Correlation between Validation Master Plan and Validation Protocols

In a news item from 12 March 2025, we described deficiencies in microbiological tests of non-sterile products. However, the warning letter in question provides further information: on process validation. What was criticized?

The FDA found that although there were requirements in the Validation Master Plan for process validation and hold times, no operating conditions such as bulk hold times, process limits or acceptance criteria for process parameters were specified in the validation protocol itself. 
In response, the inspected company submitted an updated validation protocol which, according to the FDA, still failed to address hold times and other details, such as information on sampling and the batch report that is used for the first validation batch. Subsequently, the FDA refers to its process validation guideline and describes the content of the guideline in a short section of the warning letter. 

Another point of criticism was the equipment. Contrary to the intended use, the circulation of the (water) system was stopped when it was not in operation. There was also a lack of monitoring of both chemical and microbiological parameters in accordance with the US Pharmacopoeia (USP). The response of the inspected company to operate the system permanently in the future is not sufficient. The entire system design is still to be assessed and monitoring introduced. In addition, the FDA requires interim measures and an investigation into the impact of the incorrectly validated system on product quality.

The FDA also expects a validation program, detailed PPQ plans, timelines for the PPQ, maintenance information, a description of monitoring and an assessment of the impact of defects on customer information and recalls.

Conclusion: Internal requirements in GMP documents must be implemented.

As part of the ECA Live Online Training The Validation Manager in the Pharmaceutical Industry on 26/27 March 2025, the qualification of a water system will be explicitly addressed in a case study.