The re-development of the standard for

the Individual Case Safety Report

(ICSR) (ICH E2B(R3)) and the
development of standards for the
Identification of Medicinal Products
(IDMP) (ICH M5)

Andrew Marr, PhD 1 November 2010

ICH M2 EWG Rapporteur
& EFPIA Topic Leader

International Conference on Harmonisation of Technical

Requirements for Registration of Pharmaceuticals for Human Use
Disclaimer :
The information within this
presentation is based on the
presenter's expertise and experience,
and represents the views of the
presenter for the purposes of a training
workshop.

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Outline of Presentation
 Why is a new version of the ICSR
needed?
 What is the added value of IDMP?
 Approach to standards development
 Status of programmes

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Why update the ICSR message?
 ICH adopted E2B(R2) in February 2001
 Past experience shows that E2B can be improved to take account of
 Advancements in pharmacovigilance practice
 Changing regulatory requirements
 Improving consistency of use, accuracy & detail of information
 Simplifying exchange of information across regions
 Changes proposed include
 Additional fields
 Greater granularity in some fields
 Greater use of terminologies
 Different/clearer usage instructions for the same field
 Consultation for enhancements (E2B(R3)) took place in 2005

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Why is IDMP needed?
 Identification of the medicinal product involved in the adverse event
report is critical
 Unique and unambiguous identification of :
 Active substance
 Units of measure
 Ingredients
 Dosage form
 Units of presentation
 Route of administration
 Specificity within an ICSR report
 Clear and accurate communication across jurisdictions (countries &
regions)
 More specificity leads to more accuracy in analysis and improved
quality of the science

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ICH M5
 November 2003
 TheICH Steering Committee (SC) approved a
Concept Paper for the development of a new tripartite
guideline:
 ICH M5 Data Elements and Standards for Drug Dictionaries

 May 2005
 ICH M5 guideline released for consultation at step 2
of the ICH process
 Including a List of Routes of Administration and Units of
Measurement

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ICH approach to development
 2006: ICH decides to no longer internally
develop its own technical specifications

 Key drivers
 Interoperability
 Robustness
 Resources & expertise
 Options for inclusiveness & collaboration with
other stakeholders

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Constraints
 FDA
 Interoperable with other healthcare standards used in US
 Single standard for all product types regulated by FDA
 Standards should be HL7
 EU
 Standards must be ISO or CEN in order to include in legislation
 Also applicable in Canada (ISO only)

 Therefore: ICH needs standards issued by ISO/CEN &

HL7
 But: ICH must be able to define how standards are used
for ICH purposes

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Joint Initiative – Initial Membership

ICH
ISO TC 215
Liaising ISO CEN = Health Informatics

Organisation TC215   TC251

HL7

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ISO TC215 Participating Countries
(Designated representative organisation in parenthesis)
 Armenia ( SARM )
 Australia ( SA )
 Austria ( ASI )
 Belgium ( NBN )
 Brazil ( ABNT )
 Canada ( SCC )
 China ( SAC )
 Czech Republic ( UNMZ )
 Denmark ( DS )
 Finland ( SFS )
 France ( AFNOR )
 Germany ( DIN )
 Ireland ( NSAI )
 Italy ( UNI )
 Japan ( JISC )
 Kenya ( KEBS )
 Korea, Republic of ( KATS )
 Malaysia ( DSM )
 Netherlands ( NEN )
 New Zealand ( SNZ )
 Norway ( SN )
 Russian Federation ( GOST R )
 Serbia ( ISS )
 Slovakia ( SUTN )
 Spain ( AENOR )
 Sweden ( SIS )
 Turkey ( TSE )
 United Kingdom ( BSI )
 USA ( ANSI )
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ISO TC215 Observing Countries
(Designated representative organisation in parenthesis)

 Argentina ( IRAM )  Mongolia ( MASM )

 Bulgaria ( BDS )  Poland ( PKN )
 Croatia ( HZN )  Portugal ( IPQ )
 Cyprus ( CYS )  Romania ( ASRO )
 Ecuador ( INEN )  Singapore ( SPRING SG )
 Hong Kong, China ( ITCHKSAR )  South Africa ( SABS )
 Hungary ( MSZT )  Switzerland ( SNV )
 India ( BIS )  Thailand ( TISI )
 Iran, Islamic Republic of ( ISIRI )  Ukraine ( DSSU )
 Israel ( SII )  Zimbabwe ( SAZ )

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Joint Initiative – Current Membership

ICH
Liaising ISO CEN
Organisation TC215  
IHT TC251
CDISC SDO GS1
HL7

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ISO balloting stages
 Standards are following ISO process
 Other
SDO have their own ballots but feed into
common process
 Stages
 Committee Draft
 Draft International Standard (DIS)
 Ballot addresses technical and editorial issues
 Final Draft International Standard (FDIS)
 Ballot addresses editorial issues only
 Publication of International Standard (IS)

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 ISO ICSR Standards
Two Draft International Standards
 ISO/DIS 27953-1
Health informatics -- Pharmacovigilance --
Individual case safety report -- Part 1: The
framework for adverse event reporting

 ISO/DIS 27953-2
Health informatics -- Pharmacovigilance --
Individual case safety report -- Part 2: Human
pharmaceutical reporting requirements for ICSR
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ISO standard based upon HL7
Model
 HL7 had ICSR standard
 Wide scope – general details
 FDA desired wider scope to deal with detail of veterinary
medicines, medical devices, food additives etc
 ICH had new requirements for ICSR (E2B(R3))
 EU had additional requirements – beyond scope of ICH
product types
 Some countries eg. Korea had additional requirements
 HL7 standard would be super-set
 Specific uses would then constrain this super-set

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 Constrained Message for ISO/ICH
use
HL7
ISO
Regional

ICH requirements

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ICH Use of ISO Standard
 ICH Implementation Guide
 Based upon E2B(R3) requirements
 Detailed description for use of all relevant fields

 Description of backwards and forwards

compatibility
 Significant
differences between model for E2B(R2)
and E2B(R3)
 Thorough testing of standards and of
implementation guide by ICH

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Current status (1)
 Initial DIS Ballot – April 2009
 Public awareness via ICH
 Provided ability to comment on (and test) standard and ICH Implementation
Guide
 Very few comments received
 Draft did not pass ballot
 Did not fully meet requirements
 Re-run of DIS Ballot – June 2010
 Shorter duration (2 months)
 One month consultation within ICH for new version of Implementation Guide
 Only minor comments received
 Passed ballot unanimously
 Details can be found on the ICH pages via
http://estri.ich.org/new-icsr/index.htm

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Current status (2)
 Some minor technical changes required
 FDIS ballot expected February 2011
 International Standard expected early 3Q 2011

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ICH Step 3 Consultation
 The target for Step 2 for the ICH Implementation
Guide is February 2011 followed by a Step 3
consultation of about 6 months duration.
 Comments will be sought on how ICH will use
the International Standard – not on the standard
itself

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 ISO IDMP Standards (1)
Five Draft International Standards
 prEN ISO 11615 Health informatics — Identification of
medicinal products - Data elements and structures for
the unique identification and exchange of regulated
medicinal products
 prEN ISO 11616 Health informatics — Identification of
medicinal products — Data elements and structures
for the unique identification and exchange of regulated
pharmaceutical product information

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 ISO IDMP Standards (2)

 prEN ISO 11238 Health Informatics — Identification of medicinal

products — Data elements and structures Health informatics —
Identification of medicinal products — Data elements and structures
for the unique identification and exchange of regulated information
on substances
 prEN ISO 11239 Health Informatics — Identification of medicinal
products — Data elements and structures for the unique
identification and exchange of regulated information on
pharmaceutical dose forms, units of presentation, routes of
administration and packaging
 prEN ISO 11240 Health informatics — Identification of medicinal
products — Data elements and structures for the unique
identification and exchange of units of measurement

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Main IDMP Concepts
Regulated Medicinal Product – by jurisdiction
Package
Package Description
Description

Pharmaceutical
Regulated Product
Medicinal Product
– common across jurisdictions
Pharmaceutical Product
Substance Substance

Strength Strength

Pharmaceutical
DoseDose
Form Form

Standard Terminology
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Current status
 Initial CD Ballot – June 2009
 Large number of comments

 DIS Ballot commenced September 2010

 5 months duration

 ICH is developing an Implementation Guide

 ICH will conduct testing internally
 It will not make the Implementation Guide public at this stage
 ICH will release a revised version – probably in early 2011
 FDIS expected mid-2011

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Combination of ICSR and IDMP
 When MPID information is included within the
ICSR the definition of the product involved will
be unambiguous

 MPIDs will be clearly connected to a PhPID

 Value of pharmacovigilance reports circulated
between jurisdictions will be increased
 Confidence of correct product identification increased
 Wider pool of reports to analyse

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Summary
 ICH Message Standards now developed with
wider input
 Partnershipwith SDOs
 ICSR currently being updated & improved
 IDMP being created

 Improved support for safety monitoring &

evaluation
 Data clarity
 Interoperability
 Enhancement for international exchange
 Thank you for your attention!

 Contact : andrew.p.marr@gsk.com

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