Episodes on Quality Assurance: part 1

1.   Impact on quality and determination of illegality

At the end of March 2022, Kyowa Pharmaceutical was administratively ordered to suspend operations for 10 days. The reasons were discrepancies between the approved contents and the actual manufacturing records, inadequate change management, and false entries in the records, which are basically the same as the reasons given to several generic drug companies since last year. However, there is one point in this administrative action that differs from previous cases. That is the consideration of "stable supply". Specifically, certain products were exempted from the administrative action due to concerns about shortages, and their continued manufacture and sale was permitted.

It is also meaningful from the perspective of making effective use of medical resources by not discarding medicines that are judged to have "no quality problems". 
In this case, even for excipients, the implementation of a manufacturing method not described in the approval document is considered a deviation from the approved items and caused a voluntary recall. In product quality regard, it would be easier to respond if there were guidelines for the exceptional operation of the recall criteria.

Next, I would like to discuss one of the points raised in this case, namely, the use of an excipient not listed in the approval document for the pharmaceuticals. This point seems to be based on the judgment that the excipient used as an external lubricant for tableting is not listed in the marketing authorization document and is in violation of the Pharmaceutical and Medical Device Act. Here, I would like to focus only on the use of a lubricant ("excipients") for external lubrication during tableting and its description in the approval document, and discuss the case from a general standpoint.

It is common that a lubricant such as "excipients" is used by external lubrication method to prevent tableting failure, but if this process is not specified in the approval document, the reasons may be as follows. (1) Validation results indicate that external lubrication is not necessary. (2) External lubrication was judged to be necessary, but since external lubrication at the time of tableting is common and is a very small amount, it is not considered to be important enough to be specified in the approval document.