The Pharmaceuticals and Medical Devices Agency (PMDA), Japan, is the first health authority worldwide that implemented eCTD v4.0 and started accepting formal application in eCTD v4.0 format from April 2022. We will share how a Japanese pharmaceutical company achieved eCTD v4.0 submissions to PMDA.
Method
Although it has been ten years since ICH M8 reached step 4 in 2015, only a few health authorities have implemented eCTD v4.0 as of today. We participated in the PMDA eCTD v4.0 pilot in 2021 and have established publishing processes in accordance with the latest ICH eCTD v4.0 implementation guide.
Results
To prepare for eCTD v4.0 implementation, we, Otsuka Pharmaceutical Co., Ltd., have actively engaged in the Japan Pharmaceutical Manufacturers Association (JPMA)’s activities and developed internal processes. First, we participated in the PMDA eCTD v4.0 pilot in 2021 as a member of the JPMA’s e-Submission Task Force. We analyzed the findings from the pilot and identified challenges in eCTD v4.0 implementation. After the pilot in 2021, PMDA revised the eCTD v4.0 domestic implementation guide and specification for submission formats for eCTD in February 2022, followed by accepting voluntary applications in eCTD v4.0 format from April 2022. We examined differences between eCTD v3.2.2 and eCTD v4.0 that had key impacts on existing publishing processes such as XML messages, context of use, controlled vocabularies, keywords and lifecycle operations through JPMA task force activities as well as collaboration with eCTD tool vendors. One of the challenges with introducing eCTD v4.0 in Japan is that we are required to include CDISC datasets in the eCTD applications with keywords defined by controlled vocabularies. Thus, it is essential to review procedures for publishing clinical datasets. Given the above preparations, we had updated our eCTD publishing system by 2024, and successfully submitted applications in the eCTD v4.0 format in 2024, leveraging in-house eCTD v4.0 publishing capabilities.
Conclusion
Despite the fact that PMDA will mandate eCTD v4.0 applications from April 2026, only a few pharmaceutical companies are fully equipped with eCTD v4.0 submissions as of now. At Otsuka, the Regulatory Affairs Department is not only taking initiatives to introduce eCTD v4.0 within the company, but we are also working together with the pharmaceutical industry in Japan to streamline the processes. To accomplish successful eCTD v4.0 submissions, it is also crucial to collaborate with PMDA and get support from eCTD tool vendors. Furthermore, it is important to optimize our publishing processes and timelines while we transition to eCTD v4.0. The US FDA completed a pilot in 2023 and began accepting new applications in eCTD v4.0 format from September 2024. As Ankita Sunilkumar from Otsuka Pharmaceutical Development & Commercialization, Inc. (OPDC), US reported at the DIA Regulatory Submissions, Information, and Document Management (RSIDM) Forum 2025, OPDC successfully participated in the US FDA eCTD 4.0 pilot in 2023. We, as a global regulatory operations team, continue to collaborate on eCTD 4.0 implementation, exchange identified process challenges and ensure best practices in order to foster cross-regional collaboration while supporting global dossiers. It is expected that more and more regions will adopt eCTD v4.0 in the next few years. By sharing our insights and experiences in Japan, we hope to contribute to the promotion of eCTD v4.0 implementation around the world.
