15/16 February 2024
When it comes to process validation, FDA's Process Validation Guidance from 2011 is state-of-the-art. It is interesting to see how the FDA would like to see the guidance implemented. Here, the findings described in Warning Letters issued after FDA inspections can help. A recent Warning Letter regarding deficiencies to 21 CFR 211.100 from October 2019 mentions the following:
Missing Process Performance Qualification studies and a lack of process monitoring for showing a stable process as well as a constant product quality were criticized. This includes the identification of critical process parameters, specifically in the case of gel production. The mixing time and speed as well as the succession of process steps and process times are mentioned. The FDA also missed a manufacturing instruction as basic prerequisite for production. Undocumented changes in the manufacturing process were also criticised.
As a result, the FDA expects well defined process parameters and raw material properties for the manufacturing process of creams and ointments. The FDA expects the process validation to result in an assessment of the process reliability and controllability with regard to the life cycle. The process qualification shows that an initial "state of control" is achieved. Commercial distribution can only begin once a successful process qualification has been achieved. Thereafter, it is necessary to monitor process performance and product quality. This should ensure the control of a stable manufacturing process during the product lifecycle.
Consequently, the Warning Letter refers to the Process Validation Guidance mentioned above as a literature citation.
You can find the complete Warning Letter on the FDA website.