FDA WARNING_LETTER - Trifarma S.p.A. - January 29, 2014

On July 7, 2014, the FDA issued a Warning Letter to Trifarma S.p.A. following a January 27-29, 2014 inspection of their Rozzano, Italy, pharmaceutical manufacturing facility. The inspection identified significant deviations from current Good Manufacturing Practice (CGMP) for Active Pharmaceutical Ingredients (APIs), rendering their APIs adulterated under Section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act.

Key violations included: 1. **Failure to maintain complete data:** The firm deleted electronic raw data for HPLC testing of APIs released to the U.S. market and failed to retain basic chromatographic information (injection sequence, instrument/integration methods). Laboratory management was unaware of and did not follow procedures for analytical data review, including system suitability. The firm's proposed backup system was insufficient, lacking provisions for injection sequence, instrument method, audit trails, and preventing premature deletion. 2. **Failure to prevent unauthorized data access/changes:** Laboratory systems lacked controls to prevent unauthorized deletion or alteration of raw electronic data, with all employees having full system privileges. Prior to January 7, 2014, HPLC and GC software lacked active audit trail functions. The firm's proposed safeguards for electronic raw data retention were not yet implemented. Additionally, electronic raw data supporting cleaning, method, and process validations were absent. 3. **Failure to ensure