Qualification Deficiencies from the FDA's Perspective

There is relatively little information on FDA requirements for equipment qualification. You can find guidance in the FDA Guidance for Industry General Principles and Practices: Process Validation on 'DQ', 'IQ' and 'OQ'. However, the terms 'DQ', 'IQ' and 'OQ' are not mentioned there. A footnote refers to the ASTM standard E2500. But what does the implementation look like in practice in companies? A current Warning Letter gives some clues. 

What is it about?

An over-the-counter (OTC) drug manufacturer is criticised under 21 CFR 211.113 for finding germs in water monitoring. This water was used to manufacture OTC drugs and to clean the equipment.

Among other things, the FDA criticised the inadequate qualification of the water system. It refers to installation and functional qualifications carried out by the manufacturer in 2019, whereby data collection was only completed three years later. However, the data was not analysed. Subsequently, the company presented a PQ to the FDA, but did not check all parameters in accordance with the pharmacopoeia specifications. The company's own specifications (test for the absence of gram-negative microorganisms) were also violated as part of the PQ. This is also described by the company in the PQ report that was sent to the FDA. The company committed to set up a new validation of the water system.

This is not enough for the FDA. It emphasises the importance of a water system and demands a solid design and effective operation, maintenance and monitoring of the system. It also requires:

• A comprehensive corrective action plan for the design, control and maintenance of the water system.  
• A report on the validation of the water system. This report should also include a summary of any improvements to the system design and the monitoring and maintenance programme. 
•  The total bacteria count limits used to monitor whether the system is producing water that is suitable for the intended uses for each of the OTC products. 
• A detailed risk assessment that addresses the potential impact of the inadequately qualified water system with respect to batches of drug products currently distributed in the U.S. or within the expiration date 
• An indication of the actions that will be required in response to the risk assessment, such as customer notifications and product recalls.

Conclusion: Although the qualification levels DQ, IQ, OQ, PQ are not named in the FDA Guidance for Industry: Process Validation General Principles and Practices, they are still present in the industry. The addressee of the Warning Letter performed IQ, OQ and PQ activities. The FDA additionally required consideration of the design of a water facility. Which is equivalent to a DQ.  

You can find the entire Warning Letter, as always, on the FDA website.