FDA WARNING_LETTER - Liebel-Flarsheim Company LLC - April 08, 2025

The FDA issued a Warning Letter to Liebel-Flarsheim Company LLC following an inspection from March 25 to April 8, 2025, at their Raleigh, NC, drug manufacturing facility. The letter cites significant violations of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals (21 CFR parts 210 and 211), rendering their drug products adulterated under section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act. Significant issues included the failure to thoroughly investigate unexplained discrepancies and batch failures.

Specifically, the company inadequately investigated numerous microbial excursions (bioburden) in in-process drug samples and out-of-specification (OOS) endotoxin results for finished sterile drug products. Investigations frequently lacked scientifically justified root causes, often concluding as "root cause undetermined," and corrective actions were deemed insufficient. The FDA criticized the firm"s over-reliance on terminal sterilization and final product testing as a substitute for comprehensive root cause analysis. Notably, the company released batches with OOS endotoxin failures for U.S. distribution.

As a required action, the FDA demands a retrospective, independent review of all invalidated OOS results, including those from in-process and release/stability testing, to address these critical deficiencies and ensure product safety.