Japan Master File (MF) and the in-country caretaker

What a Japanese MF does, and what it doesn't

An MF is a voluntary registration of your data with PMDA. It is not an approval, and the registration certificate is not a marketing certificate.

The legal basis is Article 80-6 of the PMD Act (the Act on Securing Quality, Efficacy and Safety of Products Including Pharmaceuticals and Medical Devices). The working rules sit in MHLW's "Guideline on Utilization of Master File for Drug Substances, etc." (PFSB/ELD Notification No. 1117-3), dated November 17, 2014 and applied from November 25, 2014, when it replaced the 2005 guideline. PMDA describes the purpose in one line: manufacturers register the information needed for review in advance, so it can be used in the approval review without disclosing know-how. The one exception is public-health safety information that is specifically requested.

Two consequences follow. First, registering does not mean anyone has checked your data. PMDA says the appropriateness of an MF is reviewed after a product application that cites it is filed. An MF that no product application cites has not had its appropriateness reviewed at all. Second, the MF is public in outline. Under Article 80-6, paragraph 3, PMDA publishes the registered items, and it updates that list about twice a month.

The system is heavily used by non-Japanese suppliers. A study by Matsuhama and Kuribayashi, published in the GaBI Journal in 2018, counted 3,804 MFs registered in Japan, 63.46% of them from foreign manufacturers in 46 countries and regions, mostly in Asia and Europe. The authors put new registrations at about 200 to 300 a year. Those are the study's figures, not today's registry counts.

Register before your customer files, not because PMDA will review it early, but because the MAH needs your registration number in its application.

Who can register: more than APIs

Drug substances and intermediates are the core. The scope reaches well beyond APIs.

PMDA's materials list new excipients and pre-mix excipients whose composition ratios differ from existing ones, and containers and packaging materials. They also cover materials used to make cellular and tissue-based products, such as cells, culture media and medium additives. An MHLW notice of December 2012 added those materials to the MF scope, partly so that companies could protect know-how about cells and media while PMDA still checked safety.

For suppliers to cell and gene therapy, PMDA's recent presentations are more specific. They give established cell lines (including ES, iPS and somatic stem cells) and medium additives such as serum additives, growth factors and cytokines as examples. A registered raw material can be cited by drugs, medical devices and regenerative medical products alike. PMDA's Office of Cellular and Tissue-based Products asks companies to use its pre-meeting to confirm whether an MF is possible.

There is a second route for those materials. PMDA's consultation menu includes a material suitability consultation (材料適格性相談). In July 2026, ACROBiosystems announced that it had received PMDA's "Material Suitability Confirmation for Regenerative Medicine Products" for its GMP-grade human IL-15, and said cell therapy developers can reference it when applying in Japan. That is the company's description; check with PMDA how a confirmation is cited before relying on one instead of an MF.

Contract manufacturing has its own rule. PMDA's Q&A says a company that outsources a drug substance to a contract manufacturer cannot register the MF for it. The contract manufacturer can register it itself.

If you make a drug substance under contract, expect the MF to be yours to register and maintain, not your client's.

The in-country caretaker does more than translate

Every foreign registrant needs a caretaker with an address in Japan. PMDA treats the caretaker as a working part of the registration, not a mailbox.

The requirement sits in Article 280-3 of the PMD Act's Enforcement Regulations, as PMDA's English materials cite it. There is no official qualification for the role. PMDA's Q&A says the registrant is responsible for choosing a capable person or company, and that the caretaker's role "is not limited to mere translation and mediation of inquiries". The caretaker's name and address are a required item on the registration application form (Form 120) and appear on the registration certificate.

Language drives much of the work. PMDA's Q&A says application forms and attachments other than the CTD must be in Japanese. PMDA's questions during the review of a citing product also come through this channel, and they need technical answers. A caretaker who can only translate will forward each question to your site and wait.

Visibility is your choice. Since January 2019, PMDA publishes the caretaker's name and address alongside your MF entry if the foreign manufacturer asks. That helps prospective customers find who to contact in Japan.

Not every message runs through the caretaker. PMDA notes that the MAH can deal with the MF registrant directly on information outside the restricted part. PMDA's GMP inspection flow charts also change when an MF is involved, so agree in advance who answers PMDA during an inspection of your site. The PMDA GMP inspection guide covers that process.

Choose a caretaker who can answer PMDA's technical questions, not only relay them, and write that duty into the contract.

How confidentiality is split between you, the MAH and PMDA

Your know-how goes to PMDA. What the MAH sees is negotiated.

PMDA's guidance describes a disclosed (open) part and a restricted part. The MAH, the registrant and the caretaker share the disclosed part. The registrant and the caretaker alone handle the restricted part, which exists to keep manufacturing know-how away from the MAH. Which information goes into the disclosed part is decided among the foreign manufacturer, the caretaker and the MAH, and PMDA stresses that its examples of what to disclose are only examples that call for thorough prior discussion.

Confidential information can be withheld from the MAH, but it must still be provided to the regulator. So your customer reads the disclosed part to build its own application and controls, while the restricted part goes to PMDA alone.

The split has limits on both sides. The MAH remains responsible for its product's quality, so it will want enough to set specifications, assess changes and investigate deviations. And the protection of know-how has one stated exception: public-health safety information that is specifically requested.

Agree the open and restricted parts in writing with each MAH before it files, because the split decides what the MAH can assess when you later change something.

Changing a registered MF: tell every user first

There are two filing routes for a change, and one duty that comes before either of them.

The routes mirror the product side. A larger change goes in as a change registration application (変更登録申請, Form 124 under Article 280-10 of the Enforcement Regulations), which includes the planned date of the change. A smaller one goes in as a minor change notification (軽微変更届, Form 125 under Article 280-12), addressed to PMDA's Chief Executive.

The duty is in PMDA's Q&A. The MF registrant must notify each applicant of changes to registered items in advance. If products using the MF are already approved, their approval holders must be told as well. The Q&A adds that this applies even to minor change notifications.

The reason is that your change can force a filing on the customer's side. The MF registrant and the MAH are expected to discuss fully whether a change could affect the product's quality. PMDA's Q&A gives an example. If an MF change touches only specifications and test methods, the product's approval can be updated by a minor change notification, but the MAH must confirm, through discussion with you, that quality after the change is comparable to before. Other changes may need the MAH's own partial change application (一部変更承認申請) for its product, which is an approval PMDA must grant, not a notice the MAH simply files.

Build Japanese MF users into your change control as a mandatory notification step, triggered before you file with PMDA, with enough lead time for the MAH's own filing.

Steps to register and keep an MF current

Work through these in order. Steps 1 and 2 decide who carries the obligations for years.

1. Decide what to register and who registers it. Check whether the item fits the MF scope, and if you manufacture under contract, plan for your site to be the registrant. For cell and tissue materials, use PMDA's pre-meeting to confirm eligibility.
2. Appoint an in-country caretaker with a Japanese address. Write the contract around the work: Japanese filings, PMDA questions and their deadlines, confidentiality, and who covers holidays.
3. Prepare the Japanese application form and attachments with the caretaker. PMDA exempts only the CTD from the Japanese-language rule.
4. Agree with each MAH, in writing, what goes in the part it sees and what stays restricted.
5. Register before the MAH files, and send it the registration number.
6. Link Japanese MF users to your change control. Classify each change as a change registration or minor change notification, notify every applicant and approval holder in advance, then file with PMDA.
7. Check PMDA's public MF list for your entries after each filing, and decide whether to publish your caretaker's details.

If you also make the material at a site that ships to Japan, the site needs its own accreditation as a foreign manufacturer. Japanese terms from the forms are in the side box and the glossary. Suppliers of media and cytokines for cell therapy can compare products in the CAR-T cell culture media directory.