Topics Report on the "eCTD v4.0 (ICH M8) Notification Revision and Start of Operation Briefing Session

Printable PDF

On March 11, 2022, the Ministry of Health, Labour and Welfare (MHLW), the Pharmaceuticals and Medical Devices Agency (PMDA), and the Pharmaceutical Manufacturers Association of Japan (PMAJ) jointly held a web-based "Information Meeting on the Revision of eCTD v4.0 (ICH M8) Notification and the Start of its Operation". The PMDA explained the basic concept and background information of eCTD v4.0, as well as the main points of the revised notice, in preparation for the start of eCTD operation. In addition, the Pharmaceutical Manufacturers Association of Japan (PMAJ) provided an explanation of the concept of the pilot test in 2021, in which PMAJ participated, and the key points of the corporate response. This paper reports on the content of the presentations*1.

1. outline of the briefing

The Pharmaceutical and Medical Devices Agency's Notification No. 0705-1, dated July 5, 2017, "Application for Approval by Electronic Common Technical Document (eCTD)" is an eCTD v4.0 implementation guide for Japan and was issued as a notice. The revised notice, 0219-1 dated February 19, 2020 and 0218-4 dated February 18, 2022, were subsequently issued. 0218-4 dated February 18, 2022 clearly states that eCTD v4.0 will be accepted on April 1, 2022, so that eCTD v4.0 operation can begin without delay. The briefing session was held promptly after the issuance of the revised notice so that eCTD v4.0 can begin its operation without delay.

In previous briefings on the topic, the number of participants in the assembly format was approximately 150 to 300, while the web-based briefing on the 2020 Revision Notice also attracted approximately 300 participants. However, even though this briefing session was in web format, over 500 people attended, indicating a high level of interest. Participants included those in charge of pharmaceutical affairs, those in charge of pharmaceutical affairs operations, those in charge of electronic data for some applications, and those involved in eCTD preparation (including outsourcing vendors).

Program

 

1.	Provision of information on the start of eCTD v4.0 operation	Mr. Ryo Saito, Review Management Department, Pharmaceuticals and Medical Devices Agency (PMDA)
2.	Contents of the 2022 Revision Notification	Mr. Ryo Saito, Review Management Department, Pharmaceuticals and Medical Devices Agency (PMDA)
3.	Use of eCTD v4.0 (from an examiner's perspective)	Ms. Yuka Sakaue, New Drug Review Department 1, Pharmaceuticals and Medical Devices Agency (PMDA)
4.	Introduction of PMDA public tools related to eCTD v4.0	Mr. Daigoro Yeonna, Review Management Department, Pharmaceuticals and Medical Devices Agency (PMDA)
5.	Key points for companies based on the pilot test	Ms. Satoko Tamamura, Topic Leader, ICH M8, ICH Project, Pharmaceutical Manufacturers Association of Japan
6.	Q&A (Answers to preliminary questions)	Pharmaceuticals and Medical Devices Agency / Japan Pharmaceutical Manufacturers Association

2. explanation from PMDA

From PMDA, three ICH M8 staff members gave presentations on four topics.

Information on the eCTD v4.0 Launch

The first topic, "Information on the eCTD v4.0 Launch," provided an overview and background of eCTD v4.0 in order to promote understanding of the overall picture. First, he touched on the background of the introduction of eCTD v4.0, noting that several high-impact changes were requested to v.3.2.2 of the eCTD specification, which had been in operation until now, and that the ICH M8 EWG had studied them with the aim of developing and implementing eCTD v4.0 to improve them. The EWG discussed the development and implementation of eCTD v4.0 for the purpose of improving the eCTD v4.0 and the agreement on Step 4 was reached in December 2015.

The notice for domestic implementation, "Application for Approval by Electronic Common Technical Document (eCTD)," was also issued with a revised notice as mentioned above and consists of Exhibits 1-4. Since each of these annexes refers to the contents of the other annexes, it was recommended to read through them comprehensively.

Next, as a technical overview and features of eCTD v4.0, he introduced the coding of terms, mastering of information, and the method of submitting differences from previously submitted documents. In addition, as changes compared to the eCTD specification v3.2.2, he introduced the method of submitting test data (including test data in the eCTD), reuse of previously submitted documents, and revision serial numbers (life cycle count) at the time of submission.

Contents of the 2022 Revision Notification

The second topic, "Contents of the 2022 Revision Notice," explained the revision notice issued on February 18, 2022. The revised notice reflects the results of the "eCTD v4.0 Pilot Test" conducted prior to the start of eCTD v4.0 acceptance, so the results of the pilot test and the revised contents were introduced.

The pilot test was incorporated into the eCTD v4.0 national implementation schedule and ran from May 1, 2021 to July 31, 2021. The outline for the pilot test and the results summary are available on the PMDA website
https://www.pmda.go.jp/int-activities/int-harmony/ich/0106.html

The pilot test reported that no major issues with the eCTD v4.0 specification were detected, and that all of the unacceptable cases that were detected could be corrected by the submitter or had clear instructions on how to respond. He also presented the main changes to the revised notice and the corresponding changes in the notice, which were in response to requests raised through the pilot test and changes to the description to further clarify the interpretation of the content of the notice.

Use of eCTD v4.0 (from an auditor's point of view)

The third topic, "Use of eCTD v4.0 (from an examiner's perspective)," introduced how eCTD is used in the review of new drugs from the perspective of PMDA examiners. In conjunction with the introduction of the screen image of the eCTD v4.0 viewing tool that the examiners plan to use, the features of the eCTD v4.0 display and how to provide information expected from the applicant to make the review more efficient were presented.

Introduction of PMDA public tools related to eCTD v4.0

The fourth topic, "Introduction of PMDA Public Tools and Other Tools Related to eCTD v4.0," provided an overview of three tools related to eCTD v4.0. First, the eCTD v4.0 Validation Tool is a tool for applicants to check, prior to eCTD submission, whether the application package has been appropriately prepared in accordance with the eCTD v4.0 specifications based on the technical and operational rules described in the related notices. This tool can be obtained from PMDA's "eCTD Domestic Information Provision Page" at
https://www.pmda.go.jp/int-activities/int-harmony/ich/0109.html

For an overview, "eCTD v4.0 Domestic Check Item List" and "eCTD v4.0 Verification Tool Operation Manual (Section 7.2)" were introduced, including their positioning and uses, main differences from the eCTD v3.2.2 Verification Tool, the structure of the verification result report, error classification, necessity of updating setting data and its The need to update configuration data and how to do so were also introduced. At the same time, it was announced that the latest version of the eCTD v3.2.2 validation tool has been released and that the file size limit will be changed to 500 MB for submissions using eCTD v3.2.2, starting with items submitted on April 1, 2022.

Next, the eCTD v4.0 offline viewer for public use was introduced, a tool for viewing eCTD v4.0 data offline without going through the PMDA's eCTD review system, and it was explained that it would be released as a reference for how reviewers are viewing eCTD The tool will be made available to the public as a reference for how reviewers view the eCTD. The tool was released on April 8, 2022 after the briefing and can be downloaded from the PMDA's eCTD domestic information page as follows
https://www.pmda.go.jp/int-activities/int-harmony/ich/0009.html

Next, the changes to the electronic data system for applications were introduced: compared to the eCTD specification v3.2.2, the changes in eCTD v4.0 submissions were explained, as well as the commonalities. The changes included the registration details at the time of notice of submission and the input of cover letter information at the time of GW submission. On the other hand, the common points included the basic flow of GW submission, how to obtain an eCTD receipt number, and the content and method of electronic data validation.

Finally, the technical contact for eCTD v4.0 (PMDA eCTD contact: ectd@pmda.go.jp) was introduced, and cooperation was requested so that the transition to eCTD v4.0 can be completed without problems during the transitional period.

3. explanation from the Pharmaceutical Manufacturers Association of Japan

As the PMDA provided a concise and easy-to-understand explanation of the eCTD v4.0 notification, outline, tools, etc. at the briefing, the Pharmaceutical Manufacturers Association of Japan (PMAJ) made a presentation titled "Key Points for Company Response Based on the Pilot Test" so that all participants could feel at ease in their future responses. The Pharmaceutical Manufacturers Association of Japan (PMAJ) explained its policies and initiatives in participating in the pilot test, and presented key points for corporate response based on the findings obtained from the test and the revised notice.

The PMDA indicated the following four objectives for conducting the pilot test at the time of the announcement.

 

1) Number of reports and countries from which data was obtained	Acceptance using eCTD v4.0, technical validation of eCTD v4.0 created based on the Domestic Implementation Guide
2)	Confirmation that there are no deficiencies in the Domestic Implementation Guide
3)	Confirmation that there are no major differences in interpretation of related notices
4)	Consideration of issuing Q&As and amending related notices, etc., as necessary

In response to this, the Pharmaceutical Manufacturers Association reported that they participated in the pilot test by comprehensively checking the use cases described in the implementation guide, with the key point being whether companies would be able to handle them without problems in interpretation and operation. The process and key points of conducting the pilot test and the types of errors were explained while showing the scenarios. In addition, the following six points for corporate response were explained.

 

1) Number of reports and countries from which data was obtained	Necessity of cooperation among related departments
2)	Points to keep in mind when reusing documents once submitted
3)	Points to keep in mind when dealing with hyperlinks, which can be a problem in the lifecycle of documents
4)	Handling and management of meta information that will increase from the current version
5)	Considerations for each company's PC environment and security settings
6)	Importance of change management

During the planning and preparation phase of the pilot test, we carefully reviewed the notice, but picked up points that were difficult to notice or understand on the notice. In fact, some points were noticed for the first time by compiling the eCTD in the pilot test, and these were introduced by focusing on the points.

4. Q&A session

Since the session was held online, the PMDA responded to questions received prior to the briefing in the form of answers. Although there was only a short period of time (two weeks) after the issuance of the revised notice to receive questions, we received questions confirming basic items that should be kept in mind as well as in-depth technical questions, indicating that all participants had read the revised notice as it was issued. We were also informed that an English translation of the notice is expected to be issued during FY2022.

5. conclusion

Two years have passed since the Corona disaster, and rapid digitization support is underway. Two years have also passed since the electronic submission of application data became mandatory. It has recently become known that electronic submission of application data cannot be submitted without incorporation into eCTD from eCTD v4.0 application, and we believe that companies are beginning to be aware of further internal collaboration as well as responding to changes to the new eCTD standard.

At this briefing, it was clearly explained that the start date for acceptance of eCTD v4.0 as stated in the Notice of Amendment is the beginning of FY2022, and that the transitional period is 4 years. The revised notice and implementation package, the release of other tools, and the preparation of the environment were also explained in detail for future use, and we believe that the briefing session helped the participants to better understand how to respond.

The Pharmaceutical Manufacturers Association of Japan (PMAJ) will continue its activities to promote eCTD v4.0 in the future.

( Satoko Tamamura and Kayoko Ichikawa, ICH Project ICH M8)

Back to Newsletter Top

TOP