FDA Warning Letter Statistics 2011 with regard to Process Validation / Qualification and Calibration

In the Warning Letter Report 2011 (GMP News from 30 November 2011), statistics have been published about FDA’s Warning Letters (issued to drugs and API manufacturers) during the fiscal year 2011 (from October 2010 to September 2011). The topics Process Validation / Qualification haven’t been considered separately as they have no independent chapter in the cGMP regulations (21 CFR 210/211). In the following, you will find a summary from the 39 Warning Letters 2011 on GMP deviations regarding Process Validation, Qualification and Calibration in the manufacturing environment.

Missing or insufficient process validation is one of the top criticised deficiencies (10 times) in 2011. Among other things, missing identification of the critical parameters, deviations in the validation batch which haven’t been questioned, reprocessing not validated, etc., have been observed. It should be noted that half of issues are regarding solid forms and the most frequent finding was insufficient validation of the mixing times.

Inadequate Media Fills have been observed 5 times: critics were made on non-representative activities, incomparable scope of the Media Fill to routine procedure, personnel without Media Fill participation, and the duration of the Media Fill. A further deviation observed concerned the use of a non-validated Media Fill medium and inexistent “oversight” of the quality control unit.

5 findings have also been made regardig equipment qualification of packaging facilities, metal detector, inexistent statistical sampling, insufficient acceptance criteria and tardy requalification (Change Control issue).

In the report, the FDA also observed 3 times missing validation of holding times for bulk material. Inexistent validations of water systems and sterilisation of filters have been criticised respectively two times. Computer validation deviations have also been noticed two times: insufficient access control, a missing review and release of a validation report. Moreover, the FDA observed one inexistent "Air Flow Pattern".

Conclusion: The top deviations haven’t really changed since 2010 (see our GMP News from 25 March 2011). Most of the findings concern the question of process validation and especially solid forms. Also the number of insufficient Media Fills remains almost the same as in the year before. Yet, water systems and their validation as well as "smoke studies" have been a little less criticised compared to 2010. Validation of holding time for bulk material is a new top deviation.

Sven Pommeranz
CONCEPT HEIDELBERG (a service provider entrusted by the ECA Foundation)

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