Current FDA Requirements for Cleaning Validation

Recommendation

4/5 October 2022
Heidelberg, Germany

Process Validation in the light of the revised Annex 15 and FDA Requirements

Since the GMP regulations are sometimes not specific, concrete regulatory guidance on implementation is very helpful. In a current Warning Letter, the FDA specifies their requirements for cleaning validation. What does the FDA require?

In the Warning Letter, the medicinal product manufacturer is criticized for not having written instructions for cleaning and for not having carried out a cleaning validation. In addition to a risk assessment regarding the cleaning in the past and its effects on the product quality, the FDA also requires a comprehensive plan with

• a cleaning validation strategy, 
• procedures
• protocols
• timelines for the cleaning validation activities  

Furthermore, the FDA still requires a cleaning validation program with special emphasis on "worst-case" scenarios. As a minimum, the following should be considered as worst-case scenarios

• Medicinal products with higher toxicities
• Medicinal products with higher medicinal potencies
• Medicinal products with lower solubility in their cleaning solvents
• Medicinal products with characteristics that make them difficult to clean
• Swabing locations for areas that are most difficult to clean
• Maximun hold times before cleaning.

Please see the FDA's Warning Letter issued to Syntec Pharma for more detailed information.