JPAL Laws, Ordinances and Notifications (relevant to GCP audits & the foreign manufacturer)
The Pharmaceutical Affairs Law (Law No. 145 Established as of August 10, 1960; Law No. 87 Revised as of July 26, 2005)MHLW Ministerial Ordinance No. 36 Clinical Tests for Medical Devices (hereinafter referred to as "Medical Device GCP" or “JGCP”)
YAKUSHOKUKIHATSU No. 0720005 Administration of Good Clinical Practice for Medical Devices
YAKUSHOKUKIHATSU No. 070720 Essential documents for criteria concerning clinical tests for medical devices
YAKUSHOKUHATSU No. 0720004 Criteria for Clinical Trials for Medical Devices
YAKUSHOKUHATSU No. 0331006 Handling of clinical study data based on clinical study that is carried out in a foreign country
MHLW Administrative Correspondence from June 23, 2006 Q&A on the Handling of Tests Records from Clinical Studies on Medical Devices Conducted Overseas
A. Ministry Ordinance 36 issued in 2005
B. Based on ICH6 and closely aligned with ISO 14155
C. Parallels the Drug GCP (MHLW Ordinance 28)
D. 6 Chapters, 79 Articles
- Chapter 1. General Provisions
- Chapter 2. Criteria for Preparations for Clinical Trial
- Chapter 3. Criteria for Clinical Trial Management
- Chapter 4. Clinical Trial Criteria
- Chapter 5. Criteria for Reevaluation Documents, Etc.
- Chapter 6. Criteria for Sponsoring Clinical Trial, Etc.
E.Audit requirement discussed mostly in Articles 21, 31 & 42
- JGCP requirements have many similarities to those the US and Europe.
- Largely due to MHLW participation in ICH and the ICH Guideline for GCP (E 6)
- Closely aligned with ISO 14155 Parts 1 & 2
- Basic functions of the Sponsor, Investigators, Informed Consent, Record Retention, and IRB’s are nearly identical to requirements currently in place for the US.
JGCP Audit Requirements
- Per Article 2, Audit is defined as “an investigation conducted by a sponsor or postmarketing sponsor, or one that a sponsor-investigator appoints a designated person to determine whether the clinical trial or postmarketing clinical trial is conducted according to this Ministerial ordinance (No. 36) and the protocol or postmarketing protocol to ensure the reliability of the technical documents collected by the clinical trial or postmarketing clinical trial.”
- When the sponsor-investigator appoints an individual within the same medical institution to conduct the audit, said individual must be a third party who is not involved in the clinical trial.
- The sponsor-investigator may also appoint a third-party organization outside of the medical institution to conduct the audit.
- Article 21, Clause 6:
"Procedures concerning auditing plan and duties" refer to a plan and procedure that the sponsor-investigator prepares to guarantee that the audit is properly conducted.
- This documentation must include:
+ Selection of the auditor (including the qualifications for the auditor)
+ Name of the auditor who will audit the clinical trial
+ Specific methods of auditing
+ Handling of auditing report and audit certificate
Article 31. Audit (by sponsor)
1. The sponsor shall prepare an audit plan as well as the operating procedures for the related duties, and conduct audits in accordance with the audit plan and the operating procedures.
2. Auditor to be independent of those in charge of medical device development or monitoring.
3. Audit report to document the matters confirmed in the audit and an audit certificate to verify that the audit has been conducted. Submit report and certificate to the sponsor
Article 42. Audit (sponsor-investigator)
1. The sponsor-investigator shall prepare an audit plan as well as the operating procedures for the related duties, and conduct audits in accordance with the audit plan and the operating procedures.
2. Auditor shall not be engaged in the clinical trial at the medical institution where the clinical trial is conducted (including its preparation and management) or in monitoring.
3. Audit report to document the matters confirmed in the audit and an audit certificate to verify that the audit has been conducted. Submit report and certificate to the sponsor-investigator and the head of the medical institution.
An audit on individual clinical trials shall be conducted by deciding on:
+ the subject of the audit, i.e. medical institution and other facilities engaged in the clinical trial
+ the timing of the audit taking into account the
* importance of the clinical trial for application to the regulatory authorities
* number of subjects
* type and complexity of the clinical trial
* level of risk posed by the clinical trial to subjects,
* various issues discovered through monitoring.
The auditor is required to
+ visit the medical institution and other facilities engaged in the clinical trial as necessary
+ directly access the source documents to confirm that the clinical trial is being properly conducted and the reliability of the data is fully ensured.
Note: “When a serious noncompliance to the GCP Ordinance is found, the regulatory authorities may request access to the audit report.”