Local Regulatory Experts
Connect with regulatory affairs consultancies specializing in this region.
Qualtech Consulting Corporation
Taiwan, China, Japan, Singapore, Hong Kong, Malaysia, Philippines, Vietnam, Australia, Germany, Korea, Thailand, USA
A specialized medical device consulting firm offering a one-stop solution for complex global regulatory challenges. We offer real-time regulatory and clinical support, local representation, and QMS services across 13 markets, ensuring efficient market entry and compliance.
Cobridge Co., Ltd.
Tokyo, Japan
We assist medical device companies with the medical device registration and approval in Japan. Regulatory consulting services and DMAH services for foreign manufacturers to enter Japanese market.
MDREX, Medical Device, Digital Health Consulting Group
Seoul, Republic of Korea (HQ), Japan Office
We offer total solutions for market entry in South Korea and global expansion (e.g., Japan, USA, Europe). Key areas include product approval, reimbursement listings (HIRA), and Quality System certification (KGMP). They are particularly strong in innovative products like SaMD, medical wearables, and 3D printing for medical use, and provide in-depth expertise in cybersecurity and clinical trial planning.
CMIC Holdings Co., Ltd.
Tokyo, Japan (HQ), Osaka, Japan, Beijing, China, Seoul, South Korea, Taipei, Taiwan, Singapore, New York, USA, London, UK, Frankfurt, Germany, Sydney, Australia
We operate globally, specializing in accelerating the development, manufacturing, and commercialization of drugs and medical devices. Their expertise spans Phase I to IV clinical trials, regulatory affairs, quality assurance, and manufacturing, with a strong focus on the Japanese and Asian markets. Key services include clinical operations (CRO), manufacturing (CDMO/CMO), site management (SMO), and comprehensive health analysis and solutions.
January 3, 2026
Approximately 5 minutes
Handling Japan’s two-step approval option for SaMD (PMDA/MHLW Notification No. 1116-2)
Handling of the Two-step Approval Based on the Characteristics of SaMD in Japan
1. Regulatory intent and positioning
Japan’s Ministry of Health, Labour and Welfare (MHLW) issued PSB/MDED Notification No. 1116-2 to clarify how an optional two-step approval concept may be applied to Software as a Medical Device (SaMD), based on the operational approach described in earlier guidance and subsequent SaMD-focused discussions.
Two-step approval is described as an option; applicants may still pursue regulatory approval without using this approach.
2. The core concept: first-step approval, then evidence-building, then second-step approval
The notification describes a development strategy in which an applicant:
- Consults PMDA and explains clinical relevance using available summaries of clinical results (even when the ultimate clinical significance is not fully established yet).
- Obtains first-step approval by limiting the intended use/effect to what can be supported by non-clinical evidence and studies of mechanical performance (e.g., measurement, detection, arithmetic performance).
- Establishes clinical evidence post-marketing (including post-marketing clinical studies and real-world data) based on real clinical use, then files a partial change or new application for second-step approval as needed.
3. Two-step approval for SaMD for disease diagnosis
3.1 When this pathway is envisioned
This pathway is expected for SaMD that calculates physiological parameters, risk scores, or characteristic values where the association with clinical symptoms/pathology is not widely recognized and clinical significance/medical determination criteria are not sufficiently established, even though the outputs may be considered as reference information for diagnosis or prognosis prediction.
3.2 Recommended interactions with PMDA
The notification emphasizes early exchange of views with reviewers via pre-development consultation with PMDA, and recommends conducting protocol consultation for the second-step approval concurrently.
3.3 Examples of eligible SaMD concepts (diagnosis)
Examples include:
- SaMD that calculates parameters from active monitoring medical devices and biological signals (e.g., testing/monitoring devices, imaging devices), sensors (including webcam of general-purpose computers), mobile devices such as smartphones, and various test information.
- SaMD that provides one of several determination criteria as reference information for diagnosis although final-target clinical significance is not yet established.
- SaMD that would not significantly impact life/health even if incorrect test results are obtained.
3.4 Examples of ineligible SaMD concepts (diagnosis) as a principle
The concept is generally not applied to cases where more detailed information is clinically expected, including:
- Programs where test/diagnosis results significantly impact medical decisions (e.g., cancer treatment policy, initial emergency treatment policy).
- Review categories where new information is provided on a daily basis (example given: gene-related tests).
- Fields where clinical significance and medical determination criteria are already established (example given: pulmonary nodules/polyps, including where similar approved products exist).
- Cases where second-step approval has already been obtained for products with the same intended use/effect and used in clinical practice.
3.5 Planning clinical evaluation for second-step approval
The notification indicates that planning for clinical evaluation to confirm clinical significance should be discussed with PMDA both at the time of consultation for the first-step application and concurrently after submission.
For second-step approval, clinical evaluation data must meet data integrity standards for product applications, and real-world data (including registries) may be used in addition to post-marketing clinical study results, with advance consultations (including on the need for clinical studies and protocol) recommended.
4. Two-step approval for SaMD for disease treatment
4.1 When this pathway is envisioned
For SaMD that assists or supports disease treatment where clinical evidence as a treatment is not established, an evidence-based explanation of clinical significance as a treatment method is generally required.
The notification highlights scenarios where clinical trial feasibility may be low (e.g., multifactorial diseases involving genetics/lifestyle, psychiatric disorders, pain/functional syndromes where subjective indicators are primary endpoints), and where some SaMD may still be useful based on exploratory trial results or other evidence of symptom relief/condition improvement.
4.2 Development strategy described
Applicants may seek first-step approval for a limited intended use/effect where a certain level of efficacy (e.g., symptom relief or improvement) is confirmed with feasibility using exploratory clinical study results and performance evaluation studies, even if final-target clinical significance is not fully established; then pursue second-step approval after post-marketing evidence (including real-world data) is established.
4.3 Practical actions and clinical evaluation planning
As with diagnosis, the notification stresses pre-development consultation with PMDA and concurrent protocol consultation for second-step approval. It also states that real-world data (including registries) may be used for second-step clinical evaluation in addition to post-marketing clinical study results, provided data integrity expectations are met and consultations are conducted in advance.
5. SaMD for disease prevention (boundary note)
Programs contributing to primary prevention (e.g., health promotion) do not meet the definition of SaMD and therefore are not medical devices. Secondary/tertiary prevention programs may fall under SaMD for diagnosis or treatment, and development policy should be consulted with PMDA from the development stage.
6. Implementation checklist (developer-oriented)
- Decide whether two-step approval is appropriate (it is optional).
- Engage PMDA early via pre-development consultation; align on what can be supported for first-step approval and what evidence will be needed for second-step approval.
- Define a limited first-step intended use/effect supported by non-clinical and mechanical performance evidence (measurement/detection/arithmetic performance as applicable).
- Plan post-market evidence generation (post-marketing clinical studies and/or real-world data such as registries) and ensure data integrity expectations are met for second-step submission.
- Prepare for a partial change or new application when clinical significance is sufficiently established in real-world clinical practice.
7. Q&A (grounded in the notification)
Q1. Is two-step approval mandatory for SaMD in Japan? A1. No. The notification explicitly describes it as an option; approval may be obtained without applying this approach.
Q2. What is the key difference between first-step and second-step approval in this concept? A2. First-step approval limits intended use/effect to what is supported by non-clinical and mechanical performance evidence; second-step approval is pursued after post-marketing clinical evidence (including real-world data) establishes clinical significance more fully.
Q3. Can real-world data be used for second-step approval? A3. Yes. The notification notes that real-world data (including registries) may be used, alongside post-marketing clinical study results, provided data integrity standards for product applications are met and PMDA consultations are conducted.
Q4. When should PMDA consultation occur? A4. The notification emphasizes pre-development consultation and indicates consultation should occur at the time of first-step consultation and concurrently after submission, including protocol consultation for second-step approval.
References
Have a Question?
Ask our experts about this topic. We'll do our best to respond to your question.
Related Articles
Approximately 5 minutes
Japan Medical Device Registration: Pathways and Requirements
The medical device registration process in Japan is overseen by the PMDA and varies significantly based on device classification (Class I to IV). Key pathways include Pre-Market Submission (PMS), Pre-Market Certification (PMC), and Pre-Market Approval (PMA).
Approximately 5 minutes
Japan Medical Device Local Labeling Requirements: Tempu Bunsho
Medical device labeling in Japan, specified by PMDA's Article 52, mandates the use of Japanese 'tempu bunsho' (package inserts/IFUs). This process involves rigorous content requirements, notification upon revision, and MAH/DMAH oversight for affixation.
Approximately 5 minutes
Japan Medical Device Post-Market Surveillance (PMS): GVP and Adverse Event Reporting
An overview of Japan's PMS requirements under the PMD Act, focusing on the MAH's GVP compliance, the mandatory reporting of adverse events (Fuguai), and the strict reporting timelines (e.g., 15 days for death or serious, unanticipated events).
Approximately 5 minutes
Japan Specialty Fulfillment for Medical Devices: Low Volume, High Value Sales
Specialty Fulfillment is a crucial service for foreign medical device manufacturers targeting low-volume, high-value sales in Japan, often utilizing an Independent License Holder to manage customs, storage, and distribution to maintain high profit margins.
Approximately 5 minutes
Regulatory Science in Japan: PMDA’s Evidence-Based Approach to Innovation and Public Health
This article explains what “regulatory science” means in Japan and how the PMDA advances it through organizational structures, expert deliberation, collaborations, and research dissemination. A practical Q&A is included for industry and academia.