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

Presented by: Sabine Brosch P t d b S bi B h PharmacoVigilance and Risk Management Sector European Medicines Agency

An agency of the European Union

Background (1)
ICH E2B(R2)* guideline: Data Elements for Transmission of Individual Case Safety Reports (ICSRs)
Provides a description of the data elements and instructions on how to use these for adverse reaction reporting

ICH M2 Version 2.1 of the DTD

Provides 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) equ es sta da ds t e FDA requires HL7 standards in the 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
3

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 HL7

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)) New g ideline Ne guideline on Identification of Medicinal Products (IDMP) (M5)

ICH Steering Committee decided that technical specifications should no longer be developed solely within ICH, but should be created in collaboration with international Standards Development Organisations (SDOs)
5

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)
6

New I N International i l 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 healthcare services h lth i
7

New I N International i l Standardisation Co-operation

Approach: U HL7 messaging standards f ICSRs Use i t d d for ICSR and acknowledgements ISO ICSR standard constrains HL7 messaging to its specific needs ICH develops ICSR Implementation Guide and conducts testing of new standards
8

New International Standardisation Co-operation

Approach:
Clear definition of medicinal product/device concepts in ICSRs y g HL7 ICSR fully integrates HL7 Common Product Model (CPM) ISO Identification of Medicinal Products (IDMP) will allow f structured medicinal product /device ill ll for t t d di i l d t /d i reporting in ICSRs ICH M5 will develop Implementation Guide for IDMP in context of ICSR
9

New I t N International ti l Standardisation Co-operation

ISO 27953 Part 1
Wider scope than Human Pharmaceuticals p 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
10

HL7 ICSR Standard

11

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

Package

Regulator l Manufacturer Product

Substance

12

ICSR: ICH and HL7

13

Changes to ICH E2B/M2 Ch 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 Study registration number Improved description of medication errors and drug abuse
14

Changes to ICH E2B/M2 Ch Specifications (2)

Examples for changes:
Revised drug section and full integration with ISO Identification of Medicinal Products (IDMP) d f f d l d ( ) Fields becoming repeatable Dosage information Drug indication Reporting of counterfeit medicines

15

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

B.1.7 Relevant medical history and concurrent conditions HL7 ICSR fi ld fields E2B(R3) fields B.1.7 Disease/surgical procedure/etc. procedure/etc observation Process (Disease)

procedure Process (Surgical procedure)

16

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

Dosage information B.4.k.5
E2B(R2) field B.4.k.5.1 B.4.k.5.2 B.4.k.5.3 B.4.k.5.4 B.4.k.5.5
17

E2B(R2) value 10 mg 3 1 Day

HL7 10 mg -------8 Hours

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

Submission of attachments
The new ICSR standard supports the submission of attachment files (e.g. PDF of copies of literature articles, copies of test f f results) within the ICSR message

18

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

ICSR Acknowledgment Messages
HL7 Message Transmission standard used to acknowledge ICSRs Like the new ICSR standard this will be different to the current E2B(R2) acknowledgment but the content will be aligned

19

Project Planning
Standards development has to be conducted at 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
20

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 ( ) p (IG)
Initiated on 26 June 2009

21

ISO/ICH ICSR Project Milestones

Testing of ICSR Draft International Standard (DIS) Regional ICH testing of ISO ICSR Standard
Completed in August 2009 EU Regional Testing involving 18 Testers: Nine Regulatory Authority and Pharmaceutical Industry testers each

Japan and US conducted similar regional testing

22

ISO/ICH ICSR Project Milestones

ISO ICSR DIS ballot outcome Six 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)
Agreement on how all comments received would be addressed
23

Estimated duration two months (completion in June 2010)

ISO/ICH ICSR Project Milestones

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 Acknowledgements

Agree o ICH M5 integration in E2B(R3) g ee on C 5 teg at o ( 3)

24

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 and submission to ISO member bodies

25

ICH Implementation and I l i d 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 ICSR

26

ICH I Implementation l i 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
27

ICH I Implementation l i 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

28

ICH E2B(R3)/M2 Work Plan

29

HL7 Activities
ICSR ballot comment reconciliation within HL7 has been 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 that they become normative content

30

ISO
ISO ICSR DIS ballot documents to be provided to the ISO Central Secretariat by mid-March 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 215 meeting in the Netherlands

31

ISO
Once the standard becomes an FDIS no technical changes can be made.
If technical comments are received they will only be registered for consideration during a future revision of the International Standard

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

32

Thank you
Sabine.brosch@ema.europa.eu

33

Acknowledgements
Nick Halsey (European Medicines Agency) Anja van Haren (MEB, NL) EudraVigilance Expert Working Group (EV-EWG) conducting EU testing

34

Acronyms
CEN European Committee for Standardization CDISC Clinical Data Interchange Standards Consortium CPM Common Product Model DIS Draft International Standard DSTU Draft Standard for Trial Use DTR Draft Technical Report HL 7 Health Level 7 ICH International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use IDMP Identification of Medicinal Products IHTSDO International Health Terminology Standards Development Organisation ISO International Organization for Standardization JI Joint Initiative NMBs National Member Bodies SDOs Standards Development Organisations
35