FDA WARNING_LETTER - Legacy Pharmaceuticals International - September 28, 2007

The FDA issued a Warning Letter to Legacy Pharmaceuticals International following an inspection of its Puerto Rico facility from September 10-28, 2007, concerning the manufacture of Efudex Topical Cream 5%. The inspection revealed significant deviations from Current Good Manufacturing Practice (CGMP) Regulations (21 CFR Parts 210 and 211), rendering the drug adulterated under 21 U.S.C. § 351(a)(2)(B).

Key violations included the failure to establish adequate written procedures for production and process control (21 CFR § 211.100(a)), leading to product variability and a lack of process understanding. The firm also failed to establish scientifically sound specifications and test procedures (21 CFR § 211.160(b)), particularly for viscosity, despite observed correlations with physical stability. Furthermore, the three-year expiration date for Efudex was deemed invalid due to numerous lots failing assay and [redacted] content specifications during their expiry period (21 CFR § 211.137(a)). Finally, the Quality Control unit failed to adequately review production records, investigate errors, and ensure proper procedure implementation (21 CFR § 211.22(a) and (c)), specifically regarding uninvestigated temperature fluctuations.

The FDA requires prompt corrective actions within 15 working days, including a written explanation of steps taken to prevent recurrence and supporting documentation. Failure to comply may result in legal action, including seizure and injunction, and could impact federal contracts, export certificates, and pending drug applications. A reinspection will be necessary to verify compliance.