The characteristics of PMDA inspectors are as stated in the previous blog—For an Effective Inspection Response. Let's consider what mechanism and what level of observations are issued by Japanese regulations. The structure of Japan's regulations regarding GMP has been explained in a previous blog—Regulations related to GMP in Japan. In addition, I would like to introduce another notification (#0329-9, March 29th 2024) regarding the level of observation from the Japanese authorities.
The definitions are as below….
<Critical>
If the identified deficiencies violate the Article(s) stipulated in the GMP Ministerial Ordinance and meet any of the following conditions.
- When there is a clear risk of manufacturing harmful products or when harmful products have been produced that could adversely affect patients,
- When falsification, false statement, or tampering by the manufacturer is identified regarding the product or records.
<Major>
If the identified deficiencies violate the clauses stipulated in the GMP Ministerial Ordinance but do not constitute a "critical deficiency."
<Minor>
If the identified deficiencies do not clearly violate the clauses stipulated in the GMP Ministerial Ordinance, but improvements are needed to ensure more appropriate operation in order to achieve complete manufacturing and quality control.
From the above, in my experience, except for intentional violations, you will not receive a critical rating right away. If any serious non-compliance with the GMP Ministerial Ordinance is found, it will be handled as Major first. From there, they will evaluate whether it is malicious and if so, it may be raised to critical status organizationally based on an internal meeting. In addition, according to the structure of the regulations, if the provisions of the supplementary notification (#0428-2) are not met, the parts related to the definition of the Ministerial Ordinance are generally likely to be major, and the rest are almost always likely to be minor. If the provisions of the GMP case studies are not met, they tend to be minor.
However, please understand that this is a general trend based on my experience and may not always be the case.
By the way, the recent trends in PMDA's observations can be understood from the contents of the ORANGE (Observed Regulatory Attention Notification of GMP Elements) Letter. It is only available in Japanese, but if you use some recent translation applications, you should be able to read it without any problems.
ORANGR Letter: https://www.pmda.go.jp/review-services/gmp-qms-gctp/gmp/0011.html
