FDA takes a Look at Cleaning Validation

In a recent GMP news, we pointed out deficiencies, especially regarding stability data, of an Indian manufacturer by referencing an FDA warning Letter. This Warning Letter also offers interesting interpretation aids on the subject of cleaning validation. What is the FDA interested in?

SOPs on Cleaning Validation not followed

The FDA criticizes that the cleaning validation for non-dedicated equipment and its maintenance are not sufficient to be used for their intended purpose. This was actually acknowledged by the company's quality assurance personnel. Furthermore, standard operating procedures (SOPs) had not been followed.

It was criticized that the company had neither collected nor analysed rinse or swab samples, although this was laid down in the operating procedures. It was also pointed out that equipment was dirty and not well maintained. The FDA concluded that this presented a risk of cross-contamination.

The company's response is interesting. They admit to deficiencies in maintenance and sanitary conditions and are recalling all active ingredients that were shipped to the US. They also informed the FDA that they are initiating a "change control" to create a cleaning validation plan and to train personnel on the documentation of cleaning and equipment release.

However, the FDA responded very clearly in the Warning Letter: they want to see not just announcements, but the actual cleaning validation plan and the equipment maintenance plan.

Further demands by the FDA

Improvements to the cleaning validation program with special emphasis on worst-case scenarios for drug manufacturing. This includes the identification and assessment of worst-case scenarios for

• Drugs with higher toxicities
• Drugs with higher drug potencies
• Drugs of lower solubility in their cleaning solvents
• Drugs with characteristics that make them difficult to clean
• Swabbing locations for areas that are most difficult to clean
• Maximum hold times before cleaning
• A summary of updated standard operating procedures (SOPs) that ensure an appropriate program is in place for verification and validation of cleaning procedures for products, processes, and equipment.
• A comprehensive evaluation of the facility's cleaning and maintenance program.
• A CAPA plan to improve routine cleaning and maintenance.

Conclusion

Since it is not only the deficiencies in cleaning validation and equipment maintenance that are so significant, the FDA recommends hiring a GMP consultant.

Learn more about the state of the art in cleaning validation in the online training course Cleaning Validation from 05-07 May 2025.