Topics ICH M8 eCTD v4.0 Revision Notice Briefing Session Briefing Session on eCTD v4.0 Implementation in Japan
On June 10, 2020, the Pharmaceutical Manufacturers Association of Japan (PMAJ) hosted the "ICH M8 eCTD v4.0 Amendment Notification Briefing Session" in online format (ICH: International Conference on Harmonization of Pharmaceutical Regulations). Under the circumstances of the Corona disaster, the event welcomed approximately 300 participants online on the day, with the purpose of supporting their understanding of the notice issued on February 19, 2020, "Revision of 'Application for Approval by Electronic Common Technical Document (eCTD)'", No. 0219-1 by the Pharmaceuticals and Medical Devices Agency (PMDA), Japan. The Pharmaceuticals and Medical Devices Agency (PMDA) explained the main points of the revision, and the Pharmaceutical Manufacturers Association of Japan (PMAJ) explained the impact of eCTD v4.0 in Japan within pharmaceutical companies and the PMAJ's efforts. This paper reports on the content of the presentation.
1. outline of the briefing
At the beginning of the project, we planned to recruit 150 participants for the meeting in a rally format in consideration of the participation record of the explanatory meeting for the notification before the revision, but during the preparation of the recruitment, we decided to hold the meeting in an online format using the Web. When we started accepting applications without changing the number of applicants, we actually received more than double the number of applicants. The online format made it possible for all applicants to participate, resulting in approximately 300 participants.
The target audience was pharmaceutical affairs personnel, pharmaceutical operations personnel, and those involved in eCTD preparation (including outsourcing vendors).
Since the event was held in an online format, the Q&A session was conducted by answering the questions that were filled in at the time of application.
Table 1 Program
2. explanation from Pharmaceuticals and Medical Devices Agency
Mr. Ryo Saito, ICH M8 Topic Leader, Pharmaceuticals and Medical Devices Agency (PMDA), divided the session into two parts.
In the first part, 1) an overview of eCTD v4.0 related notifications including their structure, followed by 2) the proposed schedule for implementation of eCTD v4.0 in Japan, 3) the implementation guidelines for pilot tests for the implementation, and 4) a briefing for vendors developing systems required for the compilation of eCTD v4.0. The presentation was about the following three topics.
First, there was an explanation of the new technical terms contained within the notice. He also explained the structure of the Notice and how to read it for understanding. The said revised notice is accompanied by four annexes, where Annexes 1 and 2 are the domestic implementation guidelines, and Annexes 3 and 4 are the specifications agreed upon by ICH. In addition, there was an explanation of the contents (code lists, etc.) prepared as an implementation package. For domestic implementation, since a system is required for PMDA to accept and review eCTD packages created based on the eCTD v4.0 specifications, separate notification will be made after the date when PMDA's system can accept eCTD v4.0 becomes clear, and for a while after the acceptance of v4.0 begins, the current In addition, a "transitional measure period" will be established during which the current version, v3.2.2, will also be accepted for a while after the start of v4.0 acceptance.
The PMDA is currently constructing a review system, and plans to conduct a pilot test from May 2021, followed by a review of notifications and system modifications based on the results. He mentioned that the current schedule for implementation in Japan is to start accepting eCTD v4.0 specifications in April 2022, with a transitional period until the end of FY2025, and to make it mandatory in FY2026.
He explained that the pilot test will be conducted with the goal of confirming that eCTD v4.0 specification packages are accepted without delay and are available for approval review, with the two objectives of checking for any deficiencies in the implementation guidelines and points where differences in interpretation may occur, and identifying required correction points in the notification and system. The expected implementation timeframe is 2021/5. The expected implementation period is from May to July 2021, and the participants are companies applying for approval using eCTD v4.0, vendors creating eCTD compilation tools, vendors providing eCTD compilation services, and others. However, there was a supplementary explanation that there is no "provision of a simplified compilation tool," which was available at the time of public comments, and that "use of an electronic data system for application" is out of scope.
In addition, while companies will be required to use a compilation system for eCTD v4.0 applications, the status of system development is a matter of concern. Therefore, PMDA has planned a Q&A session for development vendors, and the call for applications was announced in early July, with the actual date to be in the fall of this year.
In the second part, there was an explanation of the revisions from the July 5, 2017, notice of the Pharmaceutical Affairs Council of Japan, No. 0705 No. 1, which organized the technical points in an easy-to-understand manner. The explanation of these amendments was the main part of this briefing, but please note that most of the technical points will be omitted from this report due to the large amount of technical content.
Twelve items were listed as major revisions. Most of them were explanations of the amendment points regarding the submission of electronic application data in the eCTD. eCTD v4.0 will require electronic application data to be submitted in the eCTD package, unlike the current operation. This specification was further discussed together with the examination system specification after the issuance of the 2017 notice, and the changes were reflected in the revised notice. In addition, as points of revision other than electronic application data, there were explanations on the reuse of documents and the method of stating attachment numbers.
3. explanation from the Pharmaceutical Manufacturers Association of Japan
The Pharmaceutical Manufacturers Association of Japan (PMAJ) explained two topics: 1) Changes in eCTD v4.0 from the viewpoint of pharmaceutical affairs, and 2) PMAJ's participation plan in the eCTD v4.0 pilot test in Japan.
From the pharmaceutical perspective, Ms. Natsuko Hamada, a member of the Pharmaceutical Affairs Committee of the Pharmaceutical Manufacturers Association of Japan (PMAJ), explained the impact and four points to keep in mind when considering the start of eCTD v4.0 operation within each company: (1) collaboration with eCTD publishers, (2) review of processes, (3) review of timelines, and (4) confirmation of eCTD creation costs when outsourcing. (3) review of timelines, and (4) confirmation of eCTD creation costs when outsourcing.
The eCTD v4.0 will still use XML files for structural information and PDF files for documents, etc., but there will be more information to describe in XML than in the current eCTD v3.2.2, which will require collaboration between the pharmaceutical affairs staff and the eCTD publisher (a cooperative system to share information as appropriate). This requires cooperation between the pharmaceutical affairs staff and the eCTD publisher (a cooperative system for sharing information as appropriate). In addition, as explained above by PMDA, the electronic submission of application data will be included in the eCTD v4.0 package. Although the eCTD lifecycle does not occur when submitting a response that does not require submission of application electronic data, when the application electronic data is submitted as a response, it must be included in the eCTD package, requiring collaboration between the statistical analysis and clinical pharmacology staff, the regulatory affairs staff, and the eCTD publisher. The impact of this change is that each company will need to review its current process for electronic data submission. He also explained that the timeline of eCTD compilation including initial application and the timeline of eCTD compilation with electronic data submission and submission of inquiry response should also be reviewed. The message was conveyed that if the compilation is outsourced to an external contractor, it is also important to confirm the cost for the eCTD lifecycle for responses.
Following the PMDA's notice of the pilot test implementation and the presentation from the pharmaceutical perspective, Kayoko Ichikawa, a member of the ICH Project Committee, explained the efforts of the Pharmaceutical Cooperative Association to participate in the pilot test. She introduced the purpose, role, and flow of the Pharmaceutical Manufacturers Association's participation, as well as the test scenario and its aims.
The purpose of the pilot test was to gain a deeper and clearer understanding of the specific business impact, changes and issues in the eCTD application "process from application to approval" so that the application process can be carried out without delay after the transition to eCTD v4.0. It was explained that the Pharmaceutical Affairs Committee, the Drug Evaluation Committee's Electronic Information Subcommittee, and the Data Science Subcommittee will be involved in the pilot test as the Pharmaceutical Manufacturers Association from their respective perspectives. He also explained that at the time of the briefing, four test scenarios were being considered: 1) basic application and review cases, 2) partial change applications including clinical trials, 3) cases where electronic data for applications are submitted in response to inquiries, and 4) cases of joint development by two companies. The technical check points and issues for each case were explained.
4. Q&A session
As mentioned earlier, the session was in the form of answering the questions received during the call for participation. Basic and in-depth technical questions were received, and the same questions were grouped together to make a total of six questions, all of which were answered and explained. Of these, five questions were explained by the PMDA and one by the Pharmaceutical Manufacturers Association. The variation in the content of the questions suggests that there were participants from a variety of perspectives at this briefing session.
5. conclusion
Electronic submission of application data has become mandatory starting this year, and with this change, submission of eCTD format has become mandatory for applications requiring data submission. Currently, many tasks are already being performed electronically and there is also a demand for even more rapid digitalization support. At this briefing session, the PMDA clearly indicated that it is looking forward to accepting eCTD v4.0 in two years' time and the timing of the mandatory submission.
The Pharmaceutical Manufacturers Association of Japan (PMAJ) will continue its activities for the implementation of the new eCTD v4.0 application format in Japan and for the promotion of the initiative. The document is also available click here for more information.
(ICH M8 EWG/IWG Topic Leader: Satoko Tamamura )