20/21 March 2024
Interpretations of the FDA's CGMP rules can often be read from Warning Letters as well as guidelines. A current Warning Letter describes the FDA's expectations of the Quality Control Unit for validations, among other things.
With reference to 21 CFR 211.22, the FDA criticises in the Warning Letter that the quality control unit is not fulfilling its responsibility to ensure that drugs are manufactured in compliance with CGMP. The FDA understands that there must be written procedures on the tasks and responsibilities of the Quality Control Unit. These should show that the Quality Control Unit also has the "authority" to review and approve quality-related functions that have an impact on product quality.
And this includes process monitoring, which shows that the processes are stable and consistently deliver quality products. On this point, the FDA refers to 21 CFR 211.100 (a). In particular, the missing stage 3 in the FDA's process life cycle, "Continued Process Verification", is admonished here.
As a further (missing) responsibility of the Quality Control Unit, the FDA criticises in the Warning Letter, written, validated, reviewed and approved cleaning processes. These must be capable of removing residues from the surfaces that come into contact with the product in equipments that are used with several different products ("non-dedicated"). The FDA refers in this regard to 21 CFR 211.67 (b).
With reference to the same paragraph, the FDA also criticises the lack of equipment maintenance procedures. These must also be established, reviewed and approved in writing in order to enable robust device operating conditions.
In detail, the FDA wants to see an overview of the validation programme and timelines for the process performance qualification (PPQ) runs of each individual product. Furthermore, the FDA expects a data-based and scientifically verifiable programme regarding process variability.
Also urged is a cleaning validation programme with special emphasis on worst case conditions with regard to:
The FDA also requires an update of the change management system with regard to the introduction of new manufacturing equipment and new products.
For assistance in obtaining more information on the responsibilities of the Quality Control Unit, the FDA recommends its guidance document Quality System Approach to Pharmaceutical CGMP Regulations.
You can find the entire Warning Letter to Skyless on the FDA website.