Japan GCTP Ordinance: how it differs from GMP for cell sites

Regenerative products have their own ordinance, not the GMP one

The PMD Act points regenerative products to a standard of their own. The GMP Ordinance, as its full title says, covers drugs and quasi-drugs.

Article 23-25 of the Act says MHLW will not approve a regenerative medical product if the manufacturing control or quality control methods at its site fail the standard set by MHLW ordinance. Article 1 of the GCTP Ordinance says it is that standard, both for regular approvals and for approvals granted to foreign manufacturers under Article 23-37. PMDA's English pages spell the acronym out as Good Gene, Cellular, and Tissue-based Products Manufacturing Practice.

The ordinance took effect on November 25, 2014, the day the 2013 amendment to the Pharmaceutical Affairs Act (Act No. 84 of 2013) came into force. Its supplementary provisions show a later amendment in force from August 1, 2021. Work from the Japanese text on e-Gov as currently in force. Any English translation is for reference only, and the Japanese prevails.

Not every cell product made for Japan falls here. Cells that a clinic orders for its own patients under the Act on the Safety of Regenerative Medicine are examined against that Act's ordinance instead, as the ASRM accreditation guide explains. PMDA's GCTP page sends readers to a separate page for those examinations.

Confirm with your Japanese partner that the product will be filed as a regenerative medical product under the PMD Act, because that answer decides whether you map to GCTP, to the GMP Ordinance or to the ASRM rules.

The MAH answers for GCTP, and your site carries it out

GCTP binds both sides of the supply contract. Article 3 puts the duty on the marketing authorization holder first.

The MAH must have each manufacturer and each foreign manufacturer run manufacturing and quality control under the ordinance. So must the Japanese MAH that a foreign approval holder appoints under Article 23-37. The manufacturers must then do it themselves, and sites that make regenerative products only for export are covered as well. How the MAH role works in general is in the MAH guide.

A site abroad has a second gate. Under PMD Act Article 23-24, a manufacturer abroad making regenerative medical products for export to Japan may obtain the Minister's accreditation, granted site by site and by category. Article 23-25 bars approval when a site named in the application lacks it for the right category. The foreign manufacturer accreditation guide covers that procedure.

Inside the site, Article 5 asks for a production unit and a quality unit, with the quality unit independent of production. Both work under a manufacturing supervisor. For a foreign manufacturer, the ordinance defines that person as the responsible person of the accredited site, or someone the manufacturer designates in advance. Under Article 6 the supervisor oversees all manufacturing and quality work and orders measures when product quality may be seriously affected.

Name your GCTP manufacturing supervisor in writing before your partner files, because Article 5 places both your production and quality units under that person.

What GCTP leaves out compared with the 2021 GMP Ordinance

Six GMP provisions have no GCTP article. All six entered the GMP Ordinance on August 1, 2021, and GCTP's own amendment of the same day added none of them.

Reading the two ordinances side by side on e-Gov shows the gaps. The GMP Ordinance requires manufacture in line with the approved matters (Article 3-2). It requires an effective pharmaceutical quality system with a quality policy and quality objectives (Article 3-3). It splits the quality unit into a QA organization and a testing organization (Article 4). It requires stability monitoring, with prompt contact to the MAH when a result fails or may fail (Article 11-2). It also requires supplier qualification with written agreements (Article 11-4) and written agreements with outsourced contractors (Article 11-5). None of these appears as an article among GCTP's 23, and none is in e-Gov's text of the GMP Ordinance as in force on July 31, 2021. The GMP Ordinance guide explains the 2021 additions for drug sites. On quality risk management, GCTP Article 4 says only that the manufacturer shall consider using it.

The substance is not entirely missing. Article 8 requires a product standard document for each product at each site, approved by the quality unit, and it must contain the approved matters. Article 11 makes the production unit check every biological raw material against that document. Article 12 allows testing at outside laboratories only under the manufacturer's own responsibility.

The ordinance text does not settle how far PMDA expects GMP-style systems at a GCTP site. MHLW has issued three GCTP Q&A notices, dated March 17, 2015, July 28, 2015 and June 29, 2017. An MHLW administrative notice of November 28, 2019 also distributed an aseptic processing guideline for regenerative medical products. PMDA lists all four on its GCTP page. Read them before the gap assessment, and ask your MAH which of them its earlier GCTP inspections drew on.

Keep your quality system, supplier program and stability program, but map them to GCTP Articles 8, 11 and 12 rather than to GMP article numbers that the GCTP text does not contain.

GCTP's records follow the cells from donor to patient

GCTP's donor and product records sit mostly in Article 11, which lists 31 production control duties. Under the GMP Ordinance, only a site making cellular or tissue-based drugs keeps similar records (Article 27).

The starting material is a person's or an animal's cells. Article 2 defines a donor as the person who provides cells or tissue used as raw material, and defines a donor animal the same way. At receipt, Article 11 requires the site to confirm from records that the cells or tissue match the product standard document. Those records must show the collecting facility, the collection date, the donor screening by interview and testing, the collection process and the transport. Cells or tissue from different donors must be protected against mix-ups and cross-contamination.

The output is tracked as well. For every product the site records the receiving facility, the shipping date and the lot. It also records what it did to protect quality during delivery. Cell strains used in production need their own records: name and container number, date received and supplier, biological properties with the test date, and passage history.

Staff rules target contamination carried by people. Health checks are due at intervals of no more than six months. A worker who handled microorganisms that could contaminate cells just before collecting or processing cells may not work in the clean or aseptic areas. Staff who culture other cells or microbes stay out of product areas unless strict procedures prevent contamination. Training under Article 21 covers hygiene, microbiology, medicine and veterinary medicine.

The building rules are in Article 10 of the ordinance itself. Rooms for transferring cells to culture media, for harvesting and for sterility testing must be aseptic rooms with a dedicated anteroom. Equipment that allows aseptic work inside the room can replace that. Products whose cross-contamination would seriously affect other products need dedicated rooms and separate air handling, unless validated inactivation and cleaning are in place.

Test one recent batch record against Article 11 before the gap assessment starts, because a record that cannot show the collecting facility, donor screening, transport and receiving facility for its lot is a gap in your documents, not your process.

Validation, samples and records run on longer clocks

Each of the three follows a GCTP rule of its own. Verification has no counterpart in the GMP Ordinance, and the sample and record periods match only its rules for biological drugs.

Article 14 requires validation when a site starts making a product, when a change may have a major effect on quality, and when otherwise needed. If validation cannot be done for an unavoidable reason, the site performs verification instead. Article 2 defines verification as confirming and documenting that the manufacturing procedures gave the expected result. The ordinance does not list the acceptable reasons, so write yours down each time.

Article 12 sets reference samples. Each lot needs at least twice the quantity its tests require, or a suitable amount when that much is hard to secure. For a designated regenerative medical product, samples are kept for the shelf life plus 10 years, and for other products for an appropriate period. When a designated product is not made in lots, the sample comes from the biological raw material used to make it. The site can also agree with the raw material collector that the collector keeps it.

Article 22 sets record retention, counted from the date each record is made. Records for designated products are kept for the shelf life plus 30 years. Records for other regenerative medical products are kept for the shelf life plus 10 years, and training records for 5 years. Article 23 lets the Minister set other periods for products the Minister designates. Raw material records may be held by the collector under an agreement with the site.

Designation itself is made under PMD Act Article 68-7. Your MAH will know whether its product is on the list.

Ask your MAH whether the product is a designated regenerative medical product before you size your archive, because that one fact moves record retention from shelf life plus 10 years to shelf life plus 30.

PMDA inspects every GCTP site, at approval and every 5 years

PMDA carries out GCTP inspections for sites in Japan and abroad. In PMDA's own overview, prefectures appear only for GMP inspections of other domestic drug sites, not for GCTP.

The inspection follows the product. PMD Act Article 23-25 requires the company applying for or holding the approval to undergo a document or on-site inspection of each site when it seeks approval. It must undergo one again each time the period in the Cabinet Order passes, and Article 43-23 of the Enforcement Order sets that period at 5 years. A partial change approval brings its own inspection, unless the change does not affect the manufacturing or quality control methods as defined by ordinance (Article 43-27). The company files the application with PMDA when PMDA conducts the inspection (Article 43-24).

So your partner files as the applicant, and your site supplies the documents. If your own company applies for approval under Article 23-37, the inspection application is yours to file. PMDA's GCTP page lists separate document sets for new, periodic and category inspections, with a checklist for each. Several forms come in English. Form 1 outlines the products subject to inspection. Form 3 outlines a foreign cellular and tissue-based product manufacturing site, and Attachment 5 is a list of procedures. An oath, a product list and an inspection history are also on the list. PMDA's administrative notice on these documents is dated August 2, 2023 and was partly revised on June 16, 2025.

A certificate can save repeat inspections. Article 23-25-2 extends the drug rules' category-based conformity certificate to regenerative product sites, including accredited sites abroad. When a site holds one for a process category, the approval holder does not need the Article 23-25 inspection for that process at that site, although the Minister may still inspect when needed. The certificate is valid for 3 years. The law leaves the choice between a document and an on-site inspection to the authority, and the PMDA inspection guide describes how PMDA makes that choice for drug sites.

Send your MAH the English Form 3 site outline and Attachment 5 procedure list as soon as the filing plan is set, because the applicant files the inspection application and both are on PMDA's list of documents to submit.

Steps before your Japanese partner files

Take these in order, starting before the filing plan is final.

1. Ask the MAH to confirm that the product will be filed as a regenerative medical product under the PMD Act, whether it is a designated regenerative medical product, and which sites the application will name.
2. Read the GCTP Ordinance, MHLW Ordinance No. 93 of 2014, in Japanese on e-Gov or in a translation checked against it, together with the GCTP Q&A notices of 2015 and 2017.
3. Apply for, or confirm, your site's accreditation as a foreign manufacturer of regenerative medical products under PMD Act Article 23-24, in the right category.
4. Name the manufacturing supervisor in writing and confirm that the quality unit is independent of production (GCTP Article 5).
5. Map your quality system to GCTP Articles 8 to 22. Check donor and receipt records, donor segregation and product-to-facility traceability (Article 11), and record the reason for every use of verification in place of validation (Article 14).
6. Set reference sample quantities and retention under Article 12, and record retention under Article 22: shelf life plus 30 years for designated products, plus 10 years for the rest.
7. Prepare Form 1, Form 3 and Attachment 5 in English and send them to the MAH. Then plan for a GCTP inspection at approval and every 5 years after it, or for a category-based certificate valid for 3 years.

For the Japanese terms on PMDA forms, see the side box and the glossary.