|E2B(R3) Individual Case Safety Report (ICSR) Specification and Related Files|
The ICH E2B EWG released an E2B guideline for Maintenance of the ICH Guideline on Clinical Safety Data Management: Data Elements for Transmission of Individual Case Safety Reports (ICSR) in 1997 and issued a revised version in 2000; a further minor revision was made in 2001 (version 4.4.1): this version was subsequently renamed as “E2B(R2) guideline”. The ICH M2 EWG developed ICH ICSR DTD version 2.1 as a message specification for implementation of the E2B(R2) guideline; this reached Step 4 in 2001. Since then, implementation of electronic submission of ICSRs based on these guidelines has become widespread in the ICH regions.
ICH E2B EWG re-formed for a revision of E2B(R2) guideline in 2004 and in May 2005 a revised guideline, E2B(R3), was released for public consultation. The ICH Steering Committee had taken a key decision that technical specifications should no longer be developed solely within ICH, but should be created in collaboration with Standards Development Organisations (SDOs) to enable wider inter-operability across the regulatory and healthcare communities. E2B(R3) was the first topic to go through this process.
The International Organisation for Standards (ISO), Health Level 7 (HL7) and European Committee for Standardization (CEN) have collaborated to form the Joint Initiative on SDO Global Health Informatics Standardization through which a single, common standard for the ICSR could be advanced. Subsequently, the Clinical Data Interchange Consortium(CDISC), the International Health Terminology Standards Development Organisation (IHTSDO) and GS1 have also become members of this Joint Initiative. ICH representatives have been heavily involved in this initiative in addition to other experts from beyond the ICH community. The overall standard is based upon an HL7 ICSR model that is capable of supporting message exchange for a wide range of product types (e.g. human medicinal products, veterinary products, medical devices etc.) The framework is described in:
The second part of the standard, which is a subset of the ISO/HL7 27953-1:2011, defines the details of the reporting requirements for human pharmaceuticals :
standards mentioned above reached International Standard status in November 2011
and were published jointly by ISO and HL7.
ICH constrained the ISO ICSR standard to meet the data exchange requirements for E2B(R3). ICH defines the way that this standard should be used by means of the ICH Implementation Guide (IG) which covers the use of the fields defined by E2B(R3). The ISO standard itself does contain additional data elements or requirements that are not used by ICH but may be used by specific regions. Such use, where appropriate, will be defined by regional Implementation Guides.
Please ensure that, when using the ISO/HL7 standard for ICSR, the following version is used: “ISO/HL7 27953-2:2011Health informatics -- Individual case safety reports (ICSRs) in pharmacovigilance -- Part 2: Human pharmaceutical reporting requirements for ICSR”. Do not use other versions of the standard since they might include changes that are not relevant for the submission of ICSRs in the regulated biopharmaceutical domain.
Step 4 ICH IG Package
To download the package click here
To download the Q&As click here
|Package Version||Publication Date||Notes|
|1.07||June, 2018||ICH E2B(R3) Core Data Elements and Business Rules was created.|
|Q&A Document Version||Publication Date||Notes|
Q&A 3.12, 4.19, 4.20, and 4.21 were added.
The latest package includes the documents listed and described below.
Summary of Document History
This spreadsheet summarises which documents in this package have been updated after ICH Step 4. More detailed change histories for each document are provided as separate spreadsheets.
IG for the Electronic Transmission of ICSRs: E2B(R3) Data Elements and Message
This document is a guide for implementing the ICH E2B(R3) requirements for the electronic transmission of ICSRs. The ICH ICSR IG is intended to support the implementation of software tools for creating, editing, sending, and receiving electronic ICSR messages. It provides instruction on how the biopharmaceutical industry, medicinal product regulatory authorities, service providers, and other stakeholders intend to use the ISO/HL7 ICSR standard to construct messages for exchanging pharmacovigilance information between and among themselves in ICH regions and in other countries that adopt ICH guidelines.
The following sections numbered 2-9 refer to particulars of Appendix I in the ICH IG that have changed since ICH issued the IG in November 2012.
Appendix I (A) List of ICH ICSR schema file names
Schema files contain technical information used by software tools and are necessary for generating and reading ICH ICSR messages. The list is derived from the set of schema files in the ISO/HL7 27953-2:2011 standard package and identifies those that are required for ICH implementation as described in the ICH IG. The list includes only the names of the schema files and a short explanation of each. The file set can be found in Appendix I (C). Note that regional IGs specify use of additional region-specific schema files.
Appendix I (B) ICH ICSR Backwards and Forwards Compatibility (BFC)
This document describes the relationship between elements from E2B(R2) and E2B(R3). It is intended to assist reporters and recipients (including pharmaceutical companies, regulatory authorities, non-commercial sponsors, and service providers) in implementing systems with special focus on the rules for conversion back and forth between E2B(R2) and E2B(R3). This includes mappings of the elements against one another, with explanations of differences, and guidance on how to convert between the two message structures. The document also addresses issues with compatibility.
Appendix I (C) ICH ICSR Schema Files
This Appendix includes a full set of XML schema files that contain rules, elements, and attributes stemming from the HL7 v3 messaging standard, as used by ICH in the ISO/HL7 27953-2:2011 standard. These are the technical files required by the IT tools which actually construct, export, read or validate the messages. A description of these schemas is found in the list in Appendix I (A).
Appendix I (D) ICH ICSR Reference Instances
This Appendix includes a reference file that illustrates the coding of an ICSR according to the constraints encoded in the schema files and in compliance with the IG. The Reference Instances use the E2B(R3) data element numbers in the xml rather than real coded data. This allows an implementer to identify how and where the ICH E2B(R3) elements would appear in an actual transmittable ICSR. Some values in the Reference Instances, such as version for codeSystem or dose information, are for reference/example only and should not be interpreted literally; an appropriate value should be used. A second example file provides a similar illustration of an Acknowledgement message.
Appendix I (E) ICH ICSR Example Instances
This Appendix includes example files that illustrate the coding of an ICSR according to the constraints defined in the schema files and in compliance with the IG. Unlike the Reference Instances, the Example Instances use real values generated from simulated typical use cases to create an E2B(R3) message. Readers should be aware how ICSR messages are created in these selected settings.
Appendix I (F) ICH ICSR OID list and ICH code lists
An Object Identifier, or OID, is a construct used to identify an object. In the context of IT standards OIDs are globally unique identifiers. The OID values have been assigned for each required code list or namespace by the ICH M2 EWG in partnership with the E2B EWG/IWG that developed this standard. These OIDs provide unambiguous and clear identification of the code lists used – always referring to a distinct object.
For detailed information about OID, please refer to an information paper
published by M2. The information paper also explains Universal Unique Identifier
(UUID) which is a different method of identifying object and used in ICSR
messages for identification of two name spaces, reference to reaction/event and
reference to drug.
Link to the M2 information paper for OIDs and UUIDs.
There are many elements within the E2B(R3) message that require specific codes to reference defined values. These may be impacted over time by changes in the regulatory environment. By separating the code lists from the IG, it becomes easier for code lists to be adapted, should this be necessary, without altering the technical message standard itself or requiring a new version of the IG. Also, technical systems can be more readily maintained if the code lists are provided in a clearly identified, traceable manner.
I (G) Additional ICH ICSR Technical Information
This document describes supplemental technical information to prepare a valid ICH ICSR message or an ICSR Acknowledgment message. For example, it provides information on ICH/HL7 data types, XPath references for each E2B(R3) element and also XML “snippets” that illustrate variation in how data elements may be described in the XML. This document is intended for technical software implementers – business users may not need to refer to this information. Technical software implementers should note that the values in the Technical Information are for reference/example only and should not be interpreted literally; an appropriate value should be used.
Appendix I (H) ICH ICSR BFC conversion
This Appendix includes a tool for conversion of E2B(R2) messages to E2B(R3) messages, and vice versa, in compliance with the conversion rules described in the BFC document (Appendix I (B)). This is an example stylesheet that illustrates how an ICSR message can be converted from one version to the other version while preserving the data contained in the message. It is an example only and should not be interpreted literally; note that the ICH E2B(R3) IWG does not maintain the stylesheet, and does not suggest that this particular tool must be implemented. However, it is provided to assist users and may be used in some countries or regions should this be mandated by their regional requirements. Implementers should refer to the ICH Implementation Package and associated Q&A to make any necessary update(s) to the stylesheet.
10. USER GUIDE: Use of EDQM terminologies for Dose Forms and Routes
of Administration for Individual Case Safety Reports in E2B(R3) message
This User Guide describes supplemental information how to use the terminologies maintained by the European Directorate for the Quality of Medicines & HealthCare (EDQM) that relate to Pharmaceutical Dose Forms (DF) and Routes of Administration (RoA) in E2B(R3) format messages. This User Guide should be used in conjunction with the ICH E2B(R3) IG and associated documents for electronic exchange of ICSRs.
Link to Explanatory Memorandum - EDQM terminologies for Dose Forms and Routes of Administration as Part of ISO/IDMP Standards for ICH Use in Individual Case Safety Reports Created in E2B(R3) Format
11. ICH E2B(R3) Core Data Elements and Business Rules
This spreadsheet provides a common template that summarises the core ICH E2B(R3) data elements, business rules and any associated questions and answers. These data elements are from the Implementation Guide (IG) and details of the data element are documented in the IG. The purpose of this document is to use it as a tool to implement a common template across all regions and implementers. Regions can download this common template, add their regional data elements and publish them regionally. It is recommended that this format of the common template is maintained by regions for global consistency.
|Last updated: August, 2018||