Partial Revision of Orphan Drug Designation Criteria in Japan

1. Background

Designation of orphan drugs, orphan medical devices, and orphan regenerative medicinal products (hereinafter referred to as “orphan drugs etc.”) based on Article 77-2 (1) of the Act on Securing Quality, Efficacy and Safety of Products Including Pharmaceuticals and Medical Devices (Act No. 145 of 1960, hereinafter referred to as “the Act”) has been made in accordance with “Designation of Orphan Drugs etc.” (Joint PSEHB/PED Notification No. 0831-7 issued by the Director, Pharmaceutical Evaluation Division and PSEHB/MDED Notification No. 0831-7 issued by the Director of Medical Device Evaluation Division, Pharmaceutical Safety and Environmental Health Bureau, Ministry of Health, Labour and Welfare, dated August 31, 2020, hereinafter referred to as the “Notification by Directors”). Designation of orphan drugs etc. has been revised as shown in the attached new/old comparison table based on the review at “Review Committee on Regulatory Affairs to Strengthen Drug Discovery and Development / Ensure Stable Supply”, and it has been decided that the revision applies from today (January 16, 2024). https://www.pmda.go.jp/files/000268408.pdf

2. Purpose

The revision aims to update the criteria and procedures for designating orphan drugs etc., including refinements to eligibility criteria, estimation methods, and consultation pathways, to strengthen drug discovery, development, and ensure stable supply. https://www.pmda.go.jp/files/000268408.pdf

3. Target Products

Orphan drugs, orphan medical devices, and orphan regenerative medicinal products (hereinafter referred to as “drugs etc.”) that are related to the application for designation. https://www.pmda.go.jp/files/000268408.pdf

4. Eligibility Types

Designation shall be made for drugs etc. that meet all of the following (1) to (3): (1) Number of subjects
A. Criteria for the number of subjects: The number of subjects pertaining to the usage of the drugs etc. is less than 50,000 in Japan. However, if the usage is for a designated intractable disease, the number of subjects should be less than the number specified in the Article (approximately 1/1,000 of the population).
B. Method of estimation: Estimate using reliable survey results from Health and Labour Sciences Research Grants or related academic societies. If unreliable due to insufficient surveys, use multiple statistical data and methods. For designated intractable diseases, no separate estimation is needed.
C. Scope of diseases: “Salami slicing” applications (e.g., artificially reducing patient numbers with prefixes like “serious” without clear reasons) are not acceptable. However, restricted parts of diseases with high unmet needs and appropriate evidence (e.g., age range, treatment algorithms) are not deemed salami slicing, but confirmation is required if overall patients exceed 50,000.
D. Use for prevention of infectious diseases: For drugs or regenerative medicinal products, the estimated number of subjects expected to use the product in 1 year upon marketing approval is regarded as the number of subjects. Includes vaccines for rare diseases in Japan, traveler vaccines, or vaccines for emerging infectious diseases. https://www.pmda.go.jp/files/000268408.pdf (2) Medical needs: With marketing approval, drugs etc. expected to have particularly excellent value for usage in its intended purpose. In principle, high medical needs for serious diseases or infectious diseases impacting public health, meeting:
A. Seriousness: Fatal diseases or those leading to very low quality of life.
B. Effectiveness: No approved drugs, or poor prognosis with existing treatments needing more options, or more effective/safer than approved drugs based on clinical studies, head-to-head comparisons, guidelines, or different safety profiles. https://www.pmda.go.jp/files/000268408.pdf (3) Possibility of development: Having organizations and plans enabling development in Japan, with clarified outline of planned clinical studies before marketing application, and mostly completed nonclinical studies for first-in-human trials. https://www.pmda.go.jp/files/000268408.pdf

5. Consultation Pathway Before Approval

Before application, applicants should consult with the person in charge of designation at Pharmaceutical Evaluation Division or Medical Device Evaluation Division, Pharmaceutical Safety Bureau, Ministry of Health, Labour and Welfare. https://www.pmda.go.jp/files/000268408.pdf

6. Approval Application and Review Expectations

Designation is made after hearing opinions from the Pharmaceutical Affairs and Food Sanitation Council. For the designated drug, the date, name, target intended use and the name and addresses of the applicant are published on the website of the Ministry of Health, Labour and Welfare. https://www.pmda.go.jp/files/000268408.pdf

7. Procedure After Approval (Post-marketing Obligations)

• Discontinuation: Designation holders must notify the Minister of Health, Labour and Welfare via Form No. 108 if discontinuing tests, research, marketing, or manufacturing.
• Rescindment: Automatic upon discontinuation notification; may occur if requirements no longer met, false descriptions found, no legitimate grounds for non-provision, or violations of the Act. Public announcement follows, with hearings for certain cases.
• Succession: Upon transfer, original holder notifies discontinuation; successor submits updated data showing compliance. Consult designation person in charge in advance with succession contract and background documents. Succession approved via separate letter. https://www.pmda.go.jp/files/000268408.pdf

8. Practical Considerations and Positioning Versus Other Pathways

• Attachments may include objective statistical data, disease info, medical care status, theoretical evidence outlines, development plans, and summaries in English.
• For foreign applicants, notify Japan-based development contact.
• Priority review/consultation: Applies only to those meeting former criteria; eligibility in Preliminary Evaluation Report. Later eligibility can be clarified via PMDA consultation before marketing application. https://www.pmda.go.jp/files/000268408.pdf

9. Effective Date

The notification states that it came into effect from January 16, 2024. https://www.pmda.go.jp/files/000268408.pdf