Designation System for Drugs for Specific Use in Japan

1. Publication Details

Issued January 12, 2024 (provisional translation as of April 2024). From Director, Pharmaceutical Evaluation Division, Pharmaceutical Safety Bureau, Ministry of Health, Labour and Welfare. https://www.pmda.go.jp/files/000268527.pdf

2. Background

In association with the issuance of the Act Partially Amending the Act on Securing Quality, Efficacy and Safety of Products Including Pharmaceuticals and Medical Devices (Act No. 63 of 2019, hereinafter referred to as the “Amendment Act”) on December 4, 2019, the designation system for drugs for specific use has been established. The purpose is to contribute to the promotion of research and development of drugs with significant unmet medical needs, for instance, dosage and administration for pediatric have not been defined etc. https://www.pmda.go.jp/files/000268527.pdf

3. Purpose

To contribute to the promotion of research and development of drugs with significant unmet medical needs. https://www.pmda.go.jp/files/000268527.pdf

4. Target Products

Drugs for specific use specified in Article 77-2 (3) of the revised 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”). https://www.pmda.go.jp/files/000268527.pdf

5. Eligibility Types

Requirements for designation

Either of the following (1) or (2) applies.

(1) Those for diagnosis, treatment or prevention of pediatric diseases which meet all of the following (A) to (C):

• A Any of the following developments for the intended use
  [1] Change in the dosage and administration
  [2] Additional dosage forms
• B Significantly unmet needs of the intended use
  Any of the following applies:
  [1] No existing therapy, preventive or diagnosis methods (hereinafter referred to as “therapy etc.”) are available (including cases where there is no standard of care except medication and there is no drug with pediatric dosage and administration)
  [2] Therapy, prevention or diagnosis methods with higher medical usefulness compared to existing therapy etc. are required from a point of view of efficacy and safety on pediatric patients and physical/mental burdens on patients or caregivers
• C Particularly excellent value for usage
  Both of the following [1] and [2] should be met:
  [1] Indicated for serious diseases or used for serious diseases in a supportive manner
  [2] Established as a standard of care by international guidelines etc. or have good evidence from the results of randomized comparative studies etc. https://www.pmda.go.jp/files/000268527.pdf

(2) Used for diagnosis, treatment or prevention of diseases caused by drug-resistant pathogens, and all of the requirements A to C apply in the case of 1) or 2)

1) In case of drugs for drug-resistant pathogens

• A Either of the following developments
  [1] Change in the indication
  [2] Change in the dosage and administration
• B Significantly unmet needs of the intended use
  Both of the following (1) and (2) should be met:
  [1] Used for pathogens resistant (or may become resistant) to drugs primarily used at present
  [2] Apart from the drugs primarily used at present, there is no drugs approved for diseases caused by the target pathogen
• C Particularly excellent value for the intended usage
  Both of the following (1) and (2) should be met:
  [1] High needs for drugs from a comprehensive point of view such as the infectivity of the target drug-resistant pathogen and seriousness of diseases by the pathogen
  [2] Established as a standard of care by international guidelines etc. or have good evidence from the results of randomized comparative studies etc. https://www.pmda.go.jp/files/000268527.pdf

2) In case of drugs to prevent the occurrence of drug-resistant pathogen

• A Either of the following developments
  [1] Change in the dosage and administration
  [2] Change in the indication
• B Significantly unmet needs of the intended use
  Either of the following (1) or (2) applies:
  [1] Likely to induce drug resistance in the pathogen of the target disease if used at the approved dosage and administration
  [2] Although it has been established as the standard of care in international guidelines etc., it is not indicated for the target disease.
• C Particularly excellent value for intended usage
  Both of the following (1) and (2) should be met:
  [1] High needs for drugs from a comprehensive point of view such as the expected infectivity of a pathogen and seriousness of diseases by the pathogen, if the drug-resistant pathogen occurs
  [2] Established as a standard of care by international guidelines etc. or have good evidence from the results of randomized comparative studies etc. https://www.pmda.go.jp/files/000268527.pdf

6. Consultation Pathway Before Approval

Procedures to application for designation

1. The Ministry of Health, Labour and Welfare collects requests or proposals for the development of drug candidates falling under the above 1.
2. The Ministry of Health, Labour and Welfare requests Study Group on Unapproved and Off-label Drugs of High Medical Need (hereinafter referred to as “the Study Group”) to assess the eligibility of the collected requests for development to drugs for specific use (hereinafter referred to as “the Eligibility Assessment”).
3. The Study Group informs the Ministry of Health, Labour and Welfare of the results of Eligibility Assessment.
4. The Ministry of Health, Labour and Welfare notifies the results of Eligibility Assessment by the Study Group to the marketing authorization holder of the requested drug.
5. If the marketing authorization holder receiving the notification in the above (4) from the Ministry of Health, Labour and Welfare wishes to have the drug designated as a drug for specific use, the marketing authorization holder should submit the application for designation of drugs for specific use to the Ministry of Health, Labour and Welfare. https://www.pmda.go.jp/files/000268527.pdf

7. Approval Application and Review Expectations

Procedures of designation

(1) Application for designation

Those who intend to apply for the designation of drugs for specific use should submit Form 107-3 specified in the revised Regulation for Enforcement of the Act on Securing Quality, Efficacy and Safety of Products Including Pharmaceuticals and Medical Devices (Order of the Ministry of Health, Labour and Welfare No. 1 of February 1, 1961, hereinafter referred to as “the Regulations”) by the Ministerial Ordinance on the Development of Related Ministerial Ordinances in Accordance with Enforcement of the Act Partially Amending the Act on Securing Quality, Efficacy and Safety of Products Including Pharmaceuticals and Medical Devices (Ordinance of Ministry of Health, Labour and Welfare No. 155 of 2020, hereinafter referred to as “the Amendment Ordinance”) together with attachment in (2) to Pharmaceutical Evaluation Division, Pharmaceutical Safety and Environmental Health Bureau, Ministry of Health, Labour and Welfare (hereinafter referred to as “Pharmaceutical Evaluation Division”). The applicant should mail or bring the data in paper form (one original, two copies) and in electronic form.
Mail to: 1-2-2 Kasumigaseki, Chiyoda-ku, Tokyo 100-8916 Pharmaceutical Evaluation Division, Pharmaceutical Safety and Environmental Health Bureau, Ministry of Health, Labour and Welfare Attention to the person in charge of the designation system for drugs for specific use https://www.pmda.go.jp/files/000268527.pdf

(2) Attachment to the application form

Article 251-2-2 of the Regulations revised by the Amendment Ordinance specifies the data to be attached to the application form. The below explains the specific details to be contained in the data: Submission of other data may be required as necessary.

• A Data on the satisfiability of needs for the intended use
  Summary of the request for development and eligibility assessment in the above 2
• B Data serving as the rationale for the use of the drug concerned
  Outline of data that are listed in Article 40-1 (i) of the Regulations revised by the Amendment Ordinance and available at the time of application filing
• C Development plan
  Document that explains the outline of the development plan such as planned investigation items and study period etc.
• D Summary of the drug for specific use
  Summary prepared in accordance with the Attachment Form 1 or Attachment Form 2 as explanation documents for the committee and documents for publication (the name of applicant and the product name as well as the target indication [or proposed indication] should accompany their English name and translation) https://www.pmda.go.jp/files/000268527.pdf

Method of designation

Designation of the drug for specific use is made after hearing the opinions of Pharmaceutical Affairs and Food Sanitation Council. For the designated drug, the date of designation, name of drugs, 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/000268527.pdf

8. Procedure After Approval (Post-marketing Obligations)

6. Discontinuation of study/research

When a person designated (hereinafter referred to as “designee”) pursuant to the provisions of Article 77-2 (3) of the Act intends to discontinue test and research or manufacturing of the drug for specific use that pertains to the designation, they must promptly notify the Minister of Health, Labour and Welfare thereof based on Article 77-5 of the Act. As a notification of discontinuation, Form No. 108 of the Enforcement Regulation should be submitted. https://www.pmda.go.jp/files/000268527.pdf

7. Rescission of designation

The Minister of Health, Labour and Welfare, when receiving a notification discontinuation under Article 77-5 of the Act, rescinds designation based on Article 77-6 (1) of the Act. Based on Article 77-6 (2) of the Act, the Minister of Health, Labour and Welfare may rescind the designation in cases that fall under any of the following items. A public announcement of the rescission of designation is made in accordance with the above 4.

• A The requirement B or C of the above 1 is no longer met due to the approval of other drugs etc.
• B When unlawfulness such as false descriptions in the application for designation is found.
• C When no test and research or marketing is provided for the drug for specific use without any legitimate grounds
• D When the designee violates the Act or other pharmaceutical laws and regulations specified by Cabinet Order, or any of the dispositions thereupon. https://www.pmda.go.jp/files/000268527.pdf

8. Succession

If the designee transfers the right of development in Japan to others (hereinafter referred to as “successor”), the designee should notify discontinuation of study/research in accordance with the above 6, and the successor should submit the data in the above 3 (1) the application form and (2). However, if the contents of the documents have been changed since the time when the designee receives the designation, data that show that the changes satisfy the requirements at the time of succession should also be submitted. Succession is approved with the letter of designation that is separately issued. Designees who consider succession should consult with Pharmaceutical Evaluation Division in advance. In so doing, the designee should also submit a copy of the contract for succession and data that explain the background of succession. https://www.pmda.go.jp/files/000268527.pdf

9. Practical Considerations

5. Priority on designated drugs

• (1) Priority consultation
  This allows a drug to be prioritized over other drugs in consultations by the Pharmaceuticals and Medical Devices Agency. https://www.pmda.go.jp/files/000268527.pdf
• (2) Priority review
  Priority review is available when a drug is designated based on Article 14-8 of the Act. https://www.pmda.go.jp/files/000268527.pdf

10. Effective Date

This notification shall be put into force on September 1, 2020. https://www.pmda.go.jp/files/000268527.pdf

11. Key Sections

• Attachment Form 1: Summary of Drug for Specific Use (Those for diagnosis, treatment or prevention of pediatric diseases)

  • Name of applicant (with English translation)
  • Name (Japanese accepted names with English name such as INN)
  • Brand name (with English translation)
  • Target indication (with English translation)
  • Proposed dosage and administration
  • Target disease (outline and status of needs)
  • Particularly excellent value for usage (summary)
  • Notes: A4 size, further explanation in attachment if required, prepared for publication. https://www.pmda.go.jp/files/000268527.pdf

• Attachment Form 2: Summary of Drug for Specific Use (Those used for diagnosis, treatment or prevention of diseases caused by drug-resistant pathogens)

  • Name of applicant (with English translation)
  • Name (Japanese accepted names with English name such as INN)
  • Brand name (with English translation)
  • Target of development (Drugs for drug-resistant pathogens or Drugs to prevent the occurrence of drug-resistant pathogen)
  • Indication (With no change or With changes, with English translation)
  • Proposed dosage and administration
  • Target disease (outline and status of needs)
  • Particularly excellent value for usage (summary)
  • Notes: A4 size, further explanation in attachment if required, prepared for publication. https://www.pmda.go.jp/files/000268527.pdf