FDA WARNING_LETTER - Fagron Group B.V. - November 18, 2021

The FDA issued a Warning Letter to Fagron, Inc. following an inspection from November 1 to November 18, 2021, at their Saint Paul, Minnesota facility, identifying significant deviations from Current Good Manufacturing Practice (CGMP) for Active Pharmaceutical Ingredients (API).

Key violations include: 1. **Failure to prevent cross-contamination during API repackaging:** The firm lacked adequate cleaning validation studies for non-dedicated production rooms and equipment, with preliminary results showing unacceptable residue levels for potent compounds like niacin and progesterone. Visible powder residue was observed on equipment after cleaning, and a cleaning log was destroyed. 2. **Inadequate investigation of out-of-specification (OOS) results:** The firm failed to investigate OOS bioburden counts in their water system, a drug component, exceeding action limits. Investigations into OOS results were not initiated or adequately documented. 3. **Quality Unit (QU) deficiencies:** The QU failed to ensure CGMP compliance, with laboratory equipment allowing unrestricted data changes/deletion and a lack of qualification for contract laboratories, a repeat observation from 2017.

The FDA requires comprehensive corrective actions, including a retrospective assessment of cleaning effectiveness, a CAPA plan for cleaning processes, improvements to the cleaning validation program, updated SOPs, and testing of retain samples for cross-contamination. For OOS issues, a retrospective review of invalidated OOS results, a comprehensive review and remediation plan for OOS investigation