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Presenter
Jean-Christophe DELUMEAU MD PhD
Head of Pharmacovigilance Asia-Pacific
Bayer Healthcare
Global R&D Center Asia, Beijing
+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.
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Harmonization in Pharmacovigilance
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Harmonization in Pharmacovigilance
ICH 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 requirements
 Europe
 USA
 Specific ICSR submission requirements e.g.
 France-specific causality assessment (imputabilite)
 Spain: Mandatory reporting in Spanish
 E2B submission of ICSRs from Global pharma databases
 USA and Canada
 All 27 countries of the European Union + Norway, Iceland and Croatia
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E2B systems for ICSR management
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WHO-UMC
 Uppsala Monitoring Center appointed by WHO
 Preferred ICSR transmission standard: E2B
 Alternative: old INTIS standard
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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
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Diversity of Safety Systems In Asia
 Japan-specific E2B submission mandatory
 E2B-Vigiflow implemented in November 2010
 Non E2B system – web submission mandatory
 Non E2B system – web submission requested
 Non E2B system – web system available
 No E2B submission – no web system
 Japan
 India
 China
 Korea
 Thailand
 Taiwan
 Malaysia
 Singapore
 Vietnam
 Indonesia
 Philippines
 Hong Kong
 Cambodia
 Pakistan
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Language for domestic ICSR Submission
 Indonesia
 Vietnam
 Cambodia
 Thailand
 Taiwan
 China
 Korea
 Japan
ENGLISH and/or
LOCAL
LANGUAGE
ACCEPTABLE
 Hong Kong
 Singapore
 Malaysia
 India
 Pakistan
 Philippines
LOCAL
LANGUAGE
MADATORY
ENGLISH
MANDATORY
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ICSR submission requirements in Asia
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Safety submission requirements
Japan
Korea
China
Hong Kong
Macao
Taiwan
Domestic
Solicited
Domestic
Non Solic.
Overseas
Solicited
Overseas
Non Solic.
Lingua
語
Web
Submiss.
E2B eSub
Aggregate
Reports
RMP
日本語 No Yes 日本語 日本語
한국어 Mandatory No 한국어 not yet
中文 Mandatory No 中文 中文
Eng.
中文 No
No
No
No
G-PSUR G-RMP
Eng.
中文 Possible No G-PSUR discussions
Expedited: Global ICSR format acceptable Unavailable or no requirement
Expedited: Country-specific ICSR format specified
G-PSUR G-RMP
Specific Specific
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ICSR Reporting requirements
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ICSR Reporting requirements
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ICSR Reporting requirements
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ICSR Reporting requirements
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ICSR Reporting requirements
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Safety submission requirements
Domestic
Solicited
Singapore
Brunei
Malaysia
Thailand
Indonesia
Philippines
Vietnam
Cambodia
Laos
Myanmar
Web
Domestic
Non Solic.
Web
Overseas
Solicited
Overseas
Non Solic.
G-PSUR G-PSUR
G-PSUR G-PSUR
Expedited: Global ICSR format acceptable
Expedited: Country-specific ICSR format
English Web
Submis.
Standard Possible
Standard
Standard Possible
Accepted Expected
Accepted
Standard
Accepted
E2B eSub
Aggregate
Reports
RMP
No G-PSUR G-RMP
No
No G-PSUR
No G-PSUR
No G-PSUR
No G-PSUR
No G-PSUR
Unavailable or no requirement specified
G-PSUR
Specific
G-RMP
Specific
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ICSR Reporting requirements
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ICSR Reporting requirements
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ICSR reporting requirements
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ICSR reporting requirements
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ICSR Reporting requirements
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ICSR Reporting requirements
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Safety submission requirements
India
Pakistan
Sri Lanka
Maldives
Bangladesh
Nepal
Domestic
Solicited
Domestic
Non Solic.
Overseas
Solicited
Overseas
Non Solic.
Expedited: Global ICSR format acceptable
Expedited: Country-specific ICSR format
Lingua
語
Web
Submiss.
E2B eSub
Aggregate
Reports
English Hospitals No G-PSUR
English No No G-PSUR
Unavailable or no requirement specified
RMP
G-PSUR G-RMP
Specific Specific
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ICSR Submission requirements
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ICSR Submission requirements
 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 days
 Causality to be assessed yes/no
 Obligation to report compensation status in case of death
 India-specific report form
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ICSR Submission requirements
 New reporting form proposed by the CDSCO
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ICSR Submission requirements
 Categories of clinical trials to be specified in the new reporting form
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Impact of country-specific requirements
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ICSR submission from global safety system is possible
 e-submission: not available in any AP country so far
 Printed on PDF or paper from the global company safety database
 ICSR submission via country-specific E2B system is possible
 Submission to the PMDA in Japan ( 日本語 )
 ICSR submission via National web system is mandatory
 China ( 中文 )
 Korea ( 한국어 )
 Thailand ( English acceptable )
 Concern: more and more counties will make it mandatory
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Impact of country-specific requirements
 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
Solutions to mitigate the impact
 Data transfer bridging applications to minimize duplicating data entry.
 Global system perspectives
 Alice (HP): only global system operating submission to PMDA
 Aris/Aris-J may be connected
 Argus/Argus-J (Oracle) not connectable so far but connecting the two platforms may be considered
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Impact of country-specific requirements
 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
Solutions to mitigate the impact
 Parallel data entry into global system and Easydrug
 Developing E2B transmission and Meddra capability
 Need for collaboration between the KFDA, Software providers and
Industry
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Impact of country-specific requirements
 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 China
 Need to submit China-specific aggregate reports
 Not fully consistent with documents submitted to EMA and FDA
 Implications
 Duplication 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
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Impact of country-specific requirements
 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
 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
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Advantages for moving toward E2B
 Advantage for Health Authorities
 Recommended by the WHO-UMC for data transfer
 Facilitate ontribution to international safety research
 Enable using advanced signal detection systems e.g Empirica or VigiMine
 Larger sample size for signal detection in specific ethnic groups
 Advantage for the pharmaceutical industry
 Avoid duplication of data entry workload
 Focus resources on signal detection and benefit/risk optimization
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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..)
 For Health Authorities e.g.
 AERS (Oracle) used by the FDA
 Eudravigilance (EMA-specific)
 Vigiflow (UMC) used by SwissMedic
 ARISg used by the French Medicinal Agency
 Safety-Easy (ABcube)
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E2B solutions
 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 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.
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E2B solutions
 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)
 Vigiflow is designed to be customised to local languages
 The 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
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Diversity of Safety Systems In Asia
News 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 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 countryspecific 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
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Different viewpoints but sharing similar goals
 National Health Authorities
 Domestic pharmaceutical companies
 International Organisation
 Multi-National pharmaceutical Companies
 All Pharmacovigilance professionals
 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)
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