ASSEMBLY - ICH · S5(R3) EWG: Revision on Detection of Toxicity to Reproduction for Medicinal...

ASSEMBLYAGENDA PAPERS

15 – 16 June 2016Lisbon, Portugal

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ICH2016/07ICH ASSEMBLY MEETING

DRAFT AGENDAJune 15-16, 2016

Lisbon, Portugal

Opening of the ICH Assembly MeetingWelcoming remarks from the ICH Assembly Chair and Vice-Chair.

Adoption of the Agenda The Assembly will be invited to agree to the agenda and timetable for the ICH Assembly

meeting.

1. ICH 2015 Annual Report The Assembly will be invited to approve the 2015 Annual Report on the activities of the

Association (for the period October 23 – December 31, 2015) which was prepared by theManagement Committee (MC) with input from the ICH Secretariat;

Based on the Annual Report, the Assembly will also be invited to discharge the MC and the ICHSecretariat for the activities undertaken by these bodies in 2015.

2. ICH Rules of Procedure and Standard Operating ProceduresThe Chair/Vice-Chair will present to the Assembly several minor proposed amendments to theAssembly Rules of Procedure (RoP) which were approved by the Assembly in December 2015.

The Assembly will be invited to consider the proposed changes to the Assembly RoP forapproval;

The MC will also update the Assembly on the status of development of the RoP for the MC, andthe MedDRA MC as well as the Standard Operating Procedures for Working Groups (WGs).

3. Membership and Observership ApplicationsThe MC will present to the Assembly its recommendation regarding Membership and Observershipapplications processed to-date.

The Assembly will be invited to provide its views and consider approval of any applications forICH Membership/Observership recommended by the MC;

The Assembly would be invited to consider MC recommendations regarding any requestsreceived from Observers to appoint experts to Working Groups.

4. ICH CommunicationCommunication ActivitiesThe MC will provide an update on current communication activities regarding the newly establishedICH Association (e.g., development of a slide deck on ICH, Q&A document etc.),

The Assembly will be invited to share its views on the communication activities.

ICH Regional Public Meetings The Assembly will be invited to share information on any ICH Regional Public Meetings in

their respective regions prior to/following the ICH meeting in Lisbon in June 2016.

Dated May 25, 2016

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5. ICH Financial MattersThe MC will provide an update on ICH financial matters including the preparation of the draft 2017Budget, the development of membership fees that will be payable by all Members at the end of thetransition period, as well as considerations regarding other financial means (e.g., participation fees).

The Assembly will be invited to provide its views and consider approval of the membership feesand any other financial means proposed.

6. Proposal for New ICH TopicsThe MC will report to the Assembly on its consideration of proposals for new ICH technical topics andwill present any recommendations for new topics for consideration by the Assembly. The MC will alsoreport on the development of a process and framework for the selection of new ICH technical topics foruse during subsequent ICH Meetings.

The Assembly will be invited to provide its views and consider approval of any new topics forICH Guidelines recommended by the MC;

The Assembly will be invited to provide its views and, if finalised, consider approval of theprocess and framework for the selection of new ICH technical topics recommended by the MC.

7. Annual Work Plan and Multi-Annual Strategic Plan of the AssociationThe MC will present to the Assembly the 2016 Work Plan and Multi-annual Strategic Plan of theAssociation.

The Assembly will be invited to approve the 2016 Work Plan and Multi-annual Strategic Planfor the Association.

8. ICH Training ActivitiesICH Cooperation with Other OrganisationsAPEC will be invited to present the status of the AHC e-learning pilot project on ICH E2 Guidelines.

ICH Training StrategyThe MC will present to the Assembly on the development of an ICH Training Strategy.

The Assembly will be invited to share its views on the draft ICH Training Strategy.

9. Update on MedDRA The Assembly will receive a report on the activities of the MedDRA Management Board; The Assembly will also receive a report on the activities of the MedDRA Management

Committee.

10. Implementation of ICH Guidelines The Assembly will be invited to share information on the status of implementation of ICH

Guidelines in their respective countries and regions.

REPORTS ON CURRENT TOPICS

11. Status Report on TopicsThe Assembly will note the current status of draft Guidelines and predictions for progress towards Step 2and Step 4.

12. S5(R3) EWG: Revision on Detection of Toxicity to Reproduction for Medicinal Products andToxicity to Male Fertility

The Rapporteur will report on the outcome of the S5(R3) EWG meeting held on June 12 – 16, 2016 andprogress made towards revising the ICH S5(R2) Guideline on Detection of Toxicity to Reproduction for

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Medicinal Products and Toxicity to Male Fertility.

The Assembly will be invited to provide its views on the report.

Step 1 sign-off and Step 2a/b endorsements are expected by Q3 2017.

13. S11 EWG: ICH Guideline on Nonclinical Safety Testing in Support of Development ofPaediatric Medicines

The Rapporteur will report on the outcome of the S11 EWG meeting held on June 13 – 16, 2016 andprogress made towards collecting data on juvenile animal studies and to develop the draft S11 Technicaldocument on Nonclinical Safety Testing in Support of Development of Paediatric Medicines.


Step 1 sign-off and Step 2a/b endorsements are expected by June 2017.

14. Q11 IWG: Q&As on API Starting MaterialsThe Rapporteur will report on the outcome of the Q11 IWG meeting held on June 13 – 16, 2016 andprogress made towards developing the draft Q11 Q&A document on API Starting Materials.


Step 1 sign-off and Step 2a/b endorsements will be determined after the IWG meeting in Lisbon..

15. Q12 EWG: ICH Guideline on Technical and Regulatory Considerations for PharmaceuticalProduct Lifecycle Management

The Rapporteur will report on the outcome of the Q12 EWG meeting held on June 12 – 16, 2016 andprogress made towards developing the draft Q12 Technical document on Technical and RegulatoryConsiderations for Pharmaceutical Product Lifecycle Management.



16. E6(R2) EWG: Integrated Addendum to Good Clinical Practice (GCP)The Rapporteur will report on the outcome of the E6(R2) EWG meeting held on June 13 – 16, 2016 andprogress made towards finalising the draft E6 Integrated Addendum on Good Clinical Practice.

The Assembly will be invited to provide its views on the report, and if the Integrated Addendumis finalised by the E6(R2) EWG, the Regulatory Members of the Assembly will be invited toadopt as final the E6(R2) Integrated Addendum.

Step 3 sign-off and Step 4 are expected in June 2016.

17. E9(R1) EWG: Addendum to Defining the Appropriate Estimand for a ClinicalTrial/Sensitivity Analyses

The Rapporteur will report on the outcome of the E9(R1) EWG meeting held on June 13 – 16, 2016 andprogress made towards developing the draft E9 Addendum on Defining the Appropriate Estimand for aClinical Trial/Sensitivity Analyses.



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18. E11(R1) EWG: Addendum to Paediatric Drug DevelopmentThe Rapporteur will report on the outcome of the E11(R1) EWG meeting held on June 13 – 16, 2016and progress made towards developing the draft E11 Addendum on Paediatric Drug Development.

The Assembly will be invited to provide its views on the report, and if Step 1 of the Addendum issigned-off by the E11(R1) EWG, the Assembly will be invited to endorse Step 2a of the E11Addendum, following which the Regulatory Members of the Assembly will be invited to endorseStep 2b of the E11 Addendum.

Step 1 sign-off and Step 2a/b endorsements are expected in June 2016.

19. E2B(R3) IWG: Revision of the Electronic Submission of Individual Case Safety ReportsThe Rapporteur will report on the outcome of the E2B(R3) IWG meeting held on June 12 – 16, 2016and progress made towards the finalisation of additional Q&As and the revision of documents in theImplementation Guide Package.

The Assembly will be invited to provide its views on the report and if the additional Q&As andthe revision of documents in the Implementation Guide Package are finalised by the E2B(R3)EWG, the Regulatory Members of the Assembly will be invited to adopt as final the E2B(R3)documents.


20. M1 PtC WG: MedDRA Points to ConsiderThe Rapporteur will report on the outcome of the M1 PtC WG meeting held on June 13 – 16, 2016 andthe group’s current activities with respect to the updating with each MedDRA release of the two PtCdocuments on Term Selection and Data Retrieval and Presentation.


21. M4E(R2) EWG: Revision of CTD-Efficacy GuidelineThe Assembly will be updated on the outcome of the M4E(R2) EWG meeting held on June 12 – 16,2016 and progress made towards updating the draft M4E(R2) Guideline on CTD-Efficacy withcomments received from the public consultation in the ICH regions.

The Assembly will be invited to provide its views on the report and if the M4E(R2) Guideline onCTD-Efficacy is finalised by the M4E(R2) EWG, the Regulatory Members of the Assembly willbe invited to adopt as final the M4E(R2) Guideline on CTD-Efficacy.


22. EWGs/IWGs/Discussion Groups Not Meeting in Lisbon

S1 EWG: Revision of the Rodent Carcinogenicity Studies for Human PharmaceuticalsGuideline

The Assembly will be updated on the current activities of the S1 EWG including the progress madetowards the collection and review of confidential submissions of Carcinogenicity AssessmentDocuments (CADs) and summary report submissions by sponsors to DRAs within each region andconsiderations regarding the timeframe for drafting the S1 Technical document.

Step 1 sign-off and Step 2a/b endorsements are expected by June/November 2019.

S3A IWG: Q&As on Note for Guidance on ToxicokineticsThe Assembly will be updated on the current activities of the S3A IWG which concluded Step 1postal sign-off of its Q&As in March 2016 and initiation of a consultation process once Step 2a andStep 2b upon electronic endorsement by the Assembly and the Regulatory Members of theAssembly respectively.

Step 3 sign-off and Step 4 are expected by Q2 2017.

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S9 IWG: Q&As on Nonclinical Evaluation for Anticancer PharmaceuticalsThe Assembly will be updated on the current activities of the S9 IWG including the progress madetowards developing the draft S9 Q&As.

If the Step 1 Q&As is signed-off by the S9 IWG by written procedure ahead of Lisbon, theAssembly will be invited to endorse Step 2a/b for these Q&As.

Step 1 postal sign-off and Step 2a/b endorsements are expected by June 2016.

M7(R1) EWG: Addendum to Assessment and Control of DNA Reactive (Mutagenic)Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk

The Assembly will be updated on the current activities of the M7(R1) EWG including the progressmade towards finalising the M7(R1) Addendum on Assessment and Control of DNA Reactive(Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk.

Step 3 sign-off and Step 4 are expected by December 2016.

Q3C(R6) Maintenance EWG: Maintenance of the Guideline for Residual SolventsThe Assembly will be updated on the current activities of the Q3C(R6) EWG including: the progressmade towards finalising the maintenance of the Q3C(R5) Guideline, and the proposal of a processfor collecting new Q3C/Q3D proposals.

If Step 3 is signed-off by the Q3C(R6) Maintenance Regulatory EWG experts by writtenprocedure ahead of Lisbon, the Regulatory Members of the Assembly will be invited to adopt asfinal the Q3C(R6) Guideline.

Step 3 postal sign-off and Step 4 are expected by June 2016.

Q3D IWG: Training Guideline for Metal ImpuritiesThe Assembly will be updated on the current activities of the Q3D IWG including: the progressmade towards finalising Modules 8-9 of the Q3D training package, the scripts and audio-recordingsfor Modules 0-7, and the outcome of the regional Q3D workshops held in the different ICH regionsin Q1/Q2 2016.

M4Q(R1) (CTD-Quality) IWG: Addressing CTD-Q-Related QuestionsThe Assembly will be updated on the current activities of the M4Q(R1) (CTD-Quality) IWG andwork to finalise the revision of the Granularity Document with the M8 EWG, and the developmentof a process to address future CTD-Q related questions.

E14/S7B Discussion Group (DG): The Clinical Evaluation of QT/QTc Interval Prolongationand Proarrhythmic Potential for Non-Antiarrhythmic Drugs

The Assembly will be updated on the current activities of the E14/S7B DG including its proposal toreview advances in science and methods related to the clinical assessment of QT prolongation and tomonitor the progress of the discussion of the Comprehensive In vitro Proarythmia AssessmentInitiative.

E14/S7B DG recommendation on whether to reopen the E14 Guideline for a complete revision isexpected by December 2017.

E17 EWG: ICH Guideline on Multi-Regional Clinical TrialsThe Assembly will be updated on the current activities of the E17 EWG including the status offinalisation of the draft E17 Technical document on Multi-Regional Clinical Trials and initiation ofthe consultation process.

Step 1 sign-off and Step 2a/b endorsements are expected by May 2016.

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E18 EWG: ICH Guideline on Genomic Sampling and Management of Genomic Data

The Assembly will be updated on the current activities of the E18 EWG including progress madetowards updating the draft E18 Guideline on Genomic Sampling and Management of Genomic Datawith comments received during the consultation period in the ICH regions.

Step 3 sign-off and Step 4 are expected by June 2017.

M2 EWG: Electronic Standards for the Transfer of Regulatory InformationThe Assembly will be updated on the current activities of the M2 EWG and the progress madetowards development of a new M2 Operating Model; finalisation of the Information Paper onRedaction by June 2016; harmonisation of the PDF Specification; finalisation of the TechnologyWatch Report by June 2016; finalisation of report of M8 SDO Project survey results by M8EWG/IWG for its review and comments.

If the PDF Specification and the Information Paper on Redaction are signed-off by the M2 EWGexperts by written procedure ahead of Lisbon, the Assembly will be invited to endorse M2documents to be published on the ESTRI website (i.e., PDF Specification and Information Paperon Redaction).

Postal sign-offs of the PDF Specification and the Information Paper on Redaction are expected byJune 2016.

M8 EWG/IWG: The Electronic Common Technical Document: eCTDThe Assembly will be updated on the current activities of the M8 EWG/IWG including: Q&Assession with eCTD Tool Vendors; finalisation of the eCTD v4.0 Orientation Materials; finalisationof the M4 Granularity Document with M4Q(R1) IWG agreement; and an updated version of theeCTD v3.2.2 Q&As/Change Request document.

If Step 3 of the revised M4 Granularity Document and the eCTD v3.2.2 Q&As v1.0 are signed-off by the M8 Regulatory EWG/IWG experts by written procedure ahead of Lisbon, theRegulatory Members of the Assembly will be invited to adopt as final these M8 documents.

If the eCTD v4.0 Support Document and Orientation Materials are signed-off by the M8EWG/IWG experts by written procedure ahead of Lisbon, the Assembly will be invited toendorse these documents to be published on the ICH website.

Step 3 postal sign-off and Step 4 of the revised M4 Granularity Document and the eCTD v3.2.2Q&As v1.0 are expected by June 2016.

Postal sign-off of the eCTD v4.0 Support Documentation and Orientation Materials are expectedby June 2016.

DATES/LOCATION OF NEXT MEETINGS FOR 2016/2017November 5-10, 2016 Osaka, Japan

Spring 2017 Canada (location to be confirmed)

The Assembly will receive an update on the organisation of the spring 2017 meeting to be held inCanada.

Summary of Decisions in Lisbon, Portugal on June 15-16, 2016

PRESS RELEASE The Assembly will be informed of the development and publication of the ICH Press Release for

the Lisbon meeting.

ANY OTHER BUSINESS

ICH2016/07

ICH ASSEMBLY MEETING

June 15-16, 2016LISBON, PORTUGAL

1. ICH 2015 Annual Report

The MC will present to the Assembly the 2015 Annual Report of the Association.

Actions:

The Assembly will be invited to approve the 2015 Annual Report on the activitiesof the Association (for the period October 23 – December 31, 2015) which wasprepared by the MC with input from the ICH Secretariat.

Based on the Annual Report, the Assembly will also be invited to discharge theMC and the ICH Secretariat for the activities undertaken by these bodies in 2015.

AGENDA ITEM 1

ICH2016/07



2. ICH Rules of Procedure and Standard Operating ProceduresThe Chair/Vice-Chair will present to the Assembly several minor proposed amendments tothe Assembly Rules of Procedure (RoP) which were approved by the Assembly inDecember 2015.

Background Document:

Assembly Rules of Procedure, dated December 10, 2015.

Chronicle:

EXTRACT FROM THE ASSEMBLY MEETING FINAL REPORT, JACKSONVILLE, FL, USA,DECEMBER 9 – 10, 2015:

The lead of the Rules of Procedure (RoP) Sub-committee of the MC reported to the ICH Assemblyon the final RoPs for the Assembly.

Assembly Decisions/Actions:

The Assembly adopted the RoPs for the Assembly;

The Assembly supported the RoPs be made available on the ICH website.

Actions:

The Assembly will be invited to consider the proposed changes to the AssemblyRoP for approval;

The MC will also update the Assembly on the status of development of the RoP forthe Management Committee and the MedDRA Management Committee, as well asthe Standard Operating Procedures for Working Groups (WGs).

AGENDA ITEM 2

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International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use

ICH Secretariat, Chemin des Mines 9, P.O. Box 195, 1211 Geneva 20, Switzerland

Telephone: +41 (22) 338 32 06 - [email protected], http://www.ich.org

The International Council for Harmonisation of

Technical Requirements for Pharmaceuticals

for Human Use

Rules of Procedure of the Assembly

Approved by the Assembly on December 10, 2015

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Table of Content

RULES OF PROCEDURE OVERVIEW ................................................................. 1

1. Member Admission, Termination and Representation ........................... 2

1.1. Membership Application for Regulatory Members ....................................... 2

1.1.1. Eligibility Criteria for a Legislative or Administrative Authority ......................... 2

1.1.2. Eligibility Criteria for Regional Harmonisation Initiative (RHI) ........................... 2

1.1.3. Implementation of ICH Guidelines ...................................................................... 3

1.2. Membership Application for Industry Members ........................................... 5

1.2.1. Eligibility Criteria for Industry ............................................................................. 5

1.3. Membership Application Process ................................................................. 6

1.3.1. Application Form ................................................................................................ 6

1.3.2. Application Review Process ................................................................................ 6

1.3.3. Decision by the Assembly ................................................................................... 6

1.4. Termination of Membership......................................................................... 7

1.5. Member Representation .............................................................................. 7

1.6. Member Appointment of Coordinators ........................................................ 7

2. Observer Admission, Termination and Representation .......................... 8

2.1. Standing Observers ...................................................................................... 8

2.2. Observers .................................................................................................... 8

2.2.1. Observership Application Process ....................................................................... 8

2.2.2. Representation ................................................................................................... 8

2.3. Ad-hoc Observers ......................................................................................... 9

2.4. Termination of Observership ........................................................................ 9

3. The Assembly ......................................................................................... 9

3.1. Election of Assembly Chair and Vice-Chair .................................................... 9

3.2. Role of Assembly Chair and Vice-Chair........................................................ 10

3.3. Calling of Assembly Meetings ..................................................................... 10

3.3.1. Regular Assembly Meetings ............................................................................. 10

3.3.2. Extraordinary Assembly Meetings .................................................................... 11

3.4. Preparation for and Conduct of Assembly Meetings ................................... 11

3.5. Participation in Assembly Meeting ............................................................. 12

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3.5.1. Member Participation in Assembly Meeting .................................................... 12

3.5.2. Standing Observer and Observer Participation in Assembly Meeting .............. 13

3.5.3. ICH Secretariat Participation in Assembly Meeting .......................................... 13

3.5.4. Notification of Non Participation in Assembly Meeting ................................... 13

3.5.5. Assignment of Vote in Event of Non Participation in Assembly Meeting ......... 13

3.5.6. Funding of Participation in Assembly Meeting ................................................. 13

3.6. Assembly Decision-Making Process ............................................................ 14

3.6.1. Decisions on Selection of ICH topics ................................................................. 14

3.6.2. Decisions on Adoption, Amendment or Withdrawal of ICH Guidelines ............ 15

3.6.3. Granting of Discharge by the Assembly............................................................ 15

3.7. Communication of Assembly Discussions.................................................... 16

3.7.1. Minutes of Assembly Meetings ........................................................................ 16

3.7.2. Press Release Following Assembly meetings .................................................... 17

4. Working Groups ................................................................................... 17

4.1. General ...................................................................................................... 17

4.2. Appointment of Regulatory Chairs and Rapporteurs ................................... 17

4.3. Expert Appointment and Participation ....................................................... 18

4.3.1. Founding Regulatory Member Experts ............................................................. 18

4.3.2. Founding Industry Member Experts ................................................................. 18

4.3.3. Standing Regulatory Member Experts .............................................................. 18

4.3.4. Regulatory Member Experts ............................................................................. 19

4.3.5. Industry Member Experts ................................................................................. 19

4.3.6. Standing Observer Experts ............................................................................... 20

4.3.7. Observer Experts ............................................................................................... 20

4.4. Working Group Quorum ............................................................................. 20

5. Financing of ICH ................................................................................... 21

5.1. Member Responsibility to Finance ICH Association ..................................... 21

5.2. Financing of ICH Association in Transition Period ........................................ 21

5.3. Determination of Annual Fees / Contributions ........................................... 21

5.4. Non-Payment of Annual Fees / Contributions ............................................. 21

5.5. Consideration of Members Organising ICH Meetings .................................. 22

5.6. Support by Other Means ............................................................................ 22

5.6.1. Additional Financial Means .............................................................................. 22

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5.6.2. Non-Financial Means ........................................................................................ 23

5.6.3. Other Means ..................................................................................................... 23

6. Cooperation ......................................................................................... 23

6.1. Cooperation with Other Organisations ....................................................... 23

7. Supporting ICH ..................................................................................... 24

7.1. Supporting Aims ........................................................................................ 24

7.2. Promoting ICH Guidelines .......................................................................... 24

7.3. Maintaining Confidentiality ........................................................................ 24

8. Legal Considerations ............................................................................ 24

8.1. Member Conflicts with Governing Laws ...................................................... 24

8.2. Liability ...................................................................................................... 25

8.3. Dissolution of Association .......................................................................... 25

8.4. Dispute Resolution ..................................................................................... 25

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RULES OF PROCEDURE OVERVIEW

Further to Article 26 of the Articles of Association, these Rules of Procedure (RoP) of the Assembly

are intended to provide guidance and clarification in respect of the various Articles of the

Association. These RoP also provide interpretation of the meaning of some of the provisions in

these Articles. The RoP cannot override the Articles of the Association as the latter have precedent

in the case of contradiction between the two.

In the event of discrepancy or inconsistency between the RoP and the Articles of Association, the

latter will prevail. In such a case, the RoP should be amended to ensure that they are consistent

with the Articles of Association. These RoP of the Assembly, in addition to the Articles of

Association, should be published on the website of the ICH Association. The RoP are amended in

accordance with Articles 25(2) and 25(4) of the Articles of Association.

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1. Member Admission, Termination and Representation

1.1. Membership Application for Regulatory Members

1.1.1. Eligibility Criteria for a Legislative or Administrative Authority

This section provides guidance and clarification on the eligibility criteria referred to in Article

11(1).

Criteria 1: The reference to legislative or administrative authority, in Article 11(1), under

Swiss law refers to the manner in which the authority functions; both types of authority are

referred to since both could be possible depending on how the body is organised in its own

jurisdiction. The term “jurisdiction” refers to a geographic area with a dedicated set of

regulation without any political connotation, e.g., a country, a constituent state, or even a

community.

Having legal personality in the sense of Article 11(1)(a) means that the authority has capacity

to assume rights and obligations in order to establish a legal relationship with the ICH

Association. The criteria of having legal personality would be met if the law applicable to the

Regulatory Member accorded it legal personality.

Criteria 2: As per Article 11(1)(b), the responsibility should normally be related to the

authorisation/registration of pharmaceutical products for human use. In most cases, this

responsibility lies with the relevant Ministry or Department and/or with a national

(regional) medicines agency. In any event, it is under the discretion of each Regulatory

Member to decide which entity represents that Member in the ICH Association as well as

to decide who to nominate as its (individual) representatives in the various bodies of the

Association, including the experts in the Working Groups.

Criteria 3: In line with Article 11(1)(c), past participation will be verified by the ICH

Secretariat from the meeting records. As regards participation in ICH meetings prior to the

establishment of the ICH Association, this means the Global Cooperation sessions.

Criteria 4: In line with Article 11(1)(d), the appointment of experts will be verified by the

ICH Secretariat from the available records.

Criteria 5: As per Article 11(1), second sub-paragraph, implementation of ICH Q1, Q7 and

E6 Guidelines – see the section on implementation of Guidelines under RoP 1.1.3 below.

1.1.2. Eligibility Criteria for Regional Harmonisation Initiative (RHI)


11(2).

Criteria 1: Further to 11(2)(a), having legal personality means that the RHI or the

representative of the RHI has the capacity to assume rights and obligations on behalf of the

RHI (i.e., all its members) in order to establish a legal relationship with the ICH Association.

The criteria of having legal personality would be met if the law applicable to the RHI

accorded it legal personality.

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Criteria 2: As per Article 11(2)(b), the responsibility should normally be related to the

authorisation/registration of pharmaceutical products for human use. For a RHI, this

means that scientific/technical Guidelines, not necessarily only ICH Guidelines, relating to

the authorisation/registration of pharmaceuticals apply to all members of the RHI.

Criteria 3: As per Article 11(2)(c) only one entity (e.g., a member of the RHI or a

Secretariat) can represent the RHI in the ICH Association. It is under the discretion of each

RHI to decide which entity represents that RHI in the ICH Association as well as to decide

who to nominate as its (individual) representatives in the various bodies of the Association,

including the experts in the Working Groups.

The RHI should not, however, as a general rule be represented by a Regulatory Member,

i.e., a legislative or administrative authority (DRA) that is itself already a Member of the

ICH Association.

Criteria 4: In line with 11(2)(d), the past participation will be verified by the ICH Secretariat

from the meeting records. As regards participation in ICH meetings prior to the

establishment of the ICH Association, this means the Global Cooperation sessions.

Criteria 5: In line with Article 11(2)(e), the appointment of experts will be verified by the


Criteria 6: As per Article 11(2)(f), the representative of the RHI should be able to commit

on behalf of all its members, e.g., that the adopted ICH Guidelines will be implemented by

all the members of the RHI.

Criteria 7: As per Article 11(2) second sub-paragraph, implementation of ICH Q1, Q7 and E6

Guidelines – see the section on implementation of Guidelines under RoP 1.1.3.

1.1.3. Implementation of ICH Guidelines

As per Article 11(5), the aim and intention is that all ICH Regulators should implement all

ICH Guidelines. ICH Regulators are encouraged to implement ICH Guidelines through direct

references. In this context, it should be recalled that the ICH Guidelines are not legally

binding and that the ultimate implementation in the different jurisdictions is a

responsibility of the competent regulator in each jurisdiction. Therefore, the notion that

ICH Regulators are “expected to implement” the ICH Guidelines needs to be considered in

this light. After the adoption of an ICH Guideline by the Assembly, the decision on any

subsequent actions is a responsibility of the competent regulator in each jurisdiction.

It is, nevertheless, expected that the adopted ICH Guidelines will be implemented by the

ICH Regulators. For the Regulatory Members, which have not been Members of ICH prior

to the establishment of the ICH Association, it is recognised that implementing all the ICH

Guidelines (which in 2015 amounted to approximately 60 in total) will take some time.

It is also recognised that not all ICH Guidelines are of equal importance. In addition to the

three (3) ICH Guidelines (Q1, Q7 and E6; also referred to internally as “Tier 1 Guidelines”)

whose implementation is included amongst the membership criteria under Article 11(1)

second sub-paragraph and Article 11(2) second sub-paragraph, once a Regulatory Member

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has become a Member of the ICH Association, that Regulatory Member is expected to

implement all the other ICH Guidelines. It is, however, recognised that this will probably be

done gradually.

When prioritising amongst the ICH Guidelines to be implemented, the ICH Guidelines

referred to below should, if possible, be implemented as a priority (also referred to

internally as “Tier 2 Guidelines”). Therefore, specific plans with identified milestones and

timeframes for implementation of these ICH Guidelines within the next five (5) years

should be submitted by the Regulatory Member after the approval of its membership:

- E2A: Clinical Safety Data Management: Definitions and Standards for Expedited

Reporting;

- E2B: Data Elements for Transmission of Individual Case Safety Reports;

- E2D: Post-approval Safety Data Management: Definitions and Standards for Expedited

Reporting;

- M4: Common Technical Document for the Registration of Pharmaceuticals;

- M1: MedDRA.

The other, remaining ICH Guidelines (also referred to internally as “Tier 3 Guidelines”)

should be implemented in the near term and as soon as possible. A plan with indicative

timeframes for the ICH Guidelines that are already foreseen to be implemented should be

provided.

There should be a process for the Assembly to monitor the progress of international

harmonisation and coordinate efforts in this regard. There should be a specific item on the

Agenda of the Assembly meeting on the current state of play of the implementation of the

ICH Guidelines where all ICH Regulators provide an update on implementation of the ICH

Guidelines. This also provides an opportunity for these Members to share their experience,

explain challenges and how to overcome them and develop good practice relating to the

implementation of ICH Guidelines.

In exceptional cases, a Regulatory Member may consider that it is not appropriate to

implement the ICH Guideline in full or may choose to implement it only partially. In such a

case, the Member should notify the ICH Secretariat thereof and provide explanations and

justification as to why the Member is not in a position to fully implement this particular

guideline. ICH Guidelines should be implemented by all Regulatory Members in accordance

with the applicable national/local/regional rules for such (technical/scientific) guidelines.

Similarly, as in the case of the Founding Regulatory Members and the Standing Regulatory

Members, the implementation of the ICH Guidelines should be made public e.g., on the

website of the Regulatory Member or through the publication in the official journal or

register of the Regulatory Member.

In order to achieve true international harmonisation, it is important that the ICH Guidelines

are implemented consistently by all ICH Regulators. There may be differences in terms of

how the guidelines are actually implemented, i.e., the procedure or whether it is

implemented through regulatory or administrative measures, but it is expected that ICH

Guidelines are implemented in the same manner as national or other international

scientific and technical guidelines (such as WHO Guidelines). Nevertheless, the Regulatory

27

Members should refrain from arbitrarily adding further requirements based on national or

regional considerations if these are not based on objective grounds as this may lead to

disharmony. Regulatory Members should also refrain from omitting requirements as this

may lead to the same situation, particularly if those requirements are important aspects of

the ICH Guideline.

Adding requirements or omitting requirements should be avoided as this would render the

ICH Guideline devoid of purpose or it would significantly reduce the purpose or meaning of

the ICH Guideline. In any case, any deviation from any of the requirements laid down in

ICH Guidelines should always be justified on objective grounds. The assessment, however,

can only be made on a case-by-case basis.

The process for discussing and monitoring the state of the implementation of the “Tier 2

and 3 ICH Guidelines” of a Regulatory Member at the Assembly is described below:

1. For ICH Guidelines that are already implemented (in addition to the “Tier 1

Guidelines”): the Regulatory Member should submit the reference to the relevant

document that implements the ICH Guideline in question. In addition, a copy of the

relevant document may be provided. If this document does not exist in English, an

English translation or at least an English summary of the document should be provided,

if possible;

2. For ICH Guidelines, part of the “Tier 2 Guidelines”, which are not yet implemented: the

Regulatory Member should submit a specific plan with identified milestones and

timeframes for their implementation in the next five (5) years (already required in the

Application form);

3. If the Regulatory Member considers that a given ICH Guideline has not been fully

implemented, it should provide information on the deviations compared to ICH

Guidelines;

4. The ICH Secretariat should keep a register of the current state of play of

implementation regarding all ICH Guidelines of all authorities that are Regulatory

Members of the ICH. It is the responsibility of the Regulatory Members to provide the

information to the ICH Secretariat with a view to ensure that the register is kept up-to-

date.

1.2. Membership Application for Industry Members

1.2.1. Eligibility Criteria for Industry


12(1).

Criteria 1: Further to Article 12(1)(a), having legal personality means that the organisation

has the capacity to assume rights and obligations on its behalf of its affiliate members in

order to establish a legal relationship with the ICH Association. The criteria of having legal

personality are met if the law applicable to the organisation has accorded it legal

personality.

Criteria 2: Further to Article 12(1)(b), as an illustration of the international character of the

organisation, the organisation should have a global constituency. In view of this, it is

28

expected that the industry organisation is present, i.e., that it has affiliate members in the

regions of the three Founding Regulatory Members.

Criteria 3: In line with Article 12(1)(c), when applying for membership, the Industry

Member should provide information about those ICH Guidelines by which it, or its affiliate

members, is affected by.

Criteria 4: In line with Article 12(1)(d), past participation should be verified by the ICH

Secretariat.

Criteria 5: In line with Article 12(1)(e), the appointment of experts will be verified by the


1.3. Membership Application Process

1.3.1. Application Form

Further to Article 13(1), the applicant should use the application form which is available for

downloading on the website of the ICH Association. All parts of the application form should

be fully filled in, and the necessary documentation should be provided. For questions or

requests for clarifications, the applicant may contact the ICH Secretariat.

1.3.2. Application Review Process

Further to Article 13(2), the Management Committee, through the ICH Secretariat, or the

ICH Secretariat may come back to the applicant in order to request missing or additional

information and/or clarification. The Management Committee should process the

applications as soon as possible, but the duration of the assessment will naturally depend

on the completeness, accuracy and complexity (e.g., evaluation of partial implementation

of ICH Guidelines) of the information provided by the applicant as well as on the workload

of the Management Committee.

The applicants for membership, irrespective of whether they have Observer status or not

in the ICH Association, whose application has been provisionally assessed and considered

by the Management Committee as fulfilling the membership criteria should, in principle,

be invited as Ad-hoc Observers within the meaning of Article 18 to the forthcoming

Assembly meeting where their application will be dealt with.

1.3.3. Decision by the Assembly

As per Article 13(3), the Assembly should take a decision on the membership admission as

soon as possible in any of its subsequent meetings. The Assembly may request that

additional information is provided by the applicant in order to take a decision. In order to

enable the Assembly to take a decision at its next meeting, it would be optimal for

applications to be submitted sufficiently in advance, e.g., preferably at least two months

before the forthcoming Assembly meeting.

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1.4. Termination of Membership

Further to Article 14(1), a Member wishing to withdraw from the Association should send a letter

to the ICH Secretariat expressing its intention to withdraw and provide explanation for its decision.

As the withdrawal takes affect at the end of the Fiscal Year during which the withdrawal was

notified to the ICH Secretariat, the Member may, if it wishes, continue its activities in ICH, including

participating in meetings, until the end of the Fiscal Year. The membership fee for that Fiscal Year

(when the Member withdraws) will not be reimbursed given that the withdrawal takes effect at the

end of the Fiscal Year.

Further to Article 14(2), exclusion of a Member should only take place in exceptional circumstances

and provided the conditions in this Article are met. Examples of continuous failure to comply with

the responsibilities of a Member are the recurrent non-payment of the required annual

membership fee or financial contribution referred to in Article 57 (for more than one Fiscal Year) or

the repeated, consecutive non-attendance of Assembly meetings. The latter should be interpreted

as meaning that if a Member has been absent during the previous two consecutive Assembly

meetings, the Member may be excluded if it does not attend the subsequent third Assembly

meeting.

Actions or behaviour which seriously impairs the proper functioning or reputation of the ICH

Association can take the form of disclosing confidential or sensitive information to outside parties

in violation of the requirement to respect professional secrecy / confidentiality undertaking

referred to in RoP 7.3 or making insulting or harmful statements publicly regarding the ICH

Association, including its bodies, or regarding any of its Members or Observers.

Before taking a decision pursuant to Article 14(2), the Assembly should hear the affected Member.

1.5. Member Representation

It is under the discretion of each Member to decide which entity represents that Member in the ICH

Association as well as to decide who to nominate as its (individual) representatives in the various

bodies of the Association, including the experts in the Working Groups.

Following the establishment of the ICH Association on October 23, 2015, the European Commission

(EC) referred to under Article 8(1)(a) has in its delegation representatives from the European

Medicines Agency (EMA). The Ministry of Health, Labour and Welfare of Japan (MHLW) is

represented by the Pharmaceuticals and Medical Devices Agency (PMDA) as referred to under

Article 8 (1)(b) and there are thus both PMDA and MHLW representatives in its delegation. The US

Food and Drug Administration (FDA) referred to under Article 8(1)(c) is represented by the Center

for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER).

The Founding Industry Members referred to under Article 9(1)(a-c) may nominate representatives

from the (umbrella) Association or from their affiliate members (individual companies).

1.6. Member Appointment of Coordinators

Members should appoint one (1) ICH Coordinator for the smooth running of ICH and who acts as the

main contact point between the Member and the ICH Secretariat, notably in relation to the work of

the Working Groups and to ensure that ICH documents are distributed to the appropriate persons

within the area of their responsibility. Considering that Founding Regulators have to appoint experts

30

in all Working Groups, the Founding ICH Regulators may in addition appoint one (1) Technical

Coordinator to support the ICH Coordinator. More details about the role of the ICH Coordinators and

Technical Coordinators are laid down in the Standard Operating Procedures (SOPs) of the Working

Groups (Note: these SOPs are currently under development).

2. Observer Admission, Termination and Representation

2.1. Standing Observers

Further to Article 16(2)(a), the participation of the Standing Observers in the Assembly and/or the

Management Committee meeting is entirely voluntary.

2.2. Observers

2.2.1. Observership Application Process

Further to Article 17(2), an application form is provided for Observership applications. The

eligibility criteria for Observership are broad and general and should be interpreted in a

flexible manner in order to be inclusive. The applicants for Observership whose application

has been provisionally assessed and considered by the Management Committee as

fulfilling the Observership criteria should, in principle, be invited as Ad-hoc Observers

within the meaning of Article 18 to the forthcoming Assembly meeting where their

application will be dealt with.

An RHI that is an Observer should not, as a general rule, be represented by a Regulatory

Member, i.e., by a legislative or administrative authority (DRA) that is already itself a

Member or an Observer of the ICH Association.

As per Article 17(3), those parties who were former Global Cooperation members are

exempt from applying for Observership and can become Observers immediately upon

submission of a confirmation letter within three months of the establishment of the

Association. This approach is intended to avoid unnecessary administrative burden both

for the applicants and for the ICH Management Committee and the Assembly. Considering

the great interest that the Global Cooperation members have shown in the ICH Association

prior to its establishment, this procedure facilitates their smooth, straightforward and swift

participation in the Assembly.

2.2.2. Representation

Further to Article 17(4), once admitted, the Observer should nominate its delegates that

will attend the Assembly meeting by notifying the ICH Secretariat of the names of the

delegates. Observers participate in the Assembly meeting and have the right to speak and

express their opinion. If in the decision-making process, the Assembly resorts to voting, the

Observers do not have the right to vote. The Observer is considered to be present if at

least one (1) delegate of the Observer is present at the Assembly.

In case there is a change of delegate, the Observer should inform the ICH Secretariat

without undue delay of the change. In addition to the maximum of two (2) delegates, there

should be no additional participants (including possible translators) from the Observer in

31

the Assembly meetings. Any request for additional participants should be properly

justified. In applying this rule, it is important to ensure equal treatment and equivalent

level of representation of all Observers.

2.3. Ad-hoc Observers

Further to Article 18(1), the invited parties can be natural or legal persons (i.e., individuals or

entities/organisations). If the invited parties accept the invitation, they are expected to cover their

own meeting expenses (unless specified otherwise, see RoP 3.5.6). In terms of entities or

organisations to be invited, one can envisage those that have not applied for or do not fulfil the

criteria for Observership. The invitations are likely to be submitted to those who have shown

interest in ICH activities or who are deemed to have an interest in ICH.

The number of invited Ad-hoc Observers should be kept reasonable for reasons of meeting

logistics, e.g., to keep the size of the Assembly manageable.

As a result, and in line with Article 18(2), Ad-hoc Observers need an invitation for each meeting.

The invitation can either concern one specific meeting or can concern more than one meeting (but

with specifications of the meeting(s) concerned). In addition to the maximum of two (2) delegates,

there should be no additional participants from the Ad-hoc Observer in the Assembly meetings.

This rule should be interpreted strictly in order to ensure equivalent level of representation of all

Ad-hoc Observers.

2.4. Termination of Observership

Further to Article 19(3), exclusion of a Standing Observer or an Observer should only take place in

exceptional circumstances and provided the conditions in this Article are met. Actions or behaviour

which seriously impairs the proper functioning or reputation of the ICH Association can take the

form of insulting or harmful statements made publicly or at the meetings of any of the bodies of

the ICH Association, in respect of the ICH Association, including its bodies, or in respect of any of its

Members or Observers.

3. The Assembly

3.1. Election of Assembly Chair and Vice-Chair

Further to Article 23(6), nominations for Chair and Vice-Chair should be submitted in writing by

the Members, specifying the name of the representative (of a Member) who is put forward as the

candidate as well as a brief résumé in support of the candidature, to the ICH Secretariat no later

than the start of the Assembly meeting at which the election is to take place. Standing Observers

and Observers do not have the right to put forward nominations for Chair or Vice-Chair.

The decision should be adopted by simple majority of the votes cast and by secret ballot in

accordance with Articles 25(7) and (8). Two tellers should be designated amongst the Members,

Standing Observers or Observers to assist in the counting of the vote. At each round, the candidate

with the lowest number of votes should withdraw. Rounds will run until one candidate receives

simple majority of favourable votes of the Members.

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From the date of election, the Member whose representative has been appointed as Chair or as

Vice-Chair should have the right to appoint another representative to represent itself at the

Assembly until the termination of the chairmanship or vice-chairmanship.

3.2. Role of Assembly Chair and Vice-Chair

In line with Article 25(2), the Chair should do his/her utmost to reach consensus amongst the

Members. The Chair should ensure that all Members, as well as Standing Observers and Observers,

have been given the opportunity to express their views and should try to reconcile any divergent

views. The discussion may be prolonged in the interest of reaching consensus.

The Vice-Chair should deputise for the Chair when the latter is unable to chair either all or part of a

meeting. The Chair may also delegate the chairing to the Vice-Chair e.g. for specific topics. The

Chair and Vice-Chair should agree on how they will work together and generally, the role of the

Vice-Chair is to provide support and assistance to the Chair. In the absence of the Vice-Chair, the

most experienced representative from amongst the Founding Regulatory Members and Standing

Regulatory Members (in terms of number of attended ICH meetings, including those that took

place prior to the establishment of the ICH Association) should deputise for the Chair. In the event

of resignation of the Chair, the Vice-Chair should take the chair until a new election takes place.

The Chair should notify the ICH Secretariat of his/her intention to resign without delay and the

resignation should take effect two (2) months after the date of the notice. The ICH Secretariat

should without delay inform the Management Committee and the Assembly of the notification.

After the taking of effect of the resignation and until a new Chair has been elected at the

subsequent Assembly meeting, the Vice-Chair should act as Chair.

The host Regulatory Member where the meeting of the Assembly takes place may appoint an

associate Vice-Chair for that meeting. The associate Vice-Chair should assist the Chair and the Vice-

Chair, especially in respect of the meeting logistics.

3.3. Calling of Assembly Meetings

3.3.1. Regular Assembly Meetings

Further to Article 23(1), it is foreseen to have regular, bi-annual meetings in spring and

autumn as it has been the case for ICH meetings in the past.

Further to Article 23(2), in exceptional cases concerning documents that contain sensitive

or confidential information, the Chair of the Assembly, after consultation of the

Management Committee or the MedDRA Management Committee, may decide that such

documents are only provided to the Members.

In exceptional cases, the timelines referred to in Article 23(2) may not be adhered to. In

case of delays, explanations for the delay should be provided to the Members, Standing

Observers and Observers.

Further to Article 23(3), any proposals by a Member, or any issues that a Member wishes

to discuss, should equally be submitted in writing no later than two (2) months before the

33

date of the Assembly meeting. This will enable the Management Committee to adequately

prepare the Assembly meeting.

3.3.2. Extraordinary Assembly Meetings

Further to Article 23(5), such extraordinary meetings of the Assembly should only take

place in urgent situations where this is essential for the functioning of the Association.

Examples are situations where there are internal or external serious threats to the

existence of the Association, such as a risk of dissolution of the Association or critical

external actions, e.g., initiation of court proceedings against the Association with

significant potential financial implications for the Association that require an urgent

response from the Assembly.

3.4. Preparation for and Conduct of Assembly Meetings

The Management Committee is responsible for submitting recommendations or proposals to the

Assembly in preparation of Assembly discussions, as referred to in Articles 23(4) and 35(2)(g). A

document or proposal/recommendation may be approved as such, without any amendments, or

with amendments or it may rejected. It is the responsibility of the Chair to decide how to proceed

if a given document is not adopted. Many of the documents, such as the ones referred under

Article 22(1) points (j), (k), (m), (n), (o), (p) and (q) need to be adopted eventually in order to allow

the continued operations of the ICH Association. Should the Assembly not approve the

membership fees, this would have a negative financial impact on the annual budget for the ICH

Association or the annual budget for MedDRA referred to in points (m), (p) and (q). Therefore, and

if no other solution can be found in the meantime, the previous year's membership fees or

relevant budgets should be automatically be carried over, at least for the recurring expenditures,

to the following Fiscal Year as an interim measure until the approval is given.

If the proposed amendments to a given document are not substantial and straightforward, they

may be approved by the Assembly at the same meeting, in which case the revised document is

adopted. However, in case of substantial amendments, the Management Committee should revise

the document in the light of comments and concerns expressed at the Assembly meeting. In its

request, the Assembly may provide a timeline by which the revised document should be submitted

to the Assembly. The Assembly should strive to express their concerns clearly and Members may

be invited to provide their comments in writing (within a given deadline) to facilitate the

preparation of the revised version.

If, a Member, a Standing Observer or an Observer put forward proposals to the Assembly during

the meeting, the Chair should propose to the Assembly how to handle the proposal (e.g., proceed

to a discussion or postpone the discussion to a later meeting). Normally, in order to be dealt with

at the Assembly meeting itself, such proposals should be limited without requiring substantial

discussions, whereas proposals that require such discussions should be submitted in advance of

the meeting in accordance with Article 23(3).

Should a Member, a Standing Observer or an Observer suggest a new topic for harmonisation, this

request, should be submitted to the ICH Secretariat for transmission to the Management

Committee. On the basis of recommendations by the Management Committee, the Assembly will

review periodically the proposals on new topics in the context of the 5-year plan. If the topic is

34

generally supported by the Assembly, a document (Concept Paper) should be submitted, normally

to be developed by the Member, Standing Observer or Observer who proposed the topic. Such a

draft Concept Paper drafted by a Member, Standing Observer or Observer should first be assessed

by the Management Committee to ensure that it complies with all the requirements laid down in

the SOP of the Working Groups before it is submitted to the Assembly. If the Member, Standing

Observer or Observer does not wish to develop a Concept Paper, the Assembly may also request

the Management Committee to assess the matter and, if the Management Committee is

supportive of the topic, put forward a proposal for a Concept Paper. In respect of ICH Guideline

development, Members of the Assembly should be kept informed of the development process of

the various guidelines that are discussed in the Working Groups. This is important particularly for

those guidelines developed by Working Groups in which not all Members have appointed experts.

Members wishing to have a presentation at the Assembly meeting by the Regulatory Chair or the

Rapporteur of a given Working Group regarding the state of play should submit such a proposal

within the timelines indicated under Article 23(3). Where the request concerns a Working Group

that is not meeting face-to-face in the ICH meeting, the request will be considered by the

Management Committee in order to assess whether a remote presentation can be organised.

3.5. Participation in Assembly Meeting

The names of the Members and Observers as well as their representatives should be published on

the website of the ICH Association.

3.5.1. Member Participation in Assembly Meeting

The Member is considered to be present if at least one (1) of its representative(s)

nominated in accordance with Article 24 is present at the Assembly.

Further to Article 24, the representatives should be acting upon a written proxy of the

Member. The proxy needs to be submitted to the ICH Secretariat at the latest at the start

of the Assembly meeting. The proxy does not need to specify the Assembly meeting as the

same proxy will continue to be valid until any (or both) of the representatives indicated on

the proxy change. When the representative(s) change, a new proxy should be provided. If

the Member has appointed two (2) representatives, either of the two (2) representatives

nominated by the Member may cast the vote under Article 25(2). This is the general rule.

For those Members who have appointed two (2) representatives, the following applies but

only in respect of decisions concerning the discharge of the Management Committee and

the MedDRA Management Committee: the Members of these respective committees are

requested to designate one (1) of their representatives as the lead representative in the

Management Committee and in the MedDRA Management Committee. If this lead

representative is also a representative of the Member in the Assembly, the lead

representative on the Management Committee or the MedDRA Management Committee

should refrain from decision-making and from casting the vote on behalf of the Member

(and thus leave this to the other representative).

As regards attendance at meetings, the delegations consisting of the two (2)

representatives of each of the Founding Regulatory Members, Founding Industry Members

and Standing Regulatory Members may, in addition, include a maximum of two (2)

35

additional participants, excluding their representatives of the Management Committee,

representatives of the MedDRA Management Committee, Coordinators and Technical

Coordinators.

The delegations consisting of the two (2) representatives of each of the Regulatory

Members and Industry Members may, in addition, include one (1) additional participant,

excluding their representatives of the Management Committee, Coordinators and

Technical Coordinators.

Notification of the number of additional participants should be made to the ICH Secretariat

at least four (4) weeks in advance of the Assembly meeting. A representative that has been

appointed by a Member to attend the Assembly meeting may give a proxy to any of the

additional participants of that Member for a part of the Assembly meeting that the

representative(s) are unable to attend.

3.5.2. Standing Observer and Observer Participation in Assembly Meeting

Further to Articles 16(3) and 17(4), the Standing Observer and Observer are considered to be

present if at least one (1) delegate of the Standing Observer and of the Observer is present

at the Assembly.

As indicated in Articles 16(2)(a) and 17(4), Standing Observers and Observers have the right

to attend the Assembly meeting (without voting rights). Standing Observers and Observers

have the right to fully participate in the discussion and to express their opinion and should

also submit a proxy. Standing Observers and Observers have no right to appoint additional

participants in the Assembly meetings in addition to the two (2) delegates.

3.5.3. ICH Secretariat Participation in Assembly Meeting

The ICH Secretariat staff should also attend the Assembly meetings and provide support

notably to the Chair and Vice-Chair, notably on procedural aspects.

3.5.4. Notification of Non Participation in Assembly Meeting

Where a Member, Standing Observer or Observer is unable to participate in an Assembly

meeting, the Member, Standing Observer or Observer concerned should inform the ICH

Secretariat in advance.

3.5.5. Assignment of Vote in Event of Non Participation in Assembly Meeting

The vote of a Member unable to participate may be assigned by a written proxy to another

Member. The ICH Secretariat should inform the Chair and Vice-Chair of the non-

attendance and of the proxy of the Member as soon as possible and at the latest at the

beginning of the meeting and this information should be recorded in the minutes. In

addition to the Member's own vote, each Member may receive a maximum of one vote by

proxy.

3.5.6. Funding of Participation in Assembly Meeting

All meeting participants are participating in the Assembly meetings at their own expense,

unless otherwise specified. However, in respect of certain Ad-hoc Observers that are

36

invited to an Assembly meeting, the Assembly or Management Committee may

exceptionally decide to provide some funding to allow for their participation.

3.6. Assembly Decision-Making Process

According to Article 25(2), each Member has one vote. Votes may be cast by either of the two (2)

representatives as it is assumed that both have the right to cast the vote for the Member which

they represent. The two (2) representatives jointly decide how to dispose of the vote. To avoid

ambiguity (i.e., that the vote of one Member is counted twice due to the fact that each Member

may have two representatives), each Member should be given one voting card with the name of

the Member. As mentioned under RoP 3.5.1, if one of the two representatives of a given Member

in the Assembly is also the lead representative of the Member in the Management Committee

and/or in the MedDRA Management Committee, the lead representatives should refrain from

casting the vote on behalf of the Member in the Assembly, in respect of the discharge of the

Management Committee and/or the MedDRA Management Committee.

Decisions by majority in accordance with this Article should be passed if consensus is not reached.

Prior to voting, the Chair may allow for several rounds of discussions in order to reach consensus,

including postponing the voting to a later stage (especially if there is no urgency). Members are

free to abstain from voting, i.e., not casting a vote. Abstentions do not count in tallying the vote

negatively or positively; when Members abstain, they are in effect only contributing to a quorum.

No written procedures for the adoption of decisions are foreseen. However for simpler matters,

such as the adoption of the minutes of the Assembly meetings, approval by written procedure is

possible. As regards ICH Guidelines referred to under Article 25(5) and (6), the following applies:

For any minor changes or corrections needed to a Guideline prior to its publication which are

editorial in nature, the ICH Secretariat will consult with the Working Group which developed the

Guideline and the ICH Coordinators. Where the Working Group and the ICH Coordinators agree

with the change, the Members will be informed of the change / correction. However, if the

Working Group and/or the ICH Coordinators consider the change to be more than editorial, the ICH

Guideline with the change / correction should be put for adoption at the subsequent Assembly

meeting. In case of doubt as to whether the change requires adoption at the next Assembly

meeting, the ICH Secretariat should consult the Management Committee.

3.6.1. Decisions on Selection of ICH topics

Article 25(5) concerns decisions on the selection of topics and also applies to the adoption

of Concept Papers (outlining the topics that have been selected) by the Assembly. All the

Members have the right to participate in the initial discussions and in the consensus-

building on the selection of topics for ICH Guidelines and should thus be given the

opportunity to express their views on all topics. The regulatory authorities that are

Members of the ICH Association (ICH Regulators) are required in good faith to consider the

opinions expressed by the Members representing industry and others. The discussion will

be reflected in the minutes. If at the end of the discussion there is consensus amongst all

Members, this will be recorded in the minutes of the Assembly meeting.

If there is no consensus, the Chair will request the ICH Regulators to express their views

and explain their position in the presence of all Members. The Chair may propose to

37

postpone the discussion or propose to proceed to voting if it appears that further

discussions are unlikely to lead to consensus. In the case of voting, only the ICH Regulators

have the right to vote on the selection of topics for harmonisation considering that

regulators have the ultimate responsibility to ensure the protection of public health and

have the responsibility to issue regulatory guidelines. The voting results should be

recorded in the minutes of the Assembly meeting. Where an ICH Regulator voted against

the decision to select a topic that was selected by the Assembly meeting, that Regulatory

Member may request that a note is added to the minutes explaining the reasons for its

objection. Notably an explanation should be provided in case an ICH Regulator considers

that it will not be in a position to implement the envisaged Guideline.

3.6.2. Decisions on Adoption, Amendment or Withdrawal of ICH Guidelines

Further to Article 25(6), to facilitate the discussion on the adoption, amendment or

withdrawal of those ICH Guidelines which are being discussed in Working Groups at the

ICH meeting, (during their different development steps), the Regulatory Chair and/or the

Rapporteur of the Working Group, accompanied by all the experts of the Working Group

concerned, should be invited to the Assembly for this particular agenda item in order to

present the results of the Working Group together and put forward proposals e.g., for

next steps of the Working Groups to the Assembly.

Subject to Articles 9(2)(a) and 12(2)(b), all the Members have the right to participate in the

initial discussions and in the consensus-building on the adoption, amendment or

withdrawal of ICH Guidelines. In respect of the development process of ICH Guidelines for

the adoption of new ICH Guidelines and amendment of existing guidelines, the views of all

Members are considered for the consensus on decisions to endorse the Technical

Document (Step 2a). However, in the subsequent stages, i.e., the endorsement of the draft

ICH Guideline (Step 2b), the adoption of the final ICH Guideline (Step 4) as well as the

withdrawal of an existing ICH Guideline, only ICH Regulators' views are considered for the

consensus as this activity is the prerogative of the regulators, considering that they have

the ultimate responsibility to ensure the protection of public health and have the

responsibility to issue regulatory guidelines. In the case of consensus, the decision will be

considered adopted and this will be recorded in the minutes of the Assembly meeting.

If there is no consensus regarding the adoption, amendment or withdrawal of a Final ICH

Guideline, the Chair may propose to postpone the discussion or propose to proceed to

voting if it appears that further discussions are unlikely to lead to consensus. Also, in the

case of voting, only ICH Regulators may cast a vote. Where an ICH Regulator voted against

the decision that was adopted by the Assembly meeting, that Regulatory Member may

request that a note is added to the minutes explaining the reasons for its objection.

Notably an explanation should be provided in case an ICH Regulator considers that it will

not be in a position to adhere to the adopted decision.

3.6.3. Granting of Discharge by the Assembly

Further to Article 22(1)(k), the granting of “discharge” amounts to stating that all actions of

those bodies that have taken decisions (the Management Committee, the MedDRA

38

Management Committee and to some extent, the ICH Secretariat) have been in

compliance with the Articles of Association. Through the act of discharging, the

representatives on these bodies are exempted from liability towards the ICH Association.

3.7. Communication of Assembly Discussions

3.7.1. Minutes of Assembly Meetings

The Minutes of the Assembly meetings should as a general rule indicate in respect of each

item on the agenda:

Documents submitted to the Assembly;

A summary record of the proceedings; at the request of Members or the Standing

Observers or Observers, the minutes may also provide further details of the discussion

of any dissenting views. If a Member wishes to abstain from participation in the

discussion and decision-making on a given agenda point, this should also be recorded in

the minutes;

The decisions taken or the conclusions reached by the Assembly. All decisions are

expected to be taken by consensus, and the Chair and Vice-Chair should make all their

endeavours to try to reach consensus. Should, however, consensus not be reached in a

given matter, the minutes should reflect the discussions, particularly the divergent

views and the efforts of trying to reach consensus, in addition to the results of the

voting. The minutes should normally indicate how the individual Members have voted

(with the exception of elections which are done by secret ballot);

The list of attendees.

The ICH Secretariat is responsible for drafting the minutes. As regards the adoption of the

draft minutes:

Draft summary of decisions taken and agreed actions, prepared by the ICH Secretariat,

should be agreed by the Assembly at the end of the meeting as this will also facilitate

the swift communication of the outcome of the meeting, e.g., the press release;

Draft minutes (prepared in English) should be sent to all Members, Standing Observers

and Observers by e-mail within two (2) weeks of the meeting, unless there are

exceptional circumstances;

Members, Standing Observers and Observers should send written objections or

comments on the minutes to the ICH Secretariat during a period of two (2) weeks of the

receipt of the draft minutes;

Minor and editorial issues should be resolved at the discretion of the Chair in

consultation with the concerned Member(s), Standing Observer(s) or Observer(s);

Major issue should be forwarded to all Members, Standing Observers and Observers,

together with a proposal from the Chair, in consultation with the Member(s), Standing

Observer(s) or Observer(s), on how to resolve the matter. This could be either not to

accept the concerns raised by a Member, Standing Observer or Observer or propose

amendments to the minutes. In case of amendments to the draft minutes, the revised

minutes should be submitted to the Members, Standing Observers and Observers at the

latest within two (2) months from the Assembly meeting;

The minutes should be adopted by written procedure after the Assembly meeting or, in

the case of substantial amendments (apart from editorial), at the next Assembly

meeting.

The adopted minutes should be published on the website of the ICH Association.

39

3.7.2. Press Release Following Assembly meetings

The ICH Secretariat should be responsible for preparing a draft press release after the

Assembly meeting. The draft should be approved by the Chair, after consultation of the

Management Committee, before being published on the website of the ICH Association

preferably within two (2) weeks of the Assembly meeting.

4. Working Groups

Further details about the working of the Working Groups are provided in the SOP for the Working

Groups (Note: these SOPs are currently under development).

4.1. General

Members should appoint maximum two (2) experts for each Working Group excluding the

Regulatory Chair. For the Member holding the Rapporteurship of a Working Group, that Member

may appoint one (1) additional expert, in addition to the Rapporteur. In exceptional cases and

where justified, this rule can be applied with some degree of flexibility in respect of the number

of experts appointed by the Founding Regulatory Members and Founding Industry Members to

ensure the adequate level of expertise and the appropriate functioning of all Working Groups.

Standing Observers and Observers should appoint maximum one (1) Observer expert and one (1)

alternate expert to replace the Observer expert when he/she is unavailable.

The Members that wish to appoint experts in Working Groups should notify the ICH Secretariat of

the names of the experts and specify the Working Group to which the experts are appointed. The

Members should inform the ICH Secretariat of any change of experts or the withdrawal of

experts.

4.2. Appointment of Regulatory Chairs and Rapporteurs

When setting up a new Working Group, a Regulatory Chair should be appointed. The Regulatory

Chair should be a representative of the Founding Regulatory Members or the Standing Regulatory

Members (at least initially until the moment in time when there will be Elected Management

Committee Representatives in the Management Committee).

In addition, a Rapporteur should be appointed for each Working Group. The Rapporteur may be a

representative of any Member. The Rapporteurships should as much as possible be attributed in

a way to ensure the widest possible geographical distribution.

As soon as a new topic is up for adoption on the agenda of the Assembly meeting, the Members

(who are eligible) are invited to confirm to the ICH Secretariat in advance of the meeting their

expression of interest to provide a Regulatory Chair or Rapporteur if the new topic is approved.

The eligible Members who express such interest should put forward the name of their candidate.

In addition to possible expressions of interest submitted prior to the Assembly meeting, and

before appointing the Regulatory Chair and the Rapporteur, the Chair of the Assembly should at

the Assembly meeting request Members (who are eligible) to put forward their expression of

interest and put forward the name of their candidate, including his / her résumé.

40

4.3. Expert Appointment and Participation

4.3.1. Founding Regulatory Member Experts

The experts appointed by the Founding Regulatory Members in all Working Groups are

expected to actively participate in and contribute to the work of the Working Group on a

continuous and regular basis to ensure continuity.

The experts that are appointed to a given Working Group should have the necessary and

adequate expertise in the area concerned as they are expected to actively contribute to

the work of the Working Group until the work is completed.

The appointment of experts by the Founding Regulatory Members in all Working Groups is

a requirement. Should the appointed expert be unable to participate in a given meeting

(face-to-face or via teleconference), this expert should be replaced by another qualified

expert for that meeting.

4.3.2. Founding Industry Member Experts

Irrespective of Article 9(2)(a), the Founding Industry Members will fully participate in the

development of a Technical Document (under Step 2a) in the Working Group. After Step

2b, the experts appointed by the Founding Industry Members will remain members of the

Working Groups and may continue participating in the meetings of the Working Groups.

The Founding Industry Members may also appoint experts in Working Groups that are

developing guidelines by which the Founding Industry Member (or its affiliate members) is

not affected for which it has appropriate experts in the field.

Once the Founding Industry Member has appointed an expert to a Working Group, this

expert is expected to actively participate in and contribute to the work of the Working

Group on a continuous and regular basis to ensure continuity. All experts that are

appointed to a given Working Group should have the necessary and adequate expertise in

the topic concerned as they are expected to actively contribute to the work of the Working

Group until the work is completed.

Should the appointed expert in a Working Group be unable to participate in a given

meeting (face-to-face or via teleconference), that expert should be replaced by another

qualified expert for that meeting.

4.3.3. Standing Regulatory Member Experts

Once the Standing Regulatory Member has appointed an expert to a Working Group, this

expert is expected to actively participate in and contribute to the work of the Working

Group on a continuous and regular basis to ensure continuity. All experts that are

appointed to a given Working Group should have the necessary and adequate expertise in

the topic concerned as they are expected to actively contribute to the work of the Working

Group until the work is completed.

41

Should the appointed expert be unable to participate in a given meeting (face-to-face or

via teleconference) of the Working Group, that expert should be replaced by another

qualified expert.

4.3.4. Regulatory Member Experts

The experts that have been appointed by the Regulatory Members in Working Groups are


continuous and regular basis to ensure continuity. The experts that are appointed to a

given Working Group should have the necessary and adequate expertise in the area

concerned as they are expected to actively contribute to the work of the Working Group.

Once an expert has been appointed to a Working Group, the Regulatory Member expert is

expected to continue participating in the work of this Working Group until the work is

completed. If the appointed expert is absent from two consecutive meetings of the

Working Group, the Regulatory Member should appoint another qualified expert. After the

Regulatory Member's expert has been absent from two consecutive meetings, and if no

other qualified expert from that Regulatory Member participates in the subsequent

meeting of the Working Group, the Regulatory Member loses its right to appoint experts in

that particular Working Group. Such interruption of participation will be noted by the ICH

Secretariat and will also be mentioned in the report of the Working Group. If the

Regulatory Member wishes to withdraw from participating in a Working Group, it should

notify the ICH Secretariat without undue delay.

The right to appoint experts is not an absolute right because the Management Committee

can exceptionally limit the number of participants in the Working Groups for meeting

logistics reasons, i.e. to avoid that a Working Group becomes too big. In addition to those

experts whose presence is required for the quorum, any limitation for the Regulatory

Members should be introduced in a fair and objective manner, e.g., by giving preference to

the experts that have been appointed earlier (on a first-come-first-served basis). Currently,

the average size of ICH Working Groups is in the range of 25-30 experts; however, larger

Working Group may exceptionally be established. Therefore, the Management Committee

should determine the appropriate size of Working Group.

4.3.5. Industry Member Experts

Irrespective of Article 12(2)(b), the Industry Members will fully participate in the

development of a Technical Document (under Step 2a) in the Working Group. After Step 2b

is reached, the experts appointed by the Industry Member will remain members of the

Working Groups and will continue participating in the meetings of the Working Groups.

The experts that are appointed to a given Working Group should have the necessary and

adequate expertise in the area concerned as they are expected to actively contribute to

the work of the Working Group.

Before appointing an expert to a Working Group, the Industry Member should provide

information to the ICH Secretariat about how it or its affiliate members will be affected or

regulated by the guideline in question.

42

Once the Industry Member has appointed an expert to a Working Group, this expert is


continuous and regular basis until the work is completed to ensure continuity. If the

appointed expert is absent from two consecutive meetings, the Industry Member should

appoint another qualified expert. An initially appointed expert to a Working Group can only

be replaced once during the time in which the Working Group is active (i.e. until the

finalisation of the work of the Working Group). After the Industry Member's expert has

been absent from two consecutive meetings, and if no other qualified expert from that

Industry Member participates in the subsequent meeting of the Working Group, the

Member loses its right to appoint experts in that particular Working Group. Such

interruption of participation will be noted by the ICH Secretariat and will also be

mentioned in the report of the Working Group. If the Industry Member wishes to withdraw

from participating in a Working Group, it should notify the ICH Secretariat without undue

delay.

If, however, in the meantime the Industry Member wishes to withdraw from participating

in a Working Group, it should notify the ICH Secretariat without undue delay.

4.3.6. Standing Observer Experts

Further to Article 16(2)(b), the appointment of experts by the Standing Observers is

entirely voluntary and it is the choice of each of them to decide whether to appoint experts

and to which Working Groups. The experts that are appointed to a given Working Group

should have the necessary and adequate expertise in the area concerned as they are

expected to actively contribute to the work of the Working Group until the work is

completed.

4.3.7. Observer Experts

Further to Article 17(5), when considering the recommendation by the Management

Committee regarding the invitation to Observers to appoint Observer experts, the

Assembly should treat all Observers fairly and make the decision objectively, e.g., on the

basis of the type of activity or available expertise of the Observer.

Observers may also request to appoint an Observer expert in a given Working Group by

informing the ICH Secretariat of their interest and providing explanations for their interest

in this Working Group, information about their available expertise and how they expect to

contribute to the work of the Working Group. Separate requests should be made for each

Working Group. The experts that are appointed to a given Working Group should have the

necessary and adequate expertise in the area concerned. The appointment is subject to a

favourable decision of the Assembly.

Once the Observer has appointed its experts, these experts are expected to fully

participate as Observer experts in the work of the Working Groups.

4.4. Working Group Quorum

Quorum for meetings (face-to-face or virtual) of the Working Groups:

43

If Founding Industry Members and/or Standing Regulatory Members have not appointed

experts in a Working Group, the presence of an expert from each of the Founding Regulatory

Members is required for the quorum of the Working Group;

For a Working Group to which Founding Industry Members and/or Standing Regulatory

Members have appointed experts, the presence of at least one expert from each of those

Members that have appointed experts, including an expert from each of the Founding

Regulatory Members, is required for the quorum of that Working Group.

5. Financing of ICH

5.1. Member Responsibility to Finance ICH Association

Further to Article 57(2), and the raising of the necessary financial means, Members are required to

contribute to the financing of the ICH Association. Members are normally expected to pay an

annual membership fee but where the payment of an annual membership fee is not possible due

to the laws and regulations that apply to the Member, it may instead pay an annual financial

contribution. No Member should be required to pay both an annual membership fee and an annual

financial contribution and the amounts of the annual payment should not depend on the form of

the payment (i.e., whether it is referred to as a membership fee or a financial contribution).

Regional flexibility is allowed regarding how and when the payments are made for the Fiscal Year

concerned.

5.2. Financing of ICH Association in Transition Period

The purpose of the provision in Article 59(1) regarding a transition period is to guarantee the

continued funding and operation of the ICH Association. While the Assembly is required to

introduce membership fees for all Members, it is unknown how long this will take until a decision is

taken. In the meantime, it is important to ensure the continued operations of the ICH Association

and therefore, the Founding Regulatory Members, Founding Industry Members and Standing

Regulatory Members bear the responsibility for the intermediate funding during a transition phase

until annual membership fees or corresponding annual financial contributions have been

introduced for all Members.

5.3. Determination of Annual Fees / Contributions

General principles: In line with Article 58(2), the amounts should be fair and proportionate so that

Members that bear similar rights and duties within the same Membership category pay similar

amounts. The amount of the fees should be based on objective criteria. There may be deviations

from this starting point, but they should be justified objectively.

The starting point is equal treatment of Members within the same membership category.

However, as per Article 58(3) when the type of Member is very different, distinguishing between

Members should be possible under objective criteria.

5.4. Non-Payment of Annual Fees / Contributions

Members are expected to contribute to the funding of the ICH Association on an annual basis.

Further to Article 57(1), the manner and format in which the Member is able to provide such

contribution will depend largely on the applicable laws and regulations applicable to the

Member.

44

However, it should be recognised that particularly regulatory authorities that are Members of the

ICH Association are dependent on their respective competent budgetary authority for obtaining

their annual budget. Each Member is likely to have different budgetary approval processes.

In the unlikely event that the budgetary authority of a Member concerned will not grant the

necessary budget for the following Fiscal Year as a result of which the Member is unable to pay

its annual membership fee or financial contribution, the Member should notify the ICH

Secretariat of this without undue delay. The Member should provide explanations for the non-

payment, notably confirming that this is beyond the control of the Member, and provide an

estimation as to whether the Member is expected to be able to provide the payment later (i.e.,

after the payment deadline) and whether the non-payment is expected to be a one-off situation.

The non-payment of the annual membership fee or the annual contribution for the following

Fiscal Year needs to be considered by the Management Committee in the preparation of the

budget for the following Fiscal Year, e.g., by cutting down or reducing some activities. If needed,

the shortfall in income may be compensated by the use of any existing reserve fund.

As regards possible consequences, the non-payment for one Fiscal Year is not a sufficient reason in

itself to exclude a Member from the Association as the exclusion requires the continuous failure to

comply with the Member's responsibilities under Article 14(2). It should also be taken into account

that if the non-payment is beyond the control of the Member itself. However, in the case of non-

payment by the Member of its annual membership fee or annual financial contribution for the

second, consecutive Fiscal Year, the Member’s status within the Association may be reviewed. The

decision on the exclusion is taken by the Assembly on the basis of the proposal of the Management

Committee (Article 22(1)(e)). The decision on the exclusion should take into account the reasons

for the non-payment, e.g., whether this is likely to be a temporary issue that is expected to be

resolved or whether it represents a non-commitment to the ICH Association. The Member itself

may naturally also voluntarily withdraw from the Association as referred to in Article 14(1).

Regional flexibility is allowed regarding how and when the payments are made for the Fiscal Year

concerned.

5.5. Consideration of Members Organising ICH Meetings

The purpose of the provision in Article 59(2) is to avoid that any of the Founding Regulatory

Members, Founding Industry Members or Standing Regulatory Members that is hosting the

meeting will have to pay both for the meeting costs relating to the organisation of the meeting as

well as the annual membership fee / financial contribution (which included the meeting costs), i.e.,

to avoid double payment. In case any of these Members has agreed to host (organise and finance

the meeting), those meeting costs will be deducted from the annual membership fee or

corresponding annual financial contribution either of that particular Fiscal Year or the following

year. The Member should submit to the ICH Secretariat proof of the expenses related to the

organisation of the meeting.

5.6. Support by Other Means

5.6.1. Additional Financial Means

In line with Article 57(3) additional financial means can be raised in case the ICH

Association needs additional funding sources to cover its budget and where an increase in

the annual membership fees or annual financial contributions is not considered as an

45

appropriate alternative. It may also be considered worthwhile to diversify the funding

sources in order not to depend entirely on annual membership fees or annual financial

contributions.

Examples of participation fees could be fees charged to participants in the ICH meetings.

It may be decided to organise specific meetings and/or events, possibly including issuing a

publication, with the purpose of raising additional funds if necessary in order to cover the

costs of the Association.

5.6.2. Non-Financial Means

Further to Article 57(4), examples of such means could be:

a. organisational support for meetings and/or workshops and the provision of documents

for the topics to be discussed in the course of such meetings;

b. production and circulation of publications about ICH-related activities, as well as other

informative material relating to ICH activities;

c. providing expertise in kind.

5.6.3. Other Means

The purpose with the provision in Article 59(3) is to keep options open for other possible

sources of funding. Where the budget is fully covered by the foreseen annual membership

fees / financial contributions, there will be no pressing need to introduce additional forms

of funding. A sustainable funding model is necessary to guarantee the continued

functioning of the ICH Association, and such a model should be based on annual

membership fees or corresponding annual financial contributions.

6. Cooperation

6.1. Cooperation with Other Organisations

As per Article 4, the ICH Association may cooperate with another organisation e.g., for the

purposes of sharing a common office in order to achieve cost savings. Other forms of cooperation

can be envisaged with other international organisations with which there are common interests,

for example to pursue training activities or organisations with similar or related activities, such as

IPRF, VICH and PIC/S. The cooperation should be laid down in written form, e.g., through an

exchange of letters or an agreement clearly spelling out the interest in the cooperation, its scope

and duration. Expected resource (both in terms of human and financial) implications for the ICH

Association should also be analysed by the Management Committee before putting forward a

proposal to the Assembly for a decision on entering into such cooperation.

The Assembly should be requested to approve such cooperation on the basis of a written proposal

by the Management Committee. This Article is not intended to cover cooperation relating to

MedDRA activities, as this will be covered in the Rules of Procedures of the MedDRA Management

Committee.

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7. Supporting ICH

7.1. Supporting Aims

In line with Articles 8(3)(e), 9(3)(e), 10(3)(d), 11(4)(a) and 12(3)(c), all Members should act in the

interest of the Association. As a Member of the ICH Association, the Member is accepting the aims

and purposes of the Association, with protection of public health being at the forefront, and should

act in accordance with these.

7.2. Promoting ICH Guidelines

The Founding Regulatory Members, Standing Regulatory Members and Regulatory Members are

expected to actively promote the use and understanding of the ICH Guidelines. A policy or strategy

should be put in place to promote the use and understanding of the ICH Guidelines by all relevant

staff of the authority. This is particularly important for an RHI in order to promote the use and

understanding of the ICH Guidelines amongst all the members of the RHI.

In line with Articles 9(3)(b) and 12(3)(a) respectively, Founding Industry and Industry Members

which have individual pharmaceutical companies as their affiliate members, are expected to

actively promote the compliance of its affiliate members with the ICH Guidelines. A policy or

strategy should be put in place to provide for the dissemination and understanding of the ICH

Guidelines amongst the affiliate members. In particular, participation in regional public meetings

on ICH as well as in other events, such as conferences, where ICH Guidelines are on the agenda is

encouraged.

7.3. Maintaining Confidentiality

The representatives of the Members, Standing Observers and Observers should be required, even

after their duties have ceased, not to disclose sensitive, confidential information of the kind

covered by the obligation of professional secrecy.

8. Legal Considerations

8.1. Member Conflicts with Governing Laws

As per Article 60, each Member will continue to be bound by the (national, supranational etc...)

laws and regulations that are applicable to that Member. Therefore, in the unlikely case of a

conflict between the applicable law of the Member and the Articles of Association of the ICH

Association, the Member will not be required under the Articles of Association (or under the Rules

of Procedure) to take any action that would breach those laws.

In any event, the Members are free to choose how they exercise their rights and deal with the

requirements under these Articles of Association. When submitting an application for membership,

it is presumed that the applicant has examined the Articles of Association and concluded that they

are not in conflict with the applicable laws of that applicant. After having become a Member and in

participating in the discussions and decision-making in the Association, the Members are expected

to ensure that they comply with the applicable laws of that Member. Any Member may always

abstain from participating in the discussions and/or decision-making on any topic. Ultimately, a

47

Member, Standing Observer and Observer may also decide to withdraw its membership or

observership in the ICH Association.

8.2. Liability

As per Article 61(1), the ICH Association being a legal entity means that any liability may only be

enforced towards the assets of the Association and thus limiting the personal liability of the

individuals who are serving on any of the bodies of the Association or in working groups.

Further to Article 61(2), under Swiss law, liability cannot be excluded in the case of intent or gross

negligence.

8.3. Dissolution of Association

Further to Article 62(2), in case of a voluntary dissolution and where the Association disposes of

any assets, the Assembly should decide on their liquidation in the same meeting. In particular, the

Assembly should appoint a liquidator in accordance with Swiss law. The Assembly should decide to

which Swiss organisation (that is pursing the same or similar non-profit purpose as the ICH

Association) the liquidator should transfer the remaining assets. The ICH Secretariat should make

any notifications required under Swiss law.

As indicated under Article 25(3)(c), the decision to dissolve the Association can only be taken by

three-quarter (3/4) majority of the Assembly, which must include the votes of each Founding

Regulatory Member.

8.4. Dispute Resolution

Further to Article 63, disputes between the Association and its Members or amongst its Members

should be referred to the ICH outside legal counsel by the Chair of the Assembly who should

provide a written summary of the subject of the dispute. The ICH outside legal counsel should act

as a mediator between the parties of the dispute and he/she should in this capacity act in a neutral

and objective manner. The ICH outside legal counsel should provide the parties involved in the

dispute with the opportunity to put forward their arguments and he/she may set up meetings

(virtual or face-to-face) in order to try to resolve the matter. If an amicable settlement cannot be

found between the parties, the ICH outside legal counsel prepares a report of his/her mediation to

the Assembly. The Assembly should consider whether it is possible to resolve the dispute.

If the latter cannot be resolved, the Assembly, upon a proposal by the Management Committee

(unless the dispute involves a Member of the Management Committee, in which case the

Management Committee should refrain from making a proposal), should designate three (3)

representatives for the Dispute Resolution Board from amongst the regulatory authorities that are

Members of the Association, including one Founding Regulatory Member (or Standing Regulatory

Member) that should act as Chair. Should the dispute involve one Founding Regulatory Member, a

representative of a Standing Regulatory Member should act as Chair. None of the Members may

be a party to the dispute.

The ICH outside legal counsel should assist the Dispute Resolution Board by providing legal advice,

and should attend all meetings of the Dispute Resolution Board. Also, the Director of the ICH

48

Secretariat should attend all meetings of the Dispute Resolution Board and keep a register of all

the documents and draw up minutes of the meetings and of any oral proceedings.

The dispute Resolution Board should be convened by its Chair who should ensure the quality and

consistency of the Board's decisions. The Chair should assign the examination of the dispute to one

of the Board's members as Rapporteur. The Rapporteur should carry out a preliminary study of the

dispute. The Rapporteur should ensure a close consultation and exchange of information with the

parties to the proceedings. For this purpose, the Rapporteur should prepare the necessary

communications to the parties and set appropriate procedural time limits. The Rapporteur should

prepare the internal meetings of the Board and should draft the decision, with the assistance of

the legal counsel of the ICH Association.

Only members of the Board should participate in the deliberations; the Chair may authorise other

persons to attend. Deliberations should be secret. During the deliberations between members of

the Board, the opinion of the Rapporteur should be heard first and the Chair last.

Decisions of the Dispute Resolution Board should be taken by a majority of its members.

Abstentions should not be permitted.

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3. Membership and Observership ApplicationsThe MC will present to the Assembly its recommendation regarding Membership andObservership applications processed to-date.

Chronicle:


The lead of the Membership Sub-committee of the MC presented to the Assembly on theMembership and Observership application process and the application forms for becoming aRegulatory Member, an Industry Member or an ICH Observer to the ICH Association.

Templates for Membership and Observership applications were shared with the participants of theAssembly meeting. The Assembly noted that the Membership and Observership application formswill be made available on the ICH website following the Jacksonville meeting. As per the Articlesof the Association, all applicants will be able to submit by email their completed application formsand the necessary documentation. The MC will be responsible for reviewing all new applicationsbefore the Assembly decides on the membership admissions at its subsequent face to face meeting.Decisions on membership admission will become effective on the date of decision taken by theAssembly.


The Assembly noted the process for Membership and Observership application;

The Assembly supported the Membership and Observership Application forms be madeavailable on the ICH website.

Actions:

The Assembly will be invited to provide its views and consider approval of anyapplications for ICH Membership/Observership recommended by the MC;

The Assembly will be invited to consider MC recommendations regarding anyrequests received from Observers to appoint experts to Working Groups.

AGENDA ITEM 3

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4. ICH CommunicationCommunication ActivitiesThe MC will provide an update on current communication activities regarding the newlyestablished ICH Association (e.g., development of a slide deck on ICH, Q&A documentetc.).

ICH Regional Public Meetings

Chronicle:


Update on Communication Activities for 2016The Lead of the Communication Sub-committee of the MC presented to the Assembly a proposedplan for ICH Communication activities in 2016 which will include the development of acommunication strategy in addition to updating the ICH website to reflect the recent establishmentof the new ICH Association.

ICH Regional Public MeetingsThe Assembly noted that JPMA will be organising an ICH regional public meeting to be organisedin Tokyo following the ICH meeting scheduled to be held in Osaka, Japan on November 5-10,2016.

Action:

The Assembly will be invited to share information on any ICH Regional PublicMeetings in their respective regions prior to/following the ICH meeting in Lisbon inJune 2016.

Action:

The Assembly will be invited to share its views on the communication activities.

AGENDA ITEM 4

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5. ICH Financial MattersThe MC will provide an update on ICH financial matters including the preparation of thedraft 2017 Budget, the development of membership fees that will be payable by allMembers at the end of the transition period, as well as considerations regarding otherfinancial means (e.g., participation fees).

Chronicle:


The lead of the Financial Sub-committee of the MC presented to the Assembly on the funding ofICH during an initial transition period and shared future considerations.

The Assembly noted that the funding of ICH operations (Secretariat, meetings etc.) will initially beensured by the Permanent Members of the MC. This will ensure continuation of ICH operationsand will contribute to a smooth transition allowing time to prepare for introducing membershipfees.

Following the transition period, the Assembly noted that the ICH Association shall be funded bymembership fees which will be payable by all Members.

It was noted that ICH Members and Observers will commit to self-financed attendance in futureICH meetings and that the membership fees once finalised would need to be approved by theAssembly, on the basis of a proposal from the MC.

Assembly Decision/Action:

The Assembly approved as final the proposed 2016 ICH Budget.

Action:

The Assembly will be invited to provide its views and consider approval of themembership fees and any other financial means proposed.

AGENDA ITEM 5

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6. Proposal for New ICH TopicsThe MC will report to the Assembly on its consideration of proposals for new ICHtechnical topics and will present any recommendations for new topics for consideration bythe Assembly. The MC will also report on the development of a process and framework forthe selection of new ICH technical topics for use during subsequent ICH Meetings.

Chronicle:


The Vice-Chair of the Assembly presented to the Assembly the draft 5-Year Strategic Plan of theAssociation including a list of proposed new ICH topics for future consideration by the Assembly.The Assembly noted the establishment of a Sub-committee of the MC to prepare a framework forcollecting and prioritising new ICH topics received.


The Assembly noted the draft ICH 5-Year Strategic Plan for current ICH topics, and a list ofnew proposed ICH topics for harmonisation which were recently suggested;

The Assembly supported the preparation of a framework for prioritisation of new topics willbe prepared by a Sub-committee of the MC ahead of its teleconference to be held in Spring2016;

In its next meeting, the Assembly will be invited to provide its views and consider approval ofthe ICH 5-Year Strategic Plan including new topics for ICH Guidelines recommended by theMC, as well as approval of the Annual Work Plan for 2016.

Actions:

The Assembly will be invited to provide its views and consider approval of anynew topics for ICH Guidelines recommended by the MC;

The Assembly will be invited to provide its views and, if finalised, considerapproval of the process and framework for the selection of new ICH technicaltopics recommended by the MC.

AGENDA ITEM 6

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7. Annual Work Plan and Multi-annual Strategic Plan of the Association

The MC will present to the Assembly the 2016 Work Plan and Multi-annual Strategic Planof the Association.

Chronicle:


The Vice-Chair of the Assembly presented to the Assembly the draft 5-Year Strategic Plan of theAssociation including a list of proposed new ICH topics for future consideration by the Assembly.The Assembly noted the establishment of a Sub-committee of the MC to prepare a framework forcollecting and prioritising new ICH topics received.


The Assembly noted the draft ICH 5-Year Strategic Plan for current ICH topics, and a list ofnew proposed ICH topics for harmonisation which were recently suggested;

The Assembly supported the preparation of a framework for prioritisation of new topics willbe prepared by a Sub-committee of the MC ahead of its teleconference to be held in Spring2016;

In its next meeting, the Assembly will be invited to provide its views and consider approval ofthe ICH 5-Year Strategic Plan including new topics for ICH Guidelines recommended by theMC, as well as approval of the Annual Work Plan for 2016.

Action:

The Assembly will be invited to approve the 2016 Work Plan and Multi-annualStrategic Plan for the Association.

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8. ICH Training ActivitiesICH Cooperation with Other Organisations

APEC will be invited to present the status of the AHC e-learning pilot project on ICH E2Guidelines.

ICH Training Strategy

The MC will present to the Assembly on the development of an ICH Training Strategy.

Chronicle:


The Assembly received a status report on the establishment of an E-learning Center by the APECHarmonisation Center (AHC); which included the development an ICH E-learning pilotprogramme for regulators and industry on the ICH E2 Series of Pharmacovigilance Guidelines. TheE-Learning Center is expected to launch the pilot programme in February 2016 which would beopen free of charge for a limited time period (6 to 12 months).


The Assembly congratulated the AHC on progress made in the development of the pilotprogramme on ICH E2 Guidelines in collaboration with ICH.

Action:

The Assembly will be invited to share its views on the draft ICH Training Strategy.

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9. Update on MedDRAThe Assembly will receive a report on the activities of the MedDRA Management Board.

The report will cover the following matters:

Training in ICH regions and beyond;

Implementation of the new 27th System Organ Class (SOC) in MedDRA Version 19.0 in March2016;

Tools to facilitate MedDRA’s use;

Development of Standardised MedDRA Queries (SMQs);

o Status of SMQ development;

o Collaboration with the Council for International Organizations of Medical Sciences(CIOMS).

The Assembly will also receive a report on the activities of the MedDRA Management Committee.

Chronicle:


The Assembly received a report on the ICH MedDRA Management Board meeting held on5 – 6 December 2015.

The Assembly noted that ahead of the meeting in Jacksonville, the Board had approved the 2016Subscription Rates with no increase over the 2015 Rates. It was noted that the ability to keep rates flat foranother consecutive year was as a result of continued growth of MedDRA subscribers throughout the world– currently numbering over 4,500 organisations – and increased efficiencies to contain costs for themaintenance and development of MedDRA.

The Assembly noted the importance of training in helping to facilitate the use of MedDRA and that theMSSO provides free training to Regulators and other MedDRA users as part of their MedDRA subscriptionpackage, with training available in several forms: face to face training; webinars; and e-learningtools/videocasts. The Assembly heard that in 2015 the MSSO had scheduled a total of 82 training courseswhich included 58 face-to-face training classes and 24 webinars. It was noted that a similar scale of trainingis planned for 2016, with all training offerings advertised on the website www.MedDRA.org.

The Assembly was updated on preparations for the implementation of the new 27th SOC (System OrganClass) with MedDRA 19.0 in March 2016. The new SOC, named Product issues will include terms relevantfor issues with product quality, devices, manufacturing quality systems, product supply and distribution, and

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counterfeit products. The Assembly noted that one of the goals of incorporating product quality terms intoMedDRA is to support the recording of product quality issues and any associated adverse events by using asingle terminology.

The Assembly was also informed of the release of a new version of the MedDRA Desktop Browser (MDB)in October 2015 which updates the user interface and the functions to match the Web-Based Browser (WBB)which was released in December 2014. Additionally, the MDB includes an option to change the userinterface to any of the currently supported MedDRA languages, as well as supporting multiple languages andthe display of hierarchy information in search result outputs.

The Assembly was also updated on ICH’s work with the Council for the International Organizations ofMedical Sciences (CIOMS) to develop Standardised MedDRA Queries (SMQs). In Jacksonville the Boardacknowledged the significant contributions of the CIOMS SMQ Working Group (WG) and the developmentto-date of 98 SMQs. The Board also renewed the Memorandum of Understanding between ICH and CIOMSfor a further year of development of new SMQs. In addition, the Board also congratulated CIOMS for itswork on the second edition of the CIOMS SMQ WG’s publication on Development and Rational Use ofStandardised MedDRA Queries, which is due for publication in 2016.


The Assembly noted the decisions taken by the MedDRA Management Board.

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10. Implementation of ICH Guidelines

Chronicle:


All regulatory participants were invited to update the Assembly on the status ofimplementation of ICH Guidelines in their respective countries and regions.

The Assembly Members and Observers took note of the written information included inthe agenda and shared further information on the status of implementation of ICHGuidelines in their respective countries and regions.

Action:

The Assembly will be invited to share information on the status of implementationof ICH Guidelines in their respective countries and regions.

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REPORT ON EWGS/IWGS/DISCUSSION GROUPS

11. Status Report of EWG/IWG/Discussion Group Activities

Hereafter please find the status of ICH Topics, before the start of the current round ofExpert/Implementation Working Group (EWG/IWG) meetings.

This is intended to assist the Assembly in setting a timetable for reports on the ICHTopics under Agenda items 12 to 21, and also to act as a background paper for thatdiscussion:

ICH Topics: Status of EWG/IWG Activities:

S5(R3) EWG: Revision of Detectionof Toxicity to Reproduction forMedicinal Products and Toxicity toMale Fertility

The S5(R3) EWG to continue its work on therevision of the S5(R2) Guideline.

Step 1 sign-off and Step 2a/b endorsements areexpected by Q3 2017.

S11 EWG: ICH Guideline onNonclinical Safety Testing in supportof Development of PaediatricMedicines

The S11 EWG to continue its work on thedevelopment of the S11 Guideline.

Step 1 sign-off and Step 2a/b endorsements areexpected by June 2017.

Q11 IWG: Q&As on API StartingMaterials

The Q11 IWG to continue its work on thedevelopment of the ICH Q11 Q&A document.

Step 1 sign-off and Step 2a/b endorsements areexpected after June 2016.

Q12 EWG: ICH Guideline onTechnical and RegulatoryConsiderations for PharmaceuticalProduct Lifecycle Management

The Q12 EWG to continue its work on thedevelopment of the Q12 Guideline.

Step 1 sign-off and Step 2a/b endorsements areexpected by June 2017.

E6(R2) EWG: Integrated Addendumto Good Clinical Practice (GCP)

The E6(R2) EWG to finalise its work on the draft E6Integrated Addendum.


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E9(R1) EWG: Addendum to Definingthe Appropriate Estimand for aClinical Trial/Sensitivity Analyses

The E9(R1) EWG to continue its work on thedevelopment of the E9 Addendum.

Step 1 sign-off and Step 2a/b endorsements areexpected by Q4 2016.

E11(R1) EWG: Addendum toPaediatric Drug Development

The E11(R1) EWG to continue its work on thedevelopment of the E11 Addendum.

Step 1 sign-off and Step 2a/b endorsements areexpected in June 2016.

E2B(R3) IWG: Revision of theElectronic Submission of IndividualCase Safety Reports

The E2B(R3) IWG to continue its work on itemsincluding the finalisation of additional Q&As, therevision of documents in the Implementation Guide(IG) Package.


M1 PtC WG: MedDRA Points toConsider

The M1 PtC WG to continue its work related to theupdate with each MedDRA release of the two PtCdocuments on Term Selection and Data Retrieval andPresentation.

M4E(R2) EWG: Revision of CTD-Efficacy Guideline

The M4E(R2) EWG to finalise its work on therevision of the M4E(R1) Guideline.


Under Agenda item 22, the Assembly will be invited to raise any issues regarding groupsnot meeting in Lisbon. The following is intended to assist the Assembly with thisdiscussion:

ICH Topics: Status of EWG/IWG/Discussion GroupActivities:

S1 EWG: Revision of the RodentCarcinogenicity Studies for HumanPharmaceuticals Guideline

The S1 EWG is not meeting in Lisbon but is workingon the collection and review of confidentialsubmissions of Carcinogenicity AssessmentDocuments (CADs).

Step 1 sign-off and Step 2a/b endorsements areexpected by June/November 2019.

S3A IWG: Q&As on Note forGuidance on Toxicokinetics

The S3A IWG is not meeting in Lisbon but isworking by email/teleconference.


S9 IWG: Q&As on NonclinicalEvaluation for AnticancerPharmaceuticals

The S9 IWG is not meeting in Lisbon but is workingby email/teleconference.

Step 1 postal sign-off and Step 2a/b endorsements areexpected by June 2016.

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M7(R1) EWG: Addendum toAssessment and Control of DNAReactive (Mutagenic) Impurities inPharmaceuticals to Limit PotentialCarcinogenic Risk

The M7(R1) EWG is not meeting in Lisbon but isworking towards finalising the M7(R1) Addendum.

Step 3 sign-off and Step 4 are expected by December2016.

Q3C(R6) Maintenance EWG:Maintenance of the Guideline forResidual Solvents

The Q3C(R6) Maintenance EWG is not meeting inLisbon but is working towards finalising themaintenance of the Q3C(R5) Guideline, andproposing a process for collecting new Q3C/Q3Dproposals.

Step 3 postal sign-off and Step 4 are expected by June2016.

Q3D IWG: Training Guideline forMetal Impurities

The Q3D IWG is not meeting in Lisbon but isworking towards finalising the Q3D training package,the scripts and audio-recordings for Modules 0-7, andorganising regional training for the Q3D Guideline.

M4Q(R1) IWG: Addressing CTD-QRelated Questions

The M4Q(R1) IWG is not meeting in Lisbon butcompleted the revision of the Granularity Documentwith the M8 EWG and is now working byemail/teleconference on the development of a processto address future CTD-Q related questions.

E14/S7B DG: The Clinical Evaluationof QT/QTc Interval Prolongation andProarrhythmic Potential for Non-Antiarrhythmic Drugs

The E14/S7B DG is not meeting in Lisbon but isworking by email/teleconference.

E14/S7B DG recommendation on whether to reopenthe E14 Guideline for a complete revision is expectedby December 2017.

E17 EWG: ICH Guideline on Multi-Regional Clinical Trials

The E17 EWG is not meeting in Lisbon but isworking towards developing the E17 Guideline.

Step 1 sign-off and Step 2a/b endorsements areexpected by May 2016.

E18 EWG: ICH Guideline onGenomic Sampling and Managementof Genomic Data

The E18 EWG is not meeting in Lisbon but isworking towards updating the draft E18 Guidelinewith comments received during the consultationperiod in the ICH regions.


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M2 EWG: Electronic Standards forthe Transfer of Regulatory Information

The M2 EWG is not meeting in Lisbon but isworking by email/teleconference on items including:development of a new M2 Operating Model;finalisation of the Information Paper on Redaction byJune 2016; harmonisation of the PDF Specification;finalisation of the Technology Watch Report by June2016; finalisation of report of M8 SDO Projectsurvey results by M8 EWG/IWG for its review andcomments.

Postal sign-offs of the PDF Specification and theInformation Paper on Redaction are expected byJune 2016.

M8 EWG/IWG: The ElectronicCommon Technical Document: eCTD

The M8 EWG/IWG is not meeting in Lisbon but isworking by email/teleconference on activitiesincluding: Q&As session with eCTD Tool Vendors;finalisation of the eCTD v4.0 Support Document andOrientation Materials; finalisation of the M4Granularity Document with M4Q(R1) IWGagreement; and an updated version of the eCTDv3.2.2 Q&As/Change Request document.

Step 3 postal sign-off and Step 4 of the revised M4Granularity Document and the eCTD v3.2.2 Q&Asv1.0 are expected by June 2016.

Postal sign-off of the eCTD v4.0 Support Documentand Orientation Materials are expected by June2016.

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12. S5(R3) EWG: Revision of Detection of Toxicity to Reproduction forMedicinal Products and Toxicity to Male Fertility

The Rapporteur will report on the outcome of the S5(R3) EWG meeting held on June 12 – 16,2016 and progress made towards revising the ICH S5(R2) Guideline on Detection of Toxicity toReproduction for Medicinal Products and Toxicity to Male Fertility.



S5(R3) EWG work plan, dated February 12, 2016.

Chronicle:


The Rapporteur reported to the Assembly on the outcome of the S5(R3) EWG meeting held onDecember 7 – 10, 2015.

The Assembly noted the group’s progress related to the revision of the majority of the sections andnotes of the ICH S5(R2) Guideline to address several identified issues such as: scope of the S5Guideline, test system selection, dose selections parameters, integrated testing strategies forembryofoetal development testing, and performance standards. The Assembly also noted thecomplexity, novelty and number of topics to be addressed.

The Assembly noted that the ICH S5(R3) draft Technical Document was expected to reach Step 1 andStep 2a/b in June 2017.

Assembly Action/Decision:

The Assembly endorsed the work plan of the S5(R3) EWG for activities to be undertaken.

Action:


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ICH S5(R3) EWG Work Plan

12 February 2016

Topic Adopted: April 2014

Last Face-to-Face Meeting: Jacksonville, FL, USA – December 2015

1. Anticipated MilestonesCompletion Date Deliverable

1Q-2Q 2016 Continuation of work on ICH S5(R3) via TCs in line with the identifiedworkpackages.

June 2016 F2F Meeting of the ICH S5 EWG

Criteria for dose selection, criteria for species selection, performancecriteria for possible regulatory acceptance of in vitro, ex vivo and non-mammalian in vivo (e.g. zebrafish) Embryo Fetal Development (EFD)assays, design of optional integrated testing strategies for EFD testing,combinations of in vivo study options for reproductive toxicity testing.integrated risk assessment, structure of the guideline

3Q 2017 Step 1 document

3Q 2019 Step 4 document

2. Timelines

Date Task / Activity Details

2-6 June 2014 ICH S5 Informal WGmeeting in Minneapolis,MN, USA.

Discussion on the topic andagreement within IWG aboutconcept-paper. Post-hoc discussionabout the further process.

10-13 November2014

ICH S5 Informal WGmeeting in Lisbon, Portugal.

Re-discussion on the topic andagreement within IWG about revisedconcept-paper and way forward.

Definition of work packages forrevision ICH S5(R2).

2Q 2015 ICH S5(R3) EWGTeleconferences.

Initiation of work on ICH S5(R3) inline with the identifiedworkpackages.

8-11 June 2015 ICH S5(R3) EWG meetingin Fukuoka, Japan.

Discussion on progress regarding thedifferent work packages; includingthe drafting of new or revising of

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existing wordings in order to worktowards a Step 1 document.

Specific discussion on the scope,criteria for dose selection, criteria forspecies selection, basic principles forpossible regulatory acceptance of invitro, ex vivo and non-mammalian invivo (e.g. zebrafish) EFD assays,design of optional integrated testingstrategies for EFD testing,combinations of in vivo study optionsfor reproductive toxicity testing.

24 September, 23October, 17November 2015

ICH S5(R3) EWGTeleconferences.

Continuation of work on ICH S5(R3)in line with the identifiedworkpackages.

7-10 December2015

ICH S5(R3) EWG meetingin Jacksonville, FL, USA.

Discussion on progress regarding thedifferent work packages; includingthe drafting of new or revising ofexisting wordings in order to worktowards a Step 1 document.

1-2Q 2016 ICH S5(R3) EWGTeleconferences.

Continuation of work on ICH S5(R3)in line with the identifiedworkpackages.

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13. S11 EWG: ICH Guideline on Nonclinical Safety Testing in Support ofDevelopment of Paediatric Medicines

The Rapporteur will report on the outcome of the S11 EWG meeting held on June 13 – 16,2016 and progress made towards collecting data on juvenile animal studies and to develop thedraft S11 Technical document on Nonclinical Safety Testing in Support of Development ofPaediatric Medicines.



S11 EWG work plan, dated January 5, 2016.

Chronicle:


The Rapporteur reported to the Assembly on the outcome of the meeting of the S11 EWG held onDecember 7 – 10, 2015 and progress made towards developing the ICH Guideline on Nonclinical SafetyTesting in support of Development of Paediatric Medicines.

The Assembly noted the group collected data on juvenile animal studies conducted to support paediatricprogrammes in the last 5-10 years. It was noted that these data will add to the collective experience inconducting studies and point to areas where specific guidance is needed.

The Assembly noted that the ICH S11 draft Technical Document was expected to reach Step 1 and Step2a/b in June 2017.

Assembly Action/Decision:

The Assembly endorsed the work plan and proposed timelines of the S11 EWG for activities to beundertaken.

Action:


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ICH S11 EWG Work Plan

5 January 2016

Topic Adopted: November 2014



June 2017 Step 2b Guideline

December 2018 Step 4 Guideline

2. Timelines


January – May2016

Teleconferences Teleconferences of the EWG orsubgroups as needed to accomplishobjectives.

January – May2016

Data collection completion byFDA, EU and Industry.

Regulatory and industry experience withjuvenile animal studies to supportpediatric development should becompleted and analysis discussed at thenext face-to-face meeting in June.

January – May2016

Drafting of guidance sections. Sections of guidance not reliant on dataanalysis are being drafted or outlined asdecided in Jacksonville.

January – June2016

Continued review of literaturerelevant to juvenile animaltoxicity studies.

Developing systems. Regulatory process (needs, design of

studies, impact on program). Value of studies for pediatric programs.

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14. Q11 IWG: Q&As on API Starting MaterialsThe Rapporteur will report on the outcome of the Q11 IWG meeting held on June 13 – 16, 2016 andprogress made towards developing the draft Q11 Q&A document on API Starting Materials.

Step 1 sign-off and Step 2a/b endorsements will be determined after the IWG meeting in Lisbon.


Q11 IWG work plan, dated March 31, 2016.

Chronicle:


The Q11 IWG did not meet in Jacksonville.

The Assembly noted the current activities of the Q11 IWG including the progress made towards developingthe ICH Q11 Q&As

The Assembly noted that Step 3 / Step 4 for the ICH Q11 IWG Q&As were expected by Q2/Q3 2016.

Assembly Action/Decision: The Assembly requested that the Q11 IWG provides an updated work plan for activities to be

undertaken to the MC ahead of its spring teleconference to be held in spring 2016.

Action:


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ICH Q11 IWG Work Plan

31 March 2016


Last Face-to-Face Meeting: Ottawa, Canada - September 2015


June 2016 A Q11 Q&A draft technical document forconstituent review

TBD Step 2 Q&A document

TBD Step 4 Q&A document

2. Timelines


28 January2015

IWG first official full teammeeting (viateleconference).

Initial drafting of IWG Work Plan. Planning meeting for teleconference

dates. Discussion on the need and scheduling of

face-to-face (F2F) meeting. Review workflow process and first

drafted set of potential questions: AllParties filled out a “Table of Issues”template in advance to begin identifyingpotential Q&A’s.

28 February2015

Brainstorming of potentialissues to be addressed.

Target brainstorming process completedby the end of February (recognizing thecollection of issues needs to remainflexible for additional issues based on theevolvement of the issues during the Q&Adevelopment process).

March – June2015

Evaluation, prioritization,and drafting of Q&As.

5 subteams identified based on clusters oftopics/issues and actively working ondrafting Q&As. Through correspondenceand teleconference calls, work within sub-Teams to address themes of issues anddrafting process.

Full IWG to hold monthly teleconferencecalls to advance work.

July – August Preparation of an initial Preparation of an initial draft Q&Adocument for further development, review

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2015 draft of a Q&A document. and finalisation during the F2F meeting. Maintaining flexibility to merge, separate,

or add new Q&A’s for new issues.

14-18-September 2015

Face-to-face (F2F) meeting(Ottawa, Canada):

During the ICH SC meetingin June 2015, the IWG wasauthorized to have a F2Fmeeting to advance thework and meet thenecessary timelines.

F2F meeting to discuss and edit (live)each Q&A.

Goal to come out of this meeting with adraft technical document for constituentreview.

Discussion on regional feedback &consensus building.

September –November 2015

Review Q&A output withconstituents.

16 October: Comments received fromconstituents.

23 October: Collated commentsdistributed to IWG.

October – November: Severalteleconferences for the IWG to continueto address comments received fromconstituents and make appropriaterevisions.

08 December2015

Presentation to ICHManagement Committee.

Update provided to ICH MC, highlightingmajor developments and revised timelinesfor the finalisation of the Step 2document.

January – 31March 2016

Updating of draft Q&ADocument.

The FDA shared with the IWG a proposedamendment to Question 6 (relating toconsiderations to assure that enough ofthe drug substance manufacturing processis provided in the application). Thisamendment introduced new proposals toutilize aspects of the pharmaceuticalquality system to support selection andjustification of starting materials, andapproaches to post-approval changemanagement. This includes the possibilityfor reduction in the description ofmanufacturing operations in theregulatory dossier and the extent to whichGMP applies. The proposals also includeprovision for ‘less burdensome’ postapproval changes to the process describedin the dossier.

The updated wording does have a numberof positive components, and it links to andprovides further clarity on the originaldrafted text

These proposals will require considerabletime to consider (e.g., potential that someof the general expectations may be

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relaxed if the applicant can provideevidence that the controlstrategy/pharmaceutical quality systemscan mitigate risks).

The IWG continues to be committed toworking through issues and commentspost Ottawa for the Q11 Q&A document.

June 2016 F2F meeting in Lisbon. F2F meeting to further develop andunderstand the new concepts proposedand their practical implementation withinregional regulatory frameworks. Todiscuss, revise and resolve all issues forthe remaining Q&As.

Discussion and consensus building. Goal to come out of this meeting with a

Q&A document as draft for constituentreview.

Post-June 2016meeting (to beconfirmed)

Continue to drive towarda Step 2 and Step 4document.

Dependent on the successful resolutionof a number of the issues related to thedraft Q&As, meeting approval, etc.

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15. Q12 EWG: ICH Guideline on Technical and Regulatory Considerationsfor Pharmaceutical Product Lifecycle Management

The Rapporteur will report on the outcome of the Q12 EWG meeting held on June 12 – 16,2016 and progress made towards developing the draft Q12 Technical document on Technicaland Regulatory Considerations for Pharmaceutical Product Lifecycle Management.



Q12 EWG work plan, dated March 23, 2016.

Chronicle:


The Rapporteur reported to the Assembly on the outcome of the Q12 EWG meeting held on December6 – 10, 2015 and progress made towards developing the ICH Guideline on Lifecyle Management.

The Assembly noted the EWG progress made in Jacksonville regarding the characterisation of aneffective Pharmaceutical Quality System (PQS), the establishment of conditions for new chemical andbiotech/biological products, and the application of Q12 for currently marketed products and lifecylemanagement plan.

The Assembly noted that the ICH Q12 Technical Document was expected to reach Step 1 and Step2a/b in June 2017.


The Assembly noted the possible delay (up to 1 year) before the Q12 EWG reaches Step 1 andStep 2a/b in June 2017;

The Assembly requested that the Q12 EWG provides a revised work plan for activities to beundertaken and timelines to the MC ahead of its teleconference to be held in spring 2016.

Action:


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ICH Q12 EWG Work Plan

23 March 2016

Topic Adopted: September 2014

Last Face-to-Face Meeting: Jacksonville, Florida, USA, December 2016


December 2015 -June 2016

Four EWG meetings, via teleconference, to assess progress on majorissues, revise current draft, and produce Q12 Technical Documentversion 4.Interim informal 2 days meeting of the established conditions teamApril 6-8, 2016 to prepare proposed text from June face-to-facemeeting.

June 2016 Face-to-face meeting, to review Q12 Technical Document version 4,and address disagreements and concerns.Agree on Q12 Technical Document version 5.

June 2016 –November 2016

Four EWG meetings, via teleconference, to assess progress on majorissues, revise current draft, and produce Q12 Technical Documentversion 6.

November 2017 Face-to-face meeting, to review Q12 Technical Document version 6,and address disagreements and concerns.Agree on Q12 Technical Document version 7 to be shared with ICHparties and stakeholders.

November 2016 –June 2017

Four EWG meetings, via teleconference, to review input from ICHparties and stakeholders on issues that must be addressed before movingto Step 1 Technical Document.

June 2017 Face–to-face meeting to finalize Step 1 Technical Document.

2. Timelines


September2014 –November2014

Step 1: Consensus building,reviewing concept paper andbusiness plan, and drafting theagenda for Lisbon meeting.

EWG continued regular interactions byemail.

November2014 – June2015

Continue EWG discussion andmeetings.

The EWG met, via teleconference , fourtimes between January and May 2015, todevelop initial draft of guideline chapters,and to prepare for June Meeting

Three sub-teams were established toprepare proposals for consideration by

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the entire EWG. January 21, 2015, EWG teleconference to

identify key topics for guideline andagree on an integrated approach for theguideline (Progress Report).

February 23, 2015, EWG teleconferenceto identify key elements of each chapterand agree on outline (Outline ofGuideline) and initiate drafting of coreguideline chapters.

March 31, EWG teleconference todiscuss key issues and agreement on‘bullet points’ content of guidelinechapters, provide instructions to draftingteams to convert ‘bullet points’ to text,and to review EWG workplan (FirstChapter Draft – Bullet points).

May 13, 2015, EWG teleconference toreview draft of document, identify majorchallenges and prepare for June ICH F2Fmeeting (Chapters Draft).

June 2015 EWG face-to-face meeting. EWG met face-to-face in June 2015, toaddress major challenges, develop guidelineversion 1 and agreed on future milestonesand timelines.

June 2015 –December2015


The EWG met, via teleconference , fourtimes between June and December 2015 toreview version 1, discuss major issues toproduce updated Q12 Technical Document,and to prepare for December Meeting. Three sub-teams continued to draft

sections for consideration by the entireEWG.

July 8, 2015, EWG teleconference toreview Fukuoka progress and identifiedchallenges and agree plan to address.

September 9, 2015, EWG teleconferenceto review drafting teams materials,discuss common issues among draftingteams and address disagreements andconcerns.

October 14, EWG teleconference toreview version 2 Technical document.

November 19, 2015, EWGteleconference to review version 2 andagree on agenda for face-to-face meetingin December.

December2015

EWG Face-to-face meeting. Face–to-face meeting to review updatedQ12 Technical Document, and address

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disagreements and concerns.

December2015 – June2016


Four EWG meetings, viateleconference, to assess progress onmajor issues, revise current draft, andproduce Q12 Technical Documentversion 4.

Interim informal 2 day meeting of theestablished conditions team April 6-8,2016.

April 6-8,2016

Interim F2F Meeting ofEstablished Conditions (EC)Team.

Face –to-face meeting of EC team toadvance the development of EC section.EC section is a pre-requisite for enablingfurther development of other Q12elements including lifecycle managementplans, expectations for life cycleapproaches in managing to legacy(currently marketed) products and overallrole of the PQS.

June 2016 EWG face-to-face meeting. Face-to-face meeting, to review Q12Technical Document version 4, andaddress disagreements and concerns.

Agree on Q12 Technical Documentversion 5.

June 2016 –November2016


Four EWG meetings, viateleconference, to assess progress onmajor issues, revise current draft, andproduce Q12 Technical Documentversion 6.

November2016

EWG face-to-face meeting. Face-to-face meeting, to review Q12Technical Document version 6, andaddress disagreements and concerns.

Agree on Q12 Technical Documentversion 7 to be shared with ICH partiesand stakeholders.

November2016 – June2017


Four EWG meetings, viateleconference, to review input fromICH Members and stakeholders on issuesthat must be addressed before moving toStep 1 Technical Document.

June 2017 EWG face-to-face meeting. Face–to-face meeting to finalise Step 1Technical Document

June 2017 –November2017


Receive Step 2a document comments,triage, and address significant issues

November2017

EWG face-to-face meeting. Face–to-face meeting to finalise Step 4document

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16. E6(R2) EWG: Integrated Addendum to Good Clinical Practice (GCP)The Rapporteur will report on the outcome of the E6(R2) EWG meeting held on June 13 – 16, 2016and progress made towards finalising the draft E6 Integrated Addendum on Good Clinical Practice.



E6(R2) EWG work plan, dated February 11, 2016.

Chronicle:


The E6(R2) EWG did not meet in Jacksonville.

The Assembly noted the current activities of the E6(R2) EWG and progress made towardscollecting public comments on the draft Addendum on Good Clinical Practice. The Assembly alsonoted that the period comment would end in January 2016 and that a webinar for which seats arestill available will be organised by the ICH Secretariat on December 15, 2015.

The Assembly also noted that Step 3 and Step 4 for the Addendum to ICH E6 were expected byJune 2016.


The Assembly endorsed the work plan of the E6(R2) EWG for activities to be undertaken.

Action:

The Assembly will be invited to provide its views on the report, and if the IntegratedAddendum is finalised by the E6(R2) EWG, the Regulatory Members of theAssembly will be invited to adopt as final the E6(R2) Integrated Addendum.

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ICH E6 EWG Work Plan11 February 2016

Topic Adopted: April 2014

Last Face-to-Face Meeting: Fukuoka, Japan - June 2015

1. Anticipated Milestones

Completion Date Deliverable

June 2016 Step 3 Expert draft Guideline

June 2016 Step 4 Final Guideline

2. Timelines


February 2016 Analyzing comments frompublic consultation.

Parties that have received comments areanalysing comments and developingcomment summary tables to share withthe EWG.

February 2016to May 2016

Webconferences (5). Reviewing and resolving commentsreceived from public consultation,drafting final guideline.

June 2016 Face to face meeting. Reaching consensus on final guideline.

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17. E9(R1) EWG: Addendum to Defining the Appropriate Estimand for aClinical Trial/Sensitivity Analyses

The Rapporteur will report on the outcome of the E9(R1) EWG meeting held on June 13 – 16,2016 and progress made towards developing the draft E9 Addendum on Defining theAppropriate Estimand for a Clinical Trial/Sensitivity Analyses.



E9(R1) EWG work plan, dated March 30, 2016.

Chronicle:


The Rapporteur reported to the Assembly on the outcome of the E9(R1) EWG meeting held onDecember 7 – 10, 2015 and progress made towards developing the E9 Addendum on Defining theAppropriate Estimand for a Clinical Trial/Sensitivity Analyses.

The Assembly noted the importance of defining ‘estimand’ and improving the framework for clinicaltrial planning, conduct, analysis and interpretation, and the role of sensitivity analyses in this pathway.It was noted that generally, an estimand reflects what is to be estimated to address the scientificquestion of interest posed by a clinical trial. The choice of an estimand involves the following threeattributes: population, endpoint, and measure of intervention effect.

The Assembly also noted that the E9(R1) EWG started the drafting of the Technical Document andproposed text to update ICH E9 and is discussing the need for and the content of a technical appendixto the E9 Addendum which will include the development of technical definitions and simple casestudies to help facilitate discussion within the EWG.

The Assembly noted that the Addendum to ICH E9 was expected to reach Step 1 and Step 2a/b in late2016.

Assembly Decision/Action: The Assembly endorsed the work plan of the E9(R1) EWG for activities to be undertaken.

Action:


AGENDA ITEM 17

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ICH E9(R1) EWG Work Plan

30 March 2016

Topic Adopted: October 2014Face-to-Face Meeting: Jacksonville, FL, USA - December 2015


Q4 2016 Step 1 and Step 2a Finalisation of the Technical Document and sign-offby all ICH Parties’ members in the EWG and endorsement by theAssembly.

Step 2b Draft Addendum and endorsement by the ICH RegulatoryMembers of the Assembly.

Q1 2017 Step 3 phase Publish draft Addendum.

Q2 2017 – Q42017

Step 3 phase Discuss regional consultation comments and consolidate theDraft Addendum.

2017 - 2018 Finalisation of the Addendum and Step 3 sign-off by topic leaders of theICH Regulatory Members. Step 4 adoption by the ICH RegulatoryMembers of the Assembly.

2. Timelines


March to June2016, and ICHMeeting June2016

Progress towards Step1 and Step 2a

Continue discussion of methodological issuesidentified at the ICH meeting in December2015.

Identify themes and aspects that would bemore relevant in a technical appendix orscientific publication.

Continue writing sections of the Step 1Technical Document and the technicalappendix.

Prepare document(s) to supportcommunication to the clinical community,including case studies.

Organise regional discussions, both withstatisticians and non-statisticians, and discussfeedback from these meetings.

Continue review of ICH E9 in relation withstatements that relate to concepts to bedeveloped in ICH E9 Addendum, andpropose annotations or modifications.

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Continue review of other ICH ‘E’ Guidelines. Follow actions to be undertaken until the ICH

meeting in June 2016, and that will contributeto the finalisation of the Step 1 TechnicalDocument.

Discuss the need to meet in June at the ICHmeeting in Europe.

Monthly full group EWG teleconferences willbe facilitated by the Rapporteur to ensureprogress.

June toNovember 2016

Progress towards Step1 and Step 2a

Aim at finalisation of the TechnicalDocument. It should be near final before theICH November meeting.

Continue discussion of methodological issuesidentified at previous meetings.

Continue regional discussions, both withstatisticians and non-statisticians.

Progress drafting of the draft technicalappendix.

Monthly full group EWG teleconferences willbe facilitated by the Rapporteur to ensureprogress.

ICH MeetingNovember 2016

Step 1, Step 2a andStep2b

Clarify outstanding issues and finalise theStep 1 Technical Document.

Step 1: Sign-off by all ICH Parties’ membersin the EWG.

Step 2a: Sign-off by the Assembly. Develop a presentation that helps users to

understand the draft Addendum. ICH Regulatory parties adapt the Step 1

Technical Document into a draft Addendumwhich is then signed by the ICH RegulatoryParties.

Finalise the presentation of the Addendum.

November 2016to November2017 (or later),including

ICH MeetingJune 2017

Progress towards Step3

Deliverables set for this period will dependon the duration of the public consultation ineach region and may be delayed.

Publish the draft Addendum in each regionfor a 3- or 6-month public consultation, underthe Step 3 procedure guidelines. The durationof public consultation, either 3 or 6 months, issubject to approval by each of the ICHRegulatory Parties.

Start discussing comments received in eachregion.

Discuss regional consultation comments andmodification of the Addendum based oncomments received. Outline plans for further

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progress towards finalisation.

ICH MeetingNovember 2017(or later)

Step 3 and Step 4 Deliverables set for this period will dependon the duration of the public consultation ineach region and may be delayed.

Finalisation of the Addendum. Step 3: Sign-off by topics leaders of

Regulatory ICH Parties. Step 4: Sign-off by all ICH Regulatory

Parties. Develop a presentation that helps users to

understand the Addendum.

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18. E11(R1) EWG: Addendum to Paediatric Drug DevelopmentThe Rapporteur will report on the outcome of the E11(R1) EWG meeting held on June 13 – 16,2016 and progress made towards developing the draft E11 Addendum on Paediatric DrugDevelopment.

Step 1 sign-off and Step 2a/b endorsements are expected in June 2016.


E11(R1) EWG work plan, dated April 19, 2016.

Chronicle:


The E11(R1) EWG did not meet in Jacksonville.

The Assembly noted the current activities of the E11(R1) EWG and progress made towards developingthe E11 Addendum on Paediatric Drug Development.

The Assembly noted that Step 1 and Step 2a/b for the Addendum to ICH E11(R1) were expected byJune 2016.

Assembly Decision/Action: The Assembly endorsed the work plan of the E11(R1) EWG for activities to be undertaken.

Action:

The Assembly will be invited to provide its views on the report, and if Step 1 of theAddendum is signed-off by the E11(R1) EWG, the Assembly will be invited toendorse Step 2a of the E11 Addendum, following which the Regulatory Members ofthe Assembly will be invited to endorse Step 2b of the E11 Addendum.

AGENDA ITEM 18

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ICH E11(R1) EWG Work Plan19 April 2016

Topic Adopted: 14 August 2014




June 2016 Step 1 Technical Document (Anticipated)

June 2016 Step 2a Technical Document

June 2016 Step 2b Draft Guideline

May 2017 Step 3 Expert draft Guideline

November 2017 Step 4 final Guideline

2. Timelines


1Q-2Q 2016 Continuation of E11 EWGMonthly online meetings torefine DRAFT Step 1 TechnicalDocument (Addendum to E11).Additional online meetings oftopic groups where needed.

All subsections of the E11 Addendumare in a draft Step 1 Technical Documenttemplate. Active EWG refinement ofthese subsections continues. Activework on Glossary, References and aGeneral Introduction will be completedby end of Q1.

Q2 will see finalization of all remainingsubsections that continue to be refinedby the topic groups (Extrapolation,MID3, Novel methodologies in clinicaltrial design), including collecting inputfrom each represented party of the E11EWG on the final wording of thetechnical document in preparation forthe face to face meeting. A final draftE11 Addendum will be circulated to allparties of the E11 EWG on April 27th forreview and alignment. This will ensurethat any issues that require furtherdiscussion will be identified andaddressed in advance of the face to faceto meeting in June.

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June 2016 Finalization of draft Step 1Technical document forsubmission to ICH Assembly atLisbon meeting.

The EWG will request to meet in Lisbonto finalize the Step 1 TechnicalDocument and present it to the ICHAssembly for advancement to Step 2.

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19. E2B(R3) IWG: Revision of the Electronic Submission of Individual CaseSafety Reports

The Rapporteur will report on the outcome of the E2B(R3) IWG meeting held on June 12 – 16,2016 and progress made towards the finalisation of additional Q&As and the revision of documentsin the Implementation Guide Package.



E2B(R3) IWG work plan, dated May 24, 2016.

Chronicle:


The E2B(R3) IWG did not meet in Jacksonville.

The Assembly was updated on the current activities of the E2B(R3) IWG and sub-group and activities. TheAssembly noted that a Q&A document will be developed by the E2B(R3) IWG.


The Assembly requested that the E2B(R3) IWG provides an updated work plan for activities to beundertaken to the MC ahead of its teleconference to be held in spring 2016 .

Action:

The Assembly will be invited to provide its views on the report and if the additionalQ&As and the revision of documents in the Implementation Guide Package arefinalised by the E2B(R3) EWG, the Regulatory Members of the Assembly will beinvited to adopt as final the E2B(R3) documents.

AGENDA ITEM 19

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ICH E2B(R3) IWG/Subgroup Work Plan

24 May 2016

Topic Adopted: July 2013

Last Face-to-Face Meeting: Lisbon, Portugal - November 2014



June 2016 Sign off on additional Q&As and revision of documents in theImplementation Guide package

March - May2016*

Determine any conflicts in ICSR messages based upon review of regionalImplementation Guides

*: anticipated, but it depends on regional implementation plan and external working group

2. Timelines


16 February 2016 Development of draft workplan

Submission of a draft work plan tocover activities between February2016 and next ICH meeting June2016

February to May2016

Monitor and discuss anycomments received by the ICHSecretariat or within theregions

Comments have been provided fromeach region and ICH E2B mail box

Assess the need to address commentsas Q&As by ICH. Determine a workplan to address the comments

February to May2016

Update documents in the IGpackage and create Q&As ifneeded

According to the results of commentresolution, the documents in the IGpackage will be updated and Q&Aswill be created in line with changecontrol process if needed

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*: anticipated, but it depends on regional implementation and external working group

February to May2016*

Assess the need for cross-regional data exchange pilot

IWG will assess the need to conductpilot testing to confirm whetherregional ICSR messages can beaccepted by other regions withoutcausing parsing errors

February to May2016*

Evaluate progress of regionalimplementations to identifyany potential conflict in ICSRmessages

Each region is responsible forevaluating impacts of other regionalIGs and will summarize any regionalissues for further discussion at ICH

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20. M1 PtC WG: MedDRA Points to ConsiderThe Rapporteur will report on the outcome of the M1 PtC WG meeting held on June 13 – 16,2016 and the group’s current activities with respect to the updating with each MedDRArelease of the two PtC documents on Term Selection and Data Retrieval and Presentation.


M1 PtC WG work plan, dated March 23, 2016.

Chronicle:


The M1 PtC WG did not meet in Jacksonville.

The Assembly noted the current activities of the M1 PtC WG with respect to the updating with eachMedDRA release of the two PtC documents on Term Selection and Data Retrieval and Presentation.

Assembly Decisions/Action: The Assembly endorsed the work plan of the M1 PtC WG for activities to be undertaken.

Action:


AGENDA ITEM 20

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ICH M1 PtC (Points to Consider) Work Plan23 March 2016

Topic Adopted: Date not applicable

This Working Group is charged with the continuing development and maintenance of the

MedDRA Points to Consider (PtC) documents. As new areas of MedDRA are developed,

refinements to the PtC documents are necessary. In addition, the documents are routinely

updated in line with MedDRA version releases twice a year. This WG also provides guidance

on ICH MedDRA initiatives (remit extended April 2014 per EU/EMA request for PtC expert

consultation).

Last Face-to-Face Meeting: London, UK - November 2014

The changes agreed in London were released on 1st March 2015 with MedDRA Version 18.0

as part of the usual scheduled updates.



1 March 2016 Release of “MedDRA Term Selection: Points to Consider” and “MedDRAData Retrieval and Presentation: Points to Consider” documents, includingupdates for MedDRA v 19.0 via MedDRA and JMO websites.

1 September 2016 Release of “MedDRA Term Selection: Points to Consider” and “MedDRAData Retrieval and Presentation: Points to Consider” documents, includingupdates for MedDRA v 19.1 via MedDRA and JMO websites.

2. Timelines


April - July2015

Discuss user comments and updates ofboth documents for MedDRA v18.1to bereleased 1st September 2015.

By email andteleconference.

October 2015 -February 2016

Discuss new and other user commentswhich could not be resolved via previousTCs.

Review and update both PtC documentsin preparation for the introduction of the27th SOC Product issues scheduled forMedDRA version 19.0 to be released on1st March 2016.

Review comments and feedback fromMSSO Expert Panel on MedicationErrors and Product Use Issues whereapplicable to the PtC documents.


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March - May2016

Review feedback and comments fromUsers.

Review comments and feedback fromMSSO Expert Panels on new SOCProduct issues and MedicationErrors/Product Use Issues whereapplicable to the PtC documents.

Develop/ReviewConcept Descriptions asnecessary, including for new concepts inthe 27th SOC Product issues and formedication errors, as well as for newconcepts/definitions arising from therevision of the EU’s GoodPharmacovigilance Practice (GVP)Module VI.


June 2016 Review condensed versions of PtCdocuments suitable for translation in all11 MedDRA languages.

Develop/review concept descriptions fornew pharmacovigilance areas.

Propose requesting meetingat the European ICHmeeting 2016 to formconsensus and completethese tasks.

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21. M4E(R2) EWG: Revision of CTD-Efficacy GuidelineThe Assembly will be updated on the outcome of the M4E(R2) EWG meeting held on June 12– 16, 2016 and progress made towards updating the draft M4E(R2) Guideline on CTD-Efficacywith comments received from the public consultation in the ICH regions.



M4E(R2) EWG work plan, dated March 21, 2016.

Chronicle:


The M4E(R2) IWG did not meet in Jacksonville.

The Assembly noted the current activities of the M4E(R2) EWG and progress made towards collectingpublic comments on the revised CTD-Efficacy Guideline.

It was noted that the public comment period was being completed in the ICH regions and all commentsreceived will be considered and discussed in monthly teleconferences beginning in January 2016.

The Assembly noted that Step 3 and Step 4 for ICH M4E(R2) were expected by June 2016.

Assembly Decision/Action: The Assembly endorsed the work plan of the M4E(R2) EWG for activities to be undertaken.

Action:

The Assembly will be invited to provide its views on the report and if the M4E(R2)Guideline on CTD-Efficacy is finalised by the M4E(R2) EWG, the RegulatoryMembers of the Assembly will be invited to adopt as final the M4E(R2) Guideline onCTD-Efficacy.

AGENDA ITEM 21

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ICH M4E(R2) EWG Work Plan

21 March 2016

Topic Adopted: June 2014


M4 reached Step 2b and launched Step 3 of the ICH process in August 2015 following the ICHmeeting in Japan. In January 2016, M4E(R2) began monthly teleconferences to discuss thepublic comments received in the United States, Europe, and Japan.


January - May2016

Review and discussion of regional comments by the EWG.

June 2016

F2F ICH meeting

Consensus reached on Step 3 Experts Draft Guideline.

Step 3 Experts Draft Guideline signed off by EWG regulatory Members.

EWG submits Step 3 Experts Draft Guideline to the Assembly requestingadoption by the Regulatory Members of the Assembly as the newlyrevised M4E(R2) (Step 4).

2. Timelines


January -May 2016

Monthly teleconferences Discuss public comments. Create a new revised draft based on the

public comments (~80 unique commentsreceived).

June 2016 Meeting F2F ICH meeting in Lisbon, Portugal. Complete discussion of regional comments. Discuss and reach consensus on revised

draft to recommend for ICH adoption.

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o S1 EWGo S3A IWGo S9 IWG

o M7(R1) EWGo Q3C(R6) Maintenance EWGo Q3D IWG

o M4Q(R1) IWGo E14/S7B DGo E17 EWGo E18 EWGo M2 EWGo M8 EWG/IWG

AGENDA ITEM 22

Actions:

o S1 EWG: Revision of the Rodent Carcinogenicity Studies for HumanPharmaceuticals GuidelineThe Assembly will be updated on the current activities of the S1 EWG including theprogress made towards the collection and review of confidential submissions ofCarcinogenicity Assessment Documents (CADs) and summary report submissions bysponsors to DRAs within each region and considerations regarding the timeframe fordrafting the S1 Technical document.

Step 1 sign-off and Step 2a/b endorsements are expected by June/November 2019.

o S3A IWG: Q&As on Note for Guidance on ToxicokineticsThe Assembly will be updated on the current activities of the S3A IWG whichconcluded Step 1 postal sign-off of its Q&As in March 2016 and initiation of aconsultation process once Step 2a and Step 2b upon electronic endorsement by theAssembly and the Regulatory Members of the Assembly respectively.


o S9 IWG: Q&As on Nonclinical Evaluation for Anticancer PharmaceuticalsThe Assembly will be updated on the current activities of the S9 IWG including theprogress made towards developing the draft S9 Q&As.

If the Step 1 Q&As is signed-off by the S9 IWG by written procedure ahead ofLisbon, the Assembly will be invited to endorse Step 2a/b for these Q&As.

Step 1 postal sign-off and Step 2a/b endorsements are expected by June 2016.

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REPORTS ON CURRENT TOPICS22. EWGs/IWGs Not Meeting in Lisbon, PortugalThe following groups will not be meeting in Lisbon:

Actions:

o M7(R1) EWG: Addendum to Assessment and Control of DNA Reactive(Mutagenic) Impurities in Pharmaceuticals to Limit Potential CarcinogenicRiskThe Assembly will be updated on the current activities of the M7(R1) EWGincluding the progress made towards finalising the M7(R1) Addendum onAssessment and Control of DNA Reactive (Mutagenic) Impurities inPharmaceuticals to Limit Potential Carcinogenic Risk.

Step 3 sign-off and Step 4 are expected by December 2016.

o Q3C(R6) Maintenance EWG: Maintenance of the Guideline for ResidualSolventsThe Assembly will be updated on the current activities of the Q3C(R6) EWGincluding: the progress made towards finalising the maintenance of the Q3C(R5)Guideline, and the proposal of a process for collecting new Q3C/Q3D proposals.

If Step 3 is signed-off by the Q3C(R6) Maintenance Regulatory EWG experts bywritten procedure ahead of Lisbon, the Regulatory Members of the Assemblywill be invited to adopt as final the Q3C(R6) Guideline.

Step 3 postal sign-off and Step 4 are expected by June 2016.

o Q3D IWG: Training Guideline for Metal ImpuritiesThe Assembly will be updated on the current activities of the Q3D IWG including:the progress made towards finalising Modules 8-9 of the Q3D training package, thescripts and audio-recordings for Modules 0-7, and the outcome of the regional Q3Dworkshops held in the different ICH regions in Q1/Q2 2016.

o M4Q(R1) (CTD-Quality) IWG: Addressing CTD-Q-Related QuestionsThe Assembly will be updated on the current activities of the M4Q(R1) (CTD-Quality) IWG and work to finalise the revision of the Granularity Document with theM8 EWG, and the development of a process to address future CTD-Q relatedquestions.

o E14/S7B Discussion Group (DG): The Clinical Evaluation of QT/QTc IntervalProlongation and Proarrhythmic Potential for Non-Antiarrhythmic DrugsThe Assembly will be updated on the current activities of the E14/S7B DG includingits proposal to review advances in science and methods related to the clinicalassessment of QT prolongation and to monitor the progress of the discussion of theComprehensive In vitro Proarythmia Assessment Initiative.

E14/S7B DG recommendation on whether to reopen the E14 Guideline for acomplete revision is expected by December 2017.

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Actions:

o E17 EWG: ICH Guideline on Multi-Regional Clinical TrialsThe Assembly will be updated on the current activities of the E17 EWG includingthe status of finalisation of the draft E17 Technical document on Multi-RegionalClinical Trials and initiation of the consultation process.

Step 1 sign-off and Step 2a/b endorsements are expected by May 2016.

o E18 EWG: ICH Guideline on Genomic Sampling and Management ofGenomic DataThe Assembly will be updated on the current activities of the E18 EWG includingprogress made towards updating the draft E18 Guideline on Genomic Samplingand Management of Genomic Data with comments received during theconsultation period in the ICH regions.


o M2 EWG: Electronic Standards for the Transfer of Regulatory InformationThe Assembly will be updated on the current activities of the M2 EWG and theprogress made towards development of a new M2 Operating Model; finalisationof the Information Paper on Redaction by June 2016; harmonisation of the PDFSpecification; finalisation of the Technology Watch Report by June 2016;finalisation of report of M8 SDO Project survey results by M8 EWG/IWG for itsreview and comments.

If the PDF Specification and the Information Paper on Redaction are signed-offby the M2 EWG experts by written procedure ahead of Lisbon, the Assemblywill be invited to endorse M2 documents to be published on the ESTRI website(i.e., PDF Specification and Information Paper on Redaction).

Postal sign-offs of the PDF Specification and the Information Paper on Redactionare expected by June 2016.

o M8 EWG/IWG: The Electronic Common Technical Document: eCTDThe Assembly will be updated on the current activities of the M8 EWG/IWGincluding: Q&As session with eCTD Tool Vendors; finalisation of the eCTD v4.0Orientation Materials; finalisation of the M4 Granularity Document withM4Q(R1) IWG agreement; and an updated version of the eCTD v3.2.2Q&As/Change Request document.

If Step 3 of the revised M4 Granularity Document and the eCTD v3.2.2 Q&Asv1.0 are signed-off by the M8 Regulatory EWG/IWG experts by writtenprocedure ahead of Lisbon, the Regulatory Members of the Assembly will beinvited to adopt as final these M8 documents.

If the eCTD v4.0 Support Documentation and Orientation Materials are signed-off by the M8 EWG/IWG experts by written procedure ahead of Lisbon, theAssembly will be updated by these documents on the timeframe for thepublication of these documents on the ICH website.

Step 3 postal sign-off and Step 4 of the revised M4 Granularity Document and theeCTD v3.2.2 Q&As v1.0 are expected by June 2016.

Postal sign-off of the eCTD v4.0 Support Documentation and OrientationMaterials are expected by June 2016.

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Background Documents:

S1 EWG work plan, dated February 1, 2016;

S3A IWG work plan, dated March 18, 2016;

S9 IWG work plan, dated March 18, 2016;

M7(R1) EWG work plan, May 26, 2016;

Q3C(R6) Maintenance EWG work plan, dated March 1, 2016;

Q3D IWG IWG work plan, dated February 12, 2016;

M4Q(R1) (CTD-Quality) IWG work plan, dated March 17, 2016;

E14/S7B Discussion Group (DG) work plan, dated March 31, 2016;

E17 EWG work plan, dated January 4, 2016;

E18 EWG work plan, dated March 1, 2016;

M2 EWG work plan, dated March 29, 2016;

M8 EWG/IWG work plan, dated March 24, 2016.

Chronicle S1 EWG:


The Rapporteur reported to the Assembly on the outcome of the S1 EWG meeting held on December 7 – 10,2015.

The Assembly noted the current activities of the S1 EWG including the progress made towards the collectionand review of confidential submissions of Carcinogenicity Assessment Documents (CADs) by sponsors toDRAs (from Europe, US, Japan, Canada and Switzerland) and the timeframe for the drafting of a Step 1Technical Document. A total of 25 CADs were received and analysed by the DRAs over the past 27 months.The Assembly noted that the S1 EWG was expecting to receive 2 new CADs per month which would delayfor about 2 years the revision of the S1 Guideline. The Assembly also noted that December 2017 was thefinal deadline for the submission of all new CADs.

In such case, the ICH S1 Guideline will be expected to reach Step 2a/b by November 2019.

The Assembly noted that the S1 EWG will continue the collection of CADs and study report evaluations.The Rapporteur also informed the Assembly that the Regulatory Notice Document (RND) currently postedon the ICH website will be updated in January 2016 to reflect a change in regulatory membership(participation of Health Canada and Swissmedic in the CAD review group). The S1 EWG will also completea Prospective Evaluation Period Status Report which will also be made available on the ICH website.

Assembly Decisions/Actions: The ICH Assembly endorsed the publication in January 2016 on the ICH website of a modified RND

to reflect the agreed upon procedural changes and the update of membership;

The Assembly endorsed the publication on the ICH website of the S1 Status Report;

The Assembly endorsed the work plan of the S1 EWG and its timelines for activities to be undertaken.

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Chronicle S3A IWG:


The S3A IWG did not meet in Jacksonville.

The Assembly noted the current activities of the S3A IWG including the progress made towards developingthe ICH S3A Q&As.

The Assembly noted that the ICH S3A Q&As document was expected to reach Step 1 and Step 2a/b inFebruary 2016.

Assembly Decisions/Actions: The Assembly requested that once Step 1 is reached, the Secretariat organises a written postal sign-off

(under Step 1) at the expert level which will be followed by Step 2a electronic endorsement by theAssembly and Step 2b electronic endorsement by the Regulatory Members of the Assembly;

The Assembly requested that the S3A IWG provides a work plan to the MC ahead of its teleconferenceto be held in spring 2016 for activities to be undertaken.

Chronicle S9 IWG:


The Rapporteur reported to the Assembly on the outcome of the meeting of the S9 IWG meeting held onDecember 7 – 10, 2015.

The Assembly noted the current activities of the S9 IWG including the progress made towards developingthe ICH S9 Q&As. It was noted that answers to questions were drafted for a majority of topics. TheRapporteur informed the Assembly that the group will continue its discussion with the ICH S11 EWGregarding the need for juvenile animal studies to clarify viewpoints of both groups. With regards to theapplication of the 3R’s principle (Replacement, Reduction and Refinement), the Rapporteur explained thatthe clarification of the scope could decrease the conduct of toxicology studies. Discussions with the S5(R3)EWG were also suggested.

The Assembly noted that the ICH S9 Q&A document was expected to reach Step 1 and Step 2a/b in Q12016.

Assembly Decisions/Actions: The Assembly noted the new proposed timelines for the S9 Q&A document to reach Step 1 in Q1 2016;

The Assembly requested that once Step 1 is reached, the Secretariat organises a postal sign-off (underStep 1) at the expert level which would be followed by Step 2a electronic endorsement by the Assemblyand Step 2b electronic endorsement by the Regulatory Members of the Assembly;

The Assembly recommended that the S9 IWG continues its discussions with the S11 EWG and engagealso in discussions with the S5(R3) EWG;

The Assembly endorsed the work plan of the S9 EWG for activities to be undertaken.

Chronicle M7(R1) EWG:


The M7(R1) EWG did not meet in Jacksonville.

The Assembly noted the current activities of the M7(R1) EWG including the progress made towardscollecting comments on the M7(R1) Addendum on Assessment and Control of DNA Reactive (Mutagenic)Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk. The Assembly also noted that thecomment period would end in January 2016.

The Assembly noted that depending on the number of comments received, the Addendum of the ICHM7(R1) Guideline was expected to reach Step 3 and Step 4 in Q2 2016.

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Assembly Decisions/Actions: The Assembly requested that once Step 3 is reached, the Secretariat organises a written postal sign-

off (under Step 3) at the Regulatory expert level;

The Assembly noted that the Regulatory Members of the Assembly would be invited to adopt as finalunder Step 4 the M7(R1) Guideline at the next Assembly meeting in Europe in June 2016;

The Assembly requested that the M7(R1) EWG provides a work plan to the MC ahead of its springteleconference to be held in Spring 2016 for activities to be undertaken.

Chronicle Q3C(R6) Maintenance EWG:


The Q3C(R6) Maintenance EWG did not meet in Jacksonville.

The Assembly noted the current activities of the Q3C(R6) EWG and progress made collecting comments onthe draft Part V of the Q3C(R5) Guideline. The Assembly also noted that the comment period would end inDecember 2015.

The Assembly noted that the ICH Q3C(R6) Guideline was expected to reach Step 3 in March/April 2016.

Assembly Decisions/Actions: The Assembly requested that once Step 3 is reached, the Secretariat organises a written postal sign-off

(under Step 3) at the Regulatory expert level;

The Assembly noted that the Regulatory Members of the Assembly would be invited to adopt as finalunder Step 4, the ICH Q3C(R6) Guideline at the next Assembly meeting in Europe in June 2016;

The Assembly endorsed the work plan of the Q3C Maintenance EWG for activities to be undertaken.

Chronicle Q3D IWG:


The Q3D EWG/IWG did not meet in Jacksonville.

The Assembly noted the Q3D IWG completed modules 0 to 7 of its Q3D training package and was finalisingmodules 8 and 9.The Assembly noted that once finalised the 9 training modules (including audio-recordings)covering the key sections of the ICH Q3D Guideline will be posted on the ICH website. The Assembly alsonoted that regional workshops will be held in the different ICH regions in Q1 2016.

Assembly Decisions/Actions: The Assembly endorsed the final training modules 0 to 7 after the Q3D Experts signed-off support of

the documents;

The Assembly noted the need to discuss and develop rules for the organisation of future regional ICH-endorsed events.

Chronicle M4Q(R1) IWG:


The M4Q(R1) IWG did not meet in Jacksonville.

The Assembly noted that the M4Q(R1) (CTD-Quality) IWG provided answers to all questions received bythe M8 EWG/IWG; and also provided recommendations to M8 on revising the Granularity document (whichis now an annex to ICH M4 Guideline).

The Assembly also noted that a remaining task for this IWG would be to develop a process for addressingfuture questions pertaining to CTD-Q.

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Assembly Decision/Action: The Assembly requested that the M4Q(R1) IWG provides a Status Report to the MC ahead of its

teleconference to be held in spring 2016.

Chronicle E14/S7B DG:


The Rapporteur reported to the Assembly on the outcome of the E14 IWG/Discussion Group (IWG/DG)meeting held on December 7 – 10, 2015 and progress made towards the finalisation (Step 4) of the revisedQ&A #5.1 on Concentration-Response Relationship.

The Assembly noted the finalisation of the revised E14 Q&A and the proposed next steps for the groupincluding the group’s recommendation to include new experts in non-clinical drug development (ICH S7B)to discuss advances in the science and methods related to the clinical assessment of QT prolongation and tocontinue the discussion of the Comprehensive In Vitro Pro-arrhythmia Assessment (CIPA) initiative.

Assembly Decisions/Actions: The Regulatory Members of the Assembly adopted the E14 Q&A under Step 4 after the E14 Experts

signed-off Step 3 of the revised E14 Q&A on Concentration Response Relationships (CRR);

The Assembly agreed to revert back to E14/S7B Discussion Group (DG) status with experts in clinical(E14) and non-clinical drug development (S7B);

The Assembly endorsed the recommendation of the E14 IWG/DG not to reopen the E14 Guideline fora full revision;

The Assembly requested the ICH Secretariat to update the membership of the E14/S7B DG;

The Assembly requested the E14/S7B DG to provide a work plan for activities to be undertaken to theMC ahead of its teleconference to be held in spring 2016.

Chronicle E17 EWG:


The Rapporteur reported to the Assembly on the outcome of the E17 EWG meeting held on December 7 –10, 2015 and progress made towards finalising the Step 1 document on Multi-Regional Clinical Trials(MRCTs).

The Assembly noted that this new ICH Guideline will provide general principles for the planning and designof MRCTs with the aim of encouraging the use of MRCTs in global regulatory submissions.

It was noted that MRCTs are generally the preferred option for investigating a new drug, which is planned tobe approved for use in multiple regions and countries. However, to increase an acceptability of MRCT datain the review by multiple regulatory agencies for drug approval, a sponsor should carefully consider theplanning and design of MRCTs in advance.

During the week, the group discussed several concepts to be included in the Guideline, such as sample sizeallocation and exploratory/confirmatory stage.

The impacts of the E17 Guideline were also presented. It will reduce the need to conduct standalone regionalor national studies including bridging studies, promote international harmonisation and provide betterevidences for drug approval in each region.

The Assembly noted that ICH E17 was expected to reach Step 1 and Step 2a/b in Q1 2016.

Assembly Decisions/Actions: The Assembly endorsed the revised work plan of the E17 EWG for activities to be undertaken;

The Assembly requested that, once Step 1 is reached, the Secretariat organises a written postal sign-off (under Step 1) at the expert level which would be followed by Step 2a electronic endorsement by theAssembly and Step 2b electronic endorsement by the Regulatory Members of the Assembly.

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Chronicle E18 EWG:


The Rapporteur reported to the Assembly on the outcome of the E18 EWG meeting held on December 6 – 9,2015 and progress made towards finalising the Step 1 Technical Document on Genomic SamplingMethodologies for Future Use.

The Assembly noted that the new E18 Guideline intends to provide considerations regarding patient privacy,data protection, informed consent and transparency and communication of findings. It was noted that thescope of this guideline pertains to genomic sampling and management of genomic data generated fromclinical studies. In order to fit with the scope and contents of the E18 Technical Document the E18 EWGsuggested changing the title of the Guideline to ‘Genomic Sampling and Management of Genomic Data’.The Assembly noted that the group reached agreement in Jacksonville on the content of the TechnicalDocument (Step 1) and that the consultation period (Step 3) will be launched very shortly.

The Assembly also noted that the ICH E17 was expected to reach Step 4 in June 2017.

Assembly Decisions/Actions: The Assembly endorsed Step 2a of the E18 Technical Document after the E18 Experts signed-off Step

1 of the E18 Technical Document;

The Regulatory Members of the Assembly endorsed Step 2b of the E18 Technical Document;

The Assembly endorsed the following new title for the E18 Guideline: ‘Genomic Sampling andManagement of Genomic Data’;

The Assembly requested the ICH Secretariat to revise the title of the E18 Concept Paper accordingly;

The Assembly recommended that the Regulatory Members of the E18 EWG evaluate the possibility ofreducing the E18 consultation period (Step 3) from the period proposed initially;

The Assembly endorsed the work plan of the E18 EWG for activities to be undertaken.

Chronicle M2 EWG:


The Rapporteur reported to the Assembly on the outcome of the M2 EWG meeting held on December 7 –10, 2015.

The report included an update on coordination of ICH projects with Information Technology Requirementsincluding: M2 Maintenance and information documents updates; coordination of ICH use of controlledvocabularies; revision of the information paper on redaction document; and addressing character lengthquestion for E2B.

The Rapporteur also presented to the Assembly an update on assessment and recommendation of technologyand information standards including: ESTRI activities; SDO Monitoring and Technology Watch reviews;structured content research project; and electronic redaction of document requirements. The Rapporteur alsohighlighted the need to review the M2 operating model.

The Assembly noted that during the week, the group has finalised its Glossary of Terms and Abbreviationdocument.

The Assembly also noted the proposed work plan for major activities to be undertaken.

Assembly Decisions/Actions: The Assembly endorsed the Glossary of Terms and Abbreviation document after the M2 Experts

signed their agreement with the document;

The Assembly requested that the Glossary of Terms and Abbreviation document be published on theESTRI website;

The Assembly requested that the M2 Experts develop a proposal for their new Operating Model (withinput from MC Members) for MC discussion at its teleconference in Spring 2016;

The Assembly endorsed the work plan including the development of the new M2 Operating Model.

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Chronicle M8 EWG/IWG:


The Rapporteur reported to the Assembly on the outcome of the M8 EWG/IWG meeting held on December7 – 10, 2015.

The report will include an update on progress made regarding the finalisation of the eCTD version4.0Implementation package v1.0 in addition to the finalisation of the Specification for Submission Formatsfor eCTD v1.0.

The Assembly noted the progress made by the group in updating the M4 Granularity Document (M4 Annex)based on Q&As from the M4Q(R1) IWG and change requests and its proposed timelines for Step 4 sign-offof the M4 Annex.

The Assembly also noted the proposed work plan for major activities to be undertaken between Jacksonvilleand the next meeting in Europe in June 2016.

Assembly Decisions/Actions: The Regulatory Members of the Assembly adopted under Step 4 the eCTD v4.0 Implementation

Package v1.0 after the M8 Experts had signed-off Step 3 of the document;

The Regulatory Members of Assembly adopted under Step 4 the Specification for Submission Formatsfor eCTD v1.0 after the M8 Experts also signed-off Step 3 of the document;

The Assembly requested that the adopted Step 4 documents be published on the ESTRI website;

The Assembly endorsed the plan and timelines after Jacksonville for Step 3 / Step 4 of the M4 Annex(Granularity document);

The Assembly requested that once Step 3 is reached, the Secretariat organises a written postal sign-off(under Step 3) at the expert level;

The Regulatory Members of Assembly noted that they would be invited to adopt as final under Step 4,the Granularity Document at the next Assembly meeting in Europe in June 2016;

The Assembly endorsed the revised version of the M8 Concept Paper for publication on the ICHwebsite;

The Assembly endorsed the work plan of the M8 EWG/IWG for work to be undertaken.

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ICH S1 EWG Work Plan

1 February 2016

Topic Adopted: May 2012



June or November2019

Step 2 Guideline

June or November2020

Step 4 Guideline

2. Timelines


February 2016– November2016

EWG members to meet everyother month by teleconference.

Regulatory members to meet todiscuss all newCarcinogenicity AssessmentDocument (CAD) submissionsand all new final summaryreport submissions.

EWG to review progress, feedback, onCAD submissions and align on plans formeeting face-to-face in November 2016 toreview regulatory member conclusionsfrom final reports derived from 6/7category 3, and 10 category 2 expectedfinal study report submissions; and toreview Drug Regulatory Authority (DRA)conclusions on 12 new CAD submissionsfollowing January 2016 RND revisionsposting.

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ICH S3A IWG Work Plan18 March 2016

Topic Adopted: October 2014

Last Face-to-Face Meeting: None



17 March 2016 Step 1 Technical Document

3 May 2016 Step 2a Technical Document

19 May 2016 Step 2b Draft Guideline

31 January 2017 Step 3 Expert draft Guideline

30 April 2017 Step 4 Final Guideline

2. Timelines


27 February2015

IWG e-mail consultation Ask addition/revision/comment of draftQ&A version 1 (drafted in Japan side),end of consultation on 23 March 2015.

7 May 2015 IWG teleconference Discussion on the 3 contraversialissues.

3 July 2015 IWG e-mail consultation Ask addition/revision of draft Q&Aversion 2 (mainly drafted in Japanside), end of consultation on 3 August2015.

19 August 2015 IWG teleconference Discussion on the revisions of the draftQ&A version 2.

3 September2015

IWG teleconference Discussion on revised draft Q&Aversion 2.

30 September2015

IWG e-mail consultation Ask revision of draft Q&A version 3(mainly drafted in Japan side), end ofconsultation on 20 October 2015.

4 December2015

IWG e-mail consultation Ask revision of draft Q&A version 4(mainly drafted in Japan side), end ofconsultation on 18 December 2015.

25 December2015

IWG e-mail consultation Ask revision of draft Q&A version 5(mainly drafted in Japan side), end ofconsultation on 15 January 2016.

19 January2016

IWG e-mail consultation All the IWG members agreed the finaldraft Q&A for Step 1.

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29 January2016

To ICH office Assigned Edior (Mr. Taniyama) sendthe formatted final draft Q&A for Step1.

17 March 2016 Step 1 sign off Step 1 sign off was Completed.

3 May 2016 Step 2a/2b endorsement Step 2a/2b endorsement by theMembers of the Assembly.

19 May 2016 Step 3 Step 3 launch of the Open consultationprocess.

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ICH S9 IWG Work Plan18 March 2016





01 January 2015 -present

Step 1 Technical Document

16 June 2016 Step 2a Technical Document

16 June 2016 Step 2b Draft Guideline

01 October 2016 Step 3 Expert draft Guideline

01 June 2017 Step 4 final Guideline

2. Timelines


17 March 2016 Most recent teleconference The Q and A is arranged into 4 sections.In Jacksonville, tentative answers wereprovided for all questions. All partiesthen recived input from constituents; todate, the IWG has worked throughabout half the comments received, withgeneral consensus on the Q and Asdiscussed to date.

31 March 2016 Input from constituents Last day to receive input on currentversion of Q and As; all subsequentcomments will be discussed at Step 3.

21 April 2016 Next teleconference Three additional teleconferences areanticipated in order to reach a Step 2document.

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ICH M7 EWG Work Plan

26 May 2016




June 2014 Reached and signed off on Step 4 Guideline in Minneapolis US

June 2015 Reached Step 2b for Addendum / monographs

December 2016 Step 4 is expected in December 2016

2. Timelines


July 2014 EWG 1st WebEx / DiscussedAddendum work plan detailand process.

Agenda and Actions: Goal of Addendum is to provide

acceptance limits for reagents to usebetween applicants and regulators i.e.consistency.

Scope of reagents to include inAddendum.

Consistent approach in collecting andreviewing the data, data quality androbustness.

Agreed to focus on Category 1&2reagents, although draft monographshave been developed for all reagents.

EMA proposed to review/discussthreshold alternatives when moreconservative linear approach is used.

August 2014 EWG 2nd WebEx / Continuediscussion of monographs anddiscussion on methodologyapproach and data/limitselection for reagents.

Agenda and Actions: Agreed to add method section to

addendum describing how data werecollected, consistency of methodologyand analysis across monographs.

Agreed to review alternativemonograph versions that use thresholdMOA to derive AIs for hemosiderosis(hydroxylamine), forstomach(epichlorhydrin), and hydrogenperoxide. If accepted, will serve astemplate for remaining category 1&2reagents with proposed thresholds

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Regulatory parties to provide statusupdate on acceptability/inclusion ofreagents and draft monographs incategory 1&2.

Monthly WebExs will be scheduledthrough December 2014.

September 2014November 2014

December 2014

EWG 3 WebEx. Introduced new title to the addendumand accepted by the EWG members.Continue to revise and incorporateedits/comments from EWG membersand included an Introduction section.Discussed individual monographs.

February 2015 Final EWG WebEx beforeStep 2.

Continue discussion of introduction/method sections and monographs withanticipation to reach Step 2 end ofFebruary.

June 2015 Reached Step 2. Last period for public comments toclose was 3 February 2016 in EC.

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ICH Q3C(R6) EWG Work Plan

1 March 2016


Last Face-to-Face Meeting: none (written procedure)


June 2016 Step 4 Guideline

2. Timelines


11 June 2015 Approval by SteeringCommittee under Step 2

Release for public consultation.

September2015-January 2016

Step 3 Internal/external consultation in ICHregions.

February 2016-April 2016

EWG teleconference/e-mailconsultation.

Reviewing and resolving commentsreceived from consultation process;preparing Step 4 document.

May/June 2016 Step 3 signoff Postal signoff Step 3 by the RegulatoryExperts.

June 2016 Step 4 Adoption by the Regulatory Membersof the Assembly.

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ICH Q3D IWG Work Plan

12 February 2016


Last Face-to-Face Meeting: Jacksonville, FL, USA - June 2015


26 July 2013 Step 2 Guideline

16 December 2014 Step 4 Guideline

21 October 2014 IWG endorsed by ICH Steering Committee

04 June 2015 Finalized Q3D Training Material

30 September2015

Completion of training modules

December 2015 IWG Sign-off on Modules 0-7

2. Timelines


18 February2016

Finalize Module 9 – FAQs Implement editorial correctionsidentified during constituent review.These have been discussed and agreedand only require final approval by theIWG.

18 May 2016 Finalize Module 8 – CaseStudies

Case studies were completed inNovember 2015. Constituent reviewresulted on over 400 comments. TheIWG will meet by t-con on 18 Feb 2016to plan the revision. It is anticipated thatthey will be complete by 18 May 2016.

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ICH CTD-Q (M4Q(R1)) IWG Work Plan17 March 2016

Topic Adopted: 11/04/2014

Last Face-to-Face Meeting: Not applicable



February 2016 Consultation with the M8 EWG/IWG on revisions to the Granularitydocument (at the request of the M8 EWG/IWG).

COMPLETED

2. Timelines


August -October 2015

Compare alternative regionalproposals and beginconsensus development withregard to responses due backto the M8 EWG/IWG.

Multiple teleconferences to try to reachagreements on proposed revisions tothe granularity document and proposalsfor which attributes (keywords) toinclude in sections 2.3 and 3 of v.4.0 ofthe eCTD.

(Completed)

November -December 2015

IWG members develop andcompare possible approachesfor dealing with potentialfuture questions pertaining toCTD-Q.

Email correspondence to develop andcompare alternative approaches fordealing with potential future questionspertaining to CTD-Q.

(Completed)

November 2015 Written response to the M8EWG/IWG.

IWG provides written response to M8EWG/IWG.

(Completed)

November 2015 Finalize answer to questionabout dealing with potentialfuture questions pertaining toCTD-Q.

Final discussion via email orteleconference.

(Completed)

December 2015 Written response to ICHSecretariat on final issue.

IWG provides draft written proposal toICH Secretariat for dealing withpotential future questions pertaining toCTD-Q.

(Completed)

January -February 2016

Consultation with ICH M8EWG on revisions to theGranularity document.

(Completed)

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ICH E14/S7B EWG/DG

31 March 2016

Topic Adopted: December 2015

Last Face-to-Face Meeting: Jacksonville, FL, USA - December 2015


December 2017 Preliminary recommendation to ICH SC regarding whether to re-openICH E14 and S7B for complete revision.

2. Timelines


QuarterlyTeleconferences

Track Progress ofCiPA Initiative.

Discuss progress of CiPA initiative, review dataas it emerges, and provide guidance ondeveloping a path towards using these assays forregulatory decision making.

When CiPA initiative is ready for widespreadimplementation, the discussion group will assessthe scope of the effort required to re-open ICHE14 and S7B for complete revision and make arecommendation.

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ICH E17 EWG Work Plan

4 January 2016




1Q 2016 Step 2 Guideline

2Q 2017 Step 4 Guideline

2. Timelines


January to March2016

Finalize all contents in thedraft guideline in sentence bysentence.

Review all sections followed bycompletion of editorial change andgrammatical check by e-mail and theweb-conference.

1Q 2016 Sign off as Step 1 andStep 2a/b.

Sign off as Step 1 in written procedure. Sign off as Step 2a/b in written

procedure.

2Q 2016 Public consultation in eachregion.

Public consultation will be taken at theperiod between April and July 2016after adoption as Step 2a/b.

3Q 2016 Comments review. Review all comments received in theperiod of public consultation by e-mailand the web-conference.

November 2016 Fourth face-to-face EWGMeeting.

Revise the guideline based oncomments received on the publicconsultation.

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ICH E18 EWG Work Plan

1 March 2016




4Q 2016 Complete public consultations including consolidation of all thecomments from each region.

2Q 2017 Step 4 document sign off.

2. Timelines


June 2016 Complete public consultationsin each region.

Progression status of the consultations.

EU: started (consultation period:1 February to 31 May).

MHLW: in preparation (Eng-Jpntranslation has been completed; Aimingto initiate a 60-day consultation by theend of March at the latest).

FDA: in the final stages of preparing thenecessary documents for theconsultation (Aiming to initiate a 60-dayconsultation by the end of March at thelatest).

4Q 2016 Consolidate all the commentsfrom each region.

Necessity to request for setting up 4thF2F meeting at Osaka (November2016) will be evaluated depend oncomments E18 EWG get during thepublic consultation, but it’s anticipatedto be needed.

2Q 2017 Step 4 document sign off

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ICH M2 EWG Work Plan

29 March 2016

Topic Adopted: 1994


The following roles and responsibilities of M2 were approved by the MC:

1) Provide overview of ICH and SDO technical standardization activities (past, current andfuture)

2) Provide a framework for a structured way of working3) Manage relations (between projects and between organizations (EWG-EWG, EWG-SDO,

ICH-SDO))4) Provide a maintenance structure5) Establish and maintain an “Information Repository” for EWGs (e.g., working practices,

best practice guides and templates)6) Deliver consultative support to EWGs requiring technical specifications7) Establish and maintain ICH Object Identifiers (OIDs)


March 2016 New M2 Operating Model – a proposal from M2

M2 Projects are generally not traditional ICH EWG projects. An alternativeoperating model that provides more structure for the MC and otherstakeholders is needed. M2 will develop a proposal for their new operatingmodel, with input from MC Members, for MC discussion in Spring 2016.

June 2016 Finalized Information Paper on Redaction

The efficient and correct redaction with respect to the regional legalrequirements is crucial. M2 EWG identified a set of requirements forredaction and used these to evaluate the usability of electronic formats andtools within the ICH regions. The findings will be provided in this paper.

June 2016 PDF Specification update

Current M2 recommendation is only on the use of specific PDF versionsand agreed restrictions, but each regulator maintains separate PDFspecification. We investigate opportunity to further harmonize existing PDFrequirements and update M2 PDF specification as necessary.

June 2016 Technology Watch Reporting, June 2016

Technology Watch reporting captures key aspects of the evolution oftechnology and information standards as it impacts the electronic transferof regulatory information. An assessment will be made of key opportunitieswith potential relevance to ICH and how these might impact existing

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guidance and/or specifications and the current or future work of ICH.Based on this assessment, specific project opportunities will be presentedand discussed with the MC. Additionally, key regulatory trends will bepresented for further technology investigation.

June 2016 M8 SDO Project survey results - final report

Since ICH M8 IG reached Step 4 in Jacksonville ICH, December 2015, M2will conduct a survey based on the ICH SDO projects evaluation criteria.The survey results will be reported to the MC.

2. Timelines


Continuous Coordination of ICH use ofControlled Vocabularies.

M2 facilitates harmonization of ICH useof CVs with appropriate experts.

The process for coordination will bedefined.

February 2016 Initiate survey on M8 SDO project. M2 provides the link to the online surveyand off-line survey form on M8 SDOproject to the M8 Rapporteur.

M8 Rapporteur requested each memberto respond to the survey.

Responses are due end of March.

February 2016to 24 March2016

Draft New M2 Operating Model. New M2 Operating Model is drafted anddiscussed by a subgroup of M2.

24 March 2016 Decide if M2 needs to meet inLisbon.

Decision is made if M2 needs to meetface-to-face at the June 2016 Lisbon ICHmeeting.

25 March 2016 New M2 Operating Model – aproposal from M2.

New M2 Operating Model is proposed tothe ICH MC.

31 March 2016 Draft Information Paper onRedaction.

Information Paper on Redaction isdrafted for M2 review.

31 March 2016 Draft M2 PDF specification update. To further harmonize existing PDFrequirements, review/remove anydifferences/ discrepancies.

Draft M2 PDF specification update..

22 April 2016 Draft Technology Watch Reporting2016.

A list of project opportunities for ICH isdrafted and initial assessment discussed.

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15 April 2016 Draft a report on M8 SDO projectsurvey.

Draft a report on the survey results.

Discuss initially with M8 Rapporteur andRegulatory Chair.

22 April 2016 Define the process for coordinationof controlled vocabularies.

The process for coordination ofcontrolled vocabularies is defined.

10 June 2016 Update M2 Operating Model. New M2 Operating Model is updatedwith input and guidance from the ICHMC.

10 June 2016 Finalize Information Paper onRedaction.

Information Paper on Redaction isfinalized and submitted to the MC afterpostal sign-off.

10 June 2016 Finalize PDF Specification update. M2 PDF Specification update is finalizedand sign-off by postal written procedure.

10 June 2016 Finalize Technology WatchReporting, June 2016.

Project opportunity assessments providedto MC.

Questions for MC on technologyassessment priorities for ICH.

10 June 2016 Finalize report of M8 SDO Projectsurvey results.

A report of M8 SDO project surveyresults is finalized and submitted to theMC.

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ICH M8 EWG/IWG Work Plan

24 March 2016

Topic Adopted: 11 November 2010




June 2016 Step 4 M4(R4) Organisation of the Common Technical Document for theRegistration of Pharmaceuticals for Human Use.

June 2016 Step 4 eCTD IWG Questions and Answers and Specification ChangeRequest Document v1.28.

June 2016 Step 4 eCTD v4 IWG Questions and Answers and Change RequestDocument v1.0.

June 2016 Sign-off by M8 Experts of the Orientation Material and SupportDocument. The Assembly Members will be invited to endorse thesedocuments.

2. Timelines


March 2016 Step 4 documents on ICHwebsite.

Agree to the webpage contents. Submit to the Secretariat.

March 2016 Finalize Support Documentation. Draft, review, and finalize the slides.

April - May2016

Communicate with eCTD ToolVendors.

Hold a Q&A session with eCTD ToolVendors.

December2015 - June2016

Create eCTD v4 OrientationMaterials.

Establish Orientation Materials sub-team. Draft, review, and finalize materials.

December2015 - April2016

Finalize Granularity Document. Hold a joint TC with M4Q. Finalize Granularity Document with M4Q

agreement.

March -June 2016

Create eCTD v4.0 Q&Adocument.

Receive questions on eCTD v4.0. Review input from communication with

eCTD Tool Vendors. Draft, review, and finalize Q&A v1.0.

March -June 2016

Update eCTD v3.2.2 Q&Adocument.

Update to describe that SSF applies tov3.2.2 as well.

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