What does "State of Control" mean for the FDA?

In the context of process validation, the FDA attaches considerable importance to a "state of control". The FDA expects evidence of this "state of control" as part of stage 3 "continued process verification" within the validation lifecycle. Now, what exactly does the FDA want to see? 

In almost every Warning Letter, also addressing deficiencies regarding pargraph 21 CFR 211.100, the requirement to demonstrate the "state of control" within the framework of process validation is included. In the case of a Korean medicinal product manufacturer, the FDA criticised the lack of validation for over-the-counter drugs and manufacturing processes that were not included in the master batch record. The company's response to conduct validation studies was not sufficient for the FDA.

FDA´s Expectation

A detailed validation plan is expected as well as "interim controls" until the CAPA measures are fully implemented. In its Warning Letter, the FDA explains what it means by process validation: The evidence of the suitability of the process coming from the development and the "state of control" over the entire life cycle. With the "process qualification" studies, the FDA wants to see that an "initial" control status is achieved. This is followed by continuous monitoring of the process, which ensures a stable process throughout the product life cycle.

The FDA would like to see this put in writing as part of a validation programme, also with regard to differences within batches as well as between batches. The programme is to be supplemented with the corresponding timelines.

For more detailed information please also see the FDA Warning Letter to Chemland Co. Ltd.