PMDA GMP inspection of overseas sites: what to prepare

Why does a Japanese inspection follow the product, not the site?

Because Japan ties GMP to each marketing approval. The MAH applies, and every site named in the approval comes along.

Under the PMD Act (the Act on Securing Quality, Efficacy and Safety of Products Including Pharmaceuticals and Medical Devices), a drug can't be approved unless its manufacturing and quality control conform to the GMP Ministerial Ordinance (GMP省令). That condition sits in Article 14, paragraph 2, item 4. Article 14, paragraph 7 then requires an inspection to confirm it, both when approval is sought and at fixed intervals afterwards. Some PMDA English slides still cite the same inspection as "Article 14.6", an older numbering, while current Japanese guidance from MHLW and prefectures cites paragraph 7. Expect to see both, and work from the Japanese text.

Three events trigger an application-based inspection. The first is a new marketing approval application. The second is a partial change application (一部変更承認申請). The third is the periodic inspection, due every five years after approval for each approved product. PMDA's guidance for foreign manufacturers says every site described in the application is in scope: formulation, drug substance, intermediates, and packaging, labeling or storage. A site that only makes an intermediate is inspected because the finished product is.

The applicant is the MAH (製造販売業者), not you. PMDA also runs inspections that no one applies for: risk-based planned inspections and for-cause inspections. Inside Japan, the 47 prefectures inspect many domestic sites. Abroad, PMDA covers every site.

Accreditation of Foreign Manufacturers is a separate step. It checks your buildings and facilities, and it does not replace the GMP compliance inspection. The accreditation guide explains how the two fit together.

Ask each Japanese customer for its product's approval date and next five-year inspection date, because without them you can't plan for PMDA at all.

PMDA chooses desk review or on-site, partly on what you send

On paper, on-site is the rule. In practice, PMDA chooses each time.

PMDA's Overview Guidance for Foreign Drugs Manufacturers (tentative translation dated September 26, 2023) says the inspection "shall be conducted by onsite inspection by the PMDA" in principle. It then allows PMDA to inspect on documents only, considering product risk, the GMP standard of the site's country and how it operates, and the GMP conformity shown in the documents submitted in advance. A PMDA presentation lists the factors behind that call: product type, dosage form, inspections by foreign authorities, past nonconformities, past recalls, and whether PMDA has inspected the site before.

Some of those factors are fixed. A sterile injectable stays a sterile injectable. Others are in your hands: your inspection history with other authorities, and the quality of the package PMDA reads before it decides. Read together, the list points one way. A site PMDA has never seen, making a high-risk dosage form, with thin pre-submission documents, gives PMDA little reason to stay home.

Mutual recognition is a separate lever. In 2018 the EU and Japan extended their mutual recognition agreement (MRA) to sterile medicines, certain biologicals including vaccines and immunologicals, and the APIs of products in scope. The European Medicines Agency says each side can rely on the other's GMP inspections for those products. PMDA's lists of documents to submit ask for the matching paperwork: a GMP certificate issued under the MRA (or a reference to its EudraGMDP entry) for sites in MRA countries, the partner authority's certificate for MOU countries, and a WHO or national authority certificate for others. The certificate must be valid. We found no PMDA statement that such a certificate removes the PMDA inspection itself, so ask the MAH how PMDA has handled comparable sites.

PIC/S is a different matter. According to PMDA, Japan's MHLW, PMDA and all 47 prefectures joined PIC/S on July 1, 2014, and the GMP Ministerial Ordinance was later revised to follow the PIC/S guide more closely. Familiarity with the PIC/S guide is a head start, but PMDA still inspects against the Japanese ordinance.

Treat the pre-submission package as the first round of the inspection, because it is what PMDA reads when it decides whether to send inspectors.

A desk review leaves the foreign site without a report

If PMDA inspects on paper, the result goes to the applicant. You get nothing directly.

PMDA's guidance states it in one line: in the case of desk-top inspection, a copy of the GMP Compliance Inspection Result Report is not issued. PMDA's Japanese flow chart for foreign manufacturers says the same, and names the party that goes without it: the foreign manufacturer.

This matters more than it looks. Questions raised during a desk review travel through the MAH. So does the final outcome, and so does anything PMDA asks you to fix before the next cycle. If your quality agreement with the MAH says nothing about this, you may learn about a concern only when the next application comes around, or when PMDA decides that the next inspection should be on-site.

The MAH is not hiding anything. The system simply treats the MAH as PMDA's counterpart and the foreign site as part of the MAH's supply chain.

Write the MAH's duty to forward PMDA questions, outcomes and findings into your quality agreement before the first Japanese filing, with a deadline in days.

The 2021 category-based certificate puts the site in charge

Since August 1, 2021, a manufacturer can apply on its own for a category-based inspection (区分適合性調査). It is the one route among the application-based GMP inspections where the site, not the MAH, is the applicant.

The legal basis is PMD Act Article 14-2, paragraph 1. PMDA inspects the site for a manufacturing process category rather than for a single product. If the site passes, it receives a certificate (基準確認証) for that category, valid for 3 years. While it is valid, an MAH whose product falls inside that category generally does not need the five-yearly periodic inspection for that site.

PMDA explained the reason openly in its own slides: within each five-year window, one manufacturing site faced frequent inspections, because each approved product carried its own. A contract manufacturer filling for several Japanese customers is the obvious case.

There are limits. The certificate can replace periodic inspections, but PMDA's guidance keeps the first periodic inspection for a new drug in place. The application asks for copies of GMP inspection reports that other authorities issued in the 2 years before the application date, where such inspections took place, and for valid MRA or MOU compliance certificates where you have them. It also asks for a list of the products you make within the applied category and the inspection history for those products.

The trade-off is the clock. A certificate runs for 3 years, against 5 years for each product's periodic inspection, and you prepare and file the application yourself.

If several Japanese products share one process category at your site, compare one category inspection every 3 years against the stack of product inspections your MAHs would otherwise file.

What PMDA asks for before it decides

The pre-submission list is short and predictable. Much of it overlaps with a PIC/S-style site master file.

PMDA's Japanese pages list five items: a company overview, an overview of the products under inspection and of the site (PMDA Form 1, plus Form 2 or Form 3), a layout of the whole premises, an overview of the pharmaceutical quality system with the GMP organization chart and the document hierarchy, and a list of every product manufactured at the site. You submit them through the Gateway or by email, by a deadline PMDA tells the applicant case by case. Documents already filed with the application need resubmitting only if they changed. For applications covering several products, new and periodic inspections use the representative product's documents.

The full product list deserves care. PMDA asks for it to include items the GMP Ministerial Ordinance does not cover, to say whether each is a drug substance, intermediate, bulk product or finished product, and to flag the items made for Japan. It shows PMDA everything else that runs through your facility, so make it complete rather than tailored.

The standard you are measured against is the GMP Ministerial Ordinance as revised in 2021. That revision made compliance with approved matters (承認事項) an explicit article, in response to manufacturing fraud cases in Japan. The MAH files the approval in Japanese, and that text, not your US or EU filing, is what the inspector compares with your batch records. The GMP Ordinance comparison covers the other Japan-specific expectations.

The stakes are concrete. Cambrex announced on August 25, 2026 that FDA, PMDA and Australia's TGA had completed pre-approval inspections at its High Point, North Carolina site, following a $38 million expansion completed in 2023. The company said the result lets the site make approved APIs for all three markets. It did not say whether the PMDA inspection was on-site or on paper.

Keep the pre-submission package as a standing document, because the same items come back with every MAH's application.

Steps to take before PMDA's request arrives

Work through these in order. The first two take the longest.

1. List every Japanese product your site touches. For each, get from the MAH the approval date, the next five-year periodic inspection date, and any new or partial change applications in preparation.
2. Ask each MAH for an English translation of the manufacturing and specification sections of the Japanese approval that name your site. Reconcile them line by line with your master batch records and specifications, and route every difference through change control.
3. Assemble the pre-submission package: company overview, the content of PMDA Form 1 and Form 2 or 3, a layout of the whole premises, quality system overview with the GMP organization chart and document hierarchy, and the full product list including non-Japanese products.
4. Collect every GMP inspection report from other authorities dated within the last 2 years, plus any MRA compliance certificate. These feed both PMDA's desk-or-site decision and a category-based application.
5. Amend the quality agreement so the MAH forwards PMDA questions, outcomes and findings within a fixed number of days. A desk review gives you no report of your own.
6. If several Japanese products share a process category, discuss a category-based inspection with your MAHs and put the certificate's 3-year expiry date in your calendar.
7. Plan for an on-site visit even if you expect a desk review. Name the host, the interpreter and the person who retrieves records, and rehearse pulling records from both the archive and your electronic systems.

For terms you will meet in PMDA's Japanese documents, see the glossary. If your site also holds a Japanese Master File, read the MF and in-country caretaker guide, since an MF changes who talks to PMDA during the inspection.