On September 27, 2024, the “Pilot of Change Procedures for Moderate Risk Changes of Manufacturing Method” (Notification from the Director of the Pharmaceutical Evaluation and Licensing Division) and the “Questions and Answers (Q&A) Regarding the Pilot of Change Procedures for Moderate Risk Changes of Manufacturing Method” (Notice from the Pharmaceutical Evaluation and Licensing Division) were issued (in Japanese).
Under the Pharmaceuticals and Medical Devices Act, when making changes to the manufacturing method of a drug, there are procedures for an application for a partial change of approved items (partial change application) and a notification for a minor change (minor change notification).
It has been pointed out that changes to manufacturing method with medium risks in Japan are not processed promptly compared to Europe and the United States.
With the issuance of this notification, the MHLW started a pilot of rapid processing of moderate risk changes in manufacturing methods. This article summarizes the key points of the notification. Since this is a pilot and optional scheme, it is possible to handle it with a normal partial change application without using moderate risk changes, as before.
First, the handling of moderate risk changes this time should be done as a type of partial change application (not a minor change notification). Therefore, the application procedure must be completed before introducing the changes to manufacturing methods.
Secondly, for drugs for which pre-market review applications will be submitted newly, it is necessary to clearly indicate what items fall into those with moderate risks in advance. For drugs that have already been approved, a Drug Procedure Consultation with PMDA must be conducted in advance to agree with the PMDA whether it is acceptable to handle changes to the manufacturing method as moderate risk changes (consultation is mandatory).
The fee for the Drug Procedure Consultation is 150,900 yen (FY2024). It also takes about three months until the actual meeting (from the PMDA website in Japanese).
For moderate risk changes, the target processing period is 40 business days from application to approval under the “moderate risk change expedited review.” Since the target total review period for a normal partial change application is 12 months, the moderate risk change expedited review is expected to be processed about 10 months earlier (however, as mentioned above, it takes 3 months for Drug Procedure Consultation).
This seems the first attempt in the implementation of the Pharmaceuticals and Medical Devices Act to specify this review period (administrative processing period) in business days. Also, it is an unprecedented rule that inquiries from the PMDA and their responses from applicants submitted after 5 p.m. should be processed on the next business day.
The flow from application to approval for a moderate risk change is as follows.
- Within 10 business days of acceptance of the application, the PMDA confirms whether the application can be accepted as a moderate risk change.
- If the PMDA has any inquiries, they should be sent to the applicant within 40 business days of acceptance of the application (i.e., in this case, the period from application to approval should not be 40 business days).
- The applicant should submit responses to the PMDA inquires within 30 business days of the date of sending the inquiries (if the responses cannot be submitted in time, the application should be processed as a regular partial change application).
- The approval decision should be made within 20 business days of the date of receipt of the responses from the applicant.
- (If the review takes even longer, the application should be processed as a regular partial change application.)
Based on this flow above, a moderate risk change may take a total of 7.5 months; 3 months for the mandatory Drug Procedure Consultation, 2 months from application to issuance of the PMDA inquiries, 1.5 months for the response to the PMDA inquiries, and 1 month for the approval decision. In order to achieve an expedited review, the key is to be able to discuss thoroughly during the Drug Procedure Consultation so that the PMDA does not issue an inquiry.
It is also specified that a GMP compliance document review will be conducted in parallel. Changes that are subject to GMP compliance onsite inspections are not currently covered by this pilot.
In addition, there is a limit on the number of applications that can be subject to the pilot. The notification says that the pilot can be applied for “about 15 cases per month for the PMDA as a whole, and about 1 to 2 cases per month for each review department, on a first-come, first-served basis.”
Moderate risk changes are also being listed in the Pharmaceutical and Medical Device Regulation Committee. Therefore, in parallel with this pilot operation, discussions are expected to proceed with a view to amending the act in preparation for full-scale implementation.
コメント