Root Cause Analysis: Again, problems discovered in GMP-Inspections

Recently, we have increasingly reported that a lack of root cause analysis for deviations and OOS results has led to observations during inspections. This has been a recurring theme in FDA Warning Letters, for example.

Now another FDA Warning Letter has been published criticising the root cause analysis carried out. In a letter to the General Manager of Chem-Tech Ltd in the USA, the following is mentioned, among other things:

• "Your firm failed to conduct adequate manufacturing investigations into out-of-specification (OOS) results obtained by your external laboratory for your (...), an over-the-counter (OTC) drug product. As such, root cause(s) for the OOS results were not determined and no corrective and preventive actions (CAPA) were identified."
• "your cursory investigation lacked appropriate CAPA"
• "As a manufacturer, you have a responsibility to fully investigate OOS results and process deviations that may impact product quality."
• "the procedures for handling deviations and complaints are inadequate. For example, the deviations procedure lacks details for the investigation process".

A 'Statement of Non-Compliance with GMP' has now also been published in the European database EudraGMDP (Report No: PE010-4529) by the Spanish Agency Of Medicines And Medical Devices for a manufacturer in Spain. It states:

• "Deviations, OOS, OOT management is very poor and no appropriate corrective and preventive actions are taken in response to the investigations."

This again shows that investigations and root cause analyses are a basis for a compliant pharmaceutical quality system and that inspectors are increasingly looking closely at the processes.