Drug Evaluation Committee 2017-11 Scope of Clinical Trial Collaborators
Related classification: Other
Initial publication date: 2017-07
Revised publication date: Mar 2021
Question
Question 1
When applying for approval in Japan using data from a global trial, are we obligated to follow not only the J-GCP but also the regulations of all participating countries?
Question 2
We have not been able to clearly grasp the definition of a clinical trial collaborator. For example, are staff members who conduct clinical trial inspections and staff members who administer investigational drugs not considered investigational collaborators?
Question 3
When we conduct a global study, we are required to submit a Delegation log, but even if the members listed in the log are not required to be on the list of investigational collaborators under J-GCP (e.g., investigational drug managers), are they not allowed to participate in the discussion and vote of the investigational review committee for the relevant clinical trial? Does this mean that they are not allowed to participate in the deliberations and voting of the investigational review committee for the relevant clinical trial?
Opinion of the Pharmaceutical Manufacturers Association of Japan (PMAJ)
Answer 1
When applying for marketing authorization of a pharmaceutical product in Japan, it is sufficient to comply with Japanese laws and regulations, and it is not necessary to comply with regulations in other countries (see GCP Article 3).
On the other hand, results from clinical trials conducted in Japan, including global clinical trials, may be used in applications for approval in other countries. In general, clinical trials conducted in compliance with ICH-GCP can clear the review criteria of many countries, so clinical trials are often conducted in accordance with ICH-GCP. In addition, such clinical trials also need to comply with regulations specific to other countries (e.g., the U.S. regulation of Financial Disclosure Forms, etc.).
Answer 2
A collaborator is defined in GCP Article 2, Paragraph 18 as "a pharmacist, nurse, or other health care professional who cooperates with the investigator or subinvestigator in the conduct of the clinical trial at the site under the guidance of the investigator or subinvestigator," and is appointed by the principal investigator and approved by the head of the site. The GCP also defines a "pharmacist, nurse, or other medical personnel cooperating in a clinical trial.
In addition to "investigator collaborator," GCP also defines the role of "investigational drug manager," who is appointed by the head of the site. These two roles are different, and the "investigational drug manager" is not included in the "investigational collaborator" role.
Normally, staff members who conduct inspections for clinical trials fall under the category of investigator, but their appointment should also take into consideration whether or not they are in charge of tasks that require special procedures or techniques specific to clinical trials. See previous Opinion 2011-02.
Answer 3
In principle, the persons listed in the Delegation Log are responsible for important clinical trial-related tasks, and therefore it is not appropriate for them to participate in the deliberations and voting at the Clinical Trial Review Committee for the relevant clinical trial in order to maintain the independence of the review process. We recommend that decisions on how to handle individual cases be made after consulting with the sponsor as well. However, we believe that there is no problem for the investigational drug manager to participate in the deliberation and voting on the clinical trial in question (see previous Opinion 2009-40 ).
Supplement to Delegation Log
ICH-GCP does not define "investigational collaborator" or "investigational drug manager," but stipulates that a list (Delegation Log) should be prepared for those who share important tasks such as those related to clinical trial data and subject safety.
On the other hand, "investigator collaborators" defined in Japanese GCP are also those who share important tasks related to clinical trials, so there is no difference between ICH-GCP and Japanese GCP in the scope of roles to be included in the "list of investigators and investigator collaborators" (however, as stated in Answer 2, investigational drug managers are not included in investigator collaborators). (However, as stated in Answer 2, investigational drug managers are not included in the list of investigational collaborators, so the list differs from the Delegation Log in that those with the role of investigational drug management are not included.)
However, some of the sites are operating the "List of investigators and collaborators" to include only investigators and coordinators, and there are operational differences compared to ICH-GCP in terms of interpretation of important tasks. In addition, there are cases where the scope of responsibility of the relevant staff is not described in detail (a simplified description of "general clinical trial support"), so some sponsors ask the site to prepare a Delegation Log separately.
Reason for revision of opinion
In accordance with the revision of the GCP Guidance (August 31, 2020, Pharmaceutical Affairs Bureau of Japan, No. 0831-15), we have changed the provisions we refer to.