Root Cause Analysis: Problems continue

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

Now, another Warning Letter from the FDA has been published, criticising the root cause analysis that was carried out. In a letter to Glenmark Pharmaceuticals (India), the following is stated, among other things:

• "One of the potential root causes ... appears to be insufficient to explain the dissolution failures."
• "Investigation report did not include sufficient scientific evidence to support [second] root cause"
• "Investigation was not sufficient to adequately determine root cause(s) of your repeated dissolution failures during long-term stability testing."
• "There is no indication you investigated (...) adequately as part of your root cause analysis for these dissolution failures."
• "Your study did not provide adequate data (...) to support your conclusion."
• "Your investigations into dissolution failures during stability testing of another drug product (...), did not adequately support your root cause."
• "[You] did not perform sufficient validation studies to confirm your root cause determination prior to distribution of more batches."
• "You do not include the test results from the delayed stability analyses or a copy of the investigation report with your written response to demonstrate whether backlogged stability testing was completed and adequately investigated for root cause."

This shows once more that root cause analyses form the basis for a compliant pharmaceutical quality system and that inspectors are increasingly scrutinising processes in this area.