Validation Findings in FDA Warning Letters 2008

The GMP news from 18 February 2009 comprised information on the FDA Warning Letters Report 2008, including the Top 5 deficiencies.

It did not cover deficiencies regarding validation (validation/qualification/calibration) though. This is due to the fact that the findings are listed according to the paragraphs in the 21 CFR 210/211, which does not contain a separate paragraph addressing (process) validation. For that reason the following information does provide an individual validation issues analysis:

In the 22 Warning Letters in the fiscal year 2008 issues regarding validation were criticised 15 times. Top of the list were deficiencies relative to process validation (9 Warning Letters). Five of the letters referred to deficiencies concerning solid dosage forms, 2 concerned semi-solid forms, one addressed radio pharmaceuticals, and one product classification remained unclear.

Two Warning Letters per subject covered issues like inappropriate validation of the sterilisation process, filter validation, "smoke studies" and cleaning validation the authority issued like

Exemplary findings for the issues mentioned above are:

Exclusion of validation batches without providing reasons within a retrospective validation
Missing sampling details in the validation plan
It seems like you did not understand the meaning of a cleaning validation
The cleaning validation master plan does not contain any "scientific rationale" for specific products, sampling locations and acceptance criteria
Swab surfaces are too small
Not all loading patterns were mapped in the validation of the sterilisation process
Inadequate Air Flow Pattern
Further deficiencies concerned issues like

An inadequate calibration of thermocouples
A Media Fill not representing a commercial process
Undocumented removal of filled vials within Media Fills
Conclusion: Although the subject validation is not specifically listed in the 21 CFR 210/211, it still is among the top deficiencies in the Warning Letters issued. Almost 70% of all letters contained one or several findings relative to this subject. 41% were related to process validation.