Handling of Situations requiring submission of “Documents related to Clinical Study Results” for Medical Devices in Japan

1. What this notice is (and why it matters)

Japan’s Ministry of Health, Labour and Welfare (MHLW) issued PSEHB/MDED Notification No. 1117 (1) and PSEHB/PSD Notification No. 1117 (1) (dated November 17, 2017) to clarify how to handle cases where a marketing approval application would ordinarily require submission of “Documents related to Clinical Study Results.”
It builds on earlier MHLW notices that described (a) the scope of clinical study documents required for approval applications and (b) handling for rare diseases, and then adds a practical, lifecycle-oriented approach suited to medical devices that undergo frequent and diverse improvements.
Reference: MHLW/PMDA Notification (English reference translation)

A key concept is consistency across pre- and post-marketing phases: in certain scenarios, approval may be considered even if no new pre-marketing clinical trial is conducted, provided that safety/effectiveness can be assured through proper controls and post-marketing data collection and risk measures planned from an early stage.
Reference: MHLW/PMDA Notification

2. Scenario A: Foreign pivotal study exists, but Japan’s medical environment is the main concern

2.1 The problem the regulator is solving

When a foreign pivotal clinical study exists, Japan still expects evaluation of efficacy and safety in light of:

• racial/ethnic factors,
• environmental differences, and
• actual medical practice in Japan (e.g., how widely a procedure is used and how complications are managed).
  Reference: MHLW/PMDA Notification

2.2 When a domestic pre-market trial may be avoidable

If the main issues are external factors (e.g., spread of the procedure in Japan), the notice explains that safety and appropriate use may, in some cases, be ensured without additional pre-marketing clinical trials by:

• estimating risks attributable to medical-environment differences,
• restricting early use to limited facilities after marketing, and
• collecting post-marketing data and implementing safety measures accordingly.
  Reference: MHLW/PMDA Notification

2.3 What applicants should do early

From early development, applicants are expected to consult PMDA on:

• whether additional clinical trials are necessary, and
• what post-marketing measures are appropriate to ensure proper use.
  Reference: MHLW/PMDA Notification

The notice also emphasizes cooperating with relevant academic societies to prepare proper-use standards and training, and explaining that cooperation status during consultations.
Reference: MHLW/PMDA Notification

3. Scenario B: Improved devices with relatively small added clinical value and no significant risks assumed

3.1 Core premise

For certain improved medical devices, where:

• differences from existing products are unlikely to introduce significant risk, and
• non-clinical data, accumulated evidence, literature, and experience with similar devices can support an “almost equivalent” safety/effectiveness profile,
  the notice recognizes that it may be possible to proceed without a small pre-market clinical study, provided risk is thoroughly analyzed and early post-market issues are rapidly identified and managed.
  Reference: MHLW/PMDA Notification

3.2 The “early post-marketing safety information collection” approach

A central tool in this scenario is an early post-marketing safety information collection plan, described as:

• frequent visits/engagement with medical institutions in the early post-marketing phase for a certain number of patients,
• careful case-by-case information capture,
• prompt actions based on information obtained, and
• a defined reporting plan to PMDA.
  Reference: MHLW/PMDA Notification

The plan should specify items such as:

• events to be intensively checked and the rationale,
• target institutions and collection period,
• information collection method,
• planned timing for reporting to PMDA, and
• planned actions based on evaluation results (e.g., updating labeling, providing safety information).
  Reference: MHLW/PMDA Notification

3.3 What must be submitted at the time of approval application (when applicable)

If, through consultation on the necessity of clinical studies, the appropriate pathway is “Improved Medical Devices (without clinical data)” on the premise that early post-marketing safety information will be properly collected, the notice states that two copies of the early post-marketing safety information collection plan should be submitted to PMDA at the time of the approval application (and a flow is illustrated in the attachment).
Reference: MHLW/PMDA Notification

4. Scenario C: Diagnostic devices that measure physiological parameters used as reference information for diagnosis

4.1 The issue: clinical significance not fully established

Some physiological parameters generated by measurement and computation may be promising as reference information for diagnosis, but their relationship to clinical symptoms/pathology may not be widely recognized, and clinical significance and judgment criteria may not be sufficiently established.
Reference: MHLW/PMDA Notification

4.2 A staged development and approval strategy

The notice describes that an approval application may be filed for:

• the intended use/effects that can be supported by past clinical results, or
• mechanical (measurement) performance study results,
  even if the final clinical significance is not fully established, with a strategy to submit a partial change application later after evidence is established through clinical practice.
  Reference: MHLW/PMDA Notification

Applicants are encouraged to use PMDA pre-development consultation in advance to align expectations with reviewers.
Reference: MHLW/PMDA Notification

5. Practical takeaways for regulatory teams

• Treat “clinical study results documents” as a lifecycle package, not just a pre-market clinical trial report: combine foreign data, non-clinical evidence, literature, risk analysis, proper-use standards, and post-market data plans as a coherent justification.
• Engage PMDA early via consultation to confirm whether a domestic trial is necessary and to agree on post-marketing controls and reporting.
• When relying on early post-marketing information collection, plan operational details upfront (events, sites, collection method, reporting timetable, and action rules), because the plan may become a submission item with the approval application in the relevant pathway.
  Reference: MHLW/PMDA Notification

Further reading (PMDA English regulatory index)

PMDA maintains an English regulatory information page where this notice is listed under the conditional approval / related regulatory information for medical devices.
Reference: PMDA Regulatory Information (Medical Devices)