In order to advance discussions related to pharmaceutical regulations with the aim of eliminating drug lag/drug loss and strengthening drug discovery, the “Council on the Form of Pharmaceutical Regulations for Strengthening Drug Discovery and Ensuring Stable Supply, etc.” was held from May 2023 to March 2024.
The report of the Council was published on April 24, 2024 (Report in Japanese). The discussion of drug use results surveys (and the use of real-world data) is described in the report and an action direction is set out there.
Based on this action direction, the following documents were issued on July 18, 2024:
The partial revision of “The procedure for proceeding with the discussion on the formulation of implementation plans for post-marketing surveillance, etc. of drugs” (Director’s Notice) (here in Japanese)
The partial revision of “Q&A on drug use results surveys using all-case surveillance method for drugs” (Administrative Notice) (here in Japanese)
Post-marketing surveillance
The notification clarifies that a post-marketing surveillance is not required simply because the number of patients in clinical trial (including Japanese patients) is small. In addition, a postscript has been added to warn against use-results surveys for investigating the frequency of important identified risks.
“When the only concern is the small number of patients in clinical trials (total or Japanese patients) or the lack of information on some patient groups… this is not a reason to uniformly conduct a survey. Note that there is limited significance in conducting a use-results survey simply for the purpose of investigating the frequency of important identified risks.”
The above addition seems to have been toned down slightly from the direction of the Council’s report. The Council’s report stated that the use-results survey “is expected to be conducted basically for the purpose of investigating important potential risks and important missing information,” but the notification only states that it is “of limited significance” (this means that it does not completely exclude the possibility). Therefore, it is important to keep an eye on how meaningful research questions are in PMDA’s operations and how much the use-results survey are required.
Next, mostly importantly, the notification is clearly stated that reexamination is not linked to the implementation of post-marketing surveillance, as follows:
“It cannot be understood that the PMD Act requires that post-marketing surveillance, etc. be conducted uniformly for new drugs that are the subject of reexamination. Furthermore, the implementation of post-marketing surveillance, etc. is not a prerequisite for granting a reexamination period.”
The legal arrangement has not changed this time. The notification intends to correcting the wrong PMDA’s practice of “conducting post-marketing surveillance as a prerequisite for granting a reexamination period.”
Finally, the notification is made clear that post-marketing surveillance should be considered not only before approval, but also when new concerns arise after marketing. This is also considered to be the way surveillance and consideration should be done. However, it is important to note that it states, “(Before approval, only the outline will be considered, and detailed implementation plans may be considered after approval.)” It is thought that PMDA may request a separate (fee-paying) consultation to consider detailed implementation plans.
All-case surveillance
The notification is made clear that all-case surveillance should be conducted simply because there are few or no Japanese patients in clinical trials. As a result, it is expected that the necessity of all-case surveillance, which imposes a considerable burden on medical institutions and marketing authorization holders, will become more meaningful, given that the purpose and effect of all-case surveillance was unclear.
The notification is also made clear that the purpose of all-case surveillance is not to minimize risk. Furthermore, the statement “early” (to collect information) that was in the old administrative notice has been deleted. This is also based on the discussions at the Council, and is the result of a clearer understanding of what purpose all-case surveillance should originally be conducted for.
Comments
This notification and administrative notice are very promising amendments that will likely move drug use surveillance, including all-case surveillance, in a more meaningful direction.
However, the significance of early post-marketing vigilance and its results (effects) to date have not been fully verified or discussed. The additional section in this administrative notice also states that early post-marketing vigilance contributes to risk minimization. I hope that the relevant parties will continue to be aware of the issue and continue to follow up on whether this is truly the case.
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