Q&A on Orphan Drug Designation Criteria in Japan

1. Background

This administrative notice compiles questions and answers (Q&A) on the designation of orphan drugs, based on the 'Designation of Orphan Drugs etc.' (Joint PSEHB/PED and PSEHB/MDED Notification No. 0831-7, dated August 31, 2020 https://www.pmda.go.jp/files/000268407.pdf). It incorporates partial revisions from the 'Partial Revision of “Designation of Orphan Drugs etc.”' (Joint PSB/PED and PSB/MDED Notification No. 0116-1, dated January 16, 2024 https://www.pmda.go.jp/files/000268407.pdf), following a review by the Review Committee on Regulatory Affairs to Strengthen Drug Discovery and Development / Ensure Stable Supply.

2. Purpose

To provide clarifications and handling guidelines for the designation of orphan drugs, aiding understanding and informing related parties through prefectural health departments. https://www.pmda.go.jp/files/000268407.pdf

3. Target Products

Primarily orphan drugs, with considerations extending to medical devices and regenerative products in the regulatory context. https://www.pmda.go.jp/files/000268407.pdf

4. Eligibility Types

Designation criteria include: serious diseases (fatal or causing very low quality of life, e.g., significant dysfunction interfering with daily activities https://www.pmda.go.jp/files/000268407.pdf); patient numbers (≤50,000, or restrictions not deemed 'salami slicing' based on medical reasons, biomarkers, treatment algorithms, or specific populations https://www.pmda.go.jp/files/000268407.pdf); high medical needs (e.g., inadequate existing therapies requiring multiple options, or new modes of action/safety profiles https://www.pmda.go.jp/files/000268407.pdf); and development possibility (clinical benefit demonstration, planned studies outline https://www.pmda.go.jp/files/000268407.pdf).

5. Consultation Pathways

Designation holders should consult the Pharmaceutical Evaluation Division if criteria may change (e.g., new drug approvals https://www.pmda.go.jp/files/000268407.pdf). For priority review/consultation changes post-early designation, use 'consultation on drug product eligibility for priority review (orphan) (tentative)' or with pre-application consultation, requested 40 working days prior to marketing application https://www.pmda.go.jp/files/000268407.pdf.

6. Approval Application and Review Expectations

Designation based on application; not withdrawn post-marketing application unless criteria unsatisfactorily met, requiring holder notification to MHLW https://www.pmda.go.jp/files/000268407.pdf. Priority review possible if orphan designation qualifies, with clinical trials planned for designated populations https://www.pmda.go.jp/files/000268407.pdf.

7. Procedure After Approval (Post-marketing Obligations)

Holders must notify MHLW if they recognize non-satisfaction of criteria post-designation; MHLW may query if needed https://www.pmda.go.jp/files/000268407.pdf. Maintain designation if criteria still met https://www.pmda.go.jp/files/000268407.pdf.

8. Practical Considerations

Number of subjects can be based on 1-year usage; restrictions (e.g., age groups, biomarkers, treatment stages) acceptable if medically justified, not 'salami slicing' https://www.pmda.go.jp/files/000268407.pdf. Clinical benefit from non-Japanese data acceptable unless ethnic differences evident https://www.pmda.go.jp/files/000268407.pdf. No Japanese data scrutiny required; protocols not mandatory—Gantt chart suffices for study outlines https://www.pmda.go.jp/files/000268407.pdf. Designation by active ingredient/indication, not route https://www.pmda.go.jp/files/000268407.pdf. Nonclinical studies mostly completed if essentials done https://www.pmda.go.jp/files/000268407.pdf.

9. Effective Date

The notification states that it came into effect from January 16, 2024. https://www.pmda.go.jp/files/000268407.pdf