Chapter III. Section 1. Standards for Clinical Trial Management by Sponsor (Articles 16 through 26): Ministerial Ordinance on Good Clinical Practice for Drugs, PMDA Japan

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 the 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 products 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.

Article 17. Supplying Investigational Products

The sponsor shall be responsible for supplying medical institutions with the
investigational products that have been manufactured at a manufacturing site which is equipped with adequate buildings and facilities to ensure the quality of the investigational products and which has appropriate manufacturing control and quality control systems in place.

Article 18. Preparing Description of Assignment

When the sponsor assigns the duties of coordination as specified in Article 2, Paragraph 16 to a coordinating investigator or a coordinating committee, the sponsor shall prepare a document describing the scope of the duties, the operating procedures and other necessary information.

Article 19. Establishment of Efficacy and Safety Assessment Committee

1. A sponsor may establish an Efficacy and Safety Assessment Committee that deliberates the appropriateness of continuing an ongoing clinical trial, or the revision of the protocol.

2. The sponsor shall prepare written operating procedures for deliberation by the Efficacy and Safety Assessment Committee specified in the preceding paragraph and have the committee conduct deliberation in compliance with the procedures.

3. The sponsor shall prepare and retain records of deliberation of the committee whenever the deliberation specified in the preceding paragraph is held.

Article 20. Information on Adverse Drug Reactions etc.

1. The sponsor shall collect and examine information necessary to conduct the clinical trial properly, such as information on the quality, efficacy, and safety of the test drug, and provide the heads of the medical institutions with such information.

2. Whenever the sponsor becomes aware of any event concerning the test drug that are specified in Article 80-2, Paragraph 6 of PAA, the sponsor shall notify the investigators and the heads of the medical institutions of such events in a list, etc. for each of the test drugs, annually after the date of submission of the first clinical trial notification etc. within 3 months after the end of each period of 1 year.

3. Whenever the sponsor becomes aware of any event, which is unexpected based on the information provided in the Investigator’s Brochure for the test drug, among those specified in the preceding paragraph, the sponsor shall immediately notify the investigators and the heads of the medical institutions of the fact.

4. Whenever the sponsor becomes aware of any information relevant to the proper conduct of the clinical trial, such as information on the quality, efficacy, and safety of the test drug, the sponsor shall revise the protocol and the Investigator’s Brochure, as necessary.
In such cases, the sponsor shall obtain the consent of the investigators on the revision of the protocol.

Article 21. Monitoring

1. The sponsor shall prepare written operating procedures for monitoring, and conduct monitoring activities in accordance with the procedures.

2. Monitoring pursuant to the preceding paragraph shall be conducted by visiting the medical institutions, except when monitoring is adequately performed by other means.

Article 22. Monitor's Responsibilities

1. If an individual engaged in monitoring (hereinafter referred to as a "monitor") has found, as a result of monitoring, that the clinical trial is not being conducted at a medical institution in compliance with the Ministerial Ordinance or the protocol, the monitor shall immediately notify the investigator of the medical institution of the fact.

2. The monitor shall submit a monitoring report documenting the following information to the sponsor after each visit to or communication with the medical institution:

(1) Date of monitoring
(2) Medical institution monitored
(3) Name of the monitor
(4) Names of investigators etc. interviewed during the monitoring visit
(5) Summary of the results of the monitoring
(6) Description of the facts of which the monitor notified the investigator pursuant to the preceding paragraph
(7) Actions to be taken concerning the matters specified in the preceding item and the monitor's comments on such actions

Article 23. Audit

1. The sponsor shall prepare an audit plan and written operating procedures for the related duties, and conduct audits in accordance with the audit plan and the operating procedures.

2. An individual engaged in auditing (hereinafter referred to as an "auditor") shall be independent of the divisions responsible for drug development or monitoring.

3. The auditor(s) shall prepare an audit report documenting the findings in the audit and an audit certificate verifying that the audit has been conducted, and submit them to the sponsor.

Article 24. Premature Termination etc. of Clinical Trial

1. If it is found that a medical institution has violated this Ministerial Ordinance, the protocol or the clinical trial contract, resulting in interference with the proper conduct of the clinical trial (excluding the cases specified in Article 46), the sponsor shall cancel the contract and prematurely terminate the clinical trial at the medical institution.

2. If a clinical trial is suspended or prematurely terminated, the sponsor shall promptly notify in writing the head(s) of the medical institution(s) of the suspension or premature termination and the reasons thereof.

3. If the sponsor has decided not to include the clinical data obtained in the clinical trial in the application specified in Article 14, Paragraph 3 of PAA, the sponsor shall notify in writing the head(s) of the medical institution(s) of the fact and the reason thereof.

4. The provisions of Article 10, Paragraphs 2 through 6 shall apply mutatis mutandis to the notification in writing as stipulated in Paragraph 2 and the preceding paragraph. In this case, "person who intends to sponsor a clinical trial" in these provisions shall be read as "sponsor."

Article 25. Clinical Trial Reports

The sponsor shall prepare the clinical trial reports (refers to documents that summarize the results etc. of the clinical trial; the same shall apply hereinafter) when the clinical trial is completed or prematurely terminated.

Article 26. Record Keeping etc.

1. The sponsor shall appropriately retain the following records (including documents and data) related to the clinical trial until the day on which marketing approval of the test drug is obtained (or the day 3 years after the date of notification in the case of a notification pursuant to Article 24, Paragraph 3) or the day 3 years after the date of premature termination or completion of the clinical trial, whichever comes later:

(1) Protocol, contracts, clinical trial reports, and other documents prepared by the sponsor in accordance with this Ministerial Ordinance, or copies thereof.
(2) Case report forms, the written notification pursuant to Article 32, Paragraph 6, and other records obtained from the heads of medical institutions or investigators etc. in accordance with this Ministerial Ordinance.
(3) Records of the duties related to sponsoring and managing the clinical trial, such as monitoring and audits (excluding those specified in the preceding two items and Item (5))
(4) Data generated in conducting the clinical trial
(5) Records specified in Article 16, Paragraph 5

2. The sponsor who resides outside Japan shall have a clinical trial in-country representative retain the records specified in Article 16, Paragraph 5, during the period specified in the preceding paragraph.

 

'Ministerial Ordinance on Good Clinical Practice for Drugs', source: Pharmaceuticals and Medical Devices Agency, Japan

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