Handling of the Conditional Approval of Medical Devices and In Vitro Diagnostic Pharmaceuticals in Japan

1. Background and policy intent

Japan introduced a structured approach for conditional approval to address situations where innovative medical devices and in vitro diagnostic pharmaceuticals (IVDs) target serious diseases yet face practical difficulty in generating the full set of clinical data needed for a standard approval application (e.g., small patient populations, lengthy trials). The system aims to promote earlier practical use while planning strict post-marketing risk measures from the development stage, including use conditions and post-marketing data collection.
Source: PSEHB/MDED Notification No. 0831 (2) (Aug 31, 2020)

The notification also explains that this handling is positioned as a legal system under the Act on Securing Quality, Efficacy, and Safety of Products Including Pharmaceuticals and Medical Devices (PMD Act), as amended (Act No. 63 of 2019), referencing conditional approvals with conditions under the Act’s relevant provisions.
Source: PSEHB/MDED Notification No. 0831 (2)

2. Target products and eligibility types

A product may be considered if it meets all requirements under Type 1 or Type 2.

Type 1 (high-impact disease + difficulty conducting new trials)

The notification describes Type 1 as generally requiring:

• Target disease has significant impact on life or irreversible progression with major impact on daily life
• No existing therapy/prevention/diagnosis, or the product offers markedly higher efficacy or safety versus existing options
• Ability to present appropriate clinical data for certain evaluations
• Applicant can reasonably explain that conducting a new clinical trial/clinical performance study is difficult
• Applicant can prepare a proper use guideline with related academic societies and present a concrete plan for collection/evaluation of post-marketing data
  Source: PSEHB/MDED Notification No. 0831 (2)

Type 2 (certain devices/IVDs with extrapolability + proper use assurance)

Type 2 is described as applicable to:

• Devices intended for ablation or other physical functions affecting human structure/function, or IVDs of particularly high medical need
• Ability to present appropriate clinical data with extrapolability to assess an expanded intended use not directly assessed by existing data
• Rational explanation that proper use can be ensured without conducting a new trial/performance study
• Applicant can prepare a proper use guideline with academic societies and a concrete post-marketing data plan
  Source: PSEHB/MDED Notification No. 0831 (2)

PMDA also maintains an English regulatory information page listing this conditional approval handling notice and related notifications.
Source: PMDA Regulatory Information (Medical Devices)

3. Consultation pathway before approval

3.1 Pre-development consultation (eligibility discussion)

If an applicant intends to pursue approval under this system, the notice describes using PMDA’s pre-development consultation (for medical devices or IVDs). In this step, the applicant, MHLW, and PMDA exchange views on eligibility based on a “summary of eligibility” in the attached format. MHLW/PMDA may request additional information and, as needed, involve a committee focused on early introduction of high-need devices to support evaluation (e.g., disease seriousness, availability of alternatives).
Source: PSEHB/MDED Notification No. 0831 (2)

The notice also describes situations where eligibility may be determined without undergoing the pre-development consultation (e.g., certain designated products), while still expecting preparation of the eligibility summary and consultation with the relevant MHLW division.
Source: PSEHB/MDED Notification No. 0831 (2)

3.2 Consultation on the necessity of clinical trials / clinical performance studies

Where the applicant plans to apply without conducting new clinical trials (or clinical performance studies for IVDs), the notice directs applicants to seek PMDA consultation to confirm whether:

• evaluation of available clinical data is sufficient, and
• the draft risk management plan is appropriate
  This consultation can include medical experts as needed and focuses on whether the risk-benefit balance can be appropriately evaluated based on existing data and the draft proper use guideline, considering disease seriousness and post-marketing measures needed for proper use.
  Source: PSEHB/MDED Notification No. 0831 (2)

4. Approval application and review expectations

4.1 Attach a draft RMP at the time of application

At the time of making the approval application, the applicant should attach a draft medical device RMP as part of the application documents, and record prior consultations (including date/time and reception number) in the application form’s remarks, consistent with the notice.
Source: PSEHB/MDED Notification No. 0831 (2)

4.2 QMS compliance review readiness

The notice highlights that extra attention should be paid to system development necessary for the QMS compliance review, because the QMS review application should be made promptly after the approval application.
Source: PSEHB/MDED Notification No. 0831 (2)

4.3 Review focus: confirm safety/efficacy premised on implementing the RMP

During approval review, the validity of the draft RMP is confirmed, and safety/efficacy are evaluated on the premise that the confirmed RMP will be appropriately implemented. The notice indicates that products under this system are, in principle, subject to use-results evaluation, and implementation of post-marketing risk management (including proper use guidelines) is secured as approval conditions.
Source: PSEHB/MDED Notification No. 0831 (2)

5. Procedure after approval (post-marketing obligations)

Key post-approval expectations described include:

• Submit the (final) medical device RMP to PMDA one month before planned start of marketing (in principle)
• Collect post-marketing information per the RMP and provide information to medical professionals and patients to ensure proper use and prevent health hazards
• If collecting use-results survey data via registries, ensure data can be verified upon MHLW/PMDA request and clarify responsibilities for data management and use in advance
• Submit annual periodic reports during the period of the use-results survey (in principle) and consider sharing latest information with clinicians
• Consult PMDA in advance when changing post-marketing plans (including proper use guideline) or expanding treatable facilities based on use-results evaluations and post-marketing trends
  Source: PSEHB/MDED Notification No. 0831 (2)

6. Practical considerations and positioning versus other pathways

The notice also flags that depending on product circumstances, it may be appropriate to consider other regulatory handling routes (e.g., certain off-label use handling, rare disease clinical data handling, or reliance on non-clinical evidence plus consultation), and encourages using PMDA consultations to determine the best approach.
Source: PSEHB/MDED Notification No. 0831 (2)

7. Effective date

The notification states that it came into effect from September 1, 2020.
Source: PSEHB/MDED Notification No. 0831 (2)