Topics “The 4th ICH Forum: ICH Efficacy Guideline Update” Held
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
The ICH supports training initiatives—both online and in each ICH region—to promote understanding of ICH guidelines among stakeholders. This forum was held as part of the Stakeholder Engagement initiative in Japan, co-hosted by the Ministry of Health, Labor and Welfare (MHLW), the Pharmaceuticals and Medical Devices Agency (PMDA), and the JPMA, with funding from the ICH Foundation.
As shown in Table 1, the forum consisted of two sessions, morning and afternoon. The morning session began with a keynote speech by Mr. Yasuhiro Fujiwara, PMDA Chief Executive, followed by the ICH Awards ceremony and a panel discussion on the latest ICH trends.In the afternoon session, following a presentation by Yuki Ando of the PMDA on the latest trends in ICH E-guidelines,experts from each working group presented the status of E8 (R1) and E19, which have reached Step 4, as well as E6 (R3), which is currently under review for Step 2. To wrap up the session, Kazuhiko Mori, Executive Director of the JPMA, delivered a presentation on the E-Guidelines as a whole. Finally, a panel discussion was held to build on these presentations.
The forum was held in a hybrid format, combining in-person attendance at the venue (AP Hamamatsuchō, Minato-ku, Tokyo) with online participation, and accepted questions submitted in advance as well as those asked on-site during the event.Please refer to the presentation materials here ( https://www.pmda.go.jp/int-activities/symposia/0126.html ). This article focuses on the presentations from the afternoon session.
Table 1: Program
ICH Awards Ceremony
The “ICH Awards,” established in 2022 to honor experts who have made significant contributions to the development of ICH guidelines, recognized 12 recipients in its inaugural year (including three from the regulatory side and two from the industry side in Japan). Commemorative plaques were presented by the ICH through Mr. Fumi Yamamoto, Deputy Director-General of the Minister’s Secretariat at the Ministry of Health, Labor and Welfare.The two industry recipients were Yasushi Komiyama, Vice Chairperson of the Data Science Subcommittee of the Drug Evaluation Committee of the JPMA, and Tomonori Nakagawa, Chairperson of the ICH Quality Group within the Quality & Technology Committee.
Scenes from the ICH Awards Ceremony
Latest Developments in ICH E Guidelines
Ms. Yuki Ando, Pharmaceuticals and Medical Devices Agency (PMDA)
During the public comment period for the revision of ICH E6 (R2) in 2016,international consortia and other groups submitted an open letter to the European Medicines Agency (EMA) and the ICH, stating that “we should aim to improve quality by focusing on more critical aspects of clinical trial design and conduct.” This led to the decision to proceed with the GCP Renovation (revision of the Good Clinical Practice guidelines).
- •To respond appropriately and flexibly to the diversification of trial types and data sources
- •Modernization of ICH E8 and the Subsequent Revision of E6 (R2)
- •Incorporating feedback from external stakeholders during the revision process
Furthermore, regarding the E-guidance under consideration other than E8, E6, and E19—which were introduced at this forum—the methods for streamlining and optimizing drug development will be further examined in the future during the creation and revision of E-guidelines.It was emphasized that, given the guidelines’ fundamental focus on principles, in addition to the importance of early communication with regulatory authorities, it is also crucial to understand the intent behind the wording, as well as to allow sufficient time for dissemination and discussion.
ICH E8(R1) (General Considerations for Clinical Studies)
Mr. Hiroshi Sakaguchi, Pharmaceuticals and Medical Devices Agency
The following key points regarding the current revision of E8 were explained.
- •Providing guidance on the clinical trial lifecycle
- •Viewing “Quality in clinical trials” as “fit for purpose”
- •The “Quality by Design” concept was incorporated into the planning and design considerations
Specifically, regarding Quality by Design, it was explained that the goal is to proactively improve quality by embedding quality control measures directly into clinical trial protocols and procedures. It was emphasized that it is crucial to manage risks associated with Critical to Quality (CTQ) factors through a risk-based approach that focuses on these factors.
Furthermore, while E8 may be difficult to grasp due to its conceptual nature, a domestic notification titled “Revisions to the ‘General Guidelines for Clinical Trials’” was issued on December 23, 2022; participants were encouraged to take this opportunity to review the guidelines once again.
ICH E6(R3) (Guideline for Good Clinical Practice)
Ms. Izumi Oba, Pharmaceuticals and Medical Devices Agency
It was explained that the purpose of this E6 revision is “to revise the current ICH E6 (R2) guideline as part of the GCP Renovation initiative, following the modernization of ICH E8, in order to address the diversification of clinical trial designs and data sources.”It was also explained that, as part of the structure of the revised guidelines—which will replace the current R2 version—“Overarching Principles and Objectives” will be created, while “Annex 1—Interventional Clinical Trials” will be reorganized as “Annex 2—Additional Considerations for Non-Traditional Interventional Clinical Trials” to address topics requiring further consideration.
It was also reported that, since this guideline revision process involves regularly holding “Stakeholder Engagement Sessions” where working groups exchange views with various stakeholders—primarily from academia—the process has gathered a greater volume of feedback from stakeholders prior to Step 2 than is typical for guideline development, and the timeline has been delayed as a result of addressing this input.
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
First, they noted that when the title of these guidelines was changed to “Step 4,” it was revised to make the content easier to understand, and then they explained the contents of the guidelines.
The term “selective safety data collection” as used in these guidelines refers to the intention to reduce the collection of certain types of data in specific late-stage clinical trials conducted prior to or after approval; however, it is first necessary to consider whether the drug’s safety profile has been sufficiently characterized and whether this approach is consistent with the objectives of the clinical trial, among other factors.On that basis, the message conveyed is that, provided selective collection is appropriately justified and accurately designed, these clinical trials should be conducted as trials utilizing selective safety data collection—a practice recognized by numerous regulatory authorities—and that these guidelines should be used as a tool to facilitate the conduct of large-scale clinical trials on efficacy and safety designed to answer important scientific questions.
Summary
During the lectures and panel discussions, participants engaged in cross-cutting explanations and discussions—ranging from past ICH activities to future prospects—focusing not on specific guidelines but on broader topics such as the Efficacy Guidelines as a whole and communication between ICH and external stakeholders.While the ICH initially consisted only of regulatory authorities and industry organizations from Japan, the U.S., and Europe, it has since expanded to an organizational structure comprising a total of 56 member organizations, broadening its sphere of influence.
Through collaboration with external stakeholders, the importance of advancing drug development in the most efficient and optimal manner has also come to be addressed in various guidelines. Furthermore, as the environment surrounding drug development is undergoing fundamental changes due to the novel coronavirus disease (COVID-19), related guidelines and other documents are being appropriately revised.
As mentioned earlier, this forum served to reaffirm the public’s awareness of the ICH’s day-to-day activities. However, given that the development of guidelines inevitably takes time and that circumstances vary depending on the purpose of the pharmaceutical product being developed, I was reminded once again that while adhering to the guidelines as a principle, it is essential to proceed in a manner appropriate to the situation through close communication with regulatory authorities.
Scenes from the afternoon panel discussion
(ICH Project: Machiko Sumi )