Topics The 4th ICH Forum: ICH Efficacy Guideline Update

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On December 8, 2022, the Ministry of Health, Labour and Welfare, the Pharmaceuticals and Medical Devices Agency (PMDA), and JPMA jointly hosted the “4th ICH Forum: ICH Efficacy Guideline Update.” This forum focused on the ICH E8(R1) General Considerations for Clinical Studies, ICH E6(R3) Guideline for Good Clinical Practice, and ICH E19 A Selective Approach to Safety Data Collection in Specific Late-Stage Pre-Approval or Post-Approval Clinical Trials (Optimizing Safety Data Collection) from the ICH E Guidelines (Efficacy Guidelines) of International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), while also covering the latest ICH developments and future expectations. Additionally, commemorative gifts were presented to five Japanese recipients of the “ICH Award,” which honors experts for their contributions to ICH guideline development.

Outline of the event

ICH supports training initiatives online and in each ICH region to promote understanding of the ICH Guidelines among stakeholders. This forum was also held as part of the Stakeholder Engagement efforts in Japan, co-hosted by the MHLW, PMDA, and JPMA under the auspices of the ICH Foundation.

The morning session began with a keynote speech by PMDA Chief Executive Yasuhiro Fujiwara, followed by the ICH Awards ceremony and a panel discussion on the latest trends in ICH, as shown in Table 1. In the afternoon session, Mr. Tomonori Ando of PMDA gave a lecture on the latest trends of the ICH E-Guideline, followed by presentations on the status of E8 (R1) and E19, which have reached Step 4, and E6 (R3), which is currently under consideration for Step 2, by experts from each working group. In review, Mr. Kazuhiko Mori, Executive Director of the Pharmaceutical Manufacturers Association of Japan, gave a lecture on the E-Guideline as a whole. Finally, a panel discussion was held in response to these presentations.

The Forum was held in a hybrid format with on-site and online participation at AP Hamamatsucho (Minato-ku, Tokyo), and questions were accepted in advance as well as on the day of the Forum. Please refer to https://www.pmda.go.jp/int-activities/symposia/0126.html for the presentation materials. This report focuses on the afternoon session.

Table 1 Program

ICH Awards Ceremony

The "ICH Award" was established in 2022 to recognize experts who have contributed to the study of the ICH Guidelines. In the first year, 12 people (3 from the regulatory side and 2 from the industry side from Japan) received the award and were presented with a commemorative plaque by ICH through Mr. Fumi Yamamoto, Deputy Director General, Minister's Secretariat, Ministry of Health, Labor and Welfare. The two recipients from the industry side were Yasushi Komiyama, Vice Chairperson of the Data Science Subcommittee of the JPMA Drug Evaluation Committee, and Tomonori Nakagawa, Chairperson of the ICH Quality Group of the Quality & Technology Committee.

Latest Developments of ICH E-Guideline

Dr. Tomonori Ando, Pharmaceuticals and Medical Devices Agency

During the call for public comments during the revision of ICH E6 (R2) (2016), an international consortium and others submitted to the European Medicines Agency (EMA) and ICH an Open The following GCP Renovation (Revision of the Standards for the Conduct of Clinical Trials on Medicinal Products) is now underway.

In addition to E8, E6, and E19, which were introduced at this forum, the E-guidelines under consideration will also be further discussed in the future development and revision of the E-guidelines to further improve the efficiency and appropriateness of drug development and the methods used to achieve this. Under the policy that what is presented in the guideline is basically a principle, the message was presented that in addition to the importance of implementing communication with the authorities from an early stage, it is also important to understand the stated language, including its intent, and the time period for its dissemination and discussion.

ICH E8(R1) (General Considerations for Clinical Studies)

Pharmaceuticals and Medical Devices Agency Mr. Hiroshi Sakaguchi

The following key points of this revision of E8 were explained.

In particular, Quality by Design aims to actively improve quality by incorporating quality into study protocols and procedures, and is being revised in a risk-based approach that focuses on critical to quality factors (CTQ factors). It is important to manage risks to CTQ factors through a risk-based approach focused on critical to quality factors (CTQ factors).

He also expressed his message that E8 may be difficult to grasp because of its conceptual nature, but since a domestic notice was issued on December 23, 2022 as "Revision of the General Guidelines for Clinical Trials," he hoped that everyone would take this opportunity to review it again.

ICH E6(R3) (Guideline for Good Clinical Practice)

Mr. Izumi Oba, Pharmaceuticals and Medical Devices Agency (Pmedical Devices Agency)

The purpose of the E6 revision was explained as "to revise the current ICH E6 (R2) guideline following the modernization of ICH E8 as part of the GCP Renovation process, in order to respond to the diversification of clinical trial designs and data sources. In addition, "Overarching Principles and Objectives" will replace the current R2 guideline, and "Annex 1-Interventional clinical trails" will be revised to "Annex 2-Additional considerations". Annex 2-Additional considerations for non-traditional interventional clinical trials" will be created to replace the current R2.

The guideline revision work is being conducted while holding regular Stakeholder Engagement Sessions where the working group exchanges opinions with each stakeholder, mainly academia, so that more opinions are heard from each stakeholder prior to Step 2 than in the usual guideline development process. Therefore, it was reported that the timeline has been delayed due to the many comments received from stakeholders prior to Step 2, rather than the usual development of the guidelines, and the response to those comments.

ICH E19 (A Selective Approach to Safety Data Collection in Specific Late-Stage Pre-Approval or Post-Approval Clinical Trials)

Ms. Kinue Nishioka, Pharmaceuticals and Medical Devices Agency, Japan

First, he mentioned that the title of this guideline was changed to Step 4, which is easier to understand the contents of the guideline.

The "selective safety data collection" in this guideline is intended to reduce certain types of data collection in certain late-stage development trials, either before or after approval, but first, the safety profile of the drug must be adequately characterized, whether it serves the purpose of the clinical trial, etc. The first step is to consider whether the safety profile of the drug is well characterized and whether it is consistent with the objectives of the clinical trial. Then, if selective collection is appropriately justified and well designed, it should be conducted as a clinical trial utilizing selective safety data collection, which is recognized by numerous regulatory authorities, and as a method that can facilitate the conduct of large-scale clinical trials of efficacy and safety to answer important scientific questions. The message was expressed that the Guidelines should be used as a tool to facilitate the conduct of large scale clinical trials for efficacy and safety to answer important scientific questions.

Summary

In this lecture and panel discussion, the past ICH activities and future prospects were explained and discussed not on a guideline-by-guideline basis but across the board, including efficacy guidelines as a whole and ICH's communication with external stakeholders. The ICH has expanded its scope of influence from its founding regulatory members in Japan, the U.S., and Europe to a total of 56 organizations today.

The importance of promoting collaboration with external stakeholders as well, thereby promoting drug development in a more efficient and optimal manner, was also discussed in each guideline. In addition, the environment surrounding drug development has drastically changed due to the new coronavirus infection (COVID-19), and guidelines related to this are being appropriately revised.

As mentioned above, our daily activities as an ICH were made known once again through this forum. However, since it inevitably takes time to establish guidelines and the situation changes depending on the purpose of the drug product to be developed, etc., I felt again that it is essential to proceed in an appropriate manner according to the situation while maintaining close communication with the regulatory authorities, while following the guidelines in principle.

( Machiko Kaku, ICH Project)

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