Quote from VigiServe Admin on November 27, 2020, 1:02 PM

The pharmacovigilance (PV) system in **Japan** is one of the most advanced and mature in the world, fully aligned with international standards (ICH guidelines) and managed by the **Pharmaceuticals and Medical Devices Agency (PMDA)** under the **Ministry of Health, Labour and Welfare (MHLW)**. Japan has been a founding member of the WHO Programme for International Drug Monitoring (PIDM) and contributes extensively to VigiBase. The system is governed by the **Pharmaceuticals and Medical Devices Act (PMD Act)** and detailed **Good Vigilance Practice (GVP)** and **Good Post-marketing Study Practice (GPSP)** ordinances, with strict post-marketing surveillance obligations.

### Legal Framework and Governance
- **PMD Act** (Act No. 145 of 1960, extensively amended) and **Ordinance on Standards for Post-marketing Safety Management** (MHLW Ordinance No. 135, 2004, as amended).
- PMDA operates the national PV center (Adverse Drug Reaction Reporting System), handles ADR/AEFI collection, signal detection, causality assessment, risk evaluation, safety communication, and regulatory actions (label changes, recalls, market withdrawal).
- Reporting is mandatory for MAHs and encouraged for healthcare professionals (HCPs) and patients.

### Organization and Personnel
- Marketing Authorization Holders (MAHs) must establish and maintain a robust PV system compliant with Japanese GVP.
- **Qualified Person for Pharmacovigilance (QPPV)**: Mandatory; a full-time employee (usually physician or pharmacist) designated as the **Safety Manager** responsible for PV activities and primary PMDA contact (must reside in Japan).
- **Pharmacovigilance System Master File (PSMF)**: Not explicitly mandatory as in EU, but MAHs must maintain comprehensive PV system documentation (SOPs, procedures, organization charts) available for PMDA inspections.

### Individual Case Safety Reports (ICSRs) – Post-Marketing
- MAHs must report all serious ADRs, unexpected ADRs, and infections associated with drugs to PMDA electronically (via the **PMDA Adverse Reaction Reporting System**).
- **Timelines** (strictly enforced):
- **Serious unexpected ADRs / infections** (domestic): Within **15 calendar days** of awareness.
- **Serious expected ADRs** (increased frequency/severity): Within **15 calendar days**.
- **Non-serious ADRs**: Within **periodic reporting** or as part of PSURs (not expedited).
- **Foreign serious unexpected ADRs**: Within **15 calendar days** if relevant to Japan.
- MedDRA coding required; reports feed into national database and VigiBase.

### Periodic Benefit-Risk Evaluation Reports (PBRER/PSUR)
- MAHs submit **Periodic Safety Update Reports (PSURs)** (ICH E2C(R2) format) to PMDA.
- Frequency: Typically every **6 months** for the first 2 years post-approval, then **annually** (or as specified in approval conditions).
- Long-term PSURs required for certain drugs (e.g., orphan drugs, biologics).

### Risk Management Plans (RMP)
- Mandatory for many new drugs, biologics, orphan drugs, and high-risk products (per PMDA risk management guidance).
- Japan-specific RMP format (not identical to EU, but similar structure: safety specification, pharmacovigilance plan, risk minimization plan).
- Updates required for new risks or significant changes; PMDA may impose additional conditions (e.g., post-marketing surveillance studies).

### Signal Management and Emerging Safety Issues
- MAHs continuously monitor global/local data and notify PMDA of validated signals or emerging safety concerns promptly (e.g., foreign regulatory actions).
- PMDA leads national signal detection and risk assessment (using advanced tools and data mining).

### Clinical Trials-Related Safety Requirements
Clinical trials require PMDA approval (Clinical Trial Notification [CTN] or IND-equivalent) and ethics committee review (aligned with ICH GCP).
- Sponsors monitor safety and report to PMDA.
- **Suspected Unexpected Serious Adverse Reactions (SUSARs)**: Expedited reporting (ICH E2A-aligned):
- Fatal/life-threatening SUSARs: **7 calendar days**.
- Other serious unexpected SUSARs: **15 calendar days**.
- **Development Safety Update Reports (DSURs)**: Annual submission required (ICH E2F format), especially for ongoing trials.
- Serious breaches of GCP/protocol must be reported promptly.
- Sponsor responsibility for monitoring, causality assessment, DSMB (if applicable), and communication to PMDA/ethics committees.

### Additional Monitoring / Other Aspects
- **Post-marketing surveillance (PMS)**: Mandatory for many new drugs (e.g., all new chemical entities, biologics, orphan drugs) — often 4–10 years or risk-based.
- **Re-examination** and **re-evaluation** systems for long-term safety data.
- **Early Post-marketing Phase Vigilance (EPPV)**: Mandatory for certain high-risk drugs (intensive monitoring in first 6 months).
- Emphasis on electronic reporting, HCP/patient submissions, and risk-based inspections.
- No black triangle scheme, but **conditional approval** and **risk minimization plans** used for high-risk products.

Japan's PV framework is ICH-harmonized, enforcement-oriented, and one of the world's strongest (mandatory local Safety Manager, PSMF-like documentation, 15/90-day ICSR timelines, routine PSUR/RMP, expedited SUSAR/DSUR, mandatory PMS/EPPV). It balances rigorous obligations with efficient approvals.

For precise, product- or trial-specific details (e.g., latest guidance, forms, or submission portals), consult **PMDA** directly via pmda.go.jp (English site: Safety Information > Pharmacovigilance) or MHLW, as requirements evolve (e.g., 2025–2026 updates on digital tools and risk management). Companies often appoint a local Safety Manager and align with PMDA guidelines for compliance in Japan.