E2B

ICH E2B Individual Case Safety Report (ICSR): Report (ICSR): Current Status and Next Steps

P t d b S bi B h

An agency of the European Union

Presented by: Sabine Brosch PharmacoVigilance and Risk Management SectorEuropean Medicines Agency

Background (1)

ICH E2B(R2)* guideline: Data Elements for Transmission of Individual Case Safety Reports (ICSRs)(ICSRs)

– Provides a description of the data elements and instructions on how to use these for adverse reaction reportingreporting

ICH M2 Version 2.1 of the DTD– Provides a messaging format for ICSRsProvides a messaging format for ICSRs

• ICH ICSR M2 Version 2.3 Specification Document• ICH ICSR Acknowledgment Message, DTD

Version 1.1

2 http://estri.ich.org/icsr/index.htm * Former E2B(M)

Background (2)

FDA introduced the HL7 ICSR message Release 1 (Normative Edition 2005)

FDA requires HL7 standards in the USequ es sta da ds t e US

HL7 ICSR supports the exchange of data and other safety reporting requirements between various public health and patient safety organizations:

– Reporting of adverse events– Product problems associated with the use of drugs– Therapeutic biologics– Vaccines

The message can support international safety reporting between public health organizations

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Background (3)

EU requires that a standard must be ISO or CEN based to be referenced in EU legislation

Such requirements are also applicable in Canada

Therefore to meet overall ICH needs a standard must be issued by ISO/CEN and HL7be issued by ISO/CEN and HL7

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Background (4)

May 2005:ICH released for public consultation

Revised guideline for Clinical Safety Data Management: Data Elements for Transmission of Individual Case Safety Reports (E2B(R3)) Ne g ideline on Identification of Medicinal New guideline on Identification of Medicinal Products (IDMP) (M5)

ICH Steering Committee decided that technical specifications should no longer be developed solely specifications should no longer be developed solely within ICH, but should be created in collaboration with international Standards Development Organisations (SDOs)

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New International Standardisation New International Standardisation Co-operation

ICSR and IDMP were recognised as joint initiative projects:

European Committee for Standardization (CEN)

Clinical Data Interchange Standards Consortium (CDISC)

Health Level 7 (HL7)

International Health Terminology Standards Development Organisation (IHTSDO)

International Organization for Standardization (ISO)

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N I i l New International Standardisation Co-operation

Objectives:

– Improve the current ICH E2B(R2) guideline

– Enable wider interoperability across the regulatory and healthcare communities (e.g. Electronic Patient/Health Record -pharmacovigilance)

– Exchange, manage and integrate data that support clinical patient care and the management, delivery and evaluation of h lth i

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healthcare services

N I i l New International Standardisation Co-operation

Approach:

U HL7 i t d d f ICSR – Use HL7 messaging standards for ICSRs and acknowledgements

– ISO ICSR standard constrains HL7 messaging to its specific needs

– ICH develops ICSR Implementation Guide and conducts testing of new standards

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standards

New International New International Standardisation Co-operation

Approach:– Clear definition of medicinal product/device Clear definition of medicinal product/device

concepts in ICSRs

– HL7 ICSR fully integrates HL7 Common y gProduct Model (CPM)

– ISO Identification of Medicinal Products (IDMP) ill ll f t t d di i l d t /d i will allow for structured medicinal product /device

reporting in ICSRs

– ICH M5 will develop Implementation Guide for

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– ICH M5 will develop Implementation Guide for IDMP in context of ICSR

N I t ti l New International Standardisation Co-operation

ISO 27953 Part 1

– Wider scope than Human Pharmaceuticalsp

– Veterinary products, Food, Feed, Dietary supplements, Medical Devices and Cosmetics

ISO 27953 Part 2

– Restricted version of Part 1 covering Human Pharmaceuticals

– ICSR and acknowledgement messaging based on HL7 standards

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HL7 ICSR Standard

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HL7 C P d M d l (CPM) HL7 Common Product Model (CPM) medicinal products and devices

Package

l

ProductManufacturer

Regulator

Substance

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ICSR: ICH and HL7

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Ch ICH E2B/M2 Changes to ICH E2B/M2 Specifications (1)

Examples for changes– Fields removed/updated

• A.3.2 Receiver• A.1.10.1 and A.1.10.2 Worldwide Case IDs merged• Seriousness at event level

– New concept of ‘amendment report’

Fields added– Fields added• Study registration number• Improved description of medication errors and drug

abuse

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abuse

Ch ICH E2B/M2 Changes to ICH E2B/M2 Specifications (2)

Examples for changes:• Revised drug section and full integration with ISO

d f f d l d ( )Identification of Medicinal Products (IDMP)

• Fields becoming repeatable• Dosage information• Dosage information• Drug indication

• Reporting of counterfeit medicines Reporting of counterfeit medicines

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Ch ICH E2B(R2)/M2 Changes to ICH E2B(R2)/M2 Specifications (3)

B.1.7 Relevant medical history and concurrent conditions

HL7 ICSR fi ld

E2B(R3) fieldsobservation Process(Disease)

HL7 ICSR fields

B.1.7Disease/surgical procedure/etc procedure Processprocedure/etc. procedure Process

(Surgical procedure)

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Ch ICH E2B(R2)/M2 Changes to ICH E2B(R2)/M2 Specifications (4)

Dosage information B.4.k.5

E2B(R2) field E2B(R2) value HL7

B.4.k.5.1 10 10

B.4.k.5.2 mg mg

B.4.k.5.3 3 --------

B.4.k.5.4 1 8

B.4.k.5.5 Day Hours

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Changes to ICH E2B(R2)/M2 Changes to ICH E2B(R2)/M2 Specifications (5)

• Submission of attachments• Submission of attachments• The new ICSR standard supports the

submission of attachment files (e.g. PDF of f fcopies of literature articles, copies of test

results) within the ICSR message

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Changes to ICH E2B(R2)/M2 Changes to ICH E2B(R2)/M2 Specifications (6)

• ICSR Acknowledgment Messages• HL7 Message Transmission standard used to HL7 Message Transmission standard used to

acknowledge ICSRs• Like the new ICSR standard this will be

different to the current E2B(R2) different to the current E2B(R2) acknowledgment but the content will be aligned

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Project Planning

Standards development has to be conducted at

three levels:three levels:

• HL7: ICSR and acknowledgement messaging standards

• ISO: HL7 ICSR constrained for human medicinal products for ICH use

• ICH: conduct ISO ICSR testing and prepare ICH ICSR Implementation Guide

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ISO/ICH ICSR ISO/ICH ICSR –Project Milestones

ISO ICSR Draft International Standard (DIS)ballot:

– Initiated 1 April 2009– Closed 30 September 2009

ICH awareness publication of the ISO ICSR Draft Standard and the ICH Implementation Guide (IG) p ( )

– Initiated on 26 June 2009

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Testing of ICSR Draft International Standard (DIS)Regional ICH testing of ISO ICSR Standard

– Completed in August 2009– EU Regional Testing involving 18 Testers:– EU Regional Testing involving 18 Testers:

• Nine Regulatory Authority and Pharmaceutical Industry testers each

– Japan and US conducted similar regional testing

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ISO ICSR DIS ballot outcome

Six countries voted negatively in ISOSix countries voted negatively in ISO

• A second ISO DIS ballot is required to progress the work in ISO

A repeat of the ICSR DIS ballot was approved in the October ISO TC 215 meeting in Durham (US)(US)

• Agreement on how all comments received would be addressed

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• Estimated duration two months (completion in June 2010)


ICH Resolve issues and comments raised with the Implementation Guide (IG) during 1st ISO ICSR DIS testing

Complete sections in the Implementation Guide− Attachments

Backwards and Forwards conversion− Backwards and Forwards conversion− Acknowledgements

Agree on ICH M5 integration in E2B(R3)

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g ee o C 5 teg at o ( 3)

ISO/ICH ICSR ISO/ICH ICSR Project Milestones

ICH – Prepare for the 2nd round of ICSR DIS testing p g

– To be completed within two months following official initiation of ICSR DIS ballot

• One month for testing

• One month of reconciliation of test results andOne month of reconciliation of test results and submission to ISO member bodies

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ICH I l i d ICH Implementation and ISO ICSR

ICH Backwards and Forwards Conversion

The current ICH E2B(R2) standard and the future ISO ICSR standard will be structured in different ways

A coordinated implementation approach is required to allow for smooth transition between current and new ICSRICSR

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ICH I l i ICH Implementation and ISO ICSR

ICH Backwards and Forwards Conversion rules

– ICH conversion rules developed to help organisations during the period of switching between the current standard and the new standard

− Rules will be provided in the ICH IG

− XML style sheets will allow for automatic conversion

− Applicable for ICSR and acknowledgement messages

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ICH I l i ICH Implementation and ISO ICSR

Use of MedDRA

− MedDRA will remain standard terminology for the coding of all medical information in ICSRs

− This will be reflected in the ICH Implementation Guide

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ICH E2B(R3)/M2 Work Plan

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HL7 Activities

ICSR ballot comment reconciliation within HL7 has been completedbeen completed• The ICSR Models are being updated for the ISO

standard• Work ongoing to include updates to ICSR to take

account of the IDMP work• Draft HL7 acknowledgements are to be balloted so • Draft HL7 acknowledgements are to be balloted so

that they become normative content

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ISO

ISO ICSR DIS ballot documents to be provided to the ISO Central Secretariat by mid-March the ISO Central Secretariat by mid March

Second DIS ballot to start beginning of May lasting two months

If the outcome of this DIS ballot is positive the standard will move to Final Draft International Standard (FDIS) after the October 2010 ISO TC Standard (FDIS) after the October 2010 ISO TC 215 meeting in the Netherlands

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ISO

Once the standard becomes an FDIS no technical changes can be made. changes can be made.

– If technical comments are received they will only be registered for consideration during a future revision of the International Standardrevision of the International Standard

The final standard following this timeline would then be published in April 2011

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Thank youThank you

[email protected]

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Acknowledgements

Nick Halsey (European Medicines Agency)

Anja van Haren (MEB, NL)

EudraVigilance Expert Working Group (EV-EWG) conducting EU testing

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Acronyms

CEN European Committee for Standardization CDISC Clinical Data Interchange Standards Consortium CPM Common Product ModelDIS Draft International Standard DSTU Draft Standard for Trial UseDTR Draft Technical Report HL 7 Health Level 7 HL 7 Health Level 7 ICH International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human UseIDMP Identification of Medicinal Products IHTSDO International Health Terminology Standards Development IHTSDO International Health Terminology Standards Development Organisation ISO International Organization for Standardization JI Joint Initiative NMBs National Member Bodies

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SDOs Standards Development Organisations

E2B

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