Warning Letter for Big Pharma Company: Root Cause Analysis a Topic

Time and again, inadequate root cause analyses for deviations and OOS results are subject of inspections and also find their way into FDA Warning Letters. Genzyme, a subsidiary of a global company in the USA, has now been hit. The inspection period lasted several days (12 June to 9 July 2024).

What happened?

During the inspection, the FDA found that around 20% of the bioreactor runs in the period from January 2022 to July 2024 were rejected due to contamination or other quality defects. According to the FDA, this calls into question the level of control of the process. Also, failure to adequately investigate critical deviations was reported. Not all potential underlying causes were identified and there were inconsistencies in root cause analyses. Also, not all investigation activities were documented (for example, a sample taken was found in a storage room).

In the response to the observations, reference was made to numerous corrective and preventive actions (CAPAs) that had been initiated. However, this response was not sufficient for the FDA.
For example, the completed investigations mentioned were not submitted, the root cause(s) were not identified, the individual CAPAs were not justified and it was not explained how the effectiveness of the CAPAs will be determined.

The FDA is now demanding, among other things, updated reports on the investigations, a "comprehensive assessment of your overall system for investigating deviations, discrepancies, complaints, OOS results, and failures", including a detailed action plan. This action plan should include significant improvements in "investigation competencies, scope determination, root cause evaluation, CAPA effectiveness, quality unit (QU) oversight, and written procedures".