E2B(R2) and E2B(R3) are standards for electronic transmission of individual case safety reports (ICSRs). E2B(R3) was developed through a new collaborative approach between several international organizations, whereas E2B(R2) was developed by ICH alone. E2B(R3) uses a hierarchical data structure and is more standardized and interoperable compared to E2B(R2). The increased standardization of E2B(R3) allows for better exchange of safety information.

1. WHAT IS THE DIFFERENCE BETWEEN
E2B(R2) AND E2B(R3) ICSR ELEMENTS?

2. ICSR TRANMISSION
The exchange of safety information is based on paper-based formats (e.g. Yellow Cards,
CIOMS I forms, MedWatch forms, etc.) or electronic media (e.g. on-line access, tape, CD, etc).
Considering the large number of potential participants in a world-wide exchange of information, there
should be a standard format that is capable of accommodating direct database-to-database transmission
using standardised message transfers. Successful electronic transmission of information relies on the consistent
and uniform interpretation of definitions for common data elements and standard transmission procedures.
Over the last decade as the number of case reports has increased, exchange of ICSRs has increasingly shifted
from paper-based to electronic reports and electronic transmission of case safety information has become an
important component of global pharmacovigilance. The ICH released a consensus electronic standard for ICSRs
in 1997 and this standard has undergone a number of revisions since it was first adopted. The ICH E2B(R2)
standard has been used for regulatory compliance purposes for several years and now the fourth revision ICH
E2B(R3) is much more standardised.

3. ADVANTAGES TO ELECTRONIC SUBMISSIONS
The ICH chose to adopt an XML schema for the ICSR as it is more suitable for the intended purpose:
• XML is portable and non-proprietary.
• It can be used to store and share information electronically across platforms.
• XML is used for encapsulating information to be passed between two computing systems which might
otherwise be unable to communicate.
• It provides a common envelope for inter-process communication (messaging).
• It is supported by an international standard and will, therefore, remain accessible.
The ICH ICSR enhances electronic adverse event reporting and analysis by facilitating the efficient reporting of
suspected product-related adverse events/reactions. The electronic environment:
• Improves the ability to efficiently exchange and process ICSR data
• Facilitates the transfer of information to organisations who need it
• Enables incoming messages to be automatically routed and processed
• Facilitates aggregation of safety data for analysis; and
• Allows minimising resources required for data (re-)entry activities.

4. After the release of E2B(R2), the ICH realized that technical specifications should no longer be developed in isolation.
E2B(R3) is the first technical specification to be developed through a new collaborative approach. The International
Organization for Standards (ISO), Health Level Seven International (HL7), and European Committee for Standardization (CEN)
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 became members of the Joint Initiative. ICH representatives have also been
heavily involved.
The overall standard is based upon a HL7 ICSR model that is capable of supporting the exchange of messages for a wide
range of product types (e.g., human medicinal products, veterinary products, medical devices).
The real benefit of E2B(R3) is interoperability, which ultimately better protects patients and consumers. Since E2B(R3) is
based on HL7, a variety of clinical systems will be able to use it to exchange data with each other. With this new structure,
more data can be passed to regulatory authorities or marketing authorization holders, making the information much more
valuable to all parties involved.
COLLABORATIVE APPROACH

5. E2B(R3) IS THE FIRST TECHNICAL SPECIFICATION TO BE
DEVELOPED THROUGH A NEW COLLABORATIVE
APPROACH.
INTERNATIONAL
ORGANIZATION FOR
STANDARDS (ISO)
HEALTH LEVEL SEVEN
INTERNATIONAL (HL7)
EUROPEAN COMMITTEE
FOR STANDARDIZATION
(CEN)

6. DEFINITION OF DATA ELEMENTS E2B(R2)
The format for individual case safety reports includes provisions for transmitting all the relevant data elements
useful to assess an individual adverse drug reaction or adverse event report.
The data elements are sufficiently comprehensive to cover complex reports from most sources, different data
sets, and transmission situations or requirements; therefore, not every data element will be available for every
transmission.
In many, if not most instances, a substantial number of the data elements will not be known and therefore not
included in the transmission. Where it was deemed important, provisions for unknown or not applicable were
included

7. CONTENT OF THE DATA ELEMENTS E2B(R2)
The data elements are divided into sections pertaining to:
A: Administrative and Identification Information
A.1 - Identification of the case safety report
A.2 - Primary source(s) of information
A.3 - Information on sender and receiver of case safety report
B: Information on the Case:
B.1 - Patient characteristics
B.2 - Reaction(s)/event(s)
B.3 - Results of tests and procedures relevant to the investigation of the patient
B.4 - Drug(s) information
B.5 - Narrative case summary and further information

8. E2B(R2)
ICSR Elements

9. DEFINITION OF DATA ELEMENTS E2B(R3)
The guidance for transmitting ICSR information includes provisions for transmitting all relevant data useful to
assess an individual adverse event/reaction report. The message standard from which this guidance is derived is
fully capable of conveying a comprehensive ICSR.
However, it is noted that each and every data element will not be available for each and every transmission. In
fact, for most ICSRs, a number of data elements will be unknown, and therefore, not transmitted in the report.
Since ICSR information will be transmitted electronically, it is unnecessary to assign values to unknown, optional
data elements. However, in certain cases it is important to understand if a data element is null because it is not
applicable or because it is unknown or because it is ‘protected’ by privacy legislation.
In those cases, provisions for expressing a null value are included in the message for a data element to indicate
the absence of data and reason.

11. MASKED
UNKNOWN

12. CONTENT OF THE DATA ELEMENTS E2B(R3)
E2B (R3) data elements have a hierarchical tree structure. It consists of two major sections A
and B, where A contains administrative and identification information, and B contains
information on the case. The subsidiary sections are categorised by the nature of the data,
and are:
Section A
C.1 - Identification of the Case Safety Report
C.2- Primary Source(s) of Information
C.3 - Information on Sender of Case Safety Report
C.4 - Literature Reference(s)
C.5 - Study Identification.
Section B
D - Patient Characteristics
E - Reaction(s)/ Event(s)
F - Results of Tests and Procedures Relevant to the Investigation of the Patient
G - Drug(s) Information
H - Narrative Case Summary and Further Information.

13. E2B(R3)
ICSR Elements

14. REFERENCE
https://www.ich.org/home.html