AQL testing in the visual inspection of parenterals (FAQs)

Questions:
Is the carrying out of a 100% inspection of parenterals to be understood as IPC testing or as final product testing? Is it possible to carry it out under the responsibility of production or must it be done by QC? Is an AQL inspection required?

Answer:
Assigning the activity of a 100% inspection is not trivial at first sight. Formally, this activity is allocated to production. By the way, this is also FDA's point of view. Hence, it also is an activity which requires a manufacturing authorisation within the meaning of § 13 German Medicine Act (AMG). Due to the fact that it is a 100% inspection, it is neither a real IPC nor a final inspection on a random basis. The 100% inspection being attributed to production, it is carried out under the responsibility of the head of production.

In order to discuss the need for an AQL inspection some thought might first be given to the necessity of a second 100% inspection. The fact that companies that deliver parenteral products to Japan carry out a second 100% inspection almost always indicates that generally there is only a limited confidence in carrying out a single 100% inspection. In the course of this second 100% inspection further objects with defects are sorted out. Another example underpins the need for a second 100% inspection:

The following has been discovered during an inspection: Because of a high rate of objects with defects (almost 15%) in a batch a second 100% inspection was carried out. Again almost 14% of objects with defects were sorted out. Even if the rate of cosmetic defects was relatively high, this example shows nevertheless quite clearly that further measures have to be taken. The security and effectiveness of the inspection process is of paramount importance and there is no regulation defining how to achieve this security. But it is regulated that the process has to be successful. In the USP you can read for example:

General Chapters <1>" FOREIGN AND PARTICULATE MATTER
"The inspection process shall be designed and qualified to ensure that every lot of all parenteral preparations is essentially free from visible particulates."

This means nothing else than that the process of visual control shall ensure that every batch of parenteral preparations is essentially free from visible particulates.

From this point of view, it is at least necessary to establish one further measure that ensures enough security. This could be a second 100% inspection but also an AQL testing. From the regulatory point of view an AQL testing is not mandatory but it is state of the art. If no AQL inspection is carried out this implies that it was shown in the course of process validation that the established method is virtually 100% successful. But this is nearly impossible in practice.