The work carried out by ICH under the Efficacy heading is concerned with the design, conduct, safety and reporting of clinical trials.  It also covers novel types of medicines derived from biotechnological processes and the use of pharmacogenetics/ pharmacogenomics techniques to produce better targeted medicines.
Zip file with all Efficacy Guidelines in Word format

  • E1 Clinical Safety for Drugs used in Long-Term Treatment

    Code Document Title Previously coded
    • Finalised Guideline:
      October 1994

      Description :

      The tripartite harmonised ICH Guideline was finalised under Step 4 in October 1994. This document gives recommendations on the numbers of patients and duration of exposure for the safety evaluation of drugs intended for the long-term treatment of non-life-threatening conditions.

      Implementation :

      Step 5

      :

      EC, EuropeAdopted by CPMP, November 1994, issued as CPMP/ICH/375/95

      :

      MHLW/PMDA, Japan Adopted May 1995, PAB/PCD Notification No. 592

      :

      FDA, US Published in the Federal Register, 1 March 1995, Vol. 60, p. 11270

      :

      Health Canada, Canada Implemented 1 June 1995, Catalogue No. H42-2/67-7-1995E

      :

      Swissmedic, Switzerland - Refer to the press release on Swissmedic, Switzerland's website

  • E2A - E2F Pharmacovigilance

    Code Document Title Previously coded
    • Finalised Guideline:
      October 1994

      Description :

      The tripartite harmonised ICH Guideline was finalised under Step 4 in October 1994. This document gives standard definitions and terminology for key aspects of clinical safety reporting. It also gives guidance on mechanisms for handling expedited (rapid) reporting of adverse drug reactions in the investigational phase of drug development.

      Implementation :

      Step 5

      :

      EC, EuropeAdopted by CPMP, November 1994, issued as CPMP/ICH/377/95

      :

      MHLW/PMDA, Japan Adopted March 95, PAB/PCD Notification No. 227

      :

      FDA, US Published in the Federal Register, 1 March 1995, Vol. 60, No. 40, p. 11284-11287

      :

      Health Canada, Canada Implemented 1 June 1995, H42-2/67-8-1995E

      :

      Swissmedic, Switzerland - Refer to the press release on Swissmedic, Switzerland's website

    • Description :

      ICH E2B EWG was re-formed to conduct a revision of E2B(R2) Guideline in 2003 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. ICH E2B(R3) was the first topic harmonized under the new process. An Implementation Guide for E2B(R3) data elements and message specification was developed by the E2B EWG, which uses the ISO/HL7 27953-2 ICSR message exchange standard developed by the SDOs, and E2B(R3) reached Step 4 in November 2012. Following minor editorial updates an updated version of the IG was published in July 2013. Minor updates were made in some documents included in the IG package in November 2014 (v1.02 of the IG package) and in April 2015 (v1.03 of the IG package). 

      Implementation :

      Step 5

      :

      EC, EuropeAdopted by CHMP, July 2013, issued as EMA/CHMP/ICH/287/1995

      :

      MHLW/PMDA, Japan -  Adopted 8 July 2013, PFSB/ELD Notification No. 070805 & PFSB/SD Notification No. 070801

      :

      FDA, US Published in the Federal Register, 21 February 2014, Vol. 79, No. 35, p. 9908-9

      :

      Health Canada, Canada To be notified

      :

      Swissmedic, Switzerland - Refer to the press release on Swissmedic, Switzerland's website

    • Description :

      In July 2013, the ICH Steering Committee endorsed the establishment of the IWG on E2B(R3) to assist with the implementation of the E2B(R3) Implementation Guide (published in July 2013) and help facilitate transition from E2B(R2) to E2B(R3). Included in its tasks is support for the use of constrained ISO IDMP terminologies in ICSRs, as well as maintenance of technical documents related to E2B(R3).

      In November 2014, the IWG finalised the first version of Questions & Answers (Q&As) to clarify questions and comments for E2B(R3) implementation, the group will continue updating the Q&As to address new questions and comments.

      Implementation :

      Step 5 - after having been signed as a Step 4, the document enters the Implementation stage by all ICH regulators.

      :

      EC, EuropeAdopted by CHMP, January 2015, issued as EMA/CHMP/ICH/3943/2003

      :

      MHLW/PMDA, Japan Adopted 2 April 2015, PFSB/Evaluation and Licensing Division and Safety Division

      :

      FDA, US To be notified

      :

      Health Canada, Canada To be notified

      :

      Swissmedic, Switzerland - Refer to the press release on Swissmedic, Switzerland's website

    • Finalised Guideline:
      November 2012

      Description :

      The tripartite core harmonised ICH 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.

      Implementation :

      Step 5

      :

      EC, EuropeAdopted by CHMP, December 2012, issued as EMA/CHMP/ICH/544553/1998

      :

      MHLW/PMDA, Japan Adopted 17 May 2013, PFSB/ELD Notification No. 0517-1

      :

      FDA, US Published in the Federal Register, 19 July 2016, No. FDA-2012-D-0315, p. 46938 - 40

      :

      Health Canada, Canada Implemented 29 November 2010, File #: 10-123674-389

      :

      Swissmedic, Switzerland - Refer to the press release on Swissmedic, Switzerland's website

    • Description :

      In November 2012, the ICH Steering Committee endorsed the establishment of the IWG on E2C(R2) to assist with the implementation of the new revision (R2) of the E2C Guideline finalised under Step 4 of the ICH Process in November 2012. This revision 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 clarify key issues.

      Status :

      Step 5

      :

      EC, EuropeTransmission to CHMP and released for information in May 2014 as EMA/CHMP/ICH/271908/2014

      :

      MHLW/PMDA, Japan Adopted 25 August 2014, PFSB/ELD Administrative Notice

      :

      FDA, US Published in the Federal Register, 19 July 2016, No. FDA-2012-D-0315, p. 46938 - 40

      :

      Health Canada, Canada Implemented 9 April 2013, File #: 13-105055-393

      :

      Swissmedic, Switzerland - Refer to the press release on Swissmedic, Switzerland's website

    • Finalised Guideline:
      November 2003

      Description :

      The tripartite harmonised ICH Guideline was finalised under Step 4 in November 2003. This document provides a standardised procedure for post-approval safety data management including expedited reporting to relevant authority. The definitions of the terms and concept specific to post-approval phase are also provided. E2A definitions in clinical safety data management was maintained in this document as post-approval safety data management, such as seriousness definition. The practices of the data management were standardised in such cases obtained from consumers, literatures, internets which are all specific to post-approval data management. Good case management practice was focused and recommended for expedited reporting with clear definitions.

      Implementation :

      Step 5

      :

      EC, EuropeAdopted by CPMP, 20 November 2003, issued as CPMP/ICH/3945/03

      :

      MHLW/PMDA, Japan -  Adopted 28 March 2005, PFSB/SD Notification No. 0328007

      :

      FDA, US Published in the Federal Register, 15 September 2003, Vol. 68, No. 178, p. 53983-4

      :

      Health Canada, Canada Implemented 02 March 2011, ISBN: 978-1-100-17663-5

      :

      Swissmedic, Switzerland - Refer to the press release on Swissmedic, Switzerland's website

    • Finalised Guideline:
      November 2004

      Description :

      The tripartite harmonised ICH Guideline was finalised under Step 4 in November 2004. This Guideline is intended to aid in planning pharmacovigilance activities, especially in preparation for the early postmarketing period of a new drug (in this Guideline, the term "drug" denotes chemical entities, biotechnology-derived products, and vaccines). The main focus of this Guideline is on a Safety Specification and Pharmacovigilance Plan that might be submitted at the time of licence application.

      Implementation :

      Step 5

      :

      EC, EuropeAdopted by CHMP, 1 December 2004, issued as CPMP/ICH/5716/03.

      Coming into operation in June 2005

      :

      MHLW/PMDA, Japan Adopted 16 September 2005, PFSB/ELD Notification No. 0916001 & PFSB/SD Notification No. 0916001

      :

      FDA, US Published in the Federal Register, 1 April 2005, Vol. 70, No. 62, p. 16827-16828

      :

      Health Canada, Canada Implemented 16 February 2009, File #: 09-103644-626

      :

      Swissmedic, Switzerland - Refer to the press release on Swissmedic, Switzerland's website

       

       

    • Description :

      The tripartite harmonised ICH Guideline was finalised under Step 4 in August 2010.
      The main focus of the DSUR is data from interventional clinical trials (referred to in this document as "clinical trials") of investigational drugs including biologicals, with or without a marketing approval, whether conducted by commercial or non-commercial sponsors.

      Following the completion of the E2F Step 4 Guideline, the E2F EWG developed DSUR Examples for commercial and non-commercial sponsors to help with the use of the E2F Guideline. It should be noted that these documents are only examples and therefore did not go through the formal ICH Step Process.

      Implementation :

      Step 5

      :

      EC, EuropeAdopted by CHMP, September 2010, issued as EMA/CHMP/ICH/309348/2008

      :

      MHLW/PMDA, Japan -  Adopted 28 December 2012, PFSB/SD Notification 1228-1

      :

      FDA, US Published in the Federal Register, 23 August 2011, Vol. 76, No. 163, p. 52667-8

      :

      Health Canada, Canada Implemented 20 December 2012, File #: 12-122199-139

      :

      Swissmedic, Switzerland - Refer to the press release on Swissmedic, Switzerland's website

  • E3 Clinical Study Reports

    Code Document Title Previously coded
    • Finalised Guideline:
      November 1995

      Description :

      The tripartite harmonised ICH Guideline was finalised under Step 4 in November 1995. This document describes the format and content of a study report that will be acceptable in all three ICH regions. It consists of a core report suitable for all submissions and appendices that need to be available but will not be submitted in all cases.

      Implementation :

      Step 5

      :

      EC, EuropeAdopted by CPMP, December 1995, issued as CPMP/ICH/137/95

      :

      MHLW/PMDA, Japan Adopted May 1996, PAB/PCD Notification No. 335

      :

      FDA, US Published in the Federal Register, 17 July 1996, Vol. 61, p. 37320

      :

      Health Canada, Canada Implemented 20 May 1997, Catalogue No. H42-2/67-10-1996E

      :

      Swissmedic, Switzerland - Refer to the press release on Swissmedic, Switzerland's website

    • Finalised Q&As:
      July 2012

      Description :

      Since reaching Step 4 and publication within the ICH regions, experiences by all parties with the implementation of the E3 Guideline have resulted in the need for some clarification. This supplementary Questions and Answers document intends to clarify key issues.

      In July 2012, minor typographical errors were corrected in the Answer to Question 6 and the document was renamed R1.

      Implementation :

      Step 5

      :

      EC, EuropeTransmission to CHMP and release for information, July 2012, issued as EMA/CHMP/ICH/435606/2012

      :

      MHLW/PMDA, Japan Adopted 18 October 2012, PFSB/ELD Administrative Notice

      :

      FDA, US Posted on FDA website on 25 January 2013

      :

      Health Canada, Canada Implemented 18 December 2015, File #: 15-113539-305

      :

      Swissmedic, Switzerland - Refer to the press release on Swissmedic, Switzerland's website

  • E4 Dose-Response Studies

    Code Document Title Previously coded
    • Finalised Guideline:
      March 1994

      Description :

      The tripartite harmonised ICH Guideline was finalised under Step 4 in March 1994. This document gives recommendations on the design and conduct of studies to assess the relationship between doses, blood levels and clinical response throughout the clinical development of a new drug.

      Implementation :

      Step 5

      :

      EC, EuropeAdopted by CPMP, May 1994, issued as CPMP/ICH/378/95

      :

      MHLW/PMDA, Japan Adopted July 1994, PAB/PCD Notification No. 494

      :

      FDA, US Published in the Federal Register, 9 November 1994, Vol. 59, No. 216, p. 55972-55976

      :

      Health Canada, Canada Implemented 1 October 1994, Catalogue No. H42-2/67-4-1994E

      :

      Swissmedic, Switzerland - Refer to the press release on Swissmedic, Switzerland's website

  • E5 Ethnic Factors

    Code Document Title Previously coded
    • Finalised Guideline:
      February 1998

      Description :

      The tripartite harmonised ICH Guideline was finalised under Step 4 in February 1998. This document addresses the intrinsic characteristics of the drug recipient and extrinsic characteristics associated with environment and culture that could affect the results of clinical studies carried out in regions and describes the concept of the "bridging study" that a new region may request to determine whether data from another region are applicable to its population.

      Implementation :

      Step 5

      :

      EC, EuropeAdopted by CPMP, March 1998, issued as CPMP/ICH/289/95

      :

      MHLW/PMDA, Japan Adopted August 1998, PMSB/ELD Notification No. 672, PMSB Notification No. 739

      :

      FDA, US Published in the Federal Register, 10 June 1998, Vol. 63, No. 111, p. 31790

      :

      Health Canada, Canada Implemented 18 December 2015, File #: 15-113552-719.

      :

      Swissmedic, Switzerland - Refer to the press release on Swissmedic, Switzerland's website

    • Finalised Q&As:
      June 2006

      Description :

      Since reaching Step 4 and publication within the ICH regions, experiences by all parties with the implementation of the E5 Guideline have resulted in the need for some clarification. This supplementary Questions and Answers document intends to clarify key issues.

      Implementation :

      Step 5

      :

      EC, EuropeAdopted by CPMP, 20 November 2003, issued as CPMP/ICH/5746/03

      :

      MHLW/PMDA, Japan Adopted 5 October 2006, PFSB/ELD Notification

      :

      FDA, US Posted on FDA website 28 September 2006

      :

      Health Canada, Canada Implemented 04 January 2016, File #: 15-113559-530

      :

      Swissmedic, Switzerland - Refer to the press release on Swissmedic, Switzerland's website

  • E6 Good Clinical Practice

    Code Document Title Previously coded
    • Finalised Integrated Addendum: November 2016

      Description :

      The first version of the ICH E6 Good Clinical Practice (GCP) Guideline was finalised in 1996 describing the responsibilities and expectations of all participants in the conduct of clinical trials, including investigators, monitors, sponsors and IRBs. GCP covers aspects of monitoring, reporting and archiving of clinical trials and incorporating addenda on the Essential Documents and on the Investigator's Brochure.

      This harmonised guideline has been amended in 2016 with an integrated Addendum to encourage implementation of improved and more efficient approaches to clinical trial design, conduct, oversight, recording and reporting while continuing to ensure human subject protection and reliability of trial results. Standards regarding electronic records and essential documents intended to increase clinical trial quality and efficiency have also been updated. 

      Implementation :

      Step 5

      :

      EC, EuropeAdopted by CHMP, 15 December 2016, issued as EMA/CHMP/ICH/135/1995

      :

      MHLW/PMDA, Japan To be notified

      :

      FDA, US To be notified

      :

      Health Canada, Canada To be notified

      :

      Swissmedic, Switzerland - Refer to the press release on Swissmedic, Switzerland's website

  • E7 Clinical Trials in Geriatric Population

    Code Document Title Previously coded
    • Finalised Guideline:
      June 1993

      Description :

      The tripartite harmonised ICH Guideline was finalised under Step 4 in June 1993. This document provides recommendations on the special considerations which apply in the design and conduct of clinical trials of medicines that are likely to have significant use in the elderly.

      Implementation :

      Step 5

      :

      EC, EuropeAdopted by CPMP, September 1993, issued as CPMP/ICH/379/95

      :

      MHLW/PMDA, Japan Adopted December 1993, PAB/NDD Notification No. 104

      :

      FDA, US Published in the Federal Register, 2 August 1994, Vol.59, No. 102, p. 39398-39400

      :

      Health Canada, Canada Implemented 1 October 1994, Catalogue No. H42-2/67-1-1994E

      :

      Swissmedic, Switzerland - Refer to the press release on Swissmedic, Switzerland's website

    • Finalised Q&As:
      July 2010

      Description :

      Since reaching Step 4 and publication within the ICH regions, experiences by all parties with the implementation of the E7 Guideline have resulted in the need for some clarification. This supplementary Questions and Answers document intends to clarify key issues.

      Implementation :

      Step 5

      :

      EC, EuropeTransmission to CHMP and released for information in July 2010 as EMA/CHMP/ICH/604661/2009

      :

      MHLW/PMDA, Japan Adopted 17 September 2010, PFSB/ELD Notification

      :

      FDA, US Published in the Federal Register, 21 February 2012, Vol. 77, No. 34, p. 9948-9

      :

      Health Canada, Canada Implemented 16 June 2015, File #: 15-107057-839

      :

      Swissmedic, Switzerland - Refer to the press release on Swissmedic, Switzerland's website

  • E8 General Considerations for Clinical Trials

    Code Document Title Previously coded
    • Finalised Guideline:
      July 1997

      Description :

      The tripartite harmonised ICH Guideline was finalised under Step 4 in July 1997. This document sets out the general scientific principles for the conduct, performance and control of clinical trials. The Guideline addresses a wide range of subjects in the design and execution of clinical trials.

      Implementation :

      Step 5

      :

      EC, EuropeAdopted by CPMP, September 1997, issued as CPMP/ICH/291/95

      :

      MHLW/PMDA, Japan Adopted April 1998, PMSB/ELD Notification No. 380

      :

      FDA, US Published in the Federal Register, 17 December 1997, Vol. 62, No. 242, p. 66113

      :

      Health Canada, Canada Implemented 1 May 1998, Catalogue No. H42-2/67-12-1997IN

      :

      Swissmedic, Switzerland - Refer to the press release on Swissmedic, Switzerland's website

  • E9 Statistical Principles for Clinical Trials

    Code Document Title Previously coded
    • Draft Guideline: August 2017

      Description :

      This topic was endorsed by the ICH Steering Committee in October 2014.

      An Addendum was proposed to provide clarification on E9 and an update on the choice of estimand in clinical trials to describe an agreed framework for planning, conducting and interpreting sensitivity analyses of clinical trial data. This Addendum is proposed to focus on statistical principles related to estimands and sensitivity analysis, not on the use or acceptability of specific statistical procedures or methods. While a variety of mid-stage and late-stage clinical trials may be in scope, the primary focus of the Addendum will be on confirmatory clinical trials. It will promote harmonised standards on the choice of estimand in clinical trials and describe on agreed framework for planning, conducting and interpreting sensitivity analyses of clinical trial data.

      Status :

      Step 3

       

      :

      EC, Europe - Deadline for comments by 28 February 2018

      :

      MHLW/PMDA, JapanDeadline for comments by 12 March 2018

      :

      FDA, US Deadline to be notified

      :

      Health Canada, Canada Deadline for comments by 3 January 2018

      :

      Swissmedic, Switzerland - refers to EC, Europe consultation

      :

      MFDS, Republic of KoreaDeadline for comments by 31 March 2018

    • Finalised Guideline:
      February 1998

      Description :

      The harmonised tripartite Guideline was finalised under Step 4 in February 1998. This biostatistical Guideline describes essential considerations on the design and analysis of clinical trials, especially the "confirmatory" (hypothesis-testing) trials that are the basis for demonstrating effectiveness.

      Implementation :

      Step 5

      :

      EC, EuropeAdopted by CPMP, March 1998, issued as CPMP/ICH/363/96

      :

      MHLW/PMDA, Japan Adopted November 1998, PMBS/ELD Notification No. 1047

      :

      FDA, US Published in the Federal Register, 16 September 1998, Vol. 63, No. 179, p. 49583

      :

      Health Canada, Canada Implemented 10 February 2003, File #: 03-102451-780

      :

      Swissmedic, Switzerland - Refer to the press release on Swissmedic, Switzerland's website

  • E10 Choice of Control Group in Clinical Trials

    Code Document Title Previously coded
    • Finalised Guideline:
      July 2000

      Description :

      The harmonised tripartite Guideline was finalised under Step 4 in July 2000. This document addresses the choice of control groups in clinical trials considering the ethical and inferential properties and limitations of different kinds of control groups. It points out the assay sensitivity problem in active control equivalence / non-inferiority trials that limits the usefulness of trial design in many circumstances.

      Implementation :

      Step 5

      :

      EC, EuropeAdopted by CPMP, July 2000, issued as CPMP/ICH/364/96

      :

      MHLW/PMDA, Japan -  Adopted 27 February 2001, PMSB/ELD Notification No. 136

      :

      FDA, US Published in the Federal Register, 14 May 2001, Vol. 66, No. 93, p. 24390-91

      :

      Health Canada, Canada Implemented 2 June 2011, File #: 11-112316-337

      :

      Swissmedic, Switzerland - Refer to the press release on Swissmedic, Switzerland's website

  • E11 Clinical Trials in Pediatric Population

    Code Document Title Previously coded
    • Finalised Guideline:
      July 2000

      Description :

      The harmonised tripartite Guideline was finalised under Step 4 in July 2000. This document addresses the conduct of clinical trials of medicines in pediatric populations. This document will facilitate the development of safe and effective use of medicinal product in pediatrics.

       

      Implementation :

      Step 5

      :

      EC, EuropeAdopted by CPMP, July 2000, issued as CPMP/ICH/2711/99

      :

      MHLW/PMDA, Japan Adopted 15 December 2000, PMSB/ELD Notification No. 1334

      :

      FDA, US Published in the Federal Register, 12 April 2000, Vol. 65, No. 71, p. 19777-81

      :

      Health Canada, Canada Implemented 17 December 2003, File #: 03-124939-507

      :

      Swissmedic, Switzerland - Refer to the press release on Swissmedic, Switzerland's website

    • Description :

      This topic was endorsed by the ICH Steering Committee in August 2014.

       

      Since the adoption of the ICH E11 Guideline on Clinical Investigation of Medicinal Products in the Pediatric Population in 2000, pediatric drug development has been enhanced by advancements in several areas of general adult drug development. Targeted scientific and technical issues relevant to pediatric populations, regulatory requirements for pediatric study plans, and infrastructures for undertaking complex trials in pediatric patient populations has been considerably advanced in the last decade, without a parallel development of harmonised guidance in these areas. This Addendum is proposed to address new scientific and technical knowledge advances in pediatric drug development.

      Implementation :

      Step 5

  • E12 Clinical Evaluation by Therapeutic Category

    Code Document Title Previously coded
    • Finalised Document:
      March 2000

      Description :

      This therapeutic area document considers the Clinical Evaluation of New Antihypertensive Drugs. It provides a set of "Principles" on which there is general agreement among all three ICH regions covering endpoints and trial designs. Since there are a few differences in the requirements of the three regions that have not been harmonised, this document should be considered an "ICH Principle Document" rather than an "ICH Guideline". It will not be subject to the usual procedures leading to a fully harmonised document.

      Implementation :

      Step 5

      :

      EC, EuropeReleased for information, June 2000, issued as CPMP/ICH/541/00

      :

      MHLW/PMDA, Japan Released for consultation, 29 May 2000, PMSB/ELD Notification No. 738

      :

      FDA, US Released for consultation, 9 August 2000, published in the Federal Register, Vol. 65, No. 154, p. 48720-21

      :

      Health Canada, Canada To be notified

      :

      Swissmedic, Switzerland - Refer to the press release on Swissmedic, Switzerland's website

  • E14 Clinical Evaluation of QT

    Code Document Title Previously coded
    • Finalised Guideline:
      May 2005

      Description :

      The harmonised tripartite Guideline was finalised under Step 4 in May 2005. This document provides recommendations to sponsors concerning the design, conduct, analysis, and interpretation of clinical studies to assess the potential of a drug to delay cardiac repolarisation.
      This assessment should include testing the effects of new agents on the QT/QTc interval as well as the collection of cardiovascular adverse events. The investigational approach used for a particular drug should be individualised, depending on the pharmacodynamic, pharmacokinetic, and safety characteristics of the product, as well as on its proposed clinical use.
      The assessment of the effects of drugs on cardiac repolarisation is the subject of active investigation. When additional data (non-clinical and clinical) are accumulated in the future, this document may be reevaluated and revised.

      Implementation :

      Step 5

      :

      EC, EuropeAdopted by CHMP, May 2005, issued as CHMP/ICH/2/04

      :

      MHLW/PMDA, Japan Adopted 23 October 2009, PFSB/ELD Notification No. 1023-1

      :

      FDA, US Published in the Federal Register, 20 October 2005, Vol. 70, No. 202, p. 61134-35

      :

      Health Canada, Canada Implemented 5 April 2006, File #: 06-106861-656

      :

      Swissmedic, Switzerland - Refer to the press release on Swissmedic, Switzerland's website

    • Description :

      Since reaching Step 4 and publication within the ICH regions, experiences by all parties with the implementation of the E14 Guideline have resulted in the need for some clarification. The Questions and Answers developed by the E14 Implementation Working Group (IWG) are intended to facilitate the implementation of the E14 Guideline by clarifying key issues.

      The document with the first set of Q&As was finalised under Step 4 in June 2008.

      In April 2012, a second set of Q&As was developed and approved by the Steering Committee for integration in the Q&A document (E14 Q&As (R1)).

      In March 2014, a third set of Q&As was developed and approved by the Steering Committee for integration in the Q&A document (E14 Q&As (R2)).

      In December 2015, the Question #5.1 of the E14 Q&As (R2) was revised to generate harmonised guidance on how concentration response modelling could be used for regulatory decision making. The document was approved by the Assembly for integration in the Q&A document (E14 Q&As (R3)).

      Implementation :

      Step 5

      :

      EC, EuropeTo be notified

      :

      MHLW/PMDA, Japan To be notified

      :

      FDA, US - Published on FDA website in 13 June 2017 

      :

      Health Canada, Canada To be notified

      :

      Swissmedic, Switzerland - Refer to the press release on Swissmedic, Switzerland's website

       

       

    • Description :

      In December 2015, the Assembly endorsed the establishment of the E14/S7B Discussion Group (DG) with participation of experts in clinical (E14) and non-clinical drug development (S7B) to discuss advances in science and methods related to the clinical assessment of QT prolongation and to continue the discussion of the Comprehensive in vitro Proarrhythmia Assessment (CiPA) initiative.

      Status :

      Step 1

       

       

  • E15 Definitions in Pharmacogenetics / Pharmacogenomics

    Code Document Title Previously coded
    • Finalised Guideline:
      November 2007

      Description :

      The harmonised tripartite Guideline was finalised under Step 4 in November 2007. This Guideline contains definitions of key terms in the discipline of pharmacogenomics and pharmacogenetics, namely genomic biomarkers, pharmacogenomics, pharmacogenetics and genomic data and sample coding categories. The validation and qualification processes for genomic biomarkers, evidence for their intended use and acceptance criteria across ICH regions are outside of the scope of this guideline. As new scientific knowledge in the discipline of pharmacogenomics and pharmacogenetics emerges, the current guidance will be reviewed and expanded if appropriate.

      Implementation :

      Step 5

      :

      EC, EuropeApproved by CHMP in November 2007, issued as EMEA/CHMP/ICH/437986/2006

      :

      MHLW/PMDA, Japan Adopted 9 January 2008, PFSB/ELD Notification No. 0109013 & PFSB/SD Notification No. 0109002

      :

      FDA, US Published in the Federal Register, 8 April 2008, Vol. 73, No. 68, p. 19074-76

      :

      Health Canada, Canada Implemented 13 August 2008, File #: 08-119122-123

      :

      Swissmedic, Switzerland - Refer to the press release on Swissmedic, Switzerland's website

  • E16 Qualification of Genomic Biomarkers

    Code Document Title Previously coded
    • Finalised Guideline:
      August 2010

      Description :

      The harmonised tripartite Guideline was finalised under Step 4 in August 2010. The Guideline describes recommendations regarding context, structure, and format of regulatory submissions for qualification of genomic biomarkers, as defined in ICH E15.

      Implementation :

      Step 5

      :

      EC, EuropeAdopted by CHMP, September 2010, issued as EMA/CHMP/ICH/380636/2009

      :

      MHLW/PMDA, Japan Adopted 20 January 2011, PFSB/ELD Notification No. 0120-1/ PFSB/SD Notification No. 0120-1

      :

      FDA, US Published in the Federal Register, 11 August 2011, Vol. 76, No. 155, p. 49773-4

      :

      Health Canada, Canada Implemented 08 Janvier 2016, File #: 15-113833-472

      :

      Swissmedic, Switzerland - Refer to the press release on Swissmedic, Switzerland's website

  • E17 Multi-Regional Clinical Trials

    Code Document Title Previously coded
    • Description :

      This topic was endorsed by the ICH Steering Committee in June 2014.

       

      This new guidance is proposed to provide guidance on general principles on planning/designing Multi-Regional Clinical Trial (MRCT).

      Drug development has been globalised and MRCT for regulatory submission has widely been conducted in ICH regions and beyond. Regulatory agencies are currently facing some challenges in evaluating data from MRCTs for drug approval and it was deemed necessary to developed a harmonised international Guideline to promote conducting MRCT appropriately, especially focusing on scientific issues in planning/designing MRCTs. This new Guideline will complement the guidance on MRCTs provided in ICH E5(R1) Guideline and facilitate MRCT data acceptance by multiple regulatory agencies.

      Status :

      Step 3

  • E18 Genomic Sampling

    Code Document Title Previously coded
    • Finalised Guideline: August 2017

      Description :

      This topic was endorsed by the ICH Steering Committee in June 2014.

       

      This new guidance is proposed to provide guidance on genomic sample collection to evaluate efficacy and safety of a drug for regulatory approval. In the past years, genomic information has been increasingly included in drug label relevant for the benefit/risk evaluation of a drug. To accumulate such data during drug development and throughout the product life cycle, genomic samples should be collected in clinical trials and other studies following a certain methodology and be stored for certain periods. It has been reported that collection rate of such samples is still low in many ICH regions and it has been deemed necessary to harmonise the guidance that was already published independently by the different ICH regulatory authorities.

      Although ICH E15 Guideline describes definition of sample coding, there is currently no harmonised ICH Guideline on genomic samples collection in clinical trials or other studies.

      Harmonisation across regions on this topic will maximise the information gathered from the studies for e.g., sample collection and analysis (including ethical considerations) and facilitate implementation of pharmacogenomics for the benefit of all stakeholders.

      Status :

      Step 5

       

       

  • E19 Safety Data Collection

    Code Document Title Previously coded
    • Description :

      This topic was endorsed by the ICH Management Committee in November 2016.

       

      This new guideline is proposed to provide harmonised guidance on when it would be appropriate to use a targeted approach to safety data collection in some late-stage pre-marketing or post-marketing studies, and how such an approach would be implemented. Recognising that protection of patient welfare during drug development is critically important, unnecessary data collection may be burdensome to patients, and serve as a disincentive to participation in clinical research. By tailoring safety data collection in some circumstances, the burden to patients would be reduced, a larger number of informative clinical studies could be carried out with greater efficiency, studies could be conducted with greater global participation, and the public health would be better served. The proposed Guideline would be consistent with risk-based approaches and quality-by-design principles.

      Status :

      Step 1

       

  • Cross-cutting Topics

    Code Document Title Previously coded