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E2B(R3) Electronic Transmission of Individual Case Safety Reports Implementation Guide — Data Elements and Message Specification; and Appendix to the Implementation Guide — Backwards and Forwards Compatibility

FinalCenter for Drug Evaluation and Research04/29/2022
Good Guidance PracticesData IntegrityPharmacovigilance

Description

This document is a guide for implementing the standard adopted by the ICH1 for electronic transmission of Individual Case Safety Reports (ICSRs) according to the ICH E2B(R3) message standard. This Implementation Guide (IG) was jointly developed by the ICH E2B(R3) and M2 Expert Working Groups (EWGs). The E2B(R3) EWG provided business requirements and the M2 EWG provided technical content for this IG. These two EWGs were reconstituted as the ICH E2B(R3) EWG in November 2010.

Key Topics

Terms and concepts identified from this document

Scope & Applicability

Product Classes

10
Drug and Biological Products

Scope of the electronic transmission guidance

Counterfeit Medicine

Medicine deliberately and fraudulently mislabelled with respect to identity and/or source

Human Pharmaceuticals

Base Model RMIM designed for pharmaceutical reports

Biologics

Products for which batch/lot information is particularly important

Vaccines

Products for which batch/lot information is particularly important

Fixed dose combination drugs

Dose unit for these should be provided as arbitrary unit {DF}

Investigational drugs

In case of investigational drugs, provide as much information as known.

Concomitant medications

concomitant medications are only those health products taken by the patient at the time the reaction is observed

Suspect medications

Suspect medications are those health products taken by the patient and suspected by the reporter to have contributed to the adverse reaction.

Medicinal product

Subject of safety reports including overdose or medication error; Substance presented as having properties for treating or preventing disease in human beings

Stakeholders

10
E2B(R3) Expert Working Group

Group that jointly developed the guidance

Marketing Authorisation Holder

Organisation that holds a valid marketing authorisation for a medicinal product

Name of Holder / Applicant

Data element G.k.3.3 defined in POCP_MT030200UV.

ACK Sender

The organisation that received the ICH ICSR message

ACK Receiver

The organisation that submitted the ICH ICSR message

Batch Receiver

The organisation that is receiving the ICH ICSR and generating the acknowledgement.

Batch Sender

The organisation that is submitting the ICH ICSR.

Company

Sender providing causality assessment via algorithms or Bayesian analysis

Holder

Holders of approved applications or master files

Primary reporter

the one reported or implied by the primary reporter

Regulatory Context

Regulatory Activities

6
Expedited Report

Case fulfillment of local criteria for expedited reporting; Does This Case Fulfil the Local Criteria for an Expedited Report?; C.1.7 indicates whether the case fulfils the local expedited requirements.; Regulatory submission type for serious adverse events

Spontaneous Reporting

An unsolicited communication describing an adverse drug reaction

Acknowledgement Batch Interaction

MCCI_IN200101UV01 interaction for grouping messages.

Clinical trial

Administering survey instruments in a clinical trial at screening and/or exit visits; obtaining patient feedback regarding various topics throughout a trial

Drug registration

Harmonisation of scientific and technical aspects by ICH

Electronic transmission

Transmission of ICSRs according to the ICH E2B(R3) message standard

Document Types

10
CIOMS I forms

Paper-based safety information exchange format

ICSR Acknowledgment message

Message sent in response to an ICSR submission

ICH ICSR Batch Acknowledgement

ACK.M/A - ICH ICSR Batch Acknowledgement Header structure and data elements.

ICH ICSR Acknowledgement

Transaction sent after receipt of an ICSR to confirm processing.

Literature article

Scientific papers attached to ICSRs using specific data elements like C.4.r.2.

ECG strips

Example of a clinical document that can be attached to an ICSR.

Autopsy reports

Example of a clinical document that can be attached to an ICSR.

Included Documents

Data element C.4.r.2 containing the actual content of referenced literature.

Literature Reference(s)

Section C.4.r for literature articles describing individual cases.

Clinical records

Documents received from the primary source (e.g. clinical records, hospital records) should be listed individually.

Attributes

10
Seriousness Criteria

Includes death, life threatening, and hospitalization; Criteria such as death, life threatening, or hospitalization

CCYYMMDDhhmmss

International standard date/time notation format.

Identification of the Country Where the Drug Was Obtained

Data element G.k.2.4 defined in POCP_MT030100UV.

CR

Commit Reject - fatal error prevents loading

CA

Commit Accept - ICSR message successfully loaded

Date of ICSR Message Creation

ACK.B.r.5 data element

Acknowledgement Date of Batch Transmission

ACK.M.4: captures the date on which the batch file was transmitted.

Transmission Acknowledgement Code

ACK.A.4: code to inform the submitter whether to take action or re-send.

Compression

Property indicating the algorithm used for data compression (e.g., deflate).

Media Type

Property identifying the type of encapsulated data (e.g., application/PDF).

Technical Details

Substances

4
Substances

Core components of pharmaceutical products identified via ISO 11238

Active ingredient

Medicinal product names or active ingredient names should be provided.; If MPID/PhPID unavailable, each active ingredient should be specified individually

Vaccine

Previous exposure history in business rules

Suspect drug

Drug taken by parent that may have caused adverse events in the child/foetus.

Testing Methods

6
XML encoding syntax

Technical method for HL7 V3 message representation

Bayesian calculation

Example of method of assessment

Global introspection

Method of causality assessment based on overall impression; Example of method of assessment

Bayesian analysis

Method of causality assessment

Serologic tests

Used to investigate non-drug causes like infectious hepatitis

Results of tests and procedures

Data block F.r relevant to the investigation of the patient

Processes

4
Electronic ICSR Exchange

Standardization of transmission between partners

Relevant Past Drug History

Section D.8.r concerning drugs administered and stopped before adverse event onset.

Concomitant Therapies

Data element D.7.3 indicating therapies like radiotherapy or dietary supplements.

Electronic adverse event reporting

Facilitated by the ICH ICSR to enhance analysis

Clinical Concepts

10
Clinical Safety Data Management

Topic of the ICH guideline elements

Serious Adverse Reaction

Any untoward medical occurrence that results in death, is life-threatening, or requires hospitalization

Causality assessment

Evaluation of the relationship between a product and an adverse event.

Diagnosis

Reporter's or sender's assessment of the medical condition.

Anaphylaxis

Example of a reaction with short time interval

Reaction

Onset of reaction/event in relation to drug administration

Adverse reaction

suspected by the reporter to have contributed to the adverse reaction described in Section E

Drug-induced hepatitis

Suspected condition requiring investigation

Seriousness

Criteria for assessing the severity of a reaction or event

Medical History

Relevant Medical History and Concurrent Conditions of Parent

Identified Hazards

Hazards

1
Patient safety

Primary driver for expedited exchange of safety information

Standards & References

External Standards

7
RFC 2046

Standard used to identify Media Type for encapsulated data.

UCUM codes

Used for time interval units

Vancouver style

Citation style developed by the International Committee of Medical Journal Editors.

ISO 3166-1 alpha-2

Country code is the 2-letter ISO 3166 part 1 code corresponding to the country of the primary source.; Two character country code list; Used for country identification in G.k.2.4 and G.k.3.2

UCUM

The Unified Code for Units of Measure for units of strength and dose; terminologies include UCUM for units of measurement; Codes for units of measurement like Year, Month, Week, Day; UCUM codes for Year: {Decade}; Unified Code for Units of Measure used for duration units; Unified Code for Units of Measure for test results; Strength units use constrained UCUM codes; Used for dose units and time interval units; Unified Code for Units of Measure used for dose and gestation units

MedDRA

Used for coding indications, reactions, and causes of death; Coding for indications and sender's diagnosis; Medical Dictionary for Regulatory Activities used for coding medical sections; Medical Dictionary for Regulatory Activities used to classify adverse event information; terminologies include MedDRA for medical history, indication, and reaction; Used for coding medical history, indications, reactions, and causes of death.; Standard terminology used for coding medical history, indications, an

HL7

Acknowledgement Message in HL7; HL7 uses a single format to represent dates and times; Both the Sender's (case) Safety Report Unique Identifier and the Worldwide Unique Case Identification Number data elements are mapped to the repeatable XML attribute in the HL7 ICSR model.; HL7 ICSR model used for mapping data elements; HL7 defines the data type of G.k.2.4 as string; Messaging standard used for the transmission infrastructure of acknowledgements.; Organization that developed the schemas; Stand

Specifications

10
ICH ICSR DTD v2.1

Message specification for electronic transmission

Standard

A technical specification addressing a business requirement

PORR_IN049016UV

Schema for individual ICSR messages including nullifications

MCCI_IN200100UV01

Schema defining root element for Batch messages

datatypes-base

Schema defining basic and generic HL7 data types

infrastructureRoot

Core schema defining properties for all elements

XML

ACK.A.5 provides a description of errors detected in the ICH ICSR batch XML.; eXtensible Markup Language used for message structure

nullFlavor

Used to describe missing or non-transmitted information in XML

Boolean

Data Type: Boolean

XML message

OIDs provided in this IG should be used in XML messages for the ICH ICSR.; it might be necessary to mask some of the elements used to identify the reporter in the transmitted message.; Format for transmitting ICSR data elements; Format for electronic transmission of ICSR data; The format into which ICSR data and attachments are embedded.

ICH References (6)

ICH E2B(R3)

Implementation Guide for Electronic Transmission of Individual Case Safety Reports; Electronic Transmission of Individual Case Safety Reports Implementation Guide; Implementation Guide for electronic transmission of Individual Case Safety Reports; fully structured format using the relevant E2B(R3) data elements; Details of ICH E2B(R3) Data Elements and message specifications.; Implementation guide for electronic transmission of ICSRs; Implementation Guide for electronic transmission of ICSRs; Im

ICH E2C(R1)

Source of the definition for Spontaneous Reporting

ICH E6(R1)

Guideline for Clinical Safety Data Management: Definitions and Standards for Expedited Reporting

ICH E2A

Provides definitions for seriousness criteria; ICH E2A recommends blinded therapy should not be reported

ICH E2D

Provides guidance on identifiable patients and reporters; Provides definitions for seriousness criteria

ICH E2B(R2)

Renamed from E2B(M) in 2005; Previous version of the ICSR standard used for regulatory compliance; nullFlavor is only allowed when sender is retransmitting a case that was first received ICH E2B (R2) format.; Guideline referenced for definitions of Reporter and Sender

Related MFDS Guidelines

Korean regulatory guidelines covering similar topics

See Also (8)