Your quality unit failed to monitor and investigate error signals generated by the computerized systems that you use for high performance liquid chromatography and gas chromatography. These signals indicated the loss or deletion of original CGMP analytical data. However, your quality unit did not comprehensively address the error signals or determine the scope or impact of lost or deleted data until after these problems were reviewed during our inspection.
For example, our investigator reviewed audit trails from August 2016 assay testing on [redacted] batch [redacted] and dissolution testing for [redacted] tablets batch [redacted]. The audit trail for these tests included the message, “deleted result set,” but neither of these two incidents were recorded in the analytical packages for these batches of drug products, nor were they reviewed or investigated by the quality unit.
In addition, during the inspection, our investigator observed that your Empower 3 system audit trail displayed many instances of a “Project Integrity Failed” message, which indicates that injections were missing from the results of analytical testing. For example, in [redacted] analysis for [redacted] tablets batch [redacted] conducted on June 20, 2016, no chromatogram was rendered for the initial run of testing. The data package for this testing clearly shows that the initial run is missing, but your quality unit did not investigate the incident.
Although you showed our investigator isolated examples of interrupted, missing, deleted, and lost data for which you had opened investigations, you reached similar conclusions in many of these investigations regarding the root cause of your loss of data integrity but failed to take appropriate corrective action and preventive action in response. Our investigator observed that you attributed numerous incidents to power interruptions, connectivity problems (disconnection of the Ethernet or power cord), and instrument malfunctions. You could not explain why these events occurred with frequency in your laboratory, nor had you undertaken a comprehensive investigation into the problem or sought to correct it and prevent its recurrence.
In your written response dated February 17, 2017, you identified seven samples from a single week of testing for which original results were lost following data acquisition interruptions at the time of initial analysis. Instead of uniformly initiating an investigation into the root cause of each interruption when it occurred or even documenting it for later review and investigation by the quality unit, you explained in your response that you retested the samples immediately after the interruptions.
Your response is inadequate because you have not identified and investigated each instance in which data acquisition was interrupted. While you assessed a limited number of error codes from a seven day period, you did not evaluate the effects of other error codes identified in your simulation exercise report on the reliability, accuracy, or completeness of the data you use to evaluate the quality of your drugs. Although you have submitted multiple responses, you have not yet:
In response to this letter, provide your validation of laboratory instrument error codes. Identify the specific codes that may impact product quality and the reliability of CGMP data, and provide your procedures to demonstrate how your quality unit will review, investigate, and respond to these specific codes.
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