21 CFR 211.192 requires a thorough review of any unexplained discrepancy whether or not the batch has been distributed.  Lack of / or poor Alarm management was identified by the FDA during an inspection of a 503B Outsourcing Facility (Observation 2, Form 483).

The firms Building Maintenance System had logged ~766 alarms since March 8, 2016 (the inspection was August/September 2016) and the firm had not documented deviations nor performed investigations on any of the alarms in conjunction with batch release.  All of the alarms at the time of inspection were deemed critical by the firm.

In the posted warning letter, the FDA reviewed the Firms corrective actions.  The Firm’s response identified that the alarm records contained within the facilities Building Management System were not reviewed concurrently with the production batch records prior to release because most of the 766 alarms were not actually critical.  However, the alarms were considered critical at the time of the inspection and the firm did not supply a rational for which alarms are critical and which are not.

Alarm and alarm management should be used as part of the control strategy to ensure the operators are informed when a Critical Process Parameter is approaching or is out of specification.  There should be a difference between a warning, an alert, and an alarm with different operator actions to restore (if necessary) the system to controlled operation.  The alarm management strategy should be developed by the firm based on understanding of the quality target product profile, the Critical Quality Attributes which have an influence on product quality and the critical process parameters that may influence CQA’s and ultimately impact product quality (ICHQ8R2).

Alarm management may be evaluated using the risk management tools contained in ICHQ9.  This will aid the facility in insuring each alarm has a purpose in terms of the overall control strategy.  Having a control strategy that generates hundreds or thousands of nuisance alarms can desensitize the operator resulting in slow or no response to an actual critical condition.

Have a question on Alarm Management? Please use our “Contact Us” form and one of PVs quality professionals will be in touch.

Previous Do you do API?
Next 503B Registrations and Inspections