§ 02 — Comparison

Compare regulatory pathways side-by-side

Benchmark MAHMAH, GMPGMP, HTAHTA and pathway requirements across up to three markets.

Country A

Country B

Country C

Highlight differences

Criterion	🇯🇵Japan	🇺🇸United States	🇪🇺European Union
Authority & dossier
Regulatory authority	PMDA	FDA	EMA
English submissions	No	Yes	Yes
CTD accepted	Yes	Yes	Yes
eCTD accepted	Yes	Yes	Yes
Reliance pathway	None	None	Available
Reference agencies	—	—	—
Lead pathway (timeline & fees) — J-NDA (New Drug Application) · New Drug Application — 505(b)(1) · Centralised Procedure
Pathway name	J-NDA (New Drug Application)	New Drug Application — 505(b)(1)	Centralised Procedure
Approval timeline	270–365 days	304–365 days	210–277 days
Application fee	JPY 38,950,800	USD 4,310,002	EUR 358,800
Annual renewal	JPY 0	USD 416,734	EUR 122,500
Local representative	Required	Not required	Required
Local manufacturing	Not required	Not required	Not required
GMP inspection	Required	Required	Required
MAH & local presence
Local entity required	Yes	No	Yes
Local responsible person	Yes	Yes	Yes
RP role	Three named Japanese-based responsible persons required: General Marketing Compliance Officer (GVP), Marketing Authorisation Holder Quality Assurance Officer, and Safety Management Officer. All must reside in Japan. Foreign manufacturers must hold a Foreign Manufacturer Accreditation (FMA) for each manufacturing site.	US Agent: a person residing or maintaining a place of business in the US, designated to act on behalf of the foreign establishment for FDA communications, including notification of inspections.	Qualified Person Responsible for Pharmacovigilance (QPPV) — must reside and operate in the EU/EEA — is responsible for the establishment and maintenance of the pharmacovigilance system. A Qualified Person (QP) in the EU/EEA performs batch certification under Article 51 of Directive 2001/83/EC. Local Contact Person for pharmacovigilance required in each Member State where the product is marketed (since 2012 GVP).
Accelerated pathways
Designations available	4 designations	6 designations	6 designations
Examples	Priority Review, Orphan Drug Designation, Conditional Early Approval (Article 14-2-3) +1	Priority Review, Breakthrough Therapy Designation, Accelerated Approval — Subpart H/E +3	Accelerated Assessment, Conditional Marketing Authorisation, Authorisation under Exceptional Circumstances +3
Post-approval lifecycle
Variations framework	Three categories: Minor Change Notification (post-implementation notification, certain low-risk CMC and labelling), Partial Change Application (PCA — prior approval, mid-tier changes, ~6 months), and full Re-Application (major changes effectively requiring new NDA).	FDA classifies post-approval changes as: Annual Reportable, Changes Being Effected (CBE-0 immediate, CBE-30 with 30-day pre-implementation notice), and Prior Approval Supplements (PAS) — the most significant changes requiring FDA approval before implementation. Major manufacturing or labelling changes typically require a PAS.	Commission Regulation (EC) 1234/2008 establishes four categories: Type IA (minor — Do and Tell, 12-month notification), Type IAIN (minor — immediate notification), Type IB (minor — Tell, Wait, and Do, 30-day default), Type II (major — prior approval, 60–90 days), and Extensions (Annex I changes — full review). Worksharing procedures consolidate variations across multiple authorisations.
Renewal cycle	Re-examination period of 4–10 years post-approval (8 years for new active substances, 10 years for orphan drugs and paediatric indications) — during which the applicant collects and submits post-marketing safety and efficacy data. Re-evaluation may follow at MHLW direction.	FDA does not require periodic renewal of NDAs or BLAs — approvals remain in effect indefinitely subject to compliance, payment of annual program fees, and post-marketing requirements. Annual reports are required.	Initial 5-year renewal — application 9 months before expiry. After the first renewal, MA is granted for unlimited duration unless the CHMP/NCA, on justified grounds relating to pharmacovigilance, decides on one additional 5-year renewal.
Pharmacovigilance	MHLW operates the Drug Safety Information Reporting System; expedited reporting of serious unexpected ADRs within 15 days. PSURs aligned with global birth dates. J-RMP required for all new approvals. The Medical Information Database Network (MID-NET) provides real-world data infrastructure for active surveillance.	Mandatory expedited reporting of serious unexpected ADRs within 15 calendar days; periodic safety reports (PADERs/PAERs) for the first 3 years post-approval, then annually. PSURs in ICH E2C(R2) format accepted in lieu of PADERs by agreement. FAERS database receives spontaneous reports. Post-Marketing Requirements (PMRs) and Commitments (PMCs) tracked publicly.	Comprehensive PV framework under Directive 2010/84/EU and Regulation (EU) 1235/2010, codified in Good Pharmacovigilance Practices (GVP). Pharmacovigilance System Master File (PSMF) required. Periodic Safety Update Reports (PSURs) on EU-harmonised birth-date list. Risk Management Plans for all new MAs and significant variations. Suspected serious ADR reporting to EudraVigilance within 15 days. Black triangle (▼) for additional monitoring of selected products.
Unlicensed access
Named Patient Supply	Available	Available	Available
Compassionate Use	Available	Available	Available
Emergency Import	Available	Available	Available
Parallel Import	Not permitted	Not permitted	Permitted
Clinical trials
CTA approval	Required	Required	Required
Ethics approval	Yes	Yes	Yes
CTA timeline	30–30 days	30–30 days	60–106 days
GCP standard	J-GCP (Ministerial Ordinance No. 28, 1997, as amended) — fully ICH E6 aligned	ICH E6(R3) (adopted via FDA guidance January 2025); 21 CFR 312, 314, 50, 56	ICH E6(R3) — Commission Regulation (EU) 2024/2748 transposing R3, applicable from 23 July 2025
Pricing & reimbursement
Price regulation	Regulated	Free pricing	Regulated
Reference pricing	Yes	No	Yes
HTA required	Yes	No	Yes
HTA body	Chuikyo (Central Social Insurance Medical Council) and C2H (Center for Outcomes Research and Economic Evaluation for Health, NIPH)	ICER (Institute for Clinical and Economic Review) — independent, non-binding	EU HTA Coordination Group (EUnetHTA legacy); national HTA bodies (NICE, HAS, G-BA/IQWiG, AIFA, AEMPS, etc.)

Verdict colours indicate lower, moderate, or higher regulatory burden — they're not value judgements on a market.

Authority & dossier

Regulatory authority

JapanPMDA
United StatesFDA
European UnionEMA

English submissions

JapanNo
United StatesYes
European UnionYes

CTD accepted

JapanYes
United StatesYes
European UnionYes

eCTD accepted

JapanYes
United StatesYes
European UnionYes

Reliance pathway

JapanNone
United StatesNone
European UnionAvailable

Reference agencies

Japan—
United States—
European Union—

Lead pathway (timeline & fees) — J-NDA (New Drug Application) · New Drug Application — 505(b)(1) · Centralised Procedure

Pathway name

JapanJ-NDA (New Drug Application)
United StatesNew Drug Application — 505(b)(1)
European UnionCentralised Procedure

Approval timeline

Japan270–365 days
United States304–365 days
European Union210–277 days

Application fee

JapanJPY 38,950,800
United StatesUSD 4,310,002
European UnionEUR 358,800

Annual renewal

JapanJPY 0
United StatesUSD 416,734
European UnionEUR 122,500

Local representative

JapanRequired
United StatesNot required
European UnionRequired

Local manufacturing

JapanNot required
United StatesNot required
European UnionNot required

GMP inspection

JapanRequired
United StatesRequired
European UnionRequired

MAH & local presence

Local entity required

JapanYes
United StatesNo
European UnionYes

Local responsible person

JapanYes
United StatesYes
European UnionYes

RP role

JapanThree named Japanese-based responsible persons required: General Marketing Compliance Officer (GVP), Marketing Authorisation Holder Quality Assurance Officer, and Safety Management Officer. All must reside in Japan. Foreign manufacturers must hold a Foreign Manufacturer Accreditation (FMA) for each manufacturing site.
United StatesUS Agent: a person residing or maintaining a place of business in the US, designated to act on behalf of the foreign establishment for FDA communications, including notification of inspections.
European UnionQualified Person Responsible for Pharmacovigilance (QPPV) — must reside and operate in the EU/EEA — is responsible for the establishment and maintenance of the pharmacovigilance system. A Qualified Person (QP) in the EU/EEA performs batch certification under Article 51 of Directive 2001/83/EC. Local Contact Person for pharmacovigilance required in each Member State where the product is marketed (since 2012 GVP).

Accelerated pathways

Designations available

Japan4 designations
United States6 designations
European Union6 designations

Examples

JapanPriority Review, Orphan Drug Designation, Conditional Early Approval (Article 14-2-3) +1
United StatesPriority Review, Breakthrough Therapy Designation, Accelerated Approval — Subpart H/E +3
European UnionAccelerated Assessment, Conditional Marketing Authorisation, Authorisation under Exceptional Circumstances +3

Post-approval lifecycle

Variations framework

JapanThree categories: Minor Change Notification (post-implementation notification, certain low-risk CMC and labelling), Partial Change Application (PCA — prior approval, mid-tier changes, ~6 months), and full Re-Application (major changes effectively requiring new NDA).
United StatesFDA classifies post-approval changes as: Annual Reportable, Changes Being Effected (CBE-0 immediate, CBE-30 with 30-day pre-implementation notice), and Prior Approval Supplements (PAS) — the most significant changes requiring FDA approval before implementation. Major manufacturing or labelling changes typically require a PAS.
European UnionCommission Regulation (EC) 1234/2008 establishes four categories: Type IA (minor — Do and Tell, 12-month notification), Type IAIN (minor — immediate notification), Type IB (minor — Tell, Wait, and Do, 30-day default), Type II (major — prior approval, 60–90 days), and Extensions (Annex I changes — full review). Worksharing procedures consolidate variations across multiple authorisations.

Renewal cycle

JapanRe-examination period of 4–10 years post-approval (8 years for new active substances, 10 years for orphan drugs and paediatric indications) — during which the applicant collects and submits post-marketing safety and efficacy data. Re-evaluation may follow at MHLW direction.
United StatesFDA does not require periodic renewal of NDAs or BLAs — approvals remain in effect indefinitely subject to compliance, payment of annual program fees, and post-marketing requirements. Annual reports are required.
European UnionInitial 5-year renewal — application 9 months before expiry. After the first renewal, MA is granted for unlimited duration unless the CHMP/NCA, on justified grounds relating to pharmacovigilance, decides on one additional 5-year renewal.

Pharmacovigilance

JapanMHLW operates the Drug Safety Information Reporting System; expedited reporting of serious unexpected ADRs within 15 days. PSURs aligned with global birth dates. J-RMP required for all new approvals. The Medical Information Database Network (MID-NET) provides real-world data infrastructure for active surveillance.
United StatesMandatory expedited reporting of serious unexpected ADRs within 15 calendar days; periodic safety reports (PADERs/PAERs) for the first 3 years post-approval, then annually. PSURs in ICH E2C(R2) format accepted in lieu of PADERs by agreement. FAERS database receives spontaneous reports. Post-Marketing Requirements (PMRs) and Commitments (PMCs) tracked publicly.
European UnionComprehensive PV framework under Directive 2010/84/EU and Regulation (EU) 1235/2010, codified in Good Pharmacovigilance Practices (GVP). Pharmacovigilance System Master File (PSMF) required. Periodic Safety Update Reports (PSURs) on EU-harmonised birth-date list. Risk Management Plans for all new MAs and significant variations. Suspected serious ADR reporting to EudraVigilance within 15 days. Black triangle (▼) for additional monitoring of selected products.

Unlicensed access

Named Patient Supply

JapanAvailable
United StatesAvailable
European UnionAvailable

Compassionate Use

JapanAvailable
United StatesAvailable
European UnionAvailable

Emergency Import

JapanAvailable
United StatesAvailable
European UnionAvailable

Parallel Import

JapanNot permitted
United StatesNot permitted
European UnionPermitted

Clinical trials

CTA approval

JapanRequired
United StatesRequired
European UnionRequired

Ethics approval

JapanYes
United StatesYes
European UnionYes

CTA timeline

Japan30–30 days
United States30–30 days
European Union60–106 days

GCP standard

JapanJ-GCP (Ministerial Ordinance No. 28, 1997, as amended) — fully ICH E6 aligned
United StatesICH E6(R3) (adopted via FDA guidance January 2025); 21 CFR 312, 314, 50, 56
European UnionICH E6(R3) — Commission Regulation (EU) 2024/2748 transposing R3, applicable from 23 July 2025

Pricing & reimbursement

Price regulation

JapanRegulated
United StatesFree pricing
European UnionRegulated

Reference pricing

JapanYes
United StatesNo
European UnionYes

HTA required

JapanYes
United StatesNo
European UnionYes

HTA body

JapanChuikyo (Central Social Insurance Medical Council) and C2H (Center for Outcomes Research and Economic Evaluation for Health, NIPH)
United StatesICER (Institute for Clinical and Economic Review) — independent, non-binding
European UnionEU HTA Coordination Group (EUnetHTA legacy); national HTA bodies (NICE, HAS, G-BA/IQWiG, AIFA, AEMPS, etc.)