Overview of ICH Procedures July 2015 International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use

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Table of Content The ICH Procedures document Overview of ICH Procedures Table of Content The ICH Procedures document Document History Glossary Introduction Classification of ICH activities in four categories ICH Process for each Category Additional Activities during the course of Harmonisation Other activities (error correction, considerations) Guideline withdrawal Annexes

Overview of ICH Procedures Introduction Unique harmonisation project involving the Regulators and research-based Industries of US, EU and Japan (funding six Parties)  started in 1990 WHO, Canada, and EFTA are observers In 2014, promotion of Health Canada and Swissmedic to ICH SC members Well-defined objectives: To improve efficiency of new drug development and registration process To promote public health, prevent duplication of clinical trials in humans and minimise the use of animal testing without compromising safety and effectiveness Accomplished through the development and implementation of harmonised Guidelines and standards Well-defined process and procedures are key to ICH success See also Section 1 of the ICH Procedures

The ICH Steering Committee Overview of ICH Procedures The ICH Steering Committee Governs the ICH Determines ICH policies and procedures Decides on the adoption of ICH projects Selects topics for harmonisation Endorses the creation of ICH Working Groups Monitors and facilitates the progress of ICH Working Groups Signs off ICH documents See also Section 1 & Annex 8 of the ICH Procedures

Classification of ICH Activities into Four Categories Overview of ICH Procedures Classification of ICH Activities into Four Categories See also Section 2 of the ICH Procedures

ICH Procedures – 5 Steps Process Overview of ICH Procedures ICH Procedures – 5 Steps Process

ICH Harmonisation Activities before Step 1 Overview of ICH Procedures ICH Harmonisation Activities before Step 1 Preparation of a Concept Paper: The Concept Paper is the trigger of all ICH harmonisation activities. It provides a short summary of the proposal. A Concept Paper can be submitted by any ICH Party or Observer to the Steering Committee (SC) or in some cases is prepared by an informal Working Group established by the SC. ICH Business Plan: A Business Plan should be submitted to the SC upon request. Endorsement by the Steering Committee: When the SC supports the adoption of the Concept Paper, the proposed action can be initiated (Step 1). An Expert WG or Implementation WG is established. Decisions by the Steering Committee: As an exceptional case when ICH Party consensus cannot be achieved, the ICH Regulatory Parties can jointly decide to adopt a Concept Paper. See also Section 2.2, Annexes 1,2,3 & 7 of the ICH Procedures

Formal ICH Procedure Overview of ICH Procedures Step 1 - Consensus Building - The EWG is established by the nomination of the Working Group members by the ICH Parties, the ICH Observer and, where applicable, by RHIs and DRAs/DoH and other Interested Parties (e.g., WSMI, IGPMA, Biotech Industry, IPEC…). In parallel, the SC designates the Rapporteur and, when applicable, the co-Rapporteur and the ICH Regulatory Parties of the SC designate the Regulatory Chair. The Rapporteur prepares an initial draft of the technical document, based on the objectives set out in the Concept Paper, and in consultation with experts designated to the EWG. The initial draft and successive revisions are circulated for comments within the EWG, giving fixed deadlines for receipt of those comments. At Step 1, the experts from the ICH Parties sign the Step 1 experts sign- off sheet when consensus on the technical document is reached. See also Section 3.1, Annexes 16 & 18 of the ICH Procedures

Formal ICH Procedure (continued) Overview of ICH Procedures Formal ICH Procedure (continued) Step 2a - Confirmation of six-party consensus on the technical document : The Step 1 consensus text along with EWG signatures are submitted to the Steering Committee (SC) for adoption under Step 2a of the ICH process. Step 2a is reached when the SC agrees, based on the report of the EWG, that there is sufficient scientific consensus on the technical issues for the Technical Document or recommendation to proceed to the next stage of regulatory consultation. At Step 2a, the ICH SC Parties are requested to sign-off the consensus technical document. The technical document is made public on the ICH website. Step 2b - Adoption of the draft Guideline: On the basis of the Technical Document, the ICH Regulatory Parties will take the actions they deem necessary to develop the “draft Guideline”. At Step 2b, the ICH Regulatory SC Parties are requested to sign-off the draft Guideline. The draft Guideline is posted on the ICH website and by the regulatory authorities and is released for public consultation. See also Section 3.1, Annexes 17 & 18 of the ICH Procedures

Formal ICH Procedure (continued) Overview of ICH Procedures Formal ICH Procedure (continued) Step 3 - Regulatory Consultation and Discussion: the Step 2b Draft Guideline leaves the ICH process and becomes the subject of normal wide-ranging regulatory consultation in the ICH regions. After obtaining all regulatory consultation results, the Working Group (WG) is resumed and works to address comments received during the consultation. The draft document to be generated as a result of the Step 3 phase is called Step 3 Experts Draft Guideline. At Step 3, the ICH regulatory experts sign the Step 3 experts sign-off sheet when consensus on the final Guideline is reached among the WG. See also Section 3.1 & Annex 18 of the ICH Procedures document

Formal ICH Procedure (continued) Overview of ICH Procedures Formal ICH Procedure (continued) Step 4 - Adoption of an ICH Harmonised Guideline : Step 4 is reached when the Steering Committee agrees, on the basis of the report from the Regulatory Chair and the regulatory Rapporteur of the EWG, that there is sufficient consensus on the draft guideline. At Step 4, the ICH regulatory SC Parties are requested to sign the Step 4 final Guideline. Step 5: Implementation - Having reached Step 4 the harmonised Guideline moves immediately to the final step of the process that is the regulatory implementation. Streamline Procedure: The Steering Committee may decide to follow an accelerated procedure for new topics, when necessary. See also Section 3.1, Annexes 10 & 18 of the ICH Procedures

Q&As Procedure Overview of ICH Procedures The Q&A Procedure is followed when additional guidance is considered necessary to help the interpretation of certain ICH harmonised Guidelines and ensure a smooth and consistent implementation in the ICH regions and beyond. The additional guidance is usually developed in the form of Questions and Answers "Q&As". The procedure is initiated with the endorsement by the Steering Committee (SC) of a Concept Paper. In the case of major implementation activities, the SC may also consider the need for a Business Plan. An Implementation Working Group (IWG) with membership as specified by the Concept Paper is subsequently established. Once developed by the IWG, the document usually follows the formal 5-Step process. In certain cases, based on the IWG’s recommendation, the SC can decide that a public consultation (Step 3) may not be necessary. The final Q&A document is posted on the ICH website. See also Section 3.2 & Annex 2 of the ICH Procedures

Revision Procedure Overview of ICH Procedures There are two approaches for revision of an existing ICH Guideline under this category: Amendments are made directly to the content of the existing guideline (e.g., in cases where the scientific/technical content is no longer up-to-date or valid). Existing guideline is not modified, but instead an Addendum or Annex to that guideline is developed. The Revision Procedure is almost identical to the formal ICH Procedure (i.e., 5-Step process). The only difference is the final outcome which will be a revised version of a current existing guideline, whereas in the formal ICH Procedure the final outcome is a new guideline. The revision of a guideline is designated by the following coding after the usual denomination of the guideline: R1, R2, R3, etc. See also Section 3.3 of the ICH Procedures

Maintenance Procedure Overview of ICH Procedures Maintenance Procedure The Maintenance Procedure follows the 5-Step process as the formal ICH Procedure. It specifically applies to Q3C residual solvents, Q4B Annexes and M2 Recommendations. This procedure also extends to any guideline that contains out-of-date information (e.g., out-of-date references, links etc…) which can be updated by the ICH Secretariat without the establishment of an EWG. Such updates require SC approval and are also considered revisions and assigned the letter R. See also Section 3.4, Annexes 4 & 5 of the ICH Procedures

Additional Activities During the Course of ICH Harmonisation Overview of ICH Procedures Additional Activities During the Course of ICH Harmonisation During the course of the ICH harmonisation activities, the Steering Committee (SC) may authorise the EWGs/IWGs to carry out other tasks intended to provide complementary information on a topic undergoing one of the above categories of harmonisation: Develop Options Papers or Points to Consider documents Conduct Proof of Concepts Conduct surveys amongst stakeholders Develop training material See also Section 4 of the ICH Procedures

Other Activities Guideline Withdrawal Overview of ICH Procedures Some ICH activities cannot fit in the above-mentioned four procedures. As of May 2005, 2 activities are considered under this category, i.e., Error Correction and Considerations. Error Correction - The ICH Secretariat may correct obvious typographical errors. In this case, no approval from the Steering Committee is required. Considerations - Under this section enter specific considerations or views expressed by a scientific discussion group: e.g., Gene Therapy and the ICH and Women. Although these topics have not been adopted as formal ICH topics, ICH supports them and the outcome of their discussions. These are posted as “Considerations” on the ICH website. Guideline Withdrawal Under exceptional circumstances a guideline may be withdrawn (e.g., ICH Q1F). Such action requires substantial justification and endorsement by the Steering Committee. See also Sections 5 & 6 of the ICH Procedures