Japan Drug Registration and DMFs for APIs, Excipients & Packaging Materials

The Pharmaceuticals and Medical Devices Agency (PMDA) is the agency that reviews submissions of applications for drug approval, foreign manufacturer accreditation, drug master file registration, etc.

Yes, pharmaceutical and API products in Japan require registration prior to being marketed.

1. Ethical Generic Drugs
2. Prescription Drugs
3. OTC Drugs
   1. Class I Drug Products
   2. Class II Drug Products
   3. Class III Drug Products
4. Orphan Drugs

1. Assign a Marketing Authorization Holder (MAH) or Designated Marketing Authorization Holder (DMAH)
   A entity that obtains a marketing authorization license is known as a market authorization holder (MAH), and only registered MAH entities may import and sell medical products to the Japanese market. Therefore, all foreign manufacturers must designate a MAH or DMAH to manage their product registrations.For more information on MAH and DMAH, please view the Local Agent Representation for Medical Products in Japan (DMAH) page.
2. Foreign Manufacturer Registration
   Foreign companies that intend to manufacture drugs overseas and import them into Japan must be registered with the Ministry of Health, Labor and Welfare (MHLW). This process is known as “Toroku”, or “Foreign Manufacturer Registration (FMR)”. It is a separate process from the product registration process, and is required for obtaining product registration approval. Previously, it was known as “Foreign Manufacturer Accreditation (FMA)” or “Accreditation of Foreign Manufacturers (AFM)”. For more information about the FMR system and process, please view the Foreign Manufacturer Registration in Japan page.
3. Good Manufacturing Practice (GMP) Conformity Investigation
   It is the investigation to determine whether manufacturing control and quality control are complied with the Ministerial Ordinance. GMP conformity of the manufacturing site is required for product approval.
4. Submit a Drug Application to the PMDA
   Requirements depend on the category of drug.
5. The PMDA conducts a regulatory review
   To evaluate the quality, efficacy, and safety of the drug, the PMDA conducts a regulatory review of characteristics including product development history, country of origin, usage in other countries, stability data, manufacturing processes, etc.
6. The PMDA conducts a review of the requisites required for licensing
   Foreign Manufacturer Registration (FMR), Good manufacturing practice (GMP) license

1. Foreign Manufacturer Registration
   Foreign companies that intend to manufacture active pharmaceutical ingredients (APIs) overseas and import them into Japan must be registered with the Ministry of Health, Labor and Welfare (MHLW). This process is known as “Toroku”, or “Foreign Manufacturer Registration (FMR)”. It is a separate process from the product registration process, and is required for obtaining product registration approval. Previously, it was known as “Foreign Manufacturer Accreditation (FMA)” or “Accreditation of Foreign Manufacturers (AFM)”. For more information about the FMR system and process, please view the Foreign Manufacturer Registration in Japan page.
2. Prepare the Drug Master File (DMF) application
   The foreign API manufacturer needs to appoint an In-Country Caretaker (ICC) in Japan to prepare and submit a Japanese DMF. Although this system is voluntary, manufacturers are recommended to go through the registration process to best protect their intellectual property. A foreign DMF must be rewritten according to Japanese regulations and then translated into Japanese. This part of the process should be done with great precision. Otherwise, the PMDA may require several rounds of supplemental documentation requests and inquiries. Documents that should be submitted to the PMDA as part of the Japanese DMF application (all in Japanese) include information on:
   1. The name of the API, excipient or other drug substance
   2. The manufacturing site
   3. The ingredients, including quantity, chemical structure, and general properties
   4. Manufacturing method, process controls, process validation, process development and material controls
   5. Quality control testing, analytical procedures, validation of analytical procedures, justification of specifications and excipients of human/animal origin information (if applicable)
   6. Safety data
   7. Non-clinical study data (primarily for new excipients)
   8. Test methods, including impurities and description of methods for determining structure
   9. Specifications, analytical procedures, validation of these procedures, batch analyses, justification of specifications and reference standards/materials
   10. Storage method, stability testing data, post-approval stability protocol and expiration date
   11. FMR or domestic manufacturing license category, number and/or date
   12. ICC name and address
3. The ICC receives a Japanese DMF application receipt which has a specific number (J-DMF number)
4. The PMDA conducts a review of the drug application and Japanese DMF
   When a drug registration application refers to the J-DMF number, the PMDA will conduct a review of the Japanese DMF. The PMDA may ask further inquiries about the DMF or request supplemental information.
5. The PMDA provides a DMF registration certificate (Form No. 43)
   When the PMDA is satisfied with the contents of the Japanese DMF, the PMDA will provide a DMF registration certificate (Form No. 43) and a copy of the application to the registrant. A brief summary of the relevant information will also be posted on the PMDA website.