Worst Case

Bracketing during cleaning validation is acceptable , however how does one determine the “Worst case”.

FDA Warning Letter

In a current warning letter, the FDA criticizes inadequate cleaning validation in connection with the topic of cleaning (21 CFR 211.67) and bracketing. The FDA criticizes the statement in the company’s validation plan that one filling machine is representative of all other filling lines. Why?

Equipment

No identical equipment is used at the filling lines – and there is no evidence or scientific justification that the filling line chosen is representative.

Cleaning Validation

Further the “worst case” product that the company had selected for cleaning validation was not accepted by the FDA.  The FDA criticised a lack of a scientific justification as to why the selected “worst case” product represents the “worst case”. Especially since there were other products with the same active ingredient in a  higher concentration than the selected “worst case” product for the validation.

Summary

From the FDA’s point of view, worst-case considerations in the field of cleaning validation must be backed up with scientific justification. 

The FDA’s comments concerning system qualification and process validation are also interesting. The missing qualification of the filling line and a lack of process validation in the drug production were criticized. The FDA highlighted the importance that the corrective measures must include a description of how the personnel is “retrained” and how it is ensured that new personnel are also involved in the qualification requirements.  

A retrospective validation as a substitute for the missing process validation was not accepted by the FDA. Here the FDA expects a much more dedicated approach that shows that the process validation cycle will be adhered to in the future.

You can access the entire Warning Letter through the FDA website .