ASSEMBLY - admin.ich.org · S5(R3) EWG: Revision on Detection of Toxicity to Reproduction for Medicinal Products and Toxicity to Male Fertility The Rapporteur will report on the outcome

ASSEMBLY AGENDA PAPERS

May 31 & June 1, 2017

Montreal, Canada

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ICH ASSEMBLY MEETING

Final DRAFT AGENDA May 31 & June 1, 2017

Montreal, Canada

Opening of the ICH Assembly Meeting

Welcoming remarks from the ICH Assembly Chair and Vice-Chair.

The Assembly is invited to note the Member Representatives and Observer Delegates appointed to the Assembly and participating in the Montreal meeting.

Adoption of the Agenda

The Assembly is invited to adopt the agenda and timetable for the ICH Assembly meeting.

1. 2016 Annual Report of the Association

The ICH Management Committee (MC) will present to the Assembly the 2016 Annual Report of the Association developed by the ICH Secretariat with the input of the ICH MC and MedDRA MC.

The Assembly is invited to take a decision to approve the 2016 Annual Report and the discharge of the ICH MC, MedDRA MC and the ICH Secretariat for the activities undertaken by these bodies in 2016.

2. Procedural Matters

Articles of Association

The Chair/Vice-Chair will inform the Assembly on amendments proposed to the Articles of Association which were last updated and approved by the Assembly in November 2016.

The Assembly is invited to take a decision to adopt the revised Articles of Association.

Assembly Rules of Procedure

The Chair/Vice-Chair will inform the Assembly on amendments proposed to the Assembly Rules of Procedure (RoP) which were last updated and approved by the Assembly in Osaka in November 2016.

The Assembly is invited to take a decision to adopt the revised Assembly RoP.

Standard Operating Procedures for EWGs/IWGs

The ICH Management Committee (MC) will inform to the Assembly on updates discussed by the ICH MC to the Standard Operating Procedures for Expert Working Groups (EWGs) / Implementation Working Groups (IWGs).

The Assembly is invited to share its views on the report. IFPMA Role

The IFPMA will be invited to present an overview of its engagement in ICH and a process to facilitate the participation of IFPMA National Association experts in EWGs/IWGs.

The Assembly is invited to share its views.

Dated May 16, 2017

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3. Membership and Observership

The ICH MC will present to the Assembly its recommendation regarding Membership and Observership applications processed since the Osaka meeting in November 2016.

The Assembly is invited to take a decision regarding the applications for ICH Membership/Observership recommended by the MC.

4. Financial Matters

The ICH MC will provide an update on ICH financial matters including; 2016 Financial Audit; 2016 costs; preparation of the 2018 ICH budget; multi-year budget planning; cash flow; and development of a proposal for a participation fee for non-membership fee paying ICH meeting participants.

The Assembly is invited to share its views on the update and to take a decision to approve the 2018 ICH budget;

The Assembly is invited to take a decision to approve the 2016 audited accounts of the ICH Association.

5. New ICH Topic Proposals & Strategic Discussions

New Topic Proposals

The ICH MC will present its recommendation on the prioritization of new ICH topic proposals which were submitted by Members before the mid-January 2017 deadline in line with the agreed process.

An update will also be provided on the status of the Adaptive Clinical Trials proposal which was revised following discussion in Osaka in November 2016.

The Assembly is invited to provide its views and to take a decision to approve any new topics for ICH Guidelines recommended by the MC.

Strategic Discussions

The ICH MC will update the Assembly on the response received from the public consultation on the GCP Renovation Reflection Paper published on the ICH website in January 2017 for a 60-day comment period, and will discuss next steps with the Assembly.

The ICH MC will update the Assembly on: the status of work by a feasibility group set-up after the November 2016 meeting to further consider the topic Compliance of Reliability for Electronic Records; a newly developed Quality Reflection Paper; and share with the Assembly any considerations regarding other strategic topics to progress.

The Assembly is invited to provide its views on the update.

6. Communication

Communication Activities

The ICH MC will provide an update on current communication activities including development of a transparency policy and stakeholder engagement plan, as well as recent updates to the ICH website.

The Assembly is invited to share its views on the update.

ICH Regional Public Meetings

The Assembly is invited to share information on any ICH Regional Public Meetings in their respective regions prior to/following the ICH meeting in Montreal in May/June 2017.

7. Training

The ICH MC will update the Assembly on the progress of the pilot supported in Osaka in November 2016 for the Training Subcommittee to partner with a small group of training providers.


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8. Update on MedDRA

The MedDRA MC Chair or Chair’s delegate will provide a report on current MedDRA activities.

The Assembly is invited to share its views on the report.

9. General Operational Matters

The ICH MC will update the Assembly on general operational matters including:

Status of transfer of assets of the former ICH (International Conference on Harmonisation) from IFPMA to the new ICH Association;

Considerations on future ICH meeting organisation in view of the expansion of ICH Membership and Observership;

Discussion with IPRF regarding the future provision of secretariat support;

Organisation of elections at the next Assembly meeting in Geneva, Switzerland in November 2017 for the election of the next Assembly Chair and Vice Chair, as well as the election of Elected MC Representatives.


10. Implementation of ICH Guidelines

The ICH MC will present the table developed by the ICH Secretariat to facilitate monitoring by the Assembly of the status of ICH Guideline implementation by ICH Regulatory Members.

The Assembly is invited to note the implementation of ICH Guidelines by ICH Regulatory Members and share views on the status of implementation across the ICH Member Regions.

REPORTS ON CURRENT TOPICS

11. Status Report on Topics

The Assembly is invited to note the current status of draft Guidelines and predictions for progress towards Step 2 and Step 4.

12. S1(R1) EWG: Revision of the Rodent Carcinogenicity Studies for Human Pharmaceuticals Guideline

The Rapporteur will report on the outcome of the S1(R1) EWG meeting held on May 29 - June 1, 2017 including progress made towards the collection and review of confidential submissions of Carcinogenicity Assessment Documents (CADs) and summary report submissions by sponsors to DRAs within each region.

The Assembly is invited to provide its views on the report.

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

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

The Rapporteur will report on the outcome of the S5(R3) EWG meeting held on May 28 - June 1, 2017, addressing feedback received from the EWG Member constituencies on a preliminary draft and progress made towards reaching Step 1 in Montreal of the S5(R3) Technical Document on Revision on Detection of Toxicity to Reproduction for Medicinal Products and Toxicity to Male Fertility.

The Assembly is invited to provide its views on the report; If Step 1 of the Technical Document is signed-off by the S5(R3) EWG, the Assembly will be

invited to take a decision to endorse Step 2a of the S5(R3) Technical Document, following which the Regulatory Members of the Assembly will be invited to endorse Step 2b of the S5(R3) draft Guideline.

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

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14. S11 EWG: Nonclinical Safety Testing in Support of Development of Paediatric Medicines

The Rapporteur will report on the outcome of the S11 EWG meeting held on May 29 - June 1, 2017, work to complete the data collection activities and progress made to develop the S11 draft Technical Document on Nonclinical Safety Testing in Support of Development of Paediatric Medicines.


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

15. Q11 IWG: Q&As on Selection and Justification of Starting Materials for the Manufacture of Drug Substances

The Rapporteur will report on the outcome of the Q11 IWG meeting held on May 29 - June 1, 2017 and progress made to address comments on the draft Q&As document received during the public consultation that ended on April, 2017.


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

16. Q12 EWG: Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management

The Rapporteur will report on the outcome of the Q12 EWG meeting held on May 28 - June 1, 2017 and progress made towards reaching Step 1 in Montreal of the Q12 Technical Document on Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management.

The Assembly is invited to provide its views on the report; If Step 1 of the Technical Document is signed-off by the Q12 EWG, the Assembly will be

invited to take a decision to endorse Step 2a of the Q12 Technical Document, following which the Regulatory Members of the Assembly will be invited to endorse Step 2b of the Q12 draft Guideline;

The Assembly is invited to take a decision to endorse the nomination of a new Regulatory Rapporteur for the Q12 EWG in line with the SOP 1.5.2.2.


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

The Rapporteur will report on the outcome of the E9(R1) EWG meeting held on May 29 - June 1, 2017 and progress made towards developing the E9 draft Technical Document on Defining the Appropriate Estimand for a Clinical Trial/Sensitivity Analyses.



18. E11(R1) EWG: Addendum to Paediatric Drug Development

The Rapporteur will report on the outcome of the E11(R1) EWG meeting held on May 29 - June 1, 2017 including progress made towards analysing and addressing comments collected on the draft E11 Addendum to Paediatric Drug Development during the public consultation that ended on April, 2017.


Step 3 sign-off and Step 4 adoption are expected electronically by November 2017.

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19. E17 EWG: Multi-Regional Clinical Trials

The Rapporteur will report on the outcome of the E17 EWG meeting held on May 29 - June 1, 2017 and progress made towards analysing and addressing comments received on the draft E17 Guideline on Multi-Regional Clinical Trials during the public consultation that ended on January 2017.



20. E19 Informal WG: Optimization of Safety Data Collection

The Lead will report on the outcome of the meeting of the E19 informal WG held on May 29 - June 1, 2017 and the finalisation of the Concept Paper and Business Plan on Optimization of Safety Data Collection.


Approvals of the Concept Paper and Business Plan by the MC are expected at the Montreal meeting in May/June 2017.

21. E2B(R3) EWG/IWG: Revision of the Electronic Submission of Individual Case Safety Reports

The Rapporteur will report on the outcome of the E2B(R3) EWG/IWG meeting held on May 29 - June 1, 2017 and progress made towards developing the annexes to the Individual Case Safety report (ICSR) Implementation Guide (IG) on the use of European Directorate for the Quality of Medicines & healthcare (EDQM) and Unified Code for Units of Measure (UCUM) lists, as well as discussion with the M2 EWG on the maintenance process for external terminologies.


Steps 3 and 4 of the annex to the ICSR IG on the use of EDQM lists and BFC document v2.03 are expected by May/June 2017.

22. M2 EWG: Electronic Standards for the Transfer of Regulatory Information

The Rapporteur will report on the outcome of the M2 EWG meeting held on May 29 - June 1, 2017 and the progress made towards developing the ICH project opportunities proposals, defining the maintenance process for external terminologies and evaluating existing ICH topics for technical opportunities.


23. M9 EWG: Biopharmaceutics Classification System-based Biowaivers

The Rapporteur will report on the outcome of the M9 EWG meeting held on May 29 - June 1, 2017 and progress made towards developing the M9 draft Technical Document on Biopharmaceutics Classification System-based Biowaivers.


Step 1 sign-off and Step 2a/b endorsements are expected by June 2018.

24. M10 EWG: Bioanalytical Method Validation

The Rapporteur will report on the outcome of the M10 EWG meeting held on May 29 - June 1, 2017 and progress made towards developing the M10 draftTechnical Document on Bioanalytical Method Validation.



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25. EWGs/IWGs/Discussion Groups Not Meeting in Montreal

S3A IWG: Q&As on Note for Guidance on Toxicokinetics

The ICH Coordinator from the Member who holds Rapporteurship will update the Assembly on the current activities of the S3A IWG and the progress made by the group analysing and addressing comments received on the draft Q&As from the public consultation.


S9 IWG: Q&As on Nonclinical Evaluation for Anticancer Pharmaceuticals

The ICH Coordinator from the Member who holds Rapporteurship will update the Assembly on the current activities of the S9 IWG and the progress made by the group analysing and addressing comments received on the draft Q&As from the public consultation.


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

The ICH Coordinator from the Member who holds Rapporteurship will update the Assembly on the current activities of the M7(R1) EWG including the finalisation of the M7(R1) Addendum.

The Assembly will note the rotation to a new Regulatory Rapporteur for the M7(R1) EWG in line with the SOP Annex #4 Maintenance Procedure prior to the next stage of work;

If Step 3 is reached ahead of Montreal, the Regulatory Members of the Assembly will be invited to take a decision to adopt Step 4 of the M7(R1) Addendum.

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

Q3C(R7) Maintenance EWG: Maintenance of the Guideline for Residual Solvents

The ICH Coordinator from the Member who holds Rapporteurship will update the Assembly on the current activities of the Q3C(R7) Maintenance EWG and the group’s recommendation on whether to undertake Q3C maintenance in relation to five new proposals received.

Based on a recommendation of the MC, the Assembly is invited to take a decision to endorse the maintenance work on any of the new proposals recommended for maintenance by the Q3C(R7) EWG;Step 1 sign-off and Step 2a/b endorsements are expected by Q1 2018.

Q3D(R1) Maintenance EWG: Maintenance of the Guideline for Elemental Impurities

The ICH Coordinator from the Member who holds Rapporteurship will update the Assembly on the current activities of the Q3D(R1) Maintenance EWG including the development of Permitted Daily Exposures and permitted concentrations of elemental impurities for products administered by the cutaneous and transdermal route for all 24 elements included in the ICH Q3D Guideline.

The Assembly is invited to take a decision to endorse the nomination of the new Regulatory Rapporteur for the Q3D(R1) Maintenance EWG (currently being led by an Acting Rapporteur) in line with the Assembly RoP 4.2.

Step 1 sign-off and Step 2a/b endorsements are expected by May 2018.

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

The ICH Coordinator from the Member who holds Rapporteurship will update the Assembly on the current activities of the E14/S7B DG to monitor the progress of the discussion of the Comprehensive in vitro Proarythmia Assessment (CiPA) Initiative.

E14/S7B DG recommendation on whether to reopen the E14 Guideline for a complete revision is expected by late 2017/early 2018.

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E18 EWG: Genomic Sampling and Management of Genomic Data

The ICH Coordinator from the Member who holds Rapporteurship will update the Assembly on the current activities of the E18 EWG and progress made towards updating the draft E18 Guideline.

The Assembly will be invited to take a decision to endorse the nomination of a new Rapporteur for the E18 EWG (currently being led by an Acting Rapporteur) in line with the Assembly RoP 4.2.

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

M1 PtC WG: MedDRA Points to Consider

The ICH Coordinator from the Member who holds Rapporteurship will update the Assembly on the current activities of the M1 PtC WG with respect to the updating with each MedDRA release of the two PtC documents on Term Selection and Data Retrieval and Presentation, as well as the development of a companion document to the PtC Documents.

The Assembly is invited to take a decision to endorse the nomination of a new Rapporteur for the M1 PtC WG (currently being led by an Acting Rapporteur) in line with the Assembly RoP 4.2.

M4Q(R1) (CTD-Quality) IWG: Addressing CTD-Q-Related Questions

The ICH Coordinator from the Member who holds Rapporteurship will update the Assembly on the MC decision to keep the M4Q(R1) IWG in a dormant state while the eCTD v4.0 Implementation Guide, including the Granularity document is currently being implemented in the ICH Regions and in case questions are raised.

M8 EWG/IWG: The Electronic Common Technical Document: eCTD

The ICH Coordinator from the Member who holds Rapporteurship will update the Assembly on the current activities of the M8 EWG/IWG including updating the eCTD v3.2.2 and v4.0 Q&As based on change requests received.

Step 3 sign-off and Step 4 adoption of the eCTD v3.2.2 Q&As and Specification Change Request Document v1.30 are expected by June 2017.

26. Organisation of Next Meetings The Assembly will receive an update on the organisation of next ICH meetings including 2018

selected dates and locations.

SUMMARY OF DECISIONS TAKEN IN MONTREAL ON MAY 31 & JUNE 1, 2017

PRESS RELEASE

The Assembly will be informed on the development and publication of the ICH Press Release for the Montreal meeting.

ANY OTHER BUSINESS

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MONTREAL, CANADA

1. 2016 Annual Report of the Association

The ICH MC will present to the Assembly the 2016 Annual Report of the Association developed by the ICH Secretariat with the input of the ICH MC and MedDRA MC.

Action:

The Assembly is invited to take a decision to approve the 2016 Annual Report and the discharge of the ICH MC, MedDRA MC and the ICH Secretariat for the activities undertaken by these bodies in 2016.

AGENDA ITEM 1

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2. Procedural Matters

Articles of Association

The Chair/Vice-Chair will inform the Assembly on amendments proposed to the Articles of Association which were last updated and approved by the Assembly in November 2016.


The Chair/Vice-Chair will inform the Assembly on amendments proposed to the Assembly Rules of Procedure (RoP) which were last updated and approved by the Assembly in Osaka in November 2016.


The ICH MC will inform the Assembly on updates discussed by the ICH MC to the Standard Operating Procedures for Expert Working Groups (EWGs) / Implementation Working Groups (IWGs).

IFPMA Role

The IFPMA will be invited to present an overview of its engagement in ICH and a process to facilitate the participation of IFPMA National Association experts in EWGs/IWGs.

Action:

The Assembly is invited to share its views.

Action:

The Assembly is invited to share its views on the report.

Action:

The Assembly is invited to take a decision to adopt the revised Assembly RoP.

Action:

The Assembly is invited to take a decision to adopt the revised Articles of Association.

AGENDA ITEM 2

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Chronicle:

EXTRACT FROM THE ASSEMBLY MEETING FINAL MINUTES, OSAKA, JAPAN, NOVEMBER 9 – 10, 2016:

ICH Articles of Association

The ICH Secretariat informed the Assembly on several minor amendments proposed to the ICH Articles of Association which were originally approved by the Founding Members at the Inaugural Assembly meeting in October 2015. The changes proposed were aimed at streamlining and smoothening the procedures, in order to maintain the efficiency of ICH’s harmonisation activities.

Decisions/Actions:

The Assembly approved the proposed changes to the ICH Articles of Association;

The revised ICH Articles of Association will be published on the ICH website.


The ICH Secretariat informed the Assembly on the amendments proposed to the Assembly Rules of Procedure (RoP) which were last updated and approved by the Assembly in June 2016. The Assembly noted that the latest amendments were made to reflect the changes made to the ICH Articles of Association, as well as for clarification and consistency. Included in the amendments was the introduction as an annex of an ICH Donation Policy.

Decisions/Actions:

The Assembly approved the proposed changes to the Assembly RoP;

The Revised Assembly RoP will be published on the ICH website.


The ICH Secretariat presented to the Assembly the v2.0 of the Standard Operating Procedures for Working Groups (WGs) approved by the ICH Management committee (MC) in Osaka.

Decisions/Actions:

The Assembly noted the proposed changes to the SOPs v1.0 for WGs and that the ICH MC approved the SOPs v2.0 for WGs at its meeting in Osaka, on November 8, 2016;

The SOPs v2.0 for WGs will be published on the ICH website.

MC Rules of Procedure

The ICH Secretariat presented to the Assembly the amendments proposed to the MC RoP which were last updated and approved by the MC in June 2016. The latest amendments included the addition of new procedures for: the organisation of ICH meetings; selection of new topics; and use of the ICH logo.

Decisions/Actions:

The Assembly noted the MC RoP that was adopted by the ICH MC at its meeting in Osaka, Japan on November 8, 2016;

The Assembly noted that the MC RoP will be published on the ICH website.

MedDRA MC Rules of Procedure

The Secretariat provided an update on the status of the development of the MedDRA MC’s RoP.

Decisions/Actions:

The Assembly noted the final version of the MedDRA MC RoP that was adopted by the MedDRA MC at its meeting in Osaka, Japan on November 5 – 6, 2016;

The Assembly noted that the MedDRA MC RoP will be published on the ICH website.

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3. Membership and Observership

The ICH MC will present to the Assembly its recommendation regarding Membership and Observership applications processed since the Osaka meeting in November 2016.

Chronicle:


The ICH MC presented to the Assembly an overview of applications for Membership/Observership processed since the Lisbon meeting in June 2016, and its recommendations on these applications. The Chair drew the attention to the high interest in ICH Observership on the part of international organisations referred to in Article 17(1)(d) of the Articles of Association and that while the expression of interest in ICH is positive, it would be important to ensure ICH expands in a manageable way. The Assembly acknowledged a need for reflection on alternative ways of interaction with ICH, as well as on the eligibility criteria for this category of Observer.

Decisions/Actions:

The Assembly approved in Osaka the following Observership applications on the basis of the recommendation of the MC:

The Active Pharmaceutical Ingredients Committee (APIC);

The Centro para el Control Estatal de Medicamentos, Equipos y Dispositivos Médicos (CECMED, Cuba);

The Medicines Control Council (MCC, South Africa);

The National Center for the Expertise of Drugs, Medical Devices and Equipment, (National Center, Kazakhstan).

The Assembly approved the following Membership applications on the basis of the recommendation of the MC:

The Agência Nacional de Vigilância Sanitária (ANVISA, Brazil);

The Biotechnology Innovation Organisation (BIO);

The Ministry of Food and Drug Safety (MFDS, Korea).

Action:

The Assembly is invited to take a decision regarding the applications for ICH Membership/Observership recommended by the MC.

AGENDA ITEM 3

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4. Financial Matters

The ICH MC will provide an update on ICH financial matters including; 2016 Financial Audit; 2016 costs; preparation of the 2018 ICH budget; multi-year budget planning; cash flow; and development of a proposal for a participation fee for non-membership fee paying ICH meeting participants.

Chronicle:


The ICH MC provided an update on ICH financial matters including: preparation of the 2017 ICH Budget; reflections regarding the level of the annual fee for new Members; development of a Donation Policy and recommendation of an auditing firm for appointment as ICH Auditors.

The ICH Secretariat provided an update on the preparation of the 2017 MedDRA Budget, including the 2017 MSSO MedDRA subscription fees.

Decisions/Actions:

The Assembly approved the 2017 ICH Budget;

The Assembly approved the annual fee for the ICH Membership Categories: Regulatory Members and Industry Members of CHF 20,000 for publication on the ICH website and confirmed agreement to a 2018 implementation. For administrative reasons the fees were rounded up to CHF 20,000. The Assembly noted that the different amounts of the annual membership fee for the new Members and for the Founding Members do not reflect the differences in their respective rights under the Articles of Association. The need to revise the annual membership fee for Regulatory and Industry Members will be assessed periodically depending on the budget situation and the number of members. Any future changes may be made with a view to making fees more proportional for all Members. As per the MC RoP #9.6, the rationale for any changes in the fee level for new members in the future should be communicated and explained at least 6 months before the Assembly decision;

Actions:

The Assembly is invited to share its views on the update and to take a decision to approve the 2018 ICH budget;

The Assembly is invited to take a decision to approve the 2016 audited accounts of the ICH Association.

AGENDA ITEM 4

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The Assembly approved the publication of the Donation Policy (adopted as part of the Assembly RoP, see Section 1 above) on the ICH website;

The Assembly agreed to appoint the auditing firm Moore Stephens Refidar SA, recommended by the MC, based on an assessment it made, as the ICH Auditors for an initial period of two years to audit the annual financial statements of the Association;

The Assembly approved the 2017 MedDRA Budget, which included the 2017 MSSO MedDRA Subscription fees.

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5. New ICH Topic Proposals & Strategic Discussions

New Topic Proposals

The ICH MC will present its recommendation on the prioritization of new ICH topic proposals which were submitted by Members before the mid-January 2017 deadline in line with the agreed process.


The ICH MC will update the Assembly on the response received from the public consultation on the GCP Renovation Reflection Paper published on the ICH website in January 2017 for a 60-day comment period, and will discuss next steps with the Assembly.

The ICH MC will update the Assembly on: the status of work by a feasibility group set-up after the November 2016 meeting to further consider the topic Compliance of Reliability for Electronic Records; a newly developed Quality Reflection Paper; and share with the Assembly any considerations regarding other strategic topics to progress.

Chronicle:


New Topic Proposals

The MC highlighted the overall status of ICH harmonisation activities on current ICH topics and the process agreed in Lisbon in June 2016 for the selection of new ICH topics.

The MC provided the Assembly with an update on its considerations since the Lisbon meeting in June 2016 of the new proposals on Safety Data Collection (proposed by FDA) and Adaptive Clinical Trials (proposed by PhRMA). The Assembly noted that for the former, an updated title was proposed in Osaka: Optimization of Safety Data Collection.

Action:

The Assembly is invited to provide its views on the update.

Action:

The Assembly is invited to provide its views and to take a decision to approve any new topics for ICH Guidelines recommended by the MC.

AGENDA ITEM 5

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Decisions/Actions:

The Assembly adopted the Concept Paper outline on Optimization of Safety Data Collection (code: ICH E19) and agreed on the establishment of an informal WG (with FDA nominated as Lead) to finalise the Concept Paper and develop a Business Plan ahead of the MC Teleconference to be held in spring 2017;

Once the final Concept Paper and the Business Plan will be approved by the MC, the informal WG will be transformed into an EWG, which is expected to meet at the June 2017 meeting in Montreal, Canada;

The Assembly acknowledged that MHLW/PMDA indicated it would only be able to take a position on sign-off at Step 1 of E19 after positive outcome of consultation with its stakeholders;

The ICH Secretariat will launch the nomination process amongst ICH Members and Observers for the establishment of the informal WG;

Further to Article 17(5) of the ICH Articles of Association, any ICH Observer interested to participate in the activities of this new WG would need to inform the ICH Secretariat in writing using the template available in the SOPs for WGs and provide explanations for their interest in the specific WG, information about their available expertise and how they would expect to contribute to the work of the WG;

Any request received by the ICH Secretariat, will be shared with the MC for approval;

The Assembly nominated FDA as the Rapporteur for the ICH E19 EWG;

The Founding Regulatory Members and the Standing Regulatory Members of the MC will confirm the respective Regulatory Chairmanship for the new EWG once established;

The Assembly noted that the new topic proposal on Adaptive Clinical Trials would undergo further revisions with a view to submitting a Concept Paper outline for consideration at the Montreal meeting. The MC at its meeting had supported that PhRMA revises the proposal to encompass a more limited scope, one that is less dependent on statistical considerations given the stated capacity concerns related to some active EWGs (e.g., E9). The revised proposal would be circulated to MC Members for their comments to the revision, with a timeline of submitting the updated proposal ahead of the Montreal meeting.


The Assembly discussed two topics, proposed by FDA and JPMA respectively, as potential strategic topics: “GCP Renovation”: Modernization of ICH E8 and Subsequent Renovation of ICH E6; and Compliance of Reliability for Electronic Records, and confirmed support for the next steps from this discussion.

Decisions/Actions:

The Assembly supported that the Reflection Paper on GCP Renovation, once updated based on comments received, will be published on the ICH website in January 2017 as an ICH Reflection Paper for a comment period of 2 months;

The Assembly noted a feasibility group will be set up to further consider the Reflection Paper on Compliance of Reliability for Electronic Records ahead of the June 2017 meeting in Montreal, Canada.

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6. Communication


The ICH MC will provide an update on current communication activities including development of a transparency policy and stakeholder engagement plan, as well as recent updates to the ICH website.


Chronicle:



The MC provided an update on current communication activities including development of: a general slide deck on ICH; a transparency policy; and stakeholder engagement plan.

The Assembly Members and Observers were encouraged to make use of the general slide deck on ICH in their communication about ICH activities, including translating the slide deck into their national language, and noted that the presentation was available on the ICH website. The Assembly also noted other recent updates to the ICH website which included publication of MC meeting minutes/summary reports, and the SOPs for WGs.

Decision/Action:

The Assembly noted the new ICH Member logo available from the ICH Secretariat for use by ICH Members to denote ICH Membership within their own publications, presentations or on their website, and that a disclaimer would need to be signed beforehand.

Action:

The Assembly is invited to share information on any ICH Regional Public Meetings

in their respective regions prior to/following the ICH meeting in Montreal in

May/June 2017.

Action:


AGENDA ITEM 6

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The Assembly was invited to share information on any ICH Regional Public Meetings in their respective regions prior to/following the ICH meeting in Osaka.

The Assembly noted the organisation of a joint FDA/Health Canada public meeting held in Ottawa, Canada on October 24, 2016, to which participants were also able to participate by webcast.

The Assembly was also informed about the organisation of an ICH/DIA Joint Workshop to be held in Tokyo on November 12, 2016 which would present on the recent ICH reform and share the major outcomes of the ICH Osaka meeting.

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7. Training

The ICH MC will update the Assembly on the progress of the pilot supported in Osaka in

November 2016 for the Training Subcommittee to partner with a small group of training

providers.

Chronicle:


ICH Training Strategy

The MC presented to the Assembly on the development of an ICH Training Strategy.

The Assembly noted that work had been undertaken on the following different items:

Criteria for Topic Selection for Training;

Coordination with Trusted Providers;

Training Approaches;

Resource Implications;

The Assembly noted that in Osaka the MC had endorsed:

A list of training modalities and which methods might work best for certain topics, criteria for training approaches, and various techniques and tools;

A slide template for ICH WGs to use when developing presentations;

A “Best Practices” document that has tips for drafting ICH slide presentations;

That the Training Strategy Subcommittee becomes a Standing Committee: “Training Subcommittee”;

Partnership with a small group of trusted training providers;

The Standing Committee to define roles & responsibilities of parties;

The Standing Committee to define expectations of each party (ex: use of ICH logo; post training avail on ICH Website, etc);

Draft short agreement/Terms of References (ToR);

Action:


AGENDA ITEM 7

11

Pilot for 12 months;

Evaluation and reporting back.

The Assembly also noted the encouragement for the Observers to fill the survey proposed by the Subcommittee and that the results would be updated accordingly.

APEC Harmonization Center (AHC) Training Programme

The Assembly congratulated the AHC on: progress made in the development of the pilot programme on the 6 ICH E2 Guidelines in collaboration with ICH; the future Q8, Q9, Q10 training programs planned for 2017 and the translation in English, Spanish and Korean.

The AHC will continue discussing with the MC regarding the development of training materials.

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MONTREAL, CANADA

8. Update on MedDRA

The MedDRA MC Chair or Chair’s delegate will provide a report on current MedDRA activities. The report will include an update on:

o Development of a patient friendly list of MedDRA terms;

o Training in ICH regions and beyond;

o Assisting Regulatory Authorities interested in using MedDRA in their regions;

o Tools to facilitate MedDRA’s use.

Chronicle:


The Assembly received a report on the ICH MedDRA Management Board/Management Committee (MB/MC) meeting held on 5 – 6 November 2016. The Assembly noted while the MedDRA MC had been established in April 2016, until MedDRA is transferred to the new ICH Association, the MedDRA MB will remain operational and the MedDRA MC will only have responsibilities for MedDRA issues which pertain to the new ICH Association.

The report covered the following matters: 2017 subscription rates; training; tools to facilitate MedDRA’s use including the development of an Unqualified Test Name term list; a new Concept Paper developed by the M1 Point to Consider (PtC) WG; and development of Standardised MedDRA Queries (SMQs) including status of SMQ development and collaboration with the Council for International Organizations of Medical Sciences (CIOMS) and the renewal of the Memorandum of Understanding (MoU) between CIOMS and ICH.

The Assembly was informed of the MedDRA MB/MC’s decision to give a reduction in the 2017 Subscription rates, based on the continued growth of MedDRA subscribers throughout the world – currently numbering over 4,500 organisations – and increased efficiencies to contain costs of maintenance and development of MedDRA.

The Assembly also noted the importance of training in helping to facilitate the use of MedDRA and that the MSSO provides free training to Regulators and other MedDRA users as part of their MedDRA subscription package, with training available in several forms: face-to-face training;

Action:

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

AGENDA ITEM 8

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webinars; and e-learning tools/videocasts. The Assembly heard that by the end of 2016 the MSSO will have had conducted a total of 101 training courses which include 70 face-to-face training classes and 31 webinars. It was noted that a similar scale of training is planned for 2017, with all training offerings advertised on the website www.meddra.org.

The Assembly was also informed of the release of a new Unqualified test name term list approved for development by the MedDRA MB in June 2016 which is intended for use in the E2B test name field and as recommendation only to report adverse events. The list and an explanatory document are available under Related Links on the Support Documentation page on the MedDRA website.

The Assembly also noted the work of the ICH M1 (PtC) WG in facilitating MedDRA’s global uptake. The WG has developed condensed versions of the PtC documents for translation into all MedDRA languages (except English and Japanese versions which will remain in full) to support the implementation and use of MedDRA worldwide. These condensed documents will be made available to MedDRA users in 2017. The Assembly was also updated on the WG’s new Concept Paper to develop a companion document to the PtC documents, to be available in English and Japanese, which would provide more detailed guidance, examples, and “Questions and Answers” on topics of regulatory importance such as data quality, medication errors, and product quality issues.

The Assembly was also updated on ICH’s work with the Council for International Organizations of Medical Sciences (CIOMS) to develop Standardised MedDRA Queries (SMQs). In Osaka, the MedDRA MB acknowledged the significant contributions of the CIOMS SMQ WG and the development to-date of 101 SMQs, as well as 1 new SMQ and four new levels 4 SMQs to go into production in v20.0. In addition, the MedDRA MB also congratulated CIOMS for its work on the second edition of the CIOMS SMQ WG’s book on Development and Rational Use of Standardised MedDRA Queries, which was published on the CIOMS website in August 2016. Furthermore, the MedDRA MB renewed the MoU with CIOMS between ICH and CIOMS for a further year of development of new SMQs.

Decision/Action:

The Assembly noted the decisions taken by the MedDRA MB/MC.

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http://www.meddra.org/

http://www.meddra.org/how-to-use/support-documentation

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9. General Operational Matters

The ICH MC will update the Assembly on general operational matters including:

Status of transfer of assets of the former ICH (International Conference on

Harmonisation) from IFPMA to the new ICH Association;

Considerations on future ICH meeting organisation in view of the expansion of ICH

Membership and Observership;

Discussion with IPRF regarding the future provision of secretariat support;

Organisation of elections at the next Assembly meeting in Geneva, Switzerland in

November 2017 for the election of the next Assembly Chair and Vice Chair, as well as

the election of Elected MC Representatives.

Action:


AGENDA ITEM 9

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MONTREAL, CANADA

10. Implementation of ICH Guidelines

The ICH MC will present the table developed by the ICH Secretariat to facilitate monitoring by the Assembly of the status of ICH Guideline implementation by ICH Regulatory Members.

Chronicle:


The Assembly noted that as per the Assembly RoP, there should be a process for the Assembly to monitor the progress of international harmonisation and coordinate efforts in this regard. Following the invitation to provide updates, several regulators informed the Assembly on the status of implementation of ICH Guidelines in their respective countries and regions.

The Assembly noted that in addition to providing the updates on the status of implementation of ICH Guidelines, this standing agenda item provides an opportunity for the Regulators to share their experience, explain challenges and how to overcome them; and develop good practice relating to the implementation of ICH Guidelines. The attention was also drawn to the fact that the Rules of Procedures (part 1.1.3) of the Assembly includes some provisions regarding the meaning of implementation.

The Assembly was informed on the development of a table regarding the implementation of ICH Guidelines by all Regulatory Members. This table, which will be maintained by the ICH Secretariat on the basis of input from the Regulatory Members, will be presented at each Assembly meeting as it allows to follow and share the status of ICH Guideline implementation by ICH Regulatory Members.

Action:

The Assembly is invited to note the implementation of ICH Guidelines by ICH Regulatory Members and share views on the status of implementation across the ICH Member Regions.

AGENDA ITEM 10

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MONTREAL, CANADA

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 of Expert/Implementation Working Group (EWG/IWG) meetings.

This is intended to assist the Assembly in setting a timetable for reports on the ICH Topics under Agenda items 12 to 24, and also to act as a background paper for that discussion:

ICH Topics: Status of EWG/IWG Activities:

S1(R1) EWG: Revision of the Rodent Carcinogenicity Studies for Human Pharmaceuticals.

The S1(R1) EWG continues its collection and review of confidential Carcinogenicity Assessment Documents (CADs) and the review of carcinogenicity study summaries submitted to the DRAs since January 2016.

Steps 1 and 2a/b are expected by June/November 2019.

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

The S5(R3) EWG addresses feedback received from the EWG Member constituencies on a preliminary draft and works on the draft Technical Document.

Steps 1 and 2a/b are expected by May/June 2017.

S11 EWG: Nonclinical Safety Testing in

Support of Development of Paediatric

Medicines.

The S11 EWG continues its data collection activities and works to develop the draft Technical Document.

Steps 1 and 2a/b are expected by November 2017.

Q11 IWG: Q&As on Selection and

Justification of Starting Materials for the

Manufacture of Drug Substances.

The Q11 IWG addresses comments received from regional public consultation completed in April 2017.

Steps 3 and 4 are expected by November 2017.

Q12 EWG: Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management.

The Q12 EWG continues its work on the draft Technical Document. Rapporteurship will have to rotate to a Regulatory Member and be approved by the ICH Assembly in Montreal, if the group reaches Steps 1 and 2a/b.

Steps 1 and 2a/b are expected by May/June 2017.

AGENDA ITEM 11

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ICH Topics: Status of EWG/IWG Activities:

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

The E9(R1) EWG addresses feedback received from the EWG Members constituencies on a preliminary draft and works on the draft Technical Document.

Steps 1 and 2a/b are expected by November 2017.

E11(R1) EWG: Addendum to Paediatric Drug Development.

The E11(R1) EWG addresses comments received from regional public consultation completed in April 2017.

Steps 3 and 4 are expected electronically by November 2017.

E17 EWG: Multi-Regional Clinical Trials.

The E17 EWG addresses comments received from regional public consultation completed in January 2017.


E19 informal WG: Optimization of Safety Data Collection.

The E19 informal WG continues its work on the finalisation of the Concept Paper and the Business Plan.

Approval of the Concept Paper and Business Plan by the MC are expected at the Montreal meeting in May/June 2017.

E2B(R3) EWG/IWG: Revision of the

Electronic Submission of Individual Case

Safety Reports.

The E2B(R3) EWG/IWG continues its work on items including developing the annexes to the ICSR Implementation Guide (IG) on the use of EDQM (European Directorate for the Quality of Medicines & healthcare) and UCUM (Unified Code for Units of Measure) lists; and discussion with the M2 EWG on the maintenance process for external terminologies.

Steps 3 and 4 of the annex to the ICSR IG on the use of EDQM lists and BFC document v2.03 are expected by May/June 2017.

M2 EWG: Electronic Standards for the Transfer of Regulatory Information.

The M2 EWG continues its activities including developing the ICH project opportunities proposals, defining the maintenance process for external terminologies and evaluating existing ICH topics for technical opportunities.

M9 EWG: Biopharmaceutics Classification System-based Biowaivers.

The M9 EWG continues its work on the development of the draft Technical Document.

Steps 1 and 2a/b are expected by June 2018.

M10 EWG: Bioanalytical Method Validation.

The M10 EWG continues its work on the development of the draft Technical Document.

Steps 1 and 2a/b are expected by June 2018.

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Under Agenda item 25, the Assembly will be invited to raise any issues regarding groups not meeting in Montreal. The following is intended to assist the Assembly with this discussion:

ICH Topics: Status of EWG/IWG/Discussion Group (DG)

Activities:

S3A IWG: Q&As on Note for Guidance on Toxicokinetics.

The S3A IWG addresses comments received from regional public consultation completed in December 2016.


S9 IWG: Q&As on Nonclinical Evaluation for Anticancer Pharmaceuticals.

The S9 IWG addresses comments received from regional public consultation completed in January 2017.


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

The M7(R1) EWG has finalised its work on the Addendum which has reached Step 3 electronically in May 2017.

A rotation in the Rapporteurship is expected prior to the next stage of work, and will be for ICH Assembly approval at the Montreal meeting, Canada, in May/June 2017.

Step 4 adoption is expected by May/June 2017.

Q3C(R7) Maintenance EWG:

Maintenance of the Guideline for

Residual Solvents.

The Q3C(R7) Maintenance EWG assesses 5 new proposals.

As per the corresponding Procedure (SOP v2.0 Annex #4), the Q3C(R7) Maintenance EWG should make a recommendation to the MC ahead of the Montreal meeting, after which the MC should make a recommendation to the ICH Assembly for endorsement for the EWG to undertake the maintenance work at the Montreal meeting.

Steps 1 and 2a/b are expected by Q1 2018.

Q3D(R1) Maintenance EWG:

Maintenance of the Guideline for

Elemental Impurities.

The Q3D(R1) Maintenance EWG continues its work on the development of Permitted Daily Exposure levels and permitted concentrations of elemental impurities, for products administered by the cutaneous and transdermal route of administration, for all 24 elements in the ICH Q3D Guideline.

The nomination of the new Rapporteur from FDA will be for ICH Assembly approval at the Montreal meeting, Canada, in May/June 2017.

Steps 1 and 2a/b are expected by May 2018.

E14/S7B DG: The Clinical Evaluation of

QT/QTc Interval Prolongation and

Proarrhythmic Potential for Non-

Antiarrhythmic Drugs.

The E14/S7B DG continues its work and the monitoring of the CiPA (Comprehensive in vitro Proarrhythmia Assessment) Initiative.


19

ICH Topics: Status of EWG/IWG/Discussion Group (DG)

Activities:

E18 EWG: Genomic Sampling and

Management of Genomic Data.

The E18 EWG continues its work on the draft E18 Guideline.

The nomination of the new Rapporteur from FDA will be for ICH Assembly approval at the Montreal meeting, Canada, in May/June 2017.

Steps 3 and 4 are expected by June 2017.

M1 PtC WG: MedDRA Points to Consider.

M1 PtC WG continues its work including: the updating with each MedDRA release of the two PtC documents on Term Selection and Data Retrieval and Presentation, as well as the development of a companion document to the PtC documents.

The nomination of the new Rapporteur from EFPIA will be for ICH Assembly approval at the Montreal meeting, Canada, in May/June 2017.

M4Q(R1) IWG: Addressing CTD-Q

Related Questions raised by eCTD.

The M4Q(R1) IWG is in a dormant state while the eCTD v4.0 Implementation Guide, including the Granularity document is currently being implemented in the ICH Regions and in case questions are raised.

M8 EWG/IWG: The electronic common

technical document: eCTD.

The M8 EWG/IWG continues its activities including: updating the eCTD v3.2.2 and v4.0 Q&As based on the change requests received, and support documentations.

Steps 3 and 4 of the eCTD v3.2.2 Q&As and STF style sheet file are expected by June 2017.

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MONTREAL, CANADA


12. S1(R1) EWG: Revision of the Rodent Carcinogenicity Studies for Human Pharmaceuticals Guideline

The Rapporteur will report on the outcome of the S1(R1) EWG meeting held on May 29 - June 1, 2017 including progress made towards the collection and review of confidential submissions of Carcinogenicity Assessment Documents (CADs) and summary report submissions by sponsors to DRAs within each region.

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

Background Document:

S1(R1) EWG work plan, dated February 3, 2017.

Chronicle:


The S1 EWG did not meet in Osaka.

The Assembly noted the current activities of the S1 EWG including the progress made towards the collection and review of confidential submissions of Carcinogenicity Assessment Documents (CADs) and summary report submissions by sponsors to Drug Regulatory Authorities (DRAs) within each region and considerations regarding the timeframe for drafting the S1 Technical document. A CAD addresses the carcinogenic potential of an investigational pharmaceutical and predicts the outcome and value of the planned 2 year rat carcinogenicity study, and based on the level of certainty a company is expected to indicate the need for such a study or to claim a (virtual) waiver. The predicted value and outcome of the 2 year rat study in the CADs will be then checked against the actual value and outcome of the 2 year rat studies as they are completed and reported to the DRAs.

The Assembly noted that the ICH S1 document is expected to reach Step 1 and Step 2a/b in June or November 2019.

Decision/Action:

The S1 EWG will provide a work plan to the MC ahead of its teleconference to be held in spring 2017 for activities to be undertaken by the EWG.

Action:

The Assembly is invited to provide its views on the report;

AGENDA ITEM 12

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ICH S1 EWG Interim Work Plan Update

3 February 2017

Topic Adopted: May 2012

Last Face-to-Face Meeting: Jacksonville, FL, USA – December 2015

1. Anticipated Milestones

Completion Date Deliverable

June or November 2019 Step 2 Guideline

June or November 2020 Step 4 Guideline

2. Timelines

Date Task / Activity Details

August 2016 - June 2017

EWG members to meet every other month by teleconference.

Regulatory members to meet periodically to discuss all new Carcinogenicity Assessment Document (CAD) submissions and all new Final Summary Report submissions (FSRs).

EWG to review progress, feedback, on CAD submissions and align on plans for meeting face-to-face in June 2017 to review regulatory member conclusions from all FSRs received and reviewed by June 2017; and to review Drug Regulatory Authorities (DRA) conclusions on all new CAD submissions following the January 2016 RND revisions posting.

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MONTREAL, CANADA


13. S5(R3) EWG: Revision of Detection of Toxicity to Reproduction for Medicinal Products and Toxicity to Male Fertility

The Rapporteur will report on the outcome of the S5(R3) EWG meeting held on May 28 - June 1, 2017, addressing feedback received from the EWG Member constituencies on a preliminary draft and progress made towards reaching Step 1 in Montreal of the S5(R3) Technical Document on Revision on Detection of Toxicity to Reproduction for Medicinal Products and Toxicity to Male Fertility.



S5(R3) EWG work plan, dated February 21, 2017.

Chronicle:


The Acting Rapporteur reported on the outcome of the S5(R3) EWG meeting held on November 6-10, 2016 and progress made towards revising the ICH S5(R2) Guideline on Detection of Toxicity to Reproduction for Medicinal Products and Toxicity to Male Fertility.

The Assembly noted that the S5(R3) EWG aims to finalise a Step 1 document in Q2 2017.

Decisions/Actions:

The Assembly supported that the S5(R3) EWG consult EWG Member constituencies on a preliminary draft in Q1 2017 with feedback received to be considered ahead of the spring ICH meeting, where the group aims to perform line by line revision of the text;

The Assembly endorsed the nomination of the new Rapporteur;

The Assembly endorsed the work plan of the S5(R3) EWG for activities to be undertaken.

Actions:


If Step 1 of the Technical Document is signed-off by the S5(R3) EWG, the

Assembly will be invited to take a decision to endorse Step 2a of the S5(R3)

Technical Document, following which the Regulatory Members of the Assembly

will be invited to endorse Step 2b of the S5(R3) draft Guideline.

AGENDA ITEM 13

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ICH S5(R3) EWG Work Plan

21 February 2017

Topic Adopted: April 2014

Last Face-to-Face Meeting: Osaka, Japan – November 2016



4Q 2016-2Q 2017 Continuation of work on ICH S5(R3) via monthly TCs in line with the remaining action items and to review input from stakeholders on issues that must be addressed before moving to Step 1 Technical Document.

June 2017 Face-to-face meeting of the ICH S5(R3) EWG to work on Step 1 Technical Document by integration of feedback from constituencies and agreement on content

2. Timelines


2-6 June 2014 ICH S5 Informal WG meeting in Minneapolis, US

Discussion on the topic and agreement within IWG about concept-paper. Post-hoc discussion about the further process.

10-13 November 2014

ICH S5 Informal WG meeting in Lisbon, Portugal

Re-discussion on the topic and agreement within IWG about revised concept-paper and way forward.

Definition of work packages for revision ICH S5(R2).

2Q 2015 ICH S5(R3) EWG Telecons

Initiation of work on ICH S5(R3) in line with the identified work packages.

8-11 June 2015 ICH S5(R3) EWG meeting in Fukuoka, Japan

Discussion on progress regarding the different work packages; including the drafting of new or revising of existing wordings in order to work towards a Step 1 document.

Specific discussion on the scope, criteria for dose selection, criteria for species selection, basic principles for possible regulatory acceptance of in vitro, ex vivo and non-mammalian in vivo (e.g. zebrafish) EFD assays, design of optional integrated testing strategies for EFD testing, combinations of in vivo

24

study options for reproductive toxicity testing.

24 September, 23 October, 17 November 2015

ICH S5(R3) EWG Teleconferences

Continuation of work on ICH S5(R3) in line with the identified work packages.

7-10 December 2015

ICH S5(R3) EWG meeting in Jacksonville, US

Discussion on progress regarding the different work packages; including the drafting of new or revising of existing wordings in order to work towards a Step 1 document.

1-2Q 2016 ICH S5(R3) EWG Teleconferences: multiple regional, 3 regulators only and 4 full EWG TCs

Continuation of work on ICH S5(R3) in line with the identified work packages, drafting a new structure for guidance.

12-16 June 2016 ICH S5(R3) EWG meeting in Lisbon

Identified gaps and completed text for all sections; Compilation of a draft list of reference compounds; Work on concepts of qualification criteria and data review and discussion on exposure multiple for high dose selection, placental transfer and lactational exposure; mature options for deferral strategies for EFD testing;

Reiteration of controversial issues around the design of the reduced EFD study(ies), fetal morphological variations and harmonization of assay qualification for regulatory acceptance; Assignment of topics to craft wording and provide proposals;

3-4Q 2016 ICH S5(R3) EWG Teleconferences

Continuation of work on ICH S5(R3) in line with the assigned topics to mature text.

6-10 Nov 2016 ICH S5(R3) EWG meeting in Osaka

Continuation of review of the drafted document, adapting the structure of the document including reorganization of the TOC

Harmonization of text based on regional proposals in the body of the guidance with agreement on general principles

Addressing disagreements and concerns

31 January 2017 ICH S5(R3) EWG Teleconference

Agreement on a technical document ready to be shared with constituents by mid-February 2017

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November 2016

– June 2017

Continue EWG discussion

and meetings

EWG teleconference meetings to review input from ICH parties and stakeholders on issues that must be addressed before moving to Step 1 Technical Document

3Q 2017 Step 1 document Making use of the Face–to-face meeting to finalize Step 1 Technical Document

3Q 2019 Step 4 document Face-to-face meeting to finalize Step 3 and Step 4 document

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14. S11 EWG: Nonclinical Safety Testing in Support of Development of Paediatric Medicines

The Rapporteur will report on the outcome of the S11 EWG meeting held on May 29 - June 1,

2017, work to complete the data collection activities and progress made to develop the S11

draft Technical Document on Nonclinical Safety Testing in Support of Development of

Paediatric Medicines.



S11 EWG work plan, dated February 6, 2017.

Chronicle:


The Rapporteur reported on the outcome of the S11 EWG meeting held on November 6-9, 2016, and progress made towards developing the draft S11 Guideline on Nonclinical Safety Testing in Support of Pediatric Drug Development. The Assembly suggested the need for additional detail and specificity in the current draft text. The Assembly recommended the S11 EWG take on a more detailed work plan following the Osaka meeting, including additional teleconferences to develop further specificity. Additionally, the Assembly noted the need to submit a revised work plan and timeline for reaching Steps 2a/b and Step 4 for the MC’s consideration.

Decision/Action:

The S11 EWG will provide a revised work plan to the MC ahead of the MC teleconference to be held in spring 2017 for activities to be undertaken by the EWG.

Action:


AGENDA ITEM 14

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ICH S11 EWG Work Plan

6 February 2017

Topic Adopted: November 2014




November 2017 Step 2b Guideline

June 2019 Step 4 Guideline

2. Timelines


Dec 2016 – May 2017

Teleconferences Teleconferences of the EWG or subgroups as needed to accomplish objectives.

Dec 2016 – May 2017

Drafting and revision of guidance sections 2, 3 and 4.

Revision of text to focus on providing guidance to the reader. Each section to be discussed in a separate teleconference.

Dec 2016 – May 2017

Development of examples/case studies to illustrate how the guidance is used.

S11 parties will provide examples of projects where the text of the guidance can be applied and tested for comprehension and utility.

May 2017 Additional work on data analysis and presentation of results at Montreal meeting.

EU oncology analysis should be completed; EU CNS analysis update will be presented;

PhRMA survey update will be presented.

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15. Q11 IWG: Q&As on Selection and Justification of Starting Materials for the Manufacture of Drug Substances

The Rapporteur will report on the outcome of the Q11 IWG meeting held on May 29 - June 1,

2017 and progress made to address comments on the draft Q&As document received during the

regional public consultation that ended in April, 2017.



Q11 IWG work plan, dated March 24, 2017.

Chronicle:


The Q11 IWG did not meet in Osaka.

The Assembly was given an update on the status of the Q11 IWG activities, including the completion of the Step 1 expert sign-off of the Q&A document on Selection and Justification of API Starting Materials.

The Assembly noted the recommendation from the Q11 IWG on a timeframe of approximately 1-3 months for public consultation in each region.

Decisions/Actions:

The Q11 Experts signed-off Step 1 of the Q11 Q&As (via written postal procedure) in advance of the Assembly meeting;

The Assembly Members endorsed Step 2a of the Q11 Q&As; The Regulatory Members of the Assembly endorsed Step 2b of the Q11 Q&As; The Assembly endorsed the nomination of the new Rapporteur; The Q11 IWG will provide a work plan to the MC ahead of its teleconference to be held in spring

2017 for activities to be undertaken.

Action:


AGENDA ITEM 15

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ICH Q11 IWG Work Plan

24 March 2017


Last Face-to-Face Meeting: Lisbon, Portugal - June 2016



November 2017 Step 4 Q&A document

2. Timelines


June 13-16, 2016 Face-to-face meeting (Lisbon, Portugal)

Completed a draft Q&A document for Constituent review

June 20, 2016 -August 15, 2016

Constituent review of draft Q&A document

Constituency review with a template for providing and collating comments

August 15, 2016 - October 13, 2016

IWG review of comments and updating of Q&A document

Applied the previously used Regional team approach to advance work (e.g., IWG representatives worked in Regional clusters). Distributed questions based on relevance and source of the feedback received

Regional teams reviewed the feedback and developed updated wording for the assigned Q&As

IWG increased the frequency of teleconference calls (initially at every 2 weeks, October was weekly)

Assessed and edited all Q&As based on constituents feedback

October 27, 2016 Sign off of Step 1 document The full IWG (experts of all Members, Observers, and Other Participants) signed off the Step 1 document.

November 2016 Deliver a consensus Step 1 document to ICH Assembly/MC

Received endorsement by the ICH Assembly/MC during Osaka meeting for proceeding to Step 2a/2b

December 2016 to April 2017

Public consultation on the Step 2b document

(start of Step 3 in ICH process)

Public consultations timelines (close date): o ANVISA: 16 Feb o MHLW/PMDA: 12 March o ICH: 15 March

30

o EU: 15 March o HC: 15 March o Swissmedic: 15 March o FDA: 23 March o MFDS: 13 April

April/May 2017 Regional review and prioritisation of comments received in public consultation. Sharing the output of regional review with IWG.

IWG Telecons scheduled through April & May

Parties in each region to convene in order to review the comments received from the consultation using a common template.

To conduct a first review of comments and prioritise for discussion in full IWG.

All comments to be retained for transparency. Regions will share the output of the reviews

with the IWG by 15 May.

May/June 2017 Face to face meeting (Montreal)

F2F meeting (see Section 4) to discuss and live edit the document based on public comments and regional review.

Goal to reach pre-Step 4 document for final constituency review.

October 2017 Finalisation of the Question & Answer Document

IWG to meet by tele/web-conference to consider any significant comments arising from constituency review.

IWG to have reached agreement on the Step 3 Experts Draft Guideline for sign off by experts.

November 2017

Step 4 Targeting a Step 4 document

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16. Q12 EWG: ICH Guideline on Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management

The Rapporteur will report on the outcome of the Q12 EWG meeting held on May 28 - June 1, 2017 and progress made towards reaching Step 1 in Montreal of the Q12 Technical Document on Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management.



Q12 EWG work plan, dated March 7, 2017.

Chronicle:


The Rapporteur reported on the outcome of the Q12 EWG meeting held on November 5-9, 2016, and progress made towards developing the draft Q12 Technical document on Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management. The Assembly noted the EWG’s progress made in Osaka in the development of all Q12 chapters including, Established Conditions, Post Approval Change Management Protocols, Product Lifecycle Management Strategy, Effective Pharmaceutical Quality System (Change Management), categorisation of change and data

Actions:


If Step 1 of the Technical Document is signed-off by the Q12 EWG, the Assembly

will be invited to take a decision to endorse Step 2a of the Q12 Technical

Document, following which the Regulatory Members of the Assembly will be

invited to endorse Step 2b of the Q12 draft Guideline;

The Assembly is invited to take a decision to endorse the nomination of a new

Regulatory Rapporteur for the Q12 EWG in line with the SOP 1.5.2.2.

AGENDA ITEM 16

32

requirements, and the application of Q12 for currently marketed products and lifecycle management plan.

The Assembly noted the Q12 EWG’s request for an interim meeting in April 2017 to continue progress on finalising the Step 1 document in order to reach Step 1 and Step 2a/b in June 2017.

Decisions/Actions:

The Assembly supported an interim meeting of the Q12 EWG in April 2017 dependent upon subsequent approval by the MC;

The Q12 EWG will provide a revised work plan to the MC ahead of the MC teleconference to be held in spring 2017 for activities to be undertaken by the EWG.

33

ICH Q12 EWG Work Plan

7 March 2017

Topic Adopted: September 2014




November 2016 – April 2017

Share ICH Q12 version 7 with constituents. 2 EWG meetings, via teleconference to review and finalize examples, and prepare for interim meeting.

April 2017 Interim Meeting

Interim face meeting of EWG, April 4-7, to review comments, identify and resolve major issues and prepare v8.0 for May/June face-to-face meeting.

May/June 2017 5-day face–to-face meeting to finalize Step 1 Technical Document

2. Timelines


September 2014 – November 2014

Step 1: Consensus building, reviewing concept paper and business plan, and drafting the agenda for Lisbon meeting

EWG continued regular interactions by email

November 2014 – June 2015

Continue EWG discussion and meetings

The EWG will meet, via teleconference, four times between January and May, 2015, to develop initial draft of guideline chapters, and to prepare for June Meeting:

Three sub-teams will be established to prepare proposals for consideration by the entire EWG

January 21, 2015, EWG teleconference to identify key topics for guideline and agree on an integrated approach for the guideline (Progress Report)

February 23, 2015, EWG teleconference to identify key elements of each chapter and agree on outline (Outline of Guideline) and initiate drafting of core guideline chapters

March 31, EWG Teleconference to discuss key issues and agreement on ‘bullet points’ content of guideline chapters, provide

34

instructions to drafting teams to convert ‘bullet points’ to text, and to review EWG workplan (First Chapter Draft – Bullet points)

May 13, 2015, EWG teleconference to review draft of document, identify major challenges and prepare for June ICH Face to face meeting (Chapters Draft)

June 2015 EWG face-to-face meeting EWG will meet face-to-face in June 2015, to address major challenges, develop guideline version 1 and agree on future milestones and timelines

June 2015 – December 2015


The EWG will meet, via teleconference, four times between June and December 2015 to review version 1, discuss major issues to produce updated Q12 Technical Document, and to prepare for December Meeting:

Three sub-teams will continue to draft sections for consideration by the entire EWG

July 8, 2015, EWG teleconference to review Fukuoka progress and identified challenges and agree plan to address

September 9, 2015, EWG teleconference to review drafting teams materials, discuss common issues among drafting teams and address disagreements and concerns:

October 14, EWG Teleconference to review version 2 Technical document

November 19, 2015, EWG Teleconference to review version 2 and agree on agenda for face-to-face meeting in December

December 2015 EWG Face-to-face meeting Face-to-face meeting to review updated Q12 Technical Document and address disagreements and concerns.

December 2015 – June 2016


Four EWG meetings, via Teleconference, to assess progress on major issues, revise current draft, and produce Q12 Technical Document version 4

Interim informal 2 day meeting of the established conditions team April 6-8, 2016

April 6-8, 2016 Interim Face-to-Face Meeting of Established Conditions (EC) Team

Face-to-face meeting of EC team to advance the development of EC section. EC section is a pre-requisite for enabling further development of other Q12 elements including lifecycle management plans, expectations for life cycle approaches in managing to legacy (currently marketed)

35

products and overall role of the PQS

June 2016 EWG face-to-face meeting 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


Five EWG meetings, via Teleconference, to assess progress on major issues, revise current draft, and produce Q12 Technical Document version 6

November 2016 EWG face-to-face meeting 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 ICH parties and stakeholders

November 2016 – June 2017


Two EWG meetings, via Teleconference, to review input from ICH parties and stakeholders on issues that must be addressed before moving to Step 1 Technical Document

April 2017 Interim face-to-face meeting of EWG

Interim 4-day meeting of EWG week of 3 April 2017 to address comments on v7.0 and prepare v8.0 for May/June face-to-face meeting.

May/June 2017 EWG face-to-face meeting Face–to-face meeting to finalize Step 1 and Step 2a/b Technical Document

June 2017 – June 2018


Receive Step 2a/b document comments, triage, and address significant issues

June 2018 EWG face-to-face meeting Face–to-face meeting to finalize Step 4 document

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ICH2017/04


May 31 & June 1, 2017

MONTREAL, CANADA


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

The Rapporteur will report on the outcome of the E9(R1) EWG meeting held on May 29 - June 1, 2017 and progress made towards developing the E9 draft Technical Document on Defining the Appropriate Estimand for a Clinical Trial/Sensitivity Analyses.



E9(R1) EWG work plan, dated February 17, 2017.

Chronicle:


The Rapporteur reported on the outcome of the E9(R1) EWG meeting held on November 4-8, 2016 and progress made towards developing the draft E9 Addendum on Defining the Appropriate Estimand for a Clinical Trial/Sensitivity Analyses.

Decisions/Actions:

The Assembly supported that the E9(R1) EWG performs internal EWG Member consultation on the draft currently being developed ahead of the spring ICH meeting based upon which the E9(R1) EWG will make a proposal on whether non-statisticians will need to support the group in reviewing the draft technical document ahead of the spring ICH meeting;

The Assembly endorsed the work plan of the E9(R1) EWG for activities to be undertaken by the EWG.

Action:


AGENDA ITEM 17

37

ICH E9(R1) EWG Work Plan

17 February 2017

Topic Adopted: October 2014

Face-to-Face Meeting: Osaka, Japan – November 2016



2017 Step 1 and Step 2a Finalisation of the Technical Document (draft Addendum) and sign-off by all ICH Parties’ members in the EWG and by the Assembly.

Step 2b Draft Addendum and sign-off by the ICH Regulatory Parties.

2017 Step 3 phase Publish draft Addendum.

2018 - 2019 Step 3 phase Discuss comments received during the public consultation period and consolidate the Draft Addendum.

2018 - 2019 Step 3 and Step 4 Finalisation of the Addendum and sign-off by topic leaders of the ICH Regulatory Parties and by the ICH Regulatory Parties.

2. Timelines


December 2016 to May 2017

Progress towards Step 1 and Step 2a

Follow actions to be undertaken until the ICH meeting in May 2017, and that will contribute to the finalisation of the Step 1 Technical Document (draft Addendum)

Update the Step 1 Technical Document based on Osaka discussions and comments received from members.

After another round of comments and update within the EWG, share the document for comments within each region, with statisticians and non-statisticians.

Review alignment of the original ICH E9 with the Step 1 Technical Document.

Draft training material, i.e. document(s) to support communication and steer comments during the public consultation.

Discuss the need to meet in May/June at the ICH

38

meeting in Canada. The draft Addendum Document should be near final before the meeting.

Full group EWG teleconferences will be facilitated by the Rapporteur monthly (or biweekly if needed) to ensure progress.

Additional meetings of EWG subteams may be organised to progress the drafting of the Addendum, training material and other relevant topics.

ICH Meeting May/June up to November 2017

Step 1, Step 2a and Step2b

Finalise the Step 1 Technical Document. Finalise annotations or changes in the original

ICH E9, if any. Develop training material that will help users to

understand the draft Addendum and implement its principles. Communication activities to support the consultation period will be agreed with the Assembly.

Once these three documents are finalised, engage the sign-off process.

Step 1: Sign-off by all ICH Parties’ members of the EWG.

Step 2a: Sign-off by the Assembly. Step 2b: ICH Regulatory parties adapt the Step 1

Technical Document into a draft Addendum which is then signed by the ICH Regulatory Parties.

Identify whether themes and aspects would be more relevant in a ‘technical’ appendix or scientific publication.

Continue the review of other ICH ‘E’ guidelines.

November 2017 to November 2018 (or later)

Step 3 phase Deliverables set for this period will depend on the duration of the public consultation in each region and may be delayed.

Publish the draft Addendum in each region under the Step 3 procedure guidelines. The duration of public consultation, either 6 or 12 months, is subject to approval by each of the ICH Regulatory Parties.

Organise meetings at a global or regional level to promote awareness and comments on the Addendum.

Discuss regional consultation comments and

39

modification of the Addendum and accompanying documents, based on comments received. Outline plans for further progress towards finalisation.

ICH Meeting November 2018 (or later)

Step 3 and Step 4 Deliverables set for this period will depend on the duration of the public consultation in each region and may be delayed.

Finalisation of the Addendum. Finalise the training package that will

accompany the Addendum. Organise an ICH training. Once all documents are finalised, engage the

sign-off process. Step 3: Sign-off by topics leaders of Regulatory

ICH Parties. Step 4: Sign-off by all ICH Regulatory Parties.

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ICH2017/04


May 31 & June 1, 2017

MONTREAL, CANADA


18. E11(R1) EWG: Addendum to Paediatric Drug Development

The Rapporteur will report on the outcome of the E11(R1) EWG meeting held on May 29 - June 1, 2017 including progress made towards analysing and addressing comments collected on the draft E11 Addendum to Paediatric Drug Development during the regional public consultation that ended in April, 2017.

Step 3 sign-off and Step 4 adoption are expected electronically by November 2017.


E11(R1) EWG work plan, dated March 1, 2017.

Chronicle:


The E11(R1) EWG did not meet in Osaka.

The Assembly was updated on the current activities of the E11(R1) EWG including progress made towards collecting comments on the draft E11 Addendum on Paediatric Drug Development which was endorsed by the Regulatory Members of the Assembly under Step 2b of the ICH process in September 2016.

Decisions/Actions:

The Assembly endorsed the nomination of the new Rapporteur; The E11(R1) EWG will provide a work plan to the MC ahead of the teleconference to be held in

spring 2017 for activities to be undertaken.

Action:


AGENDA ITEM 18

41

ICH E11(R1) EWG Work Plan

1 March 2017

Topic Adopted: August 2014

Last Face-to-Face Meeting: Lisbon, Portugal - June 2016



May – November 2017 Step 3 phase, discuss comments received on the draft Guideline to finalize Step 3 Draft Guideline

November 2017 Adoption of Step 4 Guideline

2. Timelines


February 2017 to May 2017

E11 EWG revise Step 2 document to draft Step 3 document.

Step 2b document is currently under public consultation in respective regions. EWG will analyze the comments received and start revision of Step 2b document to reflect relevant comments.

Jun 2017 F2F meeting at Montreal EWG requests the meeting to be 3.5 days (Monday AM through Thursday AM) in order to address every topic of E11(R1).

EWG convenes to discuss in detail about revision of Step 2b document reflecting comments received. Because public consultation in EU ends in April resulting in a short time for preparation before F2F meeting, EWG do not expect to be able to sign off Step 3 Draft Guideline at Montreal meeting.

Jun 2017 to Nov 2017

Finalization of Step 3 Draft Guideline

EWG continues revision of Step 2b and finalize Step 3 Draft Guideline.

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ICH2017/04


May 31 & June 1, 2017

MONTREAL, CANADA


19. E17 EWG: Multi-Regional Clinical Trials

The Rapporteur will report on the outcome of the E17 EWG meeting held on May 29 - June 1, 2017 and progress made towards analysing and addressing comments received on the draft E17 Guideline on Multi-Regional Clinical Trials during the regional public consultation that ended in January 2017.



E17 EWG work plan, dated February 21, 2017.

Chronicle:


The Rapporteur reported on the outcome of the E17 EWG meeting held on November 7-10, 2016 and progress made towards updating the draft E17 Guideline on Multi-Regional Clinical Trials with comments received during the consultation period in the ICH regions.

The Assembly noted that the E17 EWG expects to reach Step 3 sign off and Step 4 adoption in Q4 2017.

Decision/Action:

The Assembly endorsed the work plan of the E17 EWG for activities to be undertaken by the EWG.

Action:


AGENDA ITEM 19

43

ICH E17 EWG Work Plan

21 February 2017

Topic Adopted: June 2014

Last Face-to-Face Meeting: Osaka, Japan - November 2016



4Q 2017 Step 4 Guideline

2. Timelines


June 2016 Step 1 completed Experts signed off the document as Step 1

June 2016 Step 2a/b completed The Step 2a/b were completed at the ICH Lisbon meeting

July 2016 -

January 2017

Public consultation in each region

Comments period was closed in Japan and US, but is still opened in EU (closed in January 2017)

November 2016 Fourth face-to-face EWG Meeting in Osaka

Revise the guideline based on comments received on the public consultation.

June 2017 Fifth face-to-face EWG Meeting

Revise the guideline based on comments received on the public consultation.

November 2017 Sixth face-to-face EWG Meeting

Finalize guideline as Step 4

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ICH2017/04


May 31 & June 1, 2017

MONTREAL, CANADA


20. E19 Informal WG: Optimization of Safety Data Collection

The Lead will report on the outcome of the meeting of the E19 informal WG held on May 29 - June 1, 2017 and the finalisation of the Concept Paper and Business Plan on Optimization of Safety Data Collection.

Approval of the Concept Paper and Business Plan by the MC are expected by May/June 2017.


E19 informal WG work plan, dated March 28, 2017.

Chronicle:


New ICH Topics

The MC highlighted the overall status of ICH harmonisation activities on current ICH topics and the process agreed in Lisbon in June 2016 for the selection of new ICH topics.

The MC provided the Assembly with an update on its considerations since the Lisbon meeting in June 2016 of the new proposals on Safety Data Collection (proposed by FDA) and Adaptive Clinical Trials (proposed by PhRMA). The Assembly noted that for the former, an updated title was proposed in Osaka: Optimization of Safety Data Collection.

Decisions/Actions:

The Assembly adopted the Concept Paper outline on Optimization of Safety Data Collection (code: ICH E19) and agreed on the establishment of an informal WG (with FDA nominated as Lead) to finalise the Concept Paper and develop a Business Plan ahead of the MC Teleconference to be held in spring 2017;

Once the final Concept Paper and the Business Plan will be approved by the MC, the informal WG will be transformed into an EWG, which is expected to meet at the June 2017 meeting in Montreal, Canada;

The Assembly acknowledged that MHLW/PMDA indicated it would only be able to take a position on sign-off at Step 1 of E19 after positive outcome of consultation with its stakeholders;

Action:


AGENDA ITEM 20

45

The ICH Secretariat will launch the nomination process amongst ICH Members and Observers for the establishment of the informal WG;

Further to Article 17(5) of the ICH Articles of Association, any ICH Observer interested to participate in the activities of this new WG would need to inform the ICH Secretariat in writing using the template available in the SOPs for WGs and provide explanations for their interest in the specific WG, information about their available expertise and how they would expect to contribute to the work of the WG;

Any request received by the ICH Secretariat, will be shared with the MC for approval;

The Assembly nominated FDA as the Rapporteur for the ICH E19 EWG;

The Founding Regulatory Members and the Standing Regulatory Members of the MC will confirm the respective Regulatory Chairmanship for the new EWG once established;

The Assembly noted that the new topic proposal on Adaptive Clinical Trials would undergo further revisions with a view to submitting a Concept Paper outline for consideration at the Montreal meeting. The MC at its meeting had supported that PhRMA revises the proposal to encompass a more limited scope, one that is less dependent on statistical considerations given the stated capacity concerns related to some active EWGs (e.g., E9). The revised proposal would be circulated to MC Members for their comments to the revision, with a timeline of submitting the updated proposal ahead of the Montreal meeting.

46

ICH E19

Informal WG Work Plan

28 March 2017

Topic Adopted: 23 September 2016

Last Face-to-Face Meeting: Not applicable



May 2018 Endorsement of Step 2 a/b document and subject to working group

progress

May 2019 Adoption of Step 4 document

2. Timelines


March 2017-

May 2017

E-mail consultation within

WG/ EWG

Concept paper and Business plan to be

established

Agenda and documents for Montreal

meeting to be prepared and shared

27 May - 1 June

2017

Face-to-face meeting

(Montreal)

Discussions of major issues and scope

Consensus on outline of 1st draft

guideline

Begin drafting process

Discuss next steps

June-September

2017

E-mail consultation within

EWG

Tasks distributed among members

(action plan) as identified during the

face to face meeting

Draft version of the guideline prepared

based on discussions at face to face

meeting and interim email consultation

October 2017 EWG teleconference(s) Discuss major issues in drafting process

Discuss topics to be resolved at face to

face meeting.

November 2017 Face-to-face meeting

(Geneva)

Plan to meet to discuss and resolve

issues with the goal of reaching

consensus.

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ICH2017/04


May 31 & June 1, 2017

MONTREAL, CANADA


21. E2B(R3) IWG: Revision of the Electronic Submission of Individual Case Safety Reports

The Rapporteur will report on the outcome of the E2B(R3) EWG/IWG meeting held on May 29 - June 1, 2017 and progress made towards developing the annexes to the Individual Case Safety report (ICSR) Implementation Guide (IG) on the use of European Directorate for the Quality of Medicines & healthcare (EDQM) and Unified Code for Units of Measure (UCUM) lists, as well as discussion with the M2 EWG on the maintenance process for external terminologies.

Step 3 sign-off and Step 4 adoption of the annex to the ICSR IG on the use of EDQM lists and BFC document v2.03 are expected by May/June 2017.


E2B(R3) IWG work plan, dated March 15, 2017.

Chronicle:


The Rapporteur reported on the outcome of the E2B(R3) IWG meeting held on November 7-10, 2016 and progress made towards the completion of a document on how to use the EDQM Routes of Administration; progress towards an editorial update to the Implementation Guide to reflect the Q&A document; and progress towards the determination of any conflicts in ICSR messages based upon review of regional Implementation Guides.

Decisions/Actions:

The E2B(R3) IWG Regulatory Experts signed-off Step 3 of the new format of the additional Q&As in the Implementation Guide Package, the Implementation Guide v5.02 and the BFC Specification v2.02;

Actions:


If Step 3 of the annex to the ICSR IG on the use of EDQM lists and BFC document

v2.03 are reached in Montreal, the E2B(R3) Regulatory experts will be invited to

sign-off; and the Regulatory Members of the Assembly will be invited to adopt as

final under Step 4 these 2 documents.

AGENDA ITEM 21

48

The Regulatory Members of the Assembly adopted Step 4 of the new format of the additional Q&As in the Implementation Guide Package, the Implementation Guide v5.02 and the BFC Specification v2.02;

The E2B(R3) Experts signed-off the Technical Information document and E2B Code List #25;

The Assembly endorsed the Technical Information document and E2B Code List #25;

The Assembly noted that these documents will be published on the ESTRI website;

The Assembly supported the temporary change in the Rapporteurship of the E2B(R3) IWG;

The Assembly endorsed the work plan of the E2B(R3) IWG for activities to be undertaken by the IWG.

49

ICH E2B(R3) EWG/IWG/Subgroup Work Plan

15 March 2017

Topic Adopted: July 2013




March 2017 Finalise plans for cross-regional pilot

June 2017 Finalise annex to the IG for use of UCUM terms with E2B(R3)

June 2017 Finalise annex to the IG for use of EDQM terms with E2B(R3)

June 2017 Update BFC document

2. Timelines


November 2016 to March 2017

Review and finalise plans for cross-regional pilot

Discuss procedure, role, outcome and timeline of cross-regional pilot

Update the plan and finalise

March 2017 to May 2017

Conduct cross-regional pilot Create ICSR messages using regional tools Exchange ICSR messages among the regions Apply regional data validation and share ACK message

May to June 2017 Analyse results from the pilot Analyse results from the pilot Address issues (if applicable)

November 2016 to June 2017

Draft annex to the IG on use of EDQM

Draft and review the annex on use of EDQM Confirm EDQM with maintenance process (versioning,

translation, format, etc) Discuss ICH change request process with M2 Review mapping between E2B codes and EDQM terms

for route of administration


Submission of requests to EDQM

Identify the terms to be requested to EDQM for R2-R3 conversion purpose

Develop definitions for the terms

April 2017 to June 2017

Draft annex to the IG on use of UCUM

Draft and review the annex on use of UCUM Update E2B constrained code lists for R2-R3 conversion

April 2017 Address discrepancies in the BFC document

Address discrepancies in R2-R3 conversion rules Update the BFC document


Q&A Monitor and discuss any comments received by the ICH mail box or within the regions.

Add Q&As to the document if applicable.

January 2017 to February 2017

Test E2B web page E2B IWG asked ICH secretariat to update E2B web page with new layout.

After the web page is updated, E2B IWG test if the web page works correctly.


Discuss holistic maintenance process with M2

Input M2 to develop ICH change request process for SDOs Provide E2B business requirements to M2 so that M2 can

develop a detailed process for maintenance


Monitor IDMP developments Monitor ISO IDMP activities which may impact on E2B

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ICH2017/04


May 31 & June 1, 2017

MONTREAL, CANADA


22. M2 EWG: Electronic Standards for the Transfer of Regulatory Information

The Rapporteur will report on the outcome of the M2 EWG meeting held on May 29 - June 1, 2017 and the progress made towards developing the ICH project opportunities proposals, defining the maintenance process for external terminologies and evaluating existing ICH topics for technical opportunities.


M2 EWG work plan, dated March 27, 2017.

Chronicle:


The M2 EWG did not meet in Osaka.

The Assembly was updated on the outcome of MC discussions in Osaka regarding M2 activities.

Decisions/Actions:

The Assembly noted that the MC had supported that the M2 EWG be supplemented by a small Steering Group in place of a single Rapporteur and that the M2 EWG will establish the steering group’s working practice;

The Assembly noted the nomination of the new Regulatory Chair by the MC; The M2 EWG will provide a work plan to the MC ahead of the teleconference to be held in spring

2017 for activities to be undertaken by the EWG.

Action:


AGENDA ITEM 22

51

ICH M2 EWG Work Plan

27 March 2017

Topic Adopted: 1994


Anticipated Milestones

Completion

Date

Deliverable

20 April 2017 ICH Project Opportunities Proposals

An assessment will be made of potential opportunities with significant relevance to

ICH and how these might impact existing guidance and/or specifications and the

current or future work of ICH. Based on this assessment, 1-2 potential (non-consensus)

technological project proposals will be developed and provided for MC review and

discussion.

20 May 2017 Evaluation of existing ICH topics for technical opportunities

Existing ICH topics will be assessed for technical opportunities.

1) Within each party, M2 members will talk with their topic experts around Step 1 to

understand the topic and to explore potential technological issues or opportunities.

2) M2 will review EWG guidelines at Step 3 or 4 when the EWG has more fully

established its thinking on the topic. M2 will identify and discuss technological

opportunities or concerns with the EWGs.

Where technological risks or opportunities are identified for a topic, M2 will request

joint meetings with the EWG to share and discuss the risk or opportunity.

20 May 2017 Finalized Information Paper on Redaction

M2 identified a set of requirements for redaction and evaluated usability of electronic

formats and tools within the ICH regions. The findings will be provided in this paper.

This paper will be analogous to the MedDRA Points to Consider document. The

document will not identify a new standard. Instead, the document will present the

capabilities and constraints when redacting specific ICH recommended submission file

standards such as PDF and JPEG. This document will be published on the ESTRI

website where recommended submission file standards are published. It is intended to

support the redaction requirements that each region has.

20 May 2017 Finalized PDF Specification update

Current PDF recommendation is only on the use of specific PDF versions and agreed

restrictions, but each regulator maintains separate PDF specification. M2 will

investigate further harmonization of requirements and revise PDF recommendation.

52

20 May 2017 Defined Maintenance Process for External Terminologies

A process (operating model) will be defined for handling terminology change requests and appeals to external maintenance organizations (ex: EDQM, Regenstrief).

Timelines (note – periodic administrative activities such as SDO liaison activities are not included)


ICH Project Opportunities Proposals

15 Mar 2017 Consider potential project

opportunities

Discuss individual party observations and proposals. Proposals may or may not be connected with an existing EWG’s work.

Identify 1-2 opportunities to elaborate.

20 April 2017 Develop 1-2 proposals for MC Develop (non-consensus) technological project opportunity proposals.

Provide proposals to MC for review.

Montreal meeting

Present proposals to MC 1-2 project opportunity proposals are presented to the MC or a MC subgroup for discussion.

Evaluation of existing ICH topics for technical opportunities

20 Apr 2017 Evaluate new ICH topics for

technical risks and opportunities –

stage 1

M2 members in each party will talk with their topic experts in each EWG at around Step 1 to understand the topic better and to explore potential technological risks or opportunities.

30 April 2017 Discuss and confirm potential

technological risks and

opportunities

Results of discussions will be shared across M2. Potential technological risks, opportunities and

questions identified by multiple parties will be documented with next steps and shared with the EWG

15 May 2017 Evaluate mature ICH topics for

technical risks and opportunities –

stage 2

All parties review Step 3-4 documents for technological risks and opportunities. This will be accomplished through M2 subgroups to support concurrent evaluations.Review results are aggregated for discussion and development of opportunity proposals.

Montreal meeting

Joint meetings with select EWGs,

Develop outcome reports

Present outcomes to MC

Where technological risks or opportunities are identified for a topic, M2 will request joint meetings with the EWG to share and discuss the risk or opportunity.

Outcomes and next actions will be documented Outcomes will be presented to MC (presentation

may be in paper only if no immediate actions or opportunities are identified)

53

Finalized Information Paper on Redaction

20 May 2017 Finalize Information Paper on

Redaction

All parties agree on paper scope. Final draft Information Paper on Redaction is

distributed for review/agreement. This will be analogous to the MedDRA Points to

Consider document. The document will not identify a new standard. Instead, the document will present the capabilities and constraints when redacting specific ICH recommended submission file standards such as PDF and JPEG. This document will be published on the ESTRI website where recommended submission file standards are published. It is intended to support the redaction requirements that all regions have.

Montreal meeting

Sign-off at Montreal meeting

Finalized PDF Specification update

20 Apr 2017 Update M2 PDF specification for possible ESTRI recommendation revision

Review existing regional PDF requirements, identify common requirements, reconcile differences & discrepancies where possible.

Update M2 PDF specification based on review outcomes

Montreal meeting

Sign off and publish PDF updated recommendations

Defined maintenance process for external terminologies

30 April 2017 Define change request process for externally maintained vocabularies

Evaluate the request and concerns from E2B about change request process for EDQM Draft change request process; confirm actions and timeframes with EDQM

Montreal meeting

Joint meeting with E2B to explain and implement process; M2 Maintenance document revised

SDO project survey

20 Apr 2017 Draft M8 SDO project survey report

Draft a report on the survey results Discuss initially with M8 Rapporteur and

Regulatory Chair

20 May 2017 Finalize report of M8 SDO

Project survey results

A report of M8 SDO project survey results is finalized and confirmed by M8

Submit to the MC for information

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ICH2017/04


May 31 & June 1, 2017

MONTREAL, CANADA


23. M9 EWG: Biopharmaceutics Classification System-based Biowaivers

The Rapporteur will report on the outcome of the M9 EWG meeting held on May 29 - June 1, 2017 and progress made towards developing the M9 draft Technical Document on Biopharmaceutics Classification System-based Biowaivers.



M9 EWG work plan, dated February 9, 2017.

Chronicle:


The Rapporteur reported on the outcome of the first meeting of the M9 EWG held on November 7-10, 2016 and progress made towards developing the draft guideline on Biopharmaceutics Classification System-based Biowaivers. The M9 EWG started its work by performing a mapping of the relevant regional perspectives and guidelines, and will further exchange documents and supportive data on the issues under discussion, with the plan of discussing these by teleconference in early 2017.

The Assembly noted that the M9 EWG expects to reach Step 1 by the spring 2018 meeting.

Decisions/Actions:

The Assembly noted the nomination of the new Regulatory Chair by the Founding Regulatory and Standing Regulatory Members of the MC;

The Assembly endorsed the work plan of the M9 EWG for activities to be undertaken by the EWG.

Action:


AGENDA ITEM 23

55


9 February 2017

Topic Adopted: 14 June 2016




June 2018 Adoption of Step 2 a/b document

June 2019 Adoption of Step 4 document

2. Timelines


June 2016 - November 2016

E-mail consultation within WG/ EWG

Concept paper and Business plan were established.

Agenda and possible documents for Osaka meeting were prepared.

7-10 November 2016

Face-to-face meeting

(Osaka)

In depth discussion on criteria for BCS classification and biowaiving.

Preparation of draft version guideline. Preparation/consensus on next steps

towards face-to face meeting Montreal May 2017.

November-February 2017

Submission by e-mail: Collecting of supporting documents

Tasks have been distributed among members (action plan) to collect supporting documents on open issues as identified during the face to face meeting.

January 2017 Submission by e-mail: new draft version of the guideline

The Rapporteur will prepare a (new) draft version of the guideline based upon the discussions so far.

February 13, 2017

EWG teleconference Discussion of open issues based upon the collected supportive documents by members.

Drafting new version of guideline.

March - April 2017

EWG teleconference Update of progress. Discussion open/controversial issues

identified during February 2017 teleconference.

56

Drafting new version of guideline. Preparation second EWG meeting.

May 2017 Face-to-face meeting

(Montreal)

Finding consensus on controversial issues.

Update of the draft guideline through face-to-face discussion

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ICH2017/04


May 31 & June 1, 2017

MONTREAL, CANADA


24. M10 EWG: Bioanalytical Method Validation

The Rapporteur will report on the outcome of the M10 EWG meeting held on May 29 - June 1, 2017 and progress made towards developing the M10 draft Technical Document on Bioanalytical Method Validation.



M10 EWG work plan, dated March 10, 2017.

Chronicle:


The Rapporteur reported on the outcome of the first meeting of the M10 EWG held on November 7-10, 2016 and progress made towards developing the draft guideline on Bioanalytical Method Validation.

The Assembly noted that the M10 EWG will prepare the first draft technical document after the Osaka meeting in November 2016.

Decisions/Actions:

The Assembly noted the nomination of the new Regulatory Chair by the Founding Regulatory and Standing Regulatory Members of the MC;

The Assembly endorsed the work plan of the M10 EWG for activities to be undertaken by the EWG.

Action:


AGENDA ITEM 24

58


10 March 2017





June 2018 Endorsement of Step 2 a/b document

June 2019 Adoption of Step 4 document

2. Timelines


June 2016 -

Nov 2016

E-mail consultation within informal WG/EWG

Concept paper and Business plan were established.

Agenda and discussion materials for Osaka meeting were prepared.

7-10 November 2016

1st Face-to-face meeting

(Osaka)

Consensus on outline of the 1st draft guideline was build based on the gap analysis of current regional guidelines/guidances.

10 February 2017 Submission via e-mail Drafted text for the technical document was submitted to the rapporteur from each regulatory Member.

14-21 February 2017

E-mail consultation The preliminary draft version 0.0 was established and reviewed by regulatory members.

21 February - 2 March 2017

E-mail consultation The draft version 0.1 was shared by all EWG members and comments were collected.

7 March 2017 E-mail consultation Comments on the draft were shared by EWG members.

9 March 2017 EWG teleconference Major issues on the draft (Scope, Matrix effect, Accuracy and Precision, Stability) were discussed.

19 April 2017 EWG teleconference Major issues of the draft (Stability, Cross validation, Reference standard, ISR, Selectivity and Specificity) will be

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discussed.

10 May 2017 EWG teleconference Other important issues of the draft (Partial validation, Overall structure etc.) will be discussed.

11 May -28 May 2017

EWG e-mail consultation The draft will be revised based on the discussion in three teleconferences and establish the draft version 1.0

29 May -1 June 2017

2nd Face-to-face meeting (Montreal)

Issues that still be controversial will be discussed for updating the draft.

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ICH2017/04


May 31 & June 1, 2017

MONTREAL, CANADA


25. EWGs/IWGs Not Meeting in Montreal, Canada The following groups will not be meeting in Montreal:

S3A IWG

S9 IWG

Q3C(R7) Maintenance EWG

Q3D(R1) Maintenance EWG

E14/S7B DG

E18 EWG M1 PtC WG M4Q(R1) IWG

M7(R1) EWG

M8 EWG/IWG

S3A IWG: Q&As on Note for Guidance on Toxicokinetics

The ICH Coordinator from the Member who holds Rapporteurship will update the Assembly on the current activities of the S3A IWG and the progress made by the group addressing comments received on the draft Q&As from the regional public consultation.


Background Document: S3A IWG work plan, dated March 10, 2017.

Chronicle: EXTRACT FROM THE ASSEMBLY MEETING FINAL MINUTES, OSAKA, JAPAN, NOVEMBER 9 – 10, 2016:

The S3A IWG did not meet in Osaka.

The Assembly was updated on the current activities of the S3A IWG and the progress made by the group to collect comments on the draft S3A Q&As in the respective ICH regions.

Decisions/Actions:

The S3A IWG will work by email and teleconference on the finalisation of the Q&As, with Step 3 sign off and Step 4 adoption expected by June 2017;

The S3A IWG will provide a work plan to the MC ahead of the teleconference to be held in spring 2017 for activities to be undertaken by the IWG.

****

AGENDA ITEM 25

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S9 IWG: Q&As on Nonclinical Evaluation for Anticancer Pharmaceuticals

The ICH Coordinator from the Member who holds Rapporteurship will update the Assembly on the current activities of the S9 IWG and the progress made by the group addressing comments received on the draft Q&As from the regional public consultation.


Background Document: S9 IWG work plan, dated February 13, 2017.


The S9 IWG did not meet in Osaka. The Assembly noted the current activities of the S9 IWG and that the draft guideline had been issued for regional regulatory consultation. The Assembly was informed that following completion of the regional regulatory consultation, the IWG will resume its activities to develop a revised guideline. The Assembly noted that the ICH S9 IWG is expected to reach Step 3 and Step 4 by June 2017. Decision/Action: The S9 IWG will provide a work plan to the MC ahead of the teleconference to be held in spring 2017 for activities to be undertaken by the IWG.

****

Q3C(R7) Maintenance EWG: Maintenance of the Guideline for Residual Solvents

The ICH Coordinator from the Member who holds Rapporteurship will update the Assembly on the current activities of the Q3C(R7) Maintenance EWG and the group’s recommendation on whether to undertake Q3C maintenance in relation to five new proposals received.

Step 1 sign-off and Step 2a/b endorsements are expected by Q1 2018.

Background Document: Q3C(R7) Maintenance EWG work plan, dated February 2, 2017.


The Q3C(R6) Maintenance EWG did not meet in Osaka.

The Assembly was updated on the current activities of the Q3C(R6) EWG including: the progress made towards reaching Step 3 and Step 4. The Assembly noted that a new Q3C Rapporteur will be appointed for the period 2017-2018 in line with the Q3C maintenance procedure.

Decisions/Actions:

The Q3C(R6) Regulatory Experts signed-off Step 3 of the Q3C(R6) Guideline (via written postal procedure) in advance of the Assembly meeting;

The Regulatory Members of the Assembly adopted Step 4 of the Q3C(R6) Guideline as final;

The Assembly noted that per the maintenance procedure, the role of Rapporteur will rotate to FDA at the beginning of 2017;

The Q3C(R6) Maintenance EWG will provide a work plan to the MC ahead of the teleconference to be held in spring 2017 for activities to be undertaken.

****

Based on a recommendation of the MC, the Assembly is invited to take a decision to endorse the maintenance work on any of the new proposals recommended for maintenance by the Q3C(R7) EWG.

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Q3D(R1) Maintenance EWG: Maintenance of the Guideline for Elemental Impurities

The ICH Coordinator from the Member who holds Rapporteurship will update the Assembly on the current activities of the Q3D(R1) Maintenance EWG including the development of Permitted Daily Exposures and permitted concentrations of elemental impurities for products administered by the cutaneous and transdermal route for all 24 elements included in the ICH Q3D Guideline.

Step 1 sign-off and Step 2a/b endorsements are expected by May 2018.

Background Document: Q3D(R1) Maintenance EWG work plan, dated February 9, 2017.


The Q3D(R1) EWG did not meet in Osaka.

The Assembly was informed that the Q3D training package was finalised and had been published on the ICH website. Additionally, it was noted that the regional training workshops held in the founding ICH regions in 2016 had been completed.

The Assembly was informed that the Q3D(R1) EWG had updated its Concept Paper and will begin work to develop Permitted Daily Exposure levels and permitted concentrations of elemental impurities for products administered by the cutaneous and transdermal route of administration following confirmation of the experts who will participate in the EWG.

Decision/Action:

The Q3D(R1) EWG will provide a work plan to the MC ahead of the teleconference to be held in spring 2017 for activities to be undertaken by the EWG.

****

E14/S7B Discussion Group (DG): The Clinical Evaluation of QT/QTc Interval

Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs

The ICH Coordinator from the Member who holds Rapporteurship will update the Assembly on the current activities of the E14/S7B DG to monitor the progress of the discussion of the Comprehensive in vitro Proarythmia Assessment (CiPA) Initiative.


Background Document: E14/S7B DG work plan, dated August 26, 2016.


Chronicles - Extract from the Assembly meeting final minutes, Osaka, Japan, November 9-10 2016.

The E14/S7B DG did not meet in Osaka. The Assembly noted the current activities of the E14/S7B DG including its proposal to review advances in science and methods related to the clinical assessment of QT prolongation and to monitor the progress of the discussion of the Comprehensive in vitro Proarrythmia Assessment Initiative. The Assembly noted that the E14/S7B DG recommendation on whether to reopen the E14 Guideline for a complete revision was expected by December 2017. Decision/Action: The E14/S7B DG will provide a work plan to the MC ahead of its teleconference to be held in spring 2017 for activities to be undertaken.

The Assembly is invited to take a decision to endorse the nomination of the new

Regulatory Rapporteur for the Q3D(R1) Maintenance EWG (currently being led by an

Acting Rapporteur) in line with the Assembly RoP 4.2.

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****

E18 EWG: Genomic Sampling and Management of Genomic Data

The ICH Coordinator from the Member who holds Rapporteurship will update the Assembly on the current activities of the E18 EWG and progress made towards updating the draft E18 Guideline.

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

Background Document: E18 EWG work plan, dated March 13, 2017.


The Rapporteur reported on the outcome of the E18 EWG meeting held on November 7-10, 2016 and progress made towards updating the draft E18 Guideline on Genomic Sampling and Management of Genomic Data with comments received during the consultation period in the ICH regions.

The Assembly noted that the E18 EWG expects to reach Step 3 sign off and Step 4 adoption in Q2 2017.

Decision/Action:

The Assembly endorsed the work plan of the E18 EWG for activities to be undertaken by the EWG.

****

M1 PtC WG: MedDRA Points to Consider

The ICH Coordinator from the Member who holds Rapporteurship will update the Assembly on the

current activities of the M1 PtC WG with respect to the updating with each MedDRA release of the

two PtC documents on Term Selection and Data Retrieval and Presentation, as well as the

development of a companion document to the PtC Documents.

Background Document: M1 PtC WG work plan, dated March 8, 2017.


The M1 PtC WG did not meet in Osaka.

The Assembly was updated on the current activities of the M1 PtC WG with respect to the updating with each MedDRA release of the two PtC documents on Term Selection and Data Retrieval and Presentation; and the development of a proposal for a new area of work.

Decisions/Actions:

The Assembly also noted the endorsement of the MedDRA MB on the Concept Paper for the Extension of the Remit for the Points to Consider WG (M1 PtC) to Develop and Maintain a Companion Document to the PtC Documents. The M1 PtC WG will provide a work plan to the MC and MedDRA MB ahead of the teleconference to be held in spring 2017 for activities to be undertaken by the WG.

****

The Assembly is invited to take a decision to endorse the nomination of a new

Rapporteur for the M1 PtC WG (currently being led by an Acting Rapporteur) in line

with the Assembly RoP 4.2.

The Assembly will be invited to take a decision to endorse the nomination of a new

Rapporteur for the E18 EWG (currently being led by an Acting Rapporteur) in line with

the Assembly RoP 4.2.

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M7(R1) EWG: Addendum to Assessment and Control of DNA Reactive (Mutagenic)

Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk

The ICH Coordinator from the Member who holds Rapporteurship will update the Assembly on the current activities of the M7(R1) EWG including the finalisation of the M7(R1) Addendum.

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

Background Document: M7 (R1) EWG work plan, dated January 27, 2017.


The Assembly was updated on the current activities of the M7(R1) EWG including the progress made towards finalising the M7(R1) Addendum to Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk. The Assembly was informed that Step 3 sign-off is expected by December 2016 and Step 4 is expected by June 2017 for the 14 compounds Acceptable Intake and Permitted Daily Exposure levels have been developed for. Additionally, it was noted that the remaining 10 compounds will be reassessed following completion of this work.

Decision/Action:

The M7(R1) EWG will provide a work plan to the MC ahead of the teleconference to be held in spring 2017 for activities to be undertaken by the EWG.

****

M4Q(R1) (CTD-Quality) IWG: Addressing CTD-Q-Related Questions

The ICH Coordinator from the Member who holds Rapporteurship will update the Assembly on the MC decision to keep the M4Q(R1) IWG in a dormant state while the eCTD v4.0 Implementation Guide, including the Granularity document is currently being implemented in the ICH Regions and in case questions are raised.


The M4Q(R1) EWG did not meet in Osaka.

The Assembly noted that the M4Q(R1) (CTD-Quality) IWG had completed its work regarding the revision of the Granularity Document with the M8 EWG. The Assembly was provided a recommendation on the decision to disband the M4Q(R1) IWG. The Assembly acknowledged the potential for questions to be received following the implementation of the M4 Granularity document.

Decisions/Actions:

The M4Q(R1) IWG will become dormant and will not be requested to update their work plan;

A decision on the disbandment of the M4Q(R1) (CTD-Quality) IWG will be deferred to the next ICH meeting in spring 2017.

****

The Assembly will note the rotation to the a new Regulatory Rapporteur for the M7(R1) EWG

in line with the SOP Annex #4 Maintenance Procedure prior to the next stage of work.

If Step 3 is reached ahead of Montreal, the Regulatory Members of the Assembly will be

invited to take a decision to adopt Step 4 of the M7(R1) Addendum.

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M8 EWG/IWG: The Electronic Common Technical Document: eCTD

The ICH Coordinator from the Member who holds Rapporteurship will update the Assembly on the current activities of the M8 EWG/IWG including updating the eCTD v3.2.2 and v4.0 Q&As based on change requests received.

Step 3 sign-off and Step 4 adoption of the eCTD v3.2.2 Q&As and Specification Change Request Document v1.30 are expected by June 2017.

Background Document: M8 EWG/IWG work plan, dated March 13, 2017.


The Rapporteur reported on the outcome of the M8 EWG/IWG meeting held on November 7- 10, 2016 and progress made on the current activities of the M8 EWG/IWG including: updating the Implementation Package and Specification Change Request document; developing the v4.0 Q&A v1.0; and communication with vendors. Decisions/Actions: The M8 Regulatory Experts signed-off Step 3 of the eCTD v3.2.2 Q&A and Change Request Document v1.29, the eCTD v4.0 Q&A and Change Request Document v1.00, eCTD v4.0 Implementation Package v1.2, Specification for Submission Formats for eCTD v1.1 and the Valid Values File v5; The Regulatory Members of the Assembly adopted under Step 4 of the eCTD v3.2.2 Q&A and Change Request Document v1.29, the eCTD v4.0 Q&A and Change Request Document v1.00, eCTD v4.0 Implementation Package v1.2, Specification for Submission Formats for eCTD v1.1 and the Valid Values File v5; The M8 Experts signed-off the eCTD v4.0 Support Documentation v1.2 and the eCTD v.4 Orientation Material v1.2; The Assembly endorsed the eCTD v4.0 Support Documentation v1.2 and the eCTD v.4 Orientation Material v1.2; The Assembly noted that these documents will be published on the ICH and ESTRI websites; The Assembly endorsed the M8 proposal for interaction with vendors; The Assembly noted the pending nomination of the new Regulatory Chair by the Founding Regulatory and Standing Regulatory Members of the MC; The Assembly endorsed the work plan of the M8 EWG/IWG for activities to be undertaken by the EWG/IWG.

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ICH S3A IWG Work Plan

10 March 2017


Last Face-to-Face Meeting: None



31 July 2017 Step 3 Expert draft Guideline

November 2017 Step 4 Final Guideline

2. Timelines


17 March 2016 Step 1 sign off Step 1 sign off was completed.

12 May 2016 Step 2a sign off Step 2a sign off was completed.

19 May 2016 Step 2b sign off Step 2b sign off was completed and draft Q&A was publicized on ICH Web site.

31 December 2016

Public consultation Public consultation was finished in all countries/region

28 February 2017

E-mail Rapporteur summarized all the critical comments for distribution to IWG members.

31 March 2017 E-mail meeting or teleconference

Revised draft Q&A will be distributed to the IWG members for consultation.

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ICH S9 Q&A IWG Work Plan

13 February 2017





Q4 2017 Step 3 Expert draft Guideline

Q1-2 2018 Step 4 Guideline

2. Timelines


08 June 2016 Step 2b Draft Q&A posted to the ICH website with regional publication by the 5 parties pending.

Q1 2017 Step 2b Comment period closed in all regions

Q1-2 2017 Step 3 Address input from Constituents through email and telecons.

June 2017 Face to Face meeting

Address comments (see meeting workplan below)

Q3-4 2017 Step 3 Recommend adoption of finalized document

Q1 2018 Step 4 Regional publication of finalized document

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ICH Q3C(R7) EWG Work Plan

7 February 2017

Topic Adopted: February 2017

Last Face-to-Face Meeting: none (written procedure)



Q1 2018 Step 2 Guideline

Q3/4 - 2018 Step 4 Guideline

2. Timelines


1 April 2017 EWG review of proposals and recommendation for selection of new solvents via email and telecon as needed

Review proposals submitted for inclusion in ICH Q3C and identify those considered appropriate

April 2017 -

October 2017

Draft Step 2 document Review supporting data for selected solvents; identify relevant studies to support PDE calculation where possible; draft Step 2 guideline

November 2017 Approval by Steering Committee under Step 2

Release for public consultation

December 2017 – May 2018

Step 3 Internal/external consultation in ICH regions

June 2018- September 2018

EWG telecon/e-mail consultation

Reviewing and resolving comments received from consultation process; preparing Step 3/4 document

Q3/4 - 2018 Step 3 signoff Postal signoff Step 3 by the Regulatory Experts.

November 2018 Step 4 Adoption by the Regulatory Members of the Assembly.

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ICH Q3D(R1) EWG Work Plan

9 February 2017


(Maintenance for Cutaneous and Transdermal Routes approved September 2016)

Last Face-to-Face Meeting: Strasbourg, France – June 2015



May 2018 Finalize Step 2 cutaneous and transdermal PDEs document and publish for public comment

May 2019 Finalize Step 4 document

2. Timelines


1 March 2017 Confirm interest and resources to move forward with cutaneous and transdermal PDEs

EWG members will be contacted to confirm interest and time commitment.

1 April 2017 Initiate development of permitted daily exposures for the cutaneous and transdermal routes of administration. Define whether cutaneous and transdermal PDEs are necessary for all or some of the 24 elements in the ICH Q3D Guideline.

Schedule teleconferences Develop work plan and delegate work

November 2017 EWG meets for F2F meeting Review progress on cutaneous and transdermal PDE development

May 2018 Finalize Step 2 PDEs for cutaneous and transdermal route of administration. Publish for public comment.

It is anticipated that this work will require 12-18 months to complete. PDEs to be distributed for public comment.

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June 2018 – November 2018

Step 3 Internal/external consultation in ICH regions

November 2018 - April 2019

EWG telecon/e-mail consultation

Reviewing and resolving comments received from consultation process; preparing Step 3/4 document

May 2019 Step 3 signoff Postal signoff Step 3 by the Regulatory Experts.

May 2019 Step 4 Adoption by the Regulatory Members of the Assembly.

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ICH E14/S7B IWG/DG Work Plan

26 August 2016

Topic Adopted: December 2015

Last Face-to-Face Meeting: Jacksonville, FL, USA - December 2015


Completion Date

Deliverable

December 2017 Preliminary recommendation to ICH Assembly regarding whether to re-open ICH E14 and S7B for complete revision

2. Timelines


Quarterly Teleconferences

(next meeting 23 August 2016)

Track Progress of CiPA Initiative

Discuss progress of CiPA initiative, review data as it emerges, and provide guidance on developing a path towards using these assays for regulatory decision making.

When CiPA initiative is ready for widespread implementation, the discussion group will assess the scope of the effort required to re-open ICH E14 and S7B for complete revision and make a recommendation.

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ICH E18 EWG Work Plan

13 March 2017





2Q 2017 Step 4 document adoption

2. Timelines


1Q 2017 Revision of E18 guideline based on team discussion of regional consultation comments

Team discussion to address key issues to reach consensus with web-based meeting

Small groups to revise draft guideline in the ICH Working Groups online working area

2Q 2017 Step 3 sign-off and Step 4 adoption

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ICH M1 PtC (Points to Consider) EWG Work Plan

8 March 2017

Topic Adopted: 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). In November 2016 the MedDRA Management Board endorsed the extension

to the remit of the WG to produce an additional companion document to the existing PtC

documents. The companion document would provide additional guidance on high-level topics

pertaining to the use of MedDRA such as data quality issues in regulatory submissions, as well as

detailed examples and Q&A’s for special topics such as medication errors and product quality

issues.

Last Face-to-Face Meeting: Lisbon, Portugal – June 2016



Q2 2017 Condensed Versions of the “MedDRA Term Selection: Points to Consider” and “MedDRA Data Retrieval and Presentation: Points to Consider” documents available in all MedDRA languages (except English and Japanese)

1st September 2017 Release of “MedDRA Term Selection: Points to Consider” and “MedDRA Data Retrieval and Presentation: Points to Consider” documents, including updates for MedDRA Version 20.1 via MedDRA and JMO websites

Q1 2018 Release of initial version of new Companion Document to the existing PtC documents via MedDRA and JMO websites

2. Timelines


May – July 2017

Review and update PtC documents for MedDRA Version 20.1.

Decide on relevant changes to be made to PtC documents based on user feedback. Release of PtC documents for MedDRA Version 20.1 via MedDRA and JMO websites on 1st September 2017.

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February – March 2017

Finalise Condensed PtC documents in preparation for translation into 9 MedDRA languages.

MSSO finalises English master of Condensed documents including any relevant changes from v20.0 update of full PtC documents. Rapporteur and Regulatory Chair sign off. MSSO sends Condensed documents to translation vendors. Anticipated release date is Q2 2017.

April –

November

2017

Create Companion document to the PtC for finalisation in November 2017.

This companion document will provide additional guidance on high-level topics pertaining to the use of MedDRA such as data quality issues in regulatory submissions, as well as detailed examples and Q&A’s for special topics such as medication errors and product quality issues.

November 2017 Finalise Companion document to the PtC.

Finalise the initial version of the companion document for translation to Japanese. Anticipated release in Q1 2018.

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January 27 2017


Last Face-to-Face Meeting: Fukuoka, Japan – June 2014



30 December 2016 Step 3 for Addendum is anticipated in December 2016.

June 2017 Reach Step 4 and electronic sign off

2. Timelines


14 July 2014 EWG 1st WebEx / Discussed Addendum work plan detail and process

Agenda and Actions:

Goal of Addendum is to provide acceptance limits for reagents to use between applicants and regulators i.e. consistency

Scope of reagents to include in Addendum, Consistent approach in collecting and

reviewing the data, data quality and robustness,

Agreed to focus on Category 1&2 reagents, although draft monographs have been developed for all reagents

EMA proposed to review/discuss threshold alternatives when more conservative linear approach is used

13 Aug. 2014 EWG 2nd WebEx / Continue discussion of monographs and discussion on methodology approach and data/limit selection for reagents

Agenda and Actions:

Agreed to add method section to addendum describing how data were collected, consistency of methodology and analysis across monographs

Agreed to review alternative monograph versions that use threshold MOA to derive AIs for hemosiderosis (hydroxylamine), forstomach (epichlorhydrin), and hydrogen peroxide. If accepted, will serve as template for remaining category 1&2 reagents with proposed thresholds

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Regulatory parties to provide status update on acceptability/inclusion of reagents and draft monographs in category 1&2

Monthly WebExs will be scheduled through December 2014

11 Sept. 2014

5 Nov. 2014

10 Dec. 2014

EWG 3 WebEx Introduced new title to the addendum and accepted by the EWG members. Continue to revise and incorporate edits/comments from EWG members and included an Introduction section. Discussed individual monographs

4 Feb. 2015 Final EWG WebEx before Step 2

Continue discussion of introduction/ method sections and monographs with anticipation to reach Step 2 end of February.

11 June 2015 Reached Step 2 Document open for Public comment period in the 3 Regions.

3 Feb. 2016 Receipt and discussion of Public comments

Public comment period was closed in the US and Japan with the EU last to close on February 3rd, 2016. Comments collated by the FDA and distributed to the EWG for discussion.

6 April 2016 1st WebEx to discuss Public comments

Collated Public comments from all three regions were discussed. No major issues identified.

11 May 2016 2nd WebEx continue discussions of Public comments

Continue discussion of Public comments.

21 December 2016

Step 3 draft sent to Secretariat

Draft agreed to by EWG and formatted according to ICH guidelines. Draft forwarded to Secretariat for review with anticipated final Step 4 sign off in June 2017

June 2017 Reach Step 4 As per anticipated deadline, Step 4 is to be reached and parties sign off electronically at the ICH Montreal meeting in June 2017

After June 2017

New set of compounds When a new list of compounds become available, the EWG Safety group will review and identify the compounds to move forward and submit to the Assembly for approval.

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ICH M8 EWG/IWG Work Plan

13 March 2017





June 2017 Step 4 eCTD v3.2.2 Questions and Answers and Specification Change Request Document v1.30.

As needed Step 4 eCTD v4 Questions and Answers and Specification Change Request Document v1.1.

2. Timelines


February 2017 – June 2017

Develop v4.0 Q&A v1.1 (if needed)

Discuss change requests (if any) Develop and agree to the Q&As (if

any) February 2017 – June 2017

Develop v3.2.2 Q&A v1.30 (if needed)

Discuss change requests (if any) Develop and agree to the Q&As (if

any)

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