E2C – Periodic Benefit-Risk Evaluation Report

Home / Guidelines & Products

E2C – Periodic Benefit-Risk Evaluation Report

The ICH Harmonised Guideline was finalised under Step 4 in November 1996. This document gives guidance on the format and content of safety updates, which need to be provided at intervals to regulatory authorities after products have been marketed. The Guideline is intended to ensure that the worldwide safety experience is provided to authorities at defined times after marketing with maximum efficiency and avoiding duplication of effort.

Based on the comments made by the members of the Expert Working Group on CIOMS V recommendations and the PhRMA-EFPIA working document, an addendum has been finalised and reached Step 4 in February 2003 (R1).

The revised (R2) Guideline reached Step 4 of the ICH process in November 2012. The purpose of this Guideline’s revision is to ensure that the periodic safety update reports for marketed drugs have the role of being periodic benefit-risk evaluation reports by covering: safety evaluation, evaluation of all relevant available information accessible to marketing authorisation holders (MAHs) and benefit-risk evaluation.

The ICH Harmonised Guideline was finalised under Step 4 in July 1997. This document covers the preclinical safety testing requirements for biotechnological products. It addresses the use of animal models of disease, determination of when genotoxicity assays and carcinogenicity studies should be performed, and the impact of antibody formation on duration of toxicology studies.

An addendum was proposed to provide clarification on S6 and an update of the following topics discussed in the original ICH S6 Guideline: species selection, study design, immunogenicity, reproductive and developmental toxicity and assessment of carcinogenic potential. The Harmonised addendum provides further complementary guidance to the S6 Guideline and helps to define the current recommendations and reduce the likelihood that substantial differences will exist among regions.

The addendum reached Step 4 of the harmonisation process in June 2011 and was integrated as part II in the core Guideline that was then renamed S6(R1).

Guideline

E2C(R2) Guideline

Endorsed Documents

E2C(R2) Concept Paper

E2C(R2) Business Plan

WG Presentations / Trainings

E2C(R2) Training Material

Annexes

Guideline implementation

ANMAT, Argentina

Not yet implemented;

ANVISA, Brazil

Implemented; Date: 1 October 2020; Reference: RDC 406/2020 e IN 63/2020

COFEPRIS, Mexico

Implemented; Date: 1 July 2017; Reference: NOM-220-SSA1-2016

EC, Europe

Implemented; Date: 1 January 2013; Reference: CHMP/ICH/544553/1998

EDA, Egypt

Implemented; Date: 7 January 2015; Reference: Guideline on Good Pharmacovigilance Practice (GVP) in Egypt For Pharmaceutical Products

FDA, United States

Implemented; Date: 1 July 2016; Reference: FDA, US-2012-D-0315, p. 46938 - 40

HSA, Singapore

Implemented; Date: 1 January 2014; Reference: HSA, Singapore’s Guidance for industry on Post-Marketing Vigilance requirements for Therapeutic Products and Cell, Tissue and Gene Therapy Products

Health Canada, Canada

Implemented; Date: 29 November 2010; Reference: File #: 10-123674-389

JFDA, Jordan

Implemented; Date: 1 July 2015;

MFDS, Republic of Korea

Implemented; Date: 2 May 2015; Reference: Guideline on Periodic Benefit-Risk Evaluation Report [Guideline 0025-01]

MHLW/PMDA, Japan

Implemented; Date: 1 May 2013; Reference: PFSB/ELD Notification No. 0517-1

MHRA, UK

Implemented; Date: 1 December 2012;

NAFDAC, Nigeria

Not yet implemented;

NMPA, China

Implemented; Date: 21 July 2020; Reference: NMPA, China Announcement No. 86 (2020)

SAHPRA, South Africa

In the process of implementation;

SFDA, Saudi Arabia

Implemented; Date: 1 September 2015;

Swissmedic, Switzerland

Implemented; Date: 1 July 2014; Reference: Swissmedic, Switzerland press release

TFDA, Chinese Taipei

Implemented; Date: 9 September 2004; Reference: 1. Regulation for Drug Safety Monitoring 2. Guidance on Good Pharmacovigillance Practices

TITCK, Türkiye

Implemented; Date: 26 September 2014; Reference: Regulation on the Safety of Medicinal Products: Official Gazette numbered 28973 on 15 April 2014, Regulation on Amending the Regulation on the Safety of Medicinal Products: Official Gazette numbered 31899 on 21 July 2022, Good Pharmacovigilance Practice (GVP) Guide Module III - Periodic Benefit/Risk Evaluation Report www.titck.gov.tr

Q+A

Questions & Answers

E2C(R2) Q&As Questions & Answers

Endorsed Documents

E2C(R2) Q&As Concept Paper

E2C(R2) Q&As Work Plan

WG Presentations / Trainings

E2C(R2) Q&As Training Material

Q+A implementation

The revision E2C(R2) to E2C has introduced new concepts and principles linked to an evolution of the traditional PSUR from an interval safety report to cumulative benefit-risk report and with a change in focus from individual case reports to more aggregate data evaluation.

This supplementary Questions and Answers document finalised under Step 4 in March 2014 intends to facilitate practical implementation of the PBRER, including points to consider in addressing some of the more novel aspects of the new periodic safety report.

ANMAT, Argentina

Not yet implemented;

ANVISA, Brazil

In the process of implementation; Date: 24 February 2025; Reference: RDC 406/2020 e IN 63/2020

COFEPRIS, Mexico

Implemented; Date: 1 July 2017; Reference: Mexican Official Standard NOM-220-SSA1-2016

EC, Europe

Implemented; Date: 1 May 2014; Reference: CHMP/ICH/271908/2014

EDA, Egypt

Implemented; Reference: Guideline on Good Pharmacovigilance Practice (GVP) in Egypt For Pharmaceutical Products

FDA, United States

Implemented; Date: 1 July 2016; Reference: No. FDA, US-2012-D-0315, p. 46938 - 40

HSA, Singapore

Implemented; Date: 1 January 2014; Reference: HSA, Singapore’s Guidance for industry on Post-Marketing Vigilance requirements for Therapeutic Products and Cell, Tissue and Gene Therapy Products

Health Canada, Canada

Implemented; Date: 9 April 2013; Reference: File #: 13-105055-393

JFDA, Jordan

Implemented; Date: 1 July 2015;

MFDS, Republic of Korea

Implemented; Date: 29 June 2017; Reference: Guideline on Periodic Benefit-Risk Evaluation Report [Guideline 0191-02]

MHLW/PMDA, Japan

Implemented; Date: 1 August 2014; Reference: PFSB/ELD Administrative Notice

MHRA, UK

Implemented; Date: 1 May 2014;

NAFDAC, Nigeria

Not yet implemented;

NMPA, China

Implemented; Date: 21 July 2020; Reference: NMPA, China Announcement No. 86 (2020)

SAHPRA, South Africa

In the process of implementation;

SFDA, Saudi Arabia

Implemented; Date: 1 September 2015;

Swissmedic, Switzerland

Implemented; Date: 1 July 2014; Reference: Swissmedic, Switzerland press release

TFDA, Chinese Taipei

Implemented; Date: 22 December 2014; Reference: Public Announcement for ” List for ICH Guidelines Adopted.”

TITCK, Türkiye