Drug Evaluation Committee 2020-33 Decision document for unknown/known adverse reactions in studies that have progressed from clinical trials to post-marketing clinical trials
Related classification: clinical trial contracting procedures
Date of first publication: December 2020
Question
When a drug is approved and the clinical trial has moved to post-marketing clinical trials and the development of the drug is still ongoing, this document is provided to the site as "a document describing the quality, efficacy and safety of the study drug and other important information for the proper conduct of post-marketing clinical trials" and as a basis for determining known/unknown adverse reactions, Is there a problem with continuing to provide the investigational new drug summary? Or, do we need to switch to the attached document?
In the relevant post-marketing clinical study, the investigational drug label is revised and continues to be used as a post-marketing clinical study drug, not a marketed drug.
The sponsor's basis for determining known and unknown adverse reactions has been switched to the package insert.
Article 56 of the GCP states that the investigational new drug summary should be replaced with the package insert, but the description is limited to the judgment of side effects on the part of the sponsor, and we could not find any notice regarding the site side. We believe that the switch to the attached document is when a marketed drug is used or when development is not continued after approval, and does not preclude the use of the investigational new drug summary in cases such as this one.
Opinion of the Pharmaceutical Manufacturers Association of Japan (PMAJ)
Under the provisions of Article 56 Guidance 2 (2) (2) of GCP, it is not necessary to prepare an investigational new drug summary for post-marketing clinical trials conducted using an already approved drug. In addition, Article 20, Paragraph 3 of the GCP stipulates that "investigational new drug summary" should be read as "package insert" (Article 56, Guidance 2 (6) (4) of the GCP), and the post-marketing clinical trial sponsor's judgment on the predictability of adverse effects, etc. should be based on the package insert.
In the case in question, the post-marketing clinical trial sponsor's basis for judgment of known/unknown adverse reactions has been switched to the package insert, so basically the same operation should be applied as above.
In addition, according to a notice issued on August 31, 2020 (Pharmaceutical Affairs Council of Japan, No. 0831-15), it is no longer necessary for investigators to determine the predictability of serious adverse events (GCP Article 48, Paragraph 2/3, Guidance 2).