA and CanadaAll 27 countries of the European Union + Norway, Iceland and Croatia

E2B systems for ICSR management

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WHO-UMC International Safety Survey

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Uppsala Monitoring Center appointed by WHOPreferred ICSR transmission standard: E2BAlternative: old INTIS standard

High degree of diversity in Asia

Diversity of ICSR submission requirements

Diversity of aggregate reports submission requirements

Only a few countries are requesting RMPs

Most countries are still using WHO-ART

Only Japan is has an E2B safety data base, but E2B-J

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Most AP countries are still using INTIS to forward ICSRs to the UMC

Electronic submission is not possible

An increasing number of countries request entering ICSRs into a country-specific web-based system

Diversity of Safety Systems In Asia

JapanIndiaChinaKoreaThailandTaiwanMalaysia

Japan-specific E2B submission mandatory

E2B-Vigiflow implemented in November 2010

Non E2B system – web submission mandatory

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SingaporeVietnamIndonesiaPhilippinesHong KongCambodiaPakistan

Non E2B system – web submission requested

Non E2B system – web system available

No E2B submission – no web system

Language for domestic ICSR Submission

IndonesiaVietnamCambodiaThailandTaiwan

Hong KongSingaporeMalaysiaIndiaPakistanPhilippines

ENGLISH and/or LOCAL LANGUAGE ACCEPTABLE

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ChinaKoreaJapan

ENGLISHMANDATORY

LOCAL LANGUAGE MADATORY

ICSR submission requirements in Asia

ICSR submission requirements vary considerably across countries depending upon

Language requested for submissionDomestic or foreign caseSolicited or non-solicitedS i

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SeriousnessCausalitySubmission time frameDefinition of the clock startAge of the product on the marketReference used for listedness

Safety submission requirementsEast Asia

DomesticSolicited

DomesticNon Solic.

OverseasSolicited

OverseasNon Solic.

Lingua語

WebSubmiss.

E2BeSub

AggregateReports

RMP

Japan 日本語 No Yes 日本語 日本語Korea 한국어 Mandatory No 한국어 not yet

China 中文 Mandatory No 中文 中文Hong Kong Eng.中文 No No G-PSUR G-RMP

Macao No No

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No No

Taiwan Eng.中文 Possible No G-PSUR discussions

Expedited: Global ICSR format acceptable Unavailable or no requirement specified

G-PSUR G-RMP

Expedited: Country-specific ICSR format Specific Specific

ICSR Reporting requirements Hong Kong

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ICSR Reporting requirements Korea

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ICSR Reporting requirements Taiwan

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ICSR Reporting requirements China

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ICSR Reporting requirements Japan

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Safety submission requirements ASEAN

DomesticSolicited

DomesticNon Solic.

OverseasSolicited

OverseasNon Solic.

English WebSubmis.

E2BeSub

AggregateReports

RMP

Singapore Standard Possible No G-PSUR G-RMP

Brunei Standard No

Malaysia Standard Possible No G-PSUR

Thailand Web Web Accepted Expected No G-PSUR

Indonesia Accepted No G-PSUR

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Philippines G-PSUR G-PSUR Standard No G-PSUR

Vietnam G-PSUR G-PSUR Accepted No G-PSUR

Cambodia

Laos

Myanmar

Expedited: Global ICSR format acceptable Unavailable or no requirement specified

G-PSUR G-RMP

Expedited: Country-specific ICSR format Specific Specific

ICSR Reporting requirements Indonesia

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ICSR Reporting requirements Thailand

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ICSR reporting requirements Philippines

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ICSR reporting requirements Vietnam

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ICSR Reporting requirements Singapore

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ICSR Reporting requirements Malaysia

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Safety submission requirementsSouth Asia

DomesticSolicited

DomesticNon Solic.

OverseasSolicited

OverseasNon Solic.

Lingua語

WebSubmiss.

E2BeSub

AggregateReports

RMP

India English Hospitals No G-PSUR

Pakistan English No No G-PSUR

Sri Lanka

Maldives

Bangladesh

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Nepal

Expedited: Global ICSR format acceptable Unavailable or no requirement specified

G-PSUR G-RMP

Expedited: Country-specific ICSR format Specific Specific

ICSR Submission requirements Pakistan

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ICSR Submission requirements India

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2011.05.11: the Central Drugs Standard Control Organization (CDSCO) circulated a new guidance for the reporting of Serious AEs from clinical trials.

Obligation to report within 14 calendar daysCausality to be assessed yes/noObligation to report compensation status in case of deathIndia-specific report form

ICSR Submission requirements India

New reporting form proposed by the CDSCO

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ICSR Submission requirements India

Categories of clinical trials to be specified in the new reporting form

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Impact of country-specific requirements

ICSR submission from global safety system is possiblee-submission: not available in any AP country so farPrinted on PDF or paper from the global company safety database

ICSR submission via country-specific E2B system is possibleSubmission to the PMDA in Japan (日本語)

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ICSR submission via National web system is mandatoryChina (中文)Korea (한국어)Thailand (English acceptable)Concern: more and more counties will make it mandatory

Impact of country-specific requirements Japan

ICSR submitted electronically to the PMDA (E2B-J standard)

Japan-specific requirements e.g. Japanese language, specific reporting form, specific causality assessment rules

Most companies use a J-specific system e.g. Perceive, Clinical Works in addition to their Global PV system thus duplicating data entry work

S l ti t iti t th i t

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Solutions to mitigate the impact

Data transfer bridging applications to minimize duplicating data entry.

Global system perspectivesAlice (HP): only global system operating submission to PMDAAris/Aris-J may be connectedArgus/Argus-J (Oracle) not connectable so far but connecting the

two platforms may be considered

Impact of country-specific requirements Korea

All domestic ICSRs must be entered in Korean language

Into the web system Easydrug (except GCP trial cases)

e-submission not yet possible

KFDA is able to forward ICSRs to WHO’s UMC on E2B format

No Korean version of Meddra to map Korean vs English medical terms

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No Korean version of Meddra to map Korean vs English medical terms

Solutions to mitigate the impactParallel data entry into global system and EasydrugDeveloping E2B transmission and Meddra capabilityNeed for collaboration between the KFDA, Software providers and

Industry

Impact of country-specific requirementsChina

Domestic ICSRs to be entered in Chinese into ADR center web system

e-submission of ICSRs impossible (Not E2B compatible)

WHO-ART still used although a Chinese version of MEDDRA exists

Causality and Seriousness categories are specific to ChinaNeed to submit China-specific aggregate reportsNot f ll consistent ith doc ments s bmitted to EMA and FDA

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Not fully consistent with documents submitted to EMA and FDA

ImplicationsDuplication of data entry work for multinational companies

and Chinese hospitals participating into international safety research

To forward ICSRs to the UMC, the Chinese ADR Center needs to use the old INTIS or convert cases into E2B format

Impact of country-specific requirementsChina

Revised Drug Affair Law at final stage of approval at Ministry of Health anticipated to be released in 2011 but still awaited

New National ADR center database with web-based facility expected to become available by June 2011

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The need to make the replacement Chinese safety database compatible with the E2B world seems now recognized by the SFDA and ADR who are looking for bridging solutions

Advantages for moving toward E2B

Advantage for Health AuthoritiesRecommended by the WHO-UMC for data transferFacilitate ontribution to international safety researchEnable using advanced signal detection systems e.g Empirica or VigiMineLarger sample size for signal detection in specific ethnic groups

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Advantage for the pharmaceutical industryAvoid duplication of data entry workloadFocus resources on signal detection and benefit/risk optimization

E2B systems for ICSR management

Used by the Pharma Industry e.g.AERS (Oracle)ARGUS and ARGUS-J (Oracle)ARISg and ARISj (Aris Global)Safety-Easy (ABcube)Company-specific (e.g. MSD, AZ etc..)

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For Health Authorities e.g.AERS (Oracle) used by the FDAEudravigilance (EMA-specific)Vigiflow (UMC) used by SwissMedicARISg used by the French Medicinal AgencySafety-Easy (ABcube)

E2B solutionsfor National Heath Authorities

ORACLE AERS

Oracle actively promoting AERS for regulatory authorities

For signal detection, following the acquisition of Phase Forward, Oracle is working on integrating Empirica Signal (developed in

ll b ti ith th FDA) i t th AERS l tf

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collaboration with the FDA) into the AERS platform

In a second step, Empirica Signal will be integrated into the Argus platform as Argus Perceptive will be discontinued.

E2B solutionsfor National Heath Authorities

VIGIFLOW (WHO-UMC) may be set in 3 different ways

ICSRs entered locally and forwarded to the central UMC database

ICSRs entered locally and forwarded to a Country-specific database container maintained by the UMC in Uppsala

Setting a Vigiflow system in the Country (full license needed)

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Setting a Vigiflow system in the Country (full license needed)

Vigiflow is designed to be customised to local languagesThe UMC is keen to support interfacing Vigiflow with E2B-compatible ICSR submission systems of the Pharmaceutical industry

Cost-effective way to open the door to ICSR e-submission in countries with limited budget to purchase and maintain a national safety database

Diversity of Safety Systems In AsiaNews as of 2011.05.17

India: Vigiflow implemented in November 2010 at the All India Institute of Medical Sciences (AIIMS) to support the Pharmacovigilance Program of India (PvPI). In April, the Ministry of Health appointed the Indian Pharmacopoeia Commission (IPC). IPC will also be using Vigiflow. New requirements for reporting SAEs from clinical trials

China: The National ADR Center is planning to implement a new ADR-reporting web-based system in June 2011. The date of release is not confirmed. This

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system is not anticipated to be E2B compatible, however the ADR center has decided to look for solutions to bridge their new system with the E2B world

Taiwan: In January 2011, Taiwanese ADR center sent a questionnaire to the Pharma industry inquiring on the benefit for moving to an E2B system

Vietnam: The DI&ADR center is planning to set a locally designed country-specific web-based ICSR reporting system

Singapore, Malaysia, Thailand, Australia, New Zealand are considering acquiring an E2B system but there seem to be no clear decision so far

Different viewpointsbut sharing similar goals

National Health Authorities

Domestic pharmaceutical companies

International Organisation

Multi-National pharmaceutical Companies

All Pharmacovigilance professionals

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Aiming at ensuring the safe use of medicinal agents

Facing Increasing amounts of ICSRs

Dealing with limited resources

Harmonization helps avoiding duplicating work and focusing on Benefit versus Risk Management

Harmonisation for better health (ICH Mission Statement)

Thank you for your attention

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