Topics GCP Renovation Seminar" was held
On December 17, 2020, the "GCP (Good Clinical Practice) Renovation Seminar" was held jointly by the Ministry of Health, Labour and Welfare (MHLW), the Pharmaceuticals and Medical Devices Agency (PMDA), and the JPMA. The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) E-Guideline (Efficacy Guideline) and the GCP (Good Clinical Practice) Renovation Seminar were held jointly by the Ministry of Health, Labour and Welfare (MHLW), the Pharmaceuticals and Medical Devices Agency (PMDA), and the Pharmaceutical Manufacturers Association of Japan (PMAJ). The seminar featured lectures and panel discussions on the latest trends of the ICH E-Guideline (Efficacy Guideline), the status of the revised GCP Guideline (ICH-E6(R3) Guideline: hereinafter referred to as E6(R3)), and expectations and requests for the E6(R3). This seminar was held as part of the Stakeholder Engagement efforts for E6(R3) being conducted in each ICH region.
1. GCP Renovation Seminar Outline
E6 (R3) has just started full-fledged discussions from the ICH Singapore meeting in November 2019, and is proceeding with a policy to reflect various stakeholder views from an early stage, and stakeholder engagement efforts are underway not only at the ICH meetings but also in each ICH region. Stakeholder Engagement initiatives are underway not only at the ICH meetings but also in each ICH region. This seminar was also held as a part of stakeholder engagement efforts in Japan, co-hosted by the Ministry of Health, Labour and Welfare (MHLW), the Pharmaceuticals and Medical Devices Agency (PMDA), and the JPMA under the auspices of the ICH Foundation.
In light of the situation of the spread of the novel coronavirus, the seminar was held in an online format with minimal participation at the venue. Approximately 70 people attended the venue, Tokyo Conference Center Shinagawa (Minato-ku, Tokyo), and just under 1,800 people participated online, making it the largest attendance to date for an ICH event in Japan.
As shown in Table 1, the seminar was divided into two sessions, one in the morning and the other in the afternoon. The morning session began with a keynote speech by PMDA Chief Executive Yasuhiro Fujiwara, followed by a panel discussion on the latest ICH developments. In the afternoon session, Mr. Tomonori Ando of PMDA gave a lecture on the latest developments in ICH-E guidelines, followed by a presentation on the status of E6 (R3), expectations for E6 (R3) from the standpoints of academia and pharmaceutical companies, and finally a panel discussion.
Table 1 Program
Participants asked questions in advance, and some of the questions were reflected in the topics of the panel discussion in the afternoon session. Many of the questions were related to the quality of clinical trials that E6(R3) aims to achieve, its adaptation to Japanese regulations, and the impact that E6(R3) will have. Questions were also received from the audience and via the web for each presentation.
This report focuses on the topics related to E6 (R3), and describes the afternoon session and the panel discussion.
2. afternoon session
(1) The latest trend of ICH E-Guideline
Dr. Yuki Ando, Pharmaceuticals and Medical Devices Agency (PMDA)
Prior to the presentation on E6 (R3), Mr. Tomonori Ando, PMDA, gave a presentation on the latest developments in ICH E-Guidelines. Among the six E-Guidelines currently under discussion, he explained E8 (R1) (general guidelines for clinical trials), E11A (extrapolation in pediatric drug development), and E20 (adaptive clinical trials). In particular, for E8(R1), which will soon reach Step 4, in addition to explaining how the GCP renovation was reviewed, he also explained the importance of fitness for purpose, designing study quality into study protocols and procedures, and ensuring active improvement of study quality. The key messages that have a significant impact on E6 (R3) were presented, such as ensuring that study quality is designed into study protocols and procedures (Quality by design), and focusing on critical to quality factors to ensure study quality (Critical to Quality Factors).
(2) Background and Concept of E6(R3)
Dr. Aki Kitabayashi, Member of Expert Working Group (EWG) for E6(R3), Pharmaceuticals and Medical Devices Agency (PMDA)
Aki Kitabayashi, EWG Topic Leader at PMDA, then explained the background, objectives, current status of work, and future plans for the revision of E6 (R3). The types of trials included in Annex 2 are Pragmatic Trials (highly generalizable clinical trials that are close to routine clinical practice), Remote Clinical Trials (clinical trials that are not yet available in the marketplace), and Decentralized Clinical Trials (clinical trials that are not yet available in the marketplace). Decentralized Clinical Trials (DCTs), and clinical trials utilizing Real World Data (RWD). The timeline for revision is for the Overarching Principle and Annex 1 to reach Step 1 by November 2021, after which consideration of Annex 2 will begin.
In addition, it was explained that in parallel with the discussion of the guidelines within the EWG, input from academia representatives in each region is also being made. This is because many academicians commented during the public comment period for E6 (R2) that the current description does not adequately take into account the different risks associated with different types of clinical trials, and that the description should focus more on important factors related to the quality of clinical trials. He stated that he hopes that the opinions of academia will be taken into account from an early stage to make the guideline easier to use.
(3) E6(R3): Non-Traditional Interventional Clinical Trials
Drug Evaluation Committee, JPMA, Member of Clinical Evaluation Subcommittee, EWG Dr. Mitsuaki Aoyagi
JPMA member Mitsuaki Aoyagi, who serves as EWG Topic Leader, introduced clinical trials utilizing Pragmatic Trials, DCTs, and RWDs to be considered in Annex 2. This is an excerpt from the results of the JPMA Drug Evaluation Committee's Clinical Evaluation Subcommittee and Data Science Subcommittee's discussions to date. In particular, Pragmatic Trials, which are rarely conducted as clinical trials for the purpose of regulatory approval, are included in the focus of Annex 2, and the topic was presented from the perspective of how they will be incorporated into the Japanese regulations.
(4) Expectations for E6(R3): From Academia's Perspective
Dr. Kenichi Nakamura, National Cancer Center Hospital, Leader, E6(R3) Special Study Group, MHLW
Kenichi Nakamura is the Principal Investigator of the "MHLW Special Research Project (FY 2020), Research for the Involvement of Domestic Stakeholders in ICH-GCP Revision," and participates in meetings between E6 (R3) and representatives of academia in each region, providing various opinions to the EWG as a representative of academia in Japan. He also participates in meetings between E6 (R3) and representatives of academia in each region. Dr. Nakamura introduced the results of the ICH-GCP questionnaire conducted among Japanese academia (core clinical research hospitals + national centers) as expectations of E6 (R3) from the standpoint of academia. In addition, researchers in academia are very interested in how intervention research other than clinical trials will be incorporated into E6 (R3) and how it will affect specific clinical research, etc., and they are paying a lot of attention to Annex 2.
(5) Expectations for E6(R3): From the standpoint of pharmaceutical companies
Drug Evaluation Committee, JPMA, EWG Member Eiji Kawakatsu, Member
Mr. Eiji Kawakatsu, a member of the JPMA, introduced the results of a questionnaire conducted by the Clinical Evaluation Subcommittee of the Drug Evaluation Committee regarding the status of compliance with E6(R2) and expectations for E6(R3). It was also clear that the development and implementation of a quality management system remains an issue. As for the expectations for E6 (R3), the survey respondents cited "development of risk-based approaches in clinical trials," "flexible support for various clinical trial designs and data sources," and "flexible support for new technologies in clinical trials," while as issues for Step 5 in Japan, there was a delay in the transition to Step 5 compared to Europe and the U.S., and the implementation of a quality management system in Japan remains a challenge. On the other hand, the participants expressed their concerns about the delay in transitioning to Step 5 compared to Europe and the U.S., and the consistency with domestic regulations.
3. panel discussion in the afternoon session
During the panel discussion, the panelists offered a variety of opinions, mainly on the following topics
- 1.E6 (R3) in GCP Renovation
- 2.The state of GCP in light of COVID-19 and prospects for E6 (R3)
- 3.Patient involvement in clinical trials
- 4.Issues to be addressed when E6(R3) is introduced in Japan
- 5.Summary: Expectations and challenges for E6(R3)
Mr. Mitsuaki Aoyagi, JPMA EWG Topic Leader, explained the following two points as expectations and challenges for E6(R3).
- (1)In order to introduce the concept of proportionality, one of the key words of E6(R3), Japan's clinical trial system should be reformed in accordance with the GCP renovation trend, and the concept of quality control in accordance with the risk to subjects and the importance of the data and information obtained should be introduced. The Japanese clinical trial system is built around the Pharmaceuticals and Medical Devices Act, the Clinical Research Act, and ethical guidelines, which may be harmful to the introduction of the concept of proportionality, one of the key concepts in E6 (R3).
- (2)In the future, the quality of clinical trials will be positively improved through quality by design, with medical institutions themselves creating quality and monitors confirming that clinical trials are being conducted in accordance with the process, and in this way the quality of clinical trials will be ensured. Immediate efforts are needed to ensure that process management is appropriately implemented at medical institutions.
4. closing remarks
E6(R3) is expected to reach Step 1 of the Overarching Principle and Annex 1 by November 2021, and at first some thought that the timing of the seminar was a bit premature. However, the seminar proved to be very useful in this sense, as we were able to understand the expectations and concerns of many in the audience, and we were able to clarify what discussions would be necessary before moving on to Step 5 in the future.
Our mission is to deliver high quality medicines with more evidence to patients in a shorter development period, and we would like to proceed with the study of E6 (R3) while listening to various stakeholder opinions.
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( Mitsuaki Aoyagi, EWG Topic Leader, ICH Project, ICH E6(R3))