FDA WARNING_LETTER - Alexion Pharmaceuticals, Inc. - August 06, 2012

On March 22, 2013, the FDA issued a Warning Letter to Alexion Pharmaceuticals, Inc. following a July-August 2012 inspection of their Smithfield, RI facility. The inspection revealed significant Current Good Manufacturing Practice (CGMP) violations in the manufacture of Soliris API, rendering the API adulterated.

Key violations included: 1. **Inadequate investigation of critical deviations:** Six Soliris API lots were contaminated with *Bacillus thuringiensis* (TNTC/10 mL), exceeding action limits. *Acinetobacter radioresistens* was also found in one lot. The firm failed to conduct thorough root cause investigations, assess the impact of contamination on the final product, or verify cleaning effectiveness. Reliance on additional testing without scientific rationale for clearance of non-host cell impurities was noted. The toxicology assessment for pediatric use was questioned. 2. **Quality unit failure:** The quality unit released two Soliris API lots (TNTC/10mL contamination) for further manufacturing without adequate scientific justification, with inconsistent actions taken for each lot. Repeated bioreactor cleaning cycles indicated potential design or function issues.

The FDA noted a lack of a robust quality system, with repeat citations from a February 2011 inspection. The agency recommended engaging a third-party CGMP consultant. Alexion was instructed to provide a written response within fifteen working days detailing corrective actions and timelines. Failure to comply could result in legal action