5. Investigator and Investigational Product

5.1 Does local regulation require PI/CI to be approved/registered by any health authority (e.g., RA/EC)?  

No, but the PI should be a suitably qualified and experienced professional.

5.2 Does local regulation require any specific documents if PI/CI is based outside the country?

The PI must be based in Japan.

5.3 Does local authority allow electronic ICF administration, including electronic signatures?

It is to be noted that eSignatures are not allowed to be used in the informed consent form (ICF). In these documents, wet signatures are to be used.

Japan has recognized e-signatures as a legal form of signing since 2000, giving businesses the option to use them whilst trading.

According to the Act on Electronic Signatures and Certification Business (Electronic Signature Act), “electronic signature” means:

A measure to be taken with respect to information that can be recorded in an electromagnetic record (a record that is prepared in an electronic form, a magnetic form, or any other form not perceivable by human senses and used for information processing by computers), which measure satisfies both of the following requirements:

• The measure must indicate that such information was created by the person who took such measure; and
• The measure must be able to confirm that such information has not been altered.

5.4 Does local regulation require ICF to be administered as audio/visual and do these need to be recorded?

There is no specific guidance on this topic. The ICF should be appropriate for the target population. 

5.5 Is there any specific information/requirement on data capture/management (e.g., privacy regulations, etc.)?

Healthcare information is considered “special care required” information under the Japanese Act on Protection of Personal Information (APPI). This law was introduced in 2019 and is closely aligned with the EU GDPR. 

5.6 If a clinical study involves the study product as OTC and this is provided via pharmacy/amazon, etc., are there any specific regulations for IP management that need to be followed?

Sponsors are typically required to provide IMP directly to patients. Alternative means of product would be subject to ethics approval.

5.7 For a marketed study product/OTC, can a participant be compensated after confirmation of the purchased study product, or upfront prior to product acquisition? Does compensation in any way impact how the study is viewed (i.e., RWE vs. Interventional Study)?

As above, Sponsors typically provide IMP directly to patients.

5.8 Is it permitted to pay participant stipends (i.e., is it permitted to pay the patients for their participation in the clinical trial)? If so, what is the average range?

Yes, patients may be compensated for any expenses relating to their participation in the trial. These are typically very low.

5.9 Specific labeling requirements for clinical study product

The "Ministerial Ordinance on Good Clinical Practice for Drugs (2012)” states the following in regard to Informed Consent:

Article 16. Investigational Product Control/Accountability 

1. A sponsor shall indicate the following information in the Japanese language on the container or package of the investigational products: 

(1) Statement of “For clinical trial use only” 

(2) Name and address of the sponsor (if the sponsor resides outside Japan, name of the sponsor and name of the country where the sponsor is located, and name and address of the clinical trial in-country representative) 

(3) Chemical name or identification code

(4) Manufacturing number or manufacturing code 

(5) Information on storage method, expiration date, etc., if necessary 

2. The sponsor shall not indicate the following information in the documents attached to the investigational products, on the investigational products, or on their containers or packages (including the inner packages): 

(1) Proposed brand name 

(2) Proposed indications 

(3) Proposed administration and dosage 

3. When investigational products are supplied to medical institutions in such a state that the subject, investigators, etc., and clinical research coordinators cannot distinguish the test drug from the comparator, the sponsor shall take necessary measures so that the investigators, etc. can readily identify the test drug from the comparator in the event of an emergency.

4. The sponsor shall supply medical institutions with investigational products so packaged as to prevent contamination and deterioration during transport and storage. 

5. The sponsor shall retain the following records concerning the investigational products: 

(1) Records concerning the manufacture of the investigational products, such as the manufacturing date, manufacturing method, and manufactured quantity, and the results of the tests on the drug's quality, such as its stability 

(2) Records of the supply or retrieval of the investigational products, including the quantity and date, for each medical institution 

(3) Records of disposal of the investigational products 

6. After concluding the clinical trial contract, the sponsor shall prepare written operating procedures for investigational product control/accountability at the medical institutions, and deliver the procedures to the medical institutions without delay.

7. The sponsor shall prepare, as necessary, documents explaining the reconstitution procedures and other handling procedures for the investigational products and deliver the documents to the investigators, etc., clinical research coordinators, and the investigational product storage managers specified in Article 39. 

8. The provisions of Article 10, Paragraphs 2 through 6 shall apply mutatis mutandis to the delivery of the operating procedures as stipulated in Paragraph 6. In this case, "person who intends to sponsor a clinical trial" in these provisions shall be read as "sponsor." 

9. The provisions of Article 10, Paragraphs 2 through 6 shall apply mutatis mutandis to the delivery of the documents as stipulated in Paragraph 7. In this case, "person who intends to sponsor a clinical trial" and "head of the medical institution" in these provisions shall be read as "sponsor" and "investigators, etc., clinical research coordinators and the investigational product storage managers specified in Article 39," respectively.

https://www.pmda.go.jp/files/000152996.pdf

5.10 What documents need to be submitted (including relevant fee if any), and to whom, if a permit is needed for an investigational/study product being shipped from outside the country? Are there any specific requirements for biologics?

Please refer to Section 2.6.

5.11 What is the turn-around time to get an import permit?

This depends on the product type but is typically around 1 – 2 months.

5.12 Does local authority allow the destruction of clinical supplies at an off-site location (e.g. third-party vendor in or outside the country) after study completion? Are certificates of destruction required?

Yes, the Sponsor must keep records of IMP disposal. 

https://www.pmda.go.jp/files/000152996.pdf