Insufficient Root Cause Analysis leads to FDA Warning Letter

A company in Italy recently received a Warning Letter by the FDA because of failures in testing incoming raw materials, failures in investigating deviations and missing data.

What happened?

The company had some (or as FDA says "multiple") microbial excursions. But the company was too quick in determining the cause and the following actions. Without an evidence or even assessment of a possible root cause, they concluded that "the result was likely due to a sampling error". So, no further risk assessment was performed, only finished product was tested.

The FDA was clear on that stating that "without investigations into microbial failure results" one cannot ensure that minimum microbiological and chemical standards are suitable.

Additionally, the FDA found that changes were made to batch records "without adequate explanation or investigation". Here, the company didn't start an investigation "because a supervisor made this change".

The authority now requests (among other things):

• Complete investigations into all test results that were above the "microbial action limit (whether or not later invalidated) in the previous three years". These investigations should detail findings regarding the root causes of the contamination.
• A "detailed risk assessment addressing the potentially hazardous effects" on the quality of all drug product lots within expiry currently in the United States.
• A "comprehensive, independent assessment of [the] overall system for investigating deviations, discrepancies, complaints, OOS results, and failures" including "a detailed action plan to remediate this system".